Introduction To Brain and Behav - Bryan Kolb PDF
Uploaded by
elahehIntroduction To Brain and Behav - Bryan Kolb PDF
Uploaded by
elahehd
I n de x of dI sor de r s* -3
■ D eaf n e s s: §10
Each disorder name is followed by the section (§) ■ D e af fe re n t a t i
o n: §11- 4 , §14 - 4
and/or Focus feature number (s) where information appears. ■ D e m e n t i a : §2
- 6 , §5 -3, §7-1, §7-2 , §7- 4 , §7-5, Fo c
u s 14 -3, §16 -3
s i o n : § 5 - 3 , F o c u s 6 - 3 , F o c u s 7 - 2 , § 1 2- 4 , Fo c u s 16 -2 , §16 - 4
■ D e p re s
a l d i s a b i l i t y : F o c u s 6 -2 , § 8 - 4 , F o c u s 1
A ■ D eve lo p m e n t 1-2 , §16 -1
■ Ad d ic tio n: §2-3, § 6 -3, §7-2 , §12- 4 , §12- 6 p m e n t a l d i s o r d e r s : F o c u s 7 - 4 , F o c u s 8 -3, Fo c u s 14 -1,
■ D eve lo
■ Af fe c tive d iso rd e r s: Fo c u s 12-1, §16 - 4 5 -3, §16 -1, §16 -2 , §16 -3
Amygdala Fo c u s 15 -3, §1
■ A ge n e sis: of ce re b e llu m , Fo c u s 2-1; 6 -3
■ D ia s c hisis: §1
s ive d ys to nia: Fo c u s 3 -1
of f ro nt a l lo b e, Fo c u s 12-2 ■ D o pa - re s p o n
m e : § 3 -3 , § 8 - 4
■ A g n o s i a s : § 9 -2 , § 9 -5 ■ D ow n s y n d ro
e n c y in s o m nia: §13 - 6
■ A kat h e sia: §16 -3 ■ D r ug- d e pe nd
b e h av io r a l s e n sitiz a tio n : s e e B e h av
■ A k in e sia: §7-1, §16 -3 ■ D r ug-ind uced io r al
■ Alco h o l myo pia: §16 -3 se n sitiz atio n
■ Al z h eim e r d is ea s e: §2-5, §5 -3, § 6 - 4 , Fo c u s 14 -3, §16 -3 ■ D r ug-ind uced
ps yc h osis: Fo c u s 6 - 4 , Fo c u s 7-3
o c u s 5 -3, §5 -3, Fo c u s 11-2 , §11-3, §
■ A m b lyo p ia : § 8 - 4 ■ D ys k in e sia : F 16 - 2
■ A m n e sia: §7-1, §14 -2 , Fo c u s 14 -2 , §15 -7 ■ D ys le x i a : F o c u s 1 4 -1
u s 14 -5
■ A m u s i a : F o c u s 10 - 6 ■ D y s t o n i a : Fo c
■ A myot ro p hic l ate r a l s c le rosis (A L S): Fo c u s 4 - 4 , Fo c u s 11-1 e
■ A n d roge n in s e n sitiv it y s y n d ro m e: Fo c u s 12-5 ■ En ce p ha litis: §
2-2
■ A n d roge nit a l s y n d ro m e: Fo c u s 12-5 l d e p r ivatio n: Fo c u s 8 -1, § 8 - 4 , Fo c u
■ E nv iro n m e n t a s 8 - 4 , §16 -1
c t o r s: §1-2 , §2-1, §3 -3, § 6 - 4 , §7-5,
■ A n e n ce p h a ly: § 8 - 4 ■ Epige n etic fa § 8 -2 , §12-5,
4 - 4 , §15 -3, §15 - 6 , §16 -1, §16 -3
■ A n e u r y s m : F o c u s 10 -5 Fo c u s 13 -3, §1
u s 4 -1, §7-2 , Fo c u s 10 -3, Fo c u s 15
■ A n o re x ia n e r vos a: §12-5 ■ E p i l e p s y : Fo c -5, §16 -3
■ A nte rog r ad e a m n e sia: Fo c u s 14 - 4 i o n : §1 5 - 2
■ E x tinc t
■ A n x iet y d is o rd e r s: § 6 -2 , § 6 -3, Fo c u s 12-3, §16 - 4 f
s p e c t r u m d is o rd e r (FA S D): Fo c u s 6 -2
■ A p h agia: §12-5 ■ Fe t a l a l c o h o l , §14 - 4
■ A p h a sia s: §7-3, §10 - 4 , Fo c u s 15 -5 § 16 - 3
■ Fe s t i n a t i o n :
§16 -3
■ A p r a x ia: §11-5 ■ Fo c a l s e i z u r e :
■ A r te r iove n o u s m a lfo r m atio n s: §16 -2 , §16 -3 ■ Fr o n t a l l e u c o t o my : §12- 4
■ A t a x i a : § 9 -5 g
■ Attention-defcit/hyperactivity disorder (ADHD): Focus 6 -1, Focus 7- 4 ■ G end er d ysph
o r ia: Ta b le 16 -3; s e e a l s o §12-5
■ Autis m s p e c t r u m d is o rd e r (A S D): Fo c u s 8 -2 , § 8 - 4 , Fo c u s 15 -3 ■ G e n e r a lize d a
n x iet y : §12- 4 , §16 - 4
■ Autoim m u n e d is ea s e: Fo c u s 4 -2 , §16 -3 s e iz u re: §16 -3
■ G e n e r a lize d
ers: §1-2, Focus 3-1, §3-3, Focus 4 -4, Fo
b ■ Genetic disord cus 5-2, §6-4, §7-
■ B e h av io r a l s e n sitiz atio n: § 6 -1, § 6 - 4 , §14 - 4 § 10-4, §12-5, §13-6, §15-5, §16-1, §16
5, §8-2, §8-4, -2, §16-3, §16-4
3 -2
■ B e ll p a l s y : Fo c u s 2- 4 ■ G l i o m a : Fo c u s
■ B ip o l a r d is o rd e r : § 6 -2 , §16 - 4 h
s: § 6 -2 , Fo c u s 6 - 4 , Fo c u s 8 -5, §13 - 6 ,
■ B lin d sig ht : Fo c u s 9 -1, §15 -7 ■ H a lluc in atio n §15 -7
§ 9 -5
■ B r ain tu m o r s: Fo c u s 3 -2 , §7-3 ■ H e m ia n o pia :
s t ro ke: Fo c u s 2-3
c ■ H e m o r r h agic
■ C a r b o n m o n ox i d e p o i s o n i n g : Fo c u s 9 - 4 s o rd e r s: §7-5, § 8 - 4 , §12-5, §16 -1, §
■ Hor monal di 16 -2 , §16 - 4
■ C at a p le x y : §13 - 6 g t o n d i s e a s e : F o c u s 3 - 4
■ Huntin
s: §3 -1
■ C at ato nic p os tu re: §16 -3 ■ H yd r o c e p h a l u
-2
■ Ce re b r a l a n eu r ys m : Fo c u s 10 -5 ■ H y p e ro p ia : §9
Kasthuri and Lichtman,
Harvard University
: § 12-5
■ Ce re b r a l p a l s y : Fo c u s 11-2 ■ H y p e r p h a gia
■ Ch ro nic t r a um atic e n ce p h a lo pat hy : Fo c u s 16 -3 ■ H y p n ogogic h
a lluc in atio n s: §13 - 6
■ Cog nitive d is o rd e r s: §7- 4 , Fo c u s 8 - 4 , § 8 -5, §15 -7, §16 -3 ■ H y p ovo l u m i c
t hir s t : §12-5
lobe
■ Co lo r- d ef ic ie nt v isio n: Fo c u s 9 -3 i
■ Co m a: §1-2 , § 6 -2 , §7-2 , §13 -5, §16 -3 z u re: §16 -3
■ I dio pat hic s ei
-6
■ C o n c u s s i o n : F o c u s 16 - 3 ■ I n s o m nia: §13
c u s 2-3, §16 -3
■ Co nt r a l ate r al n eg le c t : §15 -2 ■ I s c h e m i a : Fo
r ia (PKU): § 8 - 4 , §16 -1
j ■ P h e n y l ke t o n u
s 12-3, §16 -2
■ J et l ag: §13 -1 ■ P h o b i a s : Fo c u
r e s sio n: §16 -3
k ■ Po s t ic t a l d e p
stress disorder (PTSD): §5 - 4, §6 -5,
■ Klü ve r– B uc y s y n d ro m e: §12- 4 ■ Po s t t r a u m a t i c §12- 4, Focus 16 -1
9 -2
■ Ko r s a kof f s y n d ro m e: Fo c u s 14 - 4 ■ P r e s byo p ia : §
§16 -3
l ■ Pr io n disea se:
- 2 , Fo c u s 6 - 4 , Fo c u s 7-3, §16 -2 , §
■ L a nguage d is o rd e r s: §7-1, Fo c u s 8 -2 , § 8 -3, § 8 - 4 , §10 -3, §10 - 4 , ■ P s yc h o s i s : § 6 16 - 3
Fo c u s 14 -1, §15 -1, §15 - 4 q
p i a : § 9 -5
■ L ea r ning d is a bilitie s: Fo c u s 7- 4 , § 8 - 4 , Fo c u s 14 -1 ■ Q uadrantano
§11-1
■ L o c ke d -in s y n d ro m e: Fo c u s 11-1, §11-1 ■ Q u a d r ip legia :
■ L o u G e h r ig ’s d is ea s e (A L S): Fo c u s 4 - 4 , Fo c u s 11-1 r
y n d ro m e (R L S): Fo c u s 13 - 4
m ■ Re s t l e s s le g s s
m n e sia: Fo c u s 14 - 4
■ M ajo r d e p re s sio n: §5 -3, Fo c u s 6 -3, Fo c u s 7-2 , §12- 4 , Fo c u s 16 -2 ■ Re t ro g r a d e a
■ M a nia: §5 -3, § 6 -2 , §16 - 4 s
: §5 -3, § 6 -1, § 6 -2 , Fo c u s 6 - 4 , §7-1,
■ M e m o r y d ef ic it s: §7-1, Fo c u s 7-2 , §14 -2 , §14 -3, Fo c u s 14 -3 ■ S c hiz o p h re nia §7- 4 , §7-5,
- 3 , F o c u s 8 - 5 , § 1 6 - 2 , § 1 6 - 4
■ M é niè re d is ea s e: §11- 4 Fo c u s 7
u s 9 -1, §9 -5
■ M e n i n g i o m a : F o c u s 3 -2 ■ S c o t o m a : Fo c
c tive d is o rd e r (SA D): Fo c u s 13 -2
■ M e ningitis: §2-2 ■ S e a s o n a l af fe
s 4 -1, Fo c u s 10 -3, §16 -3
■ M et a b o lic s y n d ro m e: Fo c u s 13 -1, §13 -1 ■ S e i z u r e : Fo c u
o c u s 13 -5
■ M e t a s t a t i c t u m o r : F o c u s 3 -2 ■ S le e p a p n ea: F
s i s : §13 - 6
■ M ig r ain e: Fo c u s 9 -1 ■ S le e p p a r a ly
8-4
■ M ild cog nitive im p air m e nt : Fo c u s 14 -3, §16 -3 ■ S p i n a b if id a : §
n j u r y : §2- 4 , § 6 -2 , Fo c u s 11-3, §11- 4
■ M inim a lly co n s c io u s s t ate (M C S): §1-2 ■ S p i n a l- c o rd i , §12-3
a i n s y n d r o m e : F o c u s 1 5 -1 , §15 - 4
■ M o n o c u l a r b l i n d n e s s : § 9 -5 ■ S p l i t- b r
6 -5, §7-5, § 8 -2 , § 8 - 4 , §12- 4 , §16 -1, §
■ M o o d d is o rd e r s: §12- 4 , §16 - 4 ■ St re s s §2-5, § 16 -2 , §16 -3,
■ M P T P p ois o ning: Fo c u s 5 - 4 , §16 -1 §16 - 4
§7-1, §7-3, §7-5, §7-7, §16 -3
■ M u ltip le s c lerosis (MS): Fo c u s 4 -2 , § 6 -2 , §16 -3 ■ St ro ke: §2-3,
s e: §2-3, § 6 -3, §12- 4 , §12- 6
■ M ya s t h e nia g r av is: § 4 - 4 , § 6 -1 ■ Substance abu
t d eat h s y n d ro m e (S I DS): §5 -3, § 8 -
■ M y o p i a : § 9 -2 ■ S ud d e n infa n 4 , Fo c u s 13 -5
: F o c u s 6 - 3 , § 7 - 5 , § 1 6 - 4
n ■ S uic id e
s eiz u re: §16 -3
■ N a rco le ps y : §13 - 6 ■ Sy m p t o m a t i c
9 -1, §15 -5, Fo c u s 15 - 6
■ N eg le c t : §15-2 , §15 -7 ■ Sy n e s t h e s i a : §
■ N e u ro d ege n e r ative d is ea s e: §16 -3 t
e sia: §16 -2
■ N e u rotox in s: Fo c u s 5 -2 , §5 -3, § 6 - 4 , §16 -1, §16 -2 , §16 -3 ■ Ta rdive d ys k in
s e a s e: §3 -3, §16 -1
■ N ig ht te r ro r s: §13 -3 ■ Tay – S a c h s d i
ro m e: §2-3, Fo c u s 11- 4
o ■ To u ret te s y n d
a i n inju r y ( T B I): Fo c u s 1-1, §7-1, §7-
■ O b e sit y : §12-5 ■ Tr a u m atic b r 5, §14 -5, §16 -3
u s 3 - 3 , §7- 3
■ O bs e s sive - co m p u l sive dis o rd e r (O CD): §5 -3, §12- 4 , §15 -7, §16 -2 ■ Tu m o r s : F o c
■ O p t i c a t a x i a : § 9 -5 v
■ O s m otic t hirs t : §12-5 ■ Ve r tigo: §11- 4
g n osia: §9 -5, §15 -7
■ O t o a c o u s t i c e m i s s i o n s : F o c u s 10 -2 ■ V i s u a l-fo r m a
a n c e : F o c u s 9 -2
p ■ V is ua l illu min
■ Pain: § 6 -2 , §11- 4 , Fo c u s 12-1, §16 -2 , §16 -3 w
atio n: §12-5
■ Pa nic d is o rd e r : Fo c u s 12-3 ■ Wa t e r i n t o x i c
■ Pa r a lysis: Fo c u s 2- 4 , §3 -1
f general treatment categor ies, see the Ch
■ Pa r a p legia: §11-1, Fo c u s 11-3 * F o r a su m m a r y o apter 16
s u mmar y of research techniques, see Tables
■ Pa r k in s o n d is ea s e: §2-3, Fo c u s 5 -2 , Fo c u s 5 -3, Summar y. For a 7-1 and 7-2.
Fo c u s 5 - 4 , §5 -3, §7-1, §7-5, §11-3, §16 -3
■ Pe r s eve r atio n: §15 -2
■ Pe r sis te nt veget ative s t ate: §1-2
■ Ph a nto m lim b p ain: Fo c u s 11-5, §11-5
this page left intentionally blank
An Introduction to Brain and Behavior
this page left intentionally blank
An Introduction to Brain and Behavior
Bryan Kolb Ian Q. Whishaw G. Campbell Teskey
University of Lethbridge University of Lethbridge University of Calgary
Fifth Edition
New York
This book is dedicated to Cornelius H. “Case” Vanderwolf
(1935–2015), with whom each of us studied. Case did his Ph.D. with
Donald O. Hebb and postdoctoral research with Konrad Ackert and
Roger Sperry, figures whose research is featured prominently in this
book. He was an advocate of the theory that the study of behavior
provided the window to the organization of the brain, and he was
especially encouraging of our first attempt at book writing.
Publisher, Psychology and Sociology: Rachel Losh Library of Congress Control Number: 2015957301
Senior Acquisitions Editor: Daniel DeBonis
Development Editor: Barbara Brooks ISBN-13: 978-1-4641-0601-9
Assistant Editor: Katie Pachnos ISBN-10: 1-4641-0601-0
Senior Marketing Manager: Lindsay Johnson
Marketing Assistant: Morgan Ratner Copyright © 2016, 2014, 2011, 2006 by Worth Publishers
Executive Media Editor: Rachel Comerford All rights reserved.
Associate Media Editor: Jessica Lauffer Printed in the United States of America
Director, Content Management Enhancement: Tracey Kuehn
Managing Editor, Sciences and Social Sciences: Lisa Kinne First printing
Project Editor: Edgar Doolan
Media Producer: Elizabeth Dougherty Worth Publishers
Copy Editor: Kate Daly One New York Plaza
Senior Photo Editor: Cecilia Varas Suite 4500
Photo Researcher: Richard Fox New York, New York 10004-1562
Senior Production Manager: Paul Rohloff www.macmillanhighered.com
Director of Design, Content Management Enhancement: Diana Blume
Design Manager: Blake Logan
Interior Design: Charles Yuen
Art Manager: Matthew McAdams
Illustration Coordinator: Janice Donnola
New Illustrations: Evelyn Pence, Matthew McAdams
Composition: codeMantra
Printing and Binding: RR Donelley
Cover Art: ALFRED PASIEKA/SCIENCE PHOTO LIBRARY/Getty Images
Chapter Opener Illustrations: Katherine Streeter
Abou t the Au thor s
Bryan Kolb received his Ph.D. from The Pennsylvania
State University in 1973. He conducted postdoctoral work at the
University of Western Ontario and the Montreal Neurological
Institute. He moved to the University of Lethbridge in 1976,
where he is Professor of Neuroscience and holds a Board of
Deborah Muirhead
Governors Chair in Neuroscience. His current research examines
how neurons of the cerebral cortex change in response to vari-
ous factors, including hormones, experience, psychoactive drugs,
neurotrophins, and injury, and how these changes are related to behavior in the normal and
diseased brain. Kolb has received the distinguished teaching medal from the University of
Lethbridge. He is a Fellow of the Royal Society of Canada and of the Canadian Psychological
Association (CPA), the American Psychological Association, and the Association of Psycho-
logical Science. He is a recipient of the Hebb Prize from CPA and from the Canadian Society
for Brain, Behaviour, and Cognitive Science and has received four honorary doctorates. He
is a Senior Fellow of the Experience-Based Brain and Behavioral Development program of
the Canadian Institute for Advanced Research. He and his wife train and show horses in
Western riding performance events.
Ian Q. Whishaw received his Ph.D. from Western
University and is a Professor of Neuroscience at the University of
Lethbridge. He has held visiting appointments at the University
of Texas, University of Michigan, Cambridge University, and the
University of Strasbourg. He is a fellow of Clair Hall, Cambridge,
David Benard
and of the Canadian Psychological Association, the American
Psychological Association, and the Royal Society of Canada. He
is a recipient of the Canadian Humane Society Bronze Medal for
bravery, the Ingrid Speaker Gold Medal for research, and the distinguished teaching medal
from the University of Lethbridge. He has received the Key to the City of Lethbridge and
has honorary doctorates from Thompson Rivers University and the University of Lethbridge.
His research addresses the neural basis of skilled movement and the neural basis of brain
disease, and the Institute for Scientific Information includes him in its list of most cited
neuroscientists. His hobby is training horses for Western performance events.
G. Campbell Teskey received his Ph.D. from Western
University in 1990 and then conducted postdoctoral work at
McMaster University. In 1992 he relocated to the University
of Calgary, where he is a professor in the Department of Cell
Biology and Anatomy and the Hotchkiss Brain Institute. His cur-
Tannis Teskey
rent research program examines the development, organization,
and plasticity of the motor cortex, as well as how seizures alter
brain function. Teskey has won numerous teaching awards, has
developed new courses, and is a founder of the Bachelor’s of Science in Neuroscience pro-
gram at his home university. He serves as Education Director for the Hotchkiss Brain Insti-
tute and chairs the Education Committee of Campus Alberta Neuroscience. His hobbies
include hiking, biking, kayaking, and skiing.
this page left intentionally blank
CoNt eNt s iN brief
Preface xix
Media and Supplements xxvii
ChApter 1 What Are the Origins of Brain and Behavior? 1
ChApter 2 What Is the Nervous System’s Functional Anatomy? 33
ChApter 3 What Are the Nervous System’s Functional Units? 73
ChApter 4 How Do Neurons Use Electrical Signals to Transmit Information? 107
ChApter 5 How Do Neurons Communicate and Adapt? 137
ChApter 6 How Do Drugs and Hormones Influence the Brain and Behavior? 171
ChApter 7 How Do We Study the Brain’s Structures and Functions? 209
ChApter 8 How Does the Nervous System Develop and Adapt? 245
ChApter 9 How Do We Sense, Perceive, and See the World? 283
ChApter 10 How Do We Hear, Speak, and Make Music? 321
ChApter 11 How Does the Nervous System Respond to Stimulation
and Produce Movement? 355
ChApter 12 What Causes Emotional and Motivated Behavior? 397
ChApter 13 Why Do We Sleep and Dream? 441
ChApter 14 How Do We Learn and Remember? 479
ChApter 15 How Does the Brain Think? 519
ChApter 16 What Happens When the Brain Misbehaves? 561
Answers to Section Review Self-Tests A-1
Glossary G-1
References R-0
Name Index N-1
Subject Index S-1
this page left intentionally blank
CoNt eNt s
PrefaCe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
MedIa and suPPleMenTs . . . . . . . . . . . . . . . . . . . . . . . . . xxvii Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
ChApter 1 ChApter 2
What Is the Nervous
Katherine Streeter
Katherine Streeter
What Are the Origins
of Brain and Behavior? . . . . . 1 System’s Functional
CliniCal Focus 1-1 Living with Traumatic Brain Anatomy? . . . . . . . . . . . . . . . . . . . . . . 33
Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 researCh Focus 2-1 Agenesis of the Cerebellum . . . . 34
1-1 neuroscience in the Twenty-first 2-1 Overview of Brain function and
Century . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Why study Brain and Behavior? . . . . . . . . . . . . . . . . . . . . 3 Plastic Patterns of neural Organization . . . . . 35
What Is the Brain? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 functional Organization of the
What Is Behavior?. . . . . . . . . . . . . . . . . . . . . . . . 5 nervous system . . . . . . . . . . . . . . . . . . . . . . . . 36
1-2 Perspectives on Brain and Behavior . . . . 6 The Brain’s surface features . . . . . . . . . . . . . . 37
aristotle and Mentalism. . . . . . . . . . . . . . . . . . . 7 THE BASICS: finding your Way around
the Brain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
descartes and dualism . . . . . . . . . . . . . . . . . . . 7
CliniCal Focus 2-2 Meningitis and Encephalitis . . . . 42
darwin and Materialism . . . . . . . . . . . . . . . . . . . 8
The Brain’s Internal features . . . . . . . . . . . . . . . . . . . . . 43
Comparative Focus 1-2 The Speaking Brain . . . . . . . . . . . 9
CliniCal Focus 2-3 Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
EXPERIMENT 1-1 Question:
How do parents
transmit heritable factors to offspring? . . . . . . . 10 2-2 The nervous system’s evolutionary
Contemporary Perspectives on Brain development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
and Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . 12 stages in Brain evolution . . . . . . . . . . . . . . . . . 48
1-3 evolution of Brains and of Behavior . . . 15 The nervous system and Intelligent
Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Origin of Brain Cells and Brains . . . . . . . . . . . . . . . . . . . 15
EXPERIMENT 2-1 Question: does intelligent
THE BASICS: Classification of life . . . . . . . . . . . . . . . . . . 16
behavior require a vertebrate nervous
evolution of nervous systems in animals . . . . . . . 16 system organization? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Chordate nervous system . . . . . . . . . . . . . . . . . . . . . . . . . 18 2-3 The Central nervous system:
evolution of the Human Brain
1-4 Mediating Behavior. . . . . . . . . . . . . . . . 50
and Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 spinal Cord . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
Humans: Members of the Primate Order . . . . . . . . 20 Brainstem. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Australopithecus: Our distant ancestor . . . . . . . . 20 forebrain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
The first Humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Cerebral Cortex . . . . . . . . . . . . . . . . . . . . . . . . 54
relating Brain size and Behavior . . . . . . . . . . . . . . . . . 22 Basal Ganglia . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Comparative Focus 1-3 The Elephant’s Brain . . . . . . . . 24 limbic system . . . . . . . . . . . . . . . . . . . . . . . . . 57
Why the Hominid Brain enlarged . . . . . . . . . . . 24 Olfactory system . . . . . . . . . . . . . . . . . . . . . . . 58
1-5 Modern Human Brain size and 2-4 somatic nervous system:
Intelligence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Transmitting Information. . . . . . . . . . . 59
Meaning of Human Brain size Cranial nerves . . . . . . . . . . . . . . . . . . . . . . . . . 59
Comparisons. . . . . . . . . . . . . . . . . . . . . . . . . . . 27 spinal nerves . . . . . . . . . . . . . . . . . . . . . . . . . . 59
acquisition of Culture . . . . . . . . . . . . . . . . . . . 29 somatic nervous system Connections. . . . . . . 61
ix
Integrating spinal functions . . . . . . . . . . . . . . 61 EXPERIMENT 3-1 Question: Can the principles of
CliniCal Focus 2-4 Magendie, Bell, and neural excitation and inhibition control the
activity of a simple robot? . . . . . . . . . . . . . . . . . . . . . . . . 81
Bell Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
CliniCal Focus 3-3 Brain Tumors . . . . . . . . . . . . . . . . . . . . . 83
autonomic and enteric nervous
2-5
systems: Visceral relations . . . . . . . . . . . . . . . . . 63 3-2 Internal structure of a Cell . . . . . . . . . . . . . . . 86
ans: Balancing Internal functions . . . . . . . . . . . . . . . 63 The Cell as a factory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
ens: Controlling the Gut . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 THE BASICS: Chemistry review . . . . . . . . . . . . . . . . . . . . . .88
2-6 Ten Principles of nervous system Cell Membrane: Barrier and Gatekeeper . . . . . . . . 90
function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 The nucleus and Protein synthesis . . . . . . . . . . . . . . 91
Principle 1: The nervous system Produces The endoplasmic reticulum and Protein
Movement in a Perceptual World the Brain Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Constructs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Proteins: The Cell’s Product . . . . . . . . . . . . . . . . . . . . . . . 93
Principle 2: neuroplasticity Is the Golgi Bodies and Microtubules: Protein
Hallmark of nervous system functioning . . . . . . . 67 Packaging and shipment . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Principle 3: Many Brain Circuits are Crossed . . . . 67 Crossing the Cell Membrane: Channels,
Principle 4: The Cns functions on Gates, and Pumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Multiple levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 3-3 Genes, Cells, and Behavior . . . . . . . . . . . . . . . 96
Principle 5: The Brain Is symmetrical and Mendelian Genetics and the Genetic Code . . . . . . 96
asymmetrical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
applying Mendel’s Principles . . . . . . . . . . . . . . . . . . . . . . 98
Principle 6: Brain systems are Organized
Hierarchically and in Parallel . . . . . . . . . . . . . . . . . . . . . 68 CliniCal Focus 3-4 Huntington Disease . . . . . . . . . . . . . 100
Principle 7: sensory and Motor divisions Genetic engineering . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .101
Permeate the nervous system . . . . . . . . . . . . . . . . . . . 69 Phenotypic Plasticity and the
Principle 8: The Brain divides sensory epigenetic Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Input for Object recognition and Motor suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
Principle 9: Brain functions are
localized and distributed . . . . . . . . . . . . . . . . . . . . . . . . . 70 ChApter 4
Principle 10: The nervous system Works by
Katherine Streeter
Juxtaposing excitation and Inhibition . . . . . . . . . . . 70 How Do Neurons Use
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Electrical Signals to
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Transmit Information? . . . .107
ChApter 3 CliniCal Focus 4-1 Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Katherine Streeter
searching for electrical activity
What Are the Nervous 4-1
in the nervous system . . . . . . . . . . . . . . . . . . . . 109
System’s Functional early Clues That linked electricity
and neuronal activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Units? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 THE BASICS electricity and electrical
researCh Focus 3-1 A Genetic Diagnosis . . . . . . . . . . . . 74 stimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110
3-1 Cells of the nervous system . . . . . . . . . . . . . . 74 Tools for Measuring a neuron’s electrical
activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
researCh Focus 3-2 Brainbow: Rainbow How Ion Movement Produces
Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 electrical Charges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .114
neurons: The Basis of Information Processing . 76
4-2 electrical activity of a Membrane . . . . .116
five Types of Glial Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
resting Potential . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .116
x
Maintaining the resting Potential . . . . . . . . . . . . . . .117 excitatory and Inhibitory Messages . . . . . . . . . . . . 146
Graded Potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119 evolution of Complex
action Potential . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 neurotransmission systems . . . . . . . . . . . . . . . . . . . . . 146
nerve Impulse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 5-2 Varieties of neurotransmitters
refractory Periods and nerve action . . . . . . . . . . . 124
and receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
four Criteria for Identifying
saltatory Conduction and the
neurotransmitters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Myelin sheath . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
four Classes of neurotransmitters . . . . . . . . . . . . . 148
CliniCal Focus 4-2 Multiple Sclerosis . . . . . . . . . . . . . . . 126
CliniCal Focus 5-3 Awakening with l-Dopa . . . . . . . . 152
How neurons Integrate
4-3
Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 Varieties of receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
excitatory and Inhibitory Postsynaptic neurotransmitter systems
5-3
Potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127 and Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
EXPERIMENT 4-1 Question: How does neurotransmission in the somatic
stimulating a neuron influence its nervous system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
excitability? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 dual activating systems of the autonomic
summation of Inputs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 nervous system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Voltage-sensitive Channels and the enteric nervous system autonomy . . . . . . . . . . . . . 158
action Potential . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 four activating systems in the Central
The Versatile neuron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 nervous system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
researCh Focus 4-3 Optogenetics and Light- CliniCal Focus 5-4 The Case of the Frozen
Sensitive Ion Channels . . . . . . . . . . . . . . . . . . . . . . . . . . .131 Addict . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .161
4-4 Into the nervous system 5-4adaptive role of synapses
and Back Out . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 in learning and Memory . . . . . . . . . . . . . . . . . . . . . 162
How sensory stimuli Produce action Habituation response . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
Potentials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 EXPERIMENT 5-2 Question: What happens to
How nerve Impulses Produce Movement . . . . . . . 133 the gill response after repeated
stimulation? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
CliniCal Focus 4-4 ALS: Lou Gehrig’s Disease . . . . . 134
sensitization response . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
EXPERIMENT 5-3 Question: What happens
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
to the gill response in sensitization? . . . . . . . . . . . 165
ChApter 5 learning as a Change in synapse number . . . . . . 166
Dendritic Spines:
Katherine Streeter
researCh Focus 5-5
How Do Neurons Small but Mighty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
Communicate and suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
Adapt? . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
researCh Focus 5-1 The Basis of Neural ChApter 6
Communication in a Heartbeat . . . . . . . . . . . . . . . . . 138
Katherine Streeter
5-1 a Chemical Message . . . . . . . . . . . . . . . . . . . . . . . 138 How Do Drugs and
EXPERIMENT 5-1 Question: How does a neuron pass Hormones Influence the
on a message? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Brain and Behavior? . . . . . . . 171
CliniCal Focus 5-2 Parkinson Disease . . . . . . . . . . . . . . 140
CliniCal Focus 6-1 Cognitive Enhancement . . . . . . . . 172
structure of synapses . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
6-1 Principles of Psychopharmacology . . . 173
neurotransmission in four steps . . . . . . . . . . . . . . . . 143
drug routes into the nervous system . . . . . . . . . . 173
Varieties of synapses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
xi
drug action at synapses: agonists ChApter 7
and antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
Katherine Streeter
an acetylcholine synapse: examples
How Do We Study
of drug action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 the Brain’s Structures
Tolerance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 and Functions? . . . . . . . . . . . . . 209
EXPERIMENT 6-1 Question: Will the consumption of
alcohol produce tolerance? . . . . . . . . . . . . . . . . . . . . . . 178 researCh Focus 7-1 Tuning In to Language . . . . . . . . . 210
sensitization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 7-1 Measuring and Manipulating Brain
EXPERIMENT 6-2 Question: does the
and Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .211
injection of a drug always produce linking neuroanatomy and Behavior . . . . . . . . . . . .211
the same behavior? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 EXPERIMENT 7-1 Question: do hippocampal
6-2 Grouping Psychoactive drugs . . . . . . . . . . 181 neurons contribute to memory formation? . . . . 213
Group I: antianxiety agents and Methods of Behavioral neuroscience . . . . . . . . . . . 214
sedative-Hypnotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 Manipulating Brain–Behavior Interactions . . . . 217
CliniCal Focus 6-2 Fetal Alcohol Spectrum Measuring the Brain’s
7-2
Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 electrical activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
Group II: antipsychotic agents . . . . . . . . . . . . . . . . . . 184 recording action Potentials
Group III: antidepressants and from single Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
Mood stabilizers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184 eeG: recording Graded Potentials
CliniCal Focus 6-3 Major Depression . . . . . . . . . . . . . . . 186 from Thousands of Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Group IV: Opioid analgesics . . . . . . . . . . . . . . . . . . . . . . 187 Mapping Brain function with
event-related Potentials . . . . . . . . . . . . . . . . . . . . . . . . 224
Group V: Psychotropics . . . . . . . . . . . . . . . . . . . . . . . . . . . 188
CliniCal Focus 7-2 Mild Head Injury and
factors Influencing Individual
6-3
Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225
responses to drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . .191
Magnetoencephalography . . . . . . . . . . . . . . . . . . . . . . . 226
Behavior on drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .191
7-3 anatomical Imaging Techniques:
addiction and dependence . . . . . . . . . . . . . . . . . . . . . . 193
CT and MrI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226
sex differences in addiction . . . . . . . . . . . . . . . . . . . . . 193
7-4 functional Brain Imaging . . . . . . . . . . . . . . . . 229
explaining and Treating
6-4
functional Magnetic resonance Imaging . . . . . . 230
drug abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194
Optical Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Wanting-and-liking Theory . . . . . . . . . . . . . . . . . . . . . . 194
Positron emission Tomography . . . . . . . . . . . . . . . . . . 232
Why doesn’t everyone abuse drugs? . . . . . . . . . . . 196
Treating drug abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
7-5 Chemical and Genetic Measures
of Brain and Behavior . . . . . . . . . . . . . . . . . . . . . . . . 234
Can drugs Cause Brain damage? . . . . . . . . . . . . . . . . 197
Measuring Brain Chemistry . . . . . . . . . . . . . . . . . . . . . . . 234
CliniCal Focus 6-4 Drug-Induced Psychosis . . . . . . . . 199
Measuring Genes in Brain
6-5 Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 and Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Hierarchical Control of Hormones . . . . . . . . . . . . . . . 200 CliniCal Focus 7-3 Cannabis Use, Psychosis,
Classes and functions of Hormones . . . . . . . . . . . . 201 and Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236
Homeostatic Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . 202 epigenetics: Measuring Gene expression . . . . . . . 236
Gonadal Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 7-6Comparing neuroscience
anabolic–androgenic steroids . . . . . . . . . . . . . . . . . . 204 research Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
Glucocorticoids and stress . . . . . . . . . . . . . . . . . . . . . . 204 7-7 using animals in
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207
Brain–Behavior research . . . . . . . . . . . . . . . . . . . 239
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .208 Benefits of animal Models of disease . . . . . . . . . . 240
xii
animal Welfare and scientific researCh Focus 8-3 Increased Cortical
experimentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240 Activation for Second Languages . . . . . . . . . . . . . . .268
researCh Focus 7-4 Attention-Deficit/ experience and neural Connectivity . . . . . . . . . . . .268
Hyperactivity Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . 241 Critical Periods for experience
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 and Brain development . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244 abnormal experience and Brain
development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
ChApter 8 Hormones and Brain development . . . . . . . . . . . . . . 271
Katherine Streeter
How Does the Nervous CliniCal Focus 8-4 Romanian Orphans . . . . . . . . . . . . . 272
Gut Bacteria and Brain development . . . . . . . . . . . 275
System Develop Injury and Brain development . . . . . . . . . . . . . . . . . . . 276
and Adapt? . . . . . . . . . . . . . . . . . . . 245 drugs and Brain development . . . . . . . . . . . . . . . . . . . 276
researCh Focus 8-1 Linking Socioeconomic Status Other sources of abnormal Brain
to Cortical Development . . . . . . . . . . . . . . . . . . . . . . . . . 246 development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Three Perspectives on Brain
8-1 CliniCal Focus 8-5 Schizophrenia . . . . . . . . . . . . . . . . . . . 278
development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 developmental disability . . . . . . . . . . . . . . . . . . . . . . . . 278
Correlating emerging Brain structures with 8-5 How do any of us develop a
emerging Behaviors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
normal Brain? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
Correlating emerging Behaviors with neural
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .280
Maturation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281
Identifying Influences on Brain
and Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
ChApter 9
8-2 neurobiology of development . . . . . . . . . 248
Katherine Streeter
Gross development of the Human How Do We Sense,
nervous system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249 Perceive, and See the
Origins of neurons and Glia . . . . . . . . . . . . . . . . . . . . . . 250
neuronal Growth and development . . . . . . . . . . . . . 252
World? . . . . . . . . . . . . . . . . . . . . . . . . . 283
CliniCal Focus 8-2 Autism Spectrum Disorder . . . . 255 CliniCal Focus 9-1 Migraines and a Case of
Blindsight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .284
unique aspects of frontal lobe
development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 9-1 nature of sensation and Perception 285
Glial development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 sensory receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
8-3 using emerging Behaviors neural relays . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
to Infer neural Maturation . . . . . . . . . . . . . . . . . 260 sensory Coding and representation . . . . . . . . . . . . 287
Motor Behaviors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260 Perception . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .288
language development . . . . . . . . . . . . . . . . . . . . . . . . . . 261 9-2 The Visual system’s functional
development of Problem-solving ability . . . . . . . 262 anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
EXPERIMENT 8-1 Question: In what sequence structure of the retina . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
do the forebrain structures required for THE BASICS Visible light and the structure
learning and memory mature? . . . . . . . . . . . . . . . . . . 264 of the eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
a Caution about linking Correlation Photoreceptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
to Causation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
CliniCal Focus 9-2 Visual Illuminance . . . . . . . . . . . . . . 294
Brain development and
8-4
Types of retinal neurons . . . . . . . . . . . . . . . . . . . . . . . . . 294
the environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
Visual Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 295
experience and Cortical Organization . . . . . . . . . . 266
dorsal and Ventral Visual streams . . . . . . . . . . . . . . 296
xiii
9-3 location in the Visual World . . . . . . . . . . . . 301 detecting Patterns in sound . . . . . . . . . . . . . . . . . . . . . 339
Coding location in the retina . . . . . . . . . . . . . . . . . . . 302 10-4 anatomy of language and Music . . . .340
location in the lateral Geniculate Processing language . . . . . . . . . . . . . . . . . . . . . . . . . . . . .340
nucleus and region V1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302
CliniCal Focus 10-4 Left-Hemisphere Dysfunction 345
Visual Corpus Callosum . . . . . . . . . . . . . . . . . . . . . . . . . . .304
Processing Music . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .346
9-4 neuronal activity . . . . . . . . . . . . . . . . . . . . . . . . . . .304
Cerebral Aneurysms . . . . . . . . . . . 347
CliniCal Focus 10-5
seeing shape . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305
researCh Focus 10-6 The Brain’s Music System . . . .348
seeing Color . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
10-5 auditory Communication
researCh Focus 9-3 Color-Deficient Vision . . . . . . . . .311
in nonhuman species . . . . . . . . . . . . . . . . . . . . . . . . . 349
neuronal activity in the dorsal stream . . . . . . . . 313
Birdsong . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349
9-5 The Visual Brain in action . . . . . . . . . . . . . . . 314 echolocation in Bats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
Injury to the Visual Pathway leading
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
to the Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
Injury to the What Pathway . . . . . . . . . . . . . . . . . . . . . . 315
CliniCal Focus 9-4 Carbon Monoxide
Poisoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315 ChApter 11
Katherine Streeter
Injury to the How Pathway . . . . . . . . . . . . . . . . . . . . . . . 316 How Does the Nervous
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 System Respond to
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
Stimulation and
ChApter 10 Produce Movement? . . . . . . 355
Katherine Streeter
How Do We Hear, Speak, researCh Focus 11-1 Neuroprosthetics . . . . . . . . . . . . . . 356
and Make Music? . . . . . . . . . . .321 11-1 a Hierarchy of Movement Control . . . . 357
THE BASICS relating the somatosensory and
researCh Focus 10-1 Evolution of Language and
Motor systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .358
Music . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
forebrain: Initiating Movement . . . . . . . . . . . . . . . . .358
10-1 sound Waves: stimulus for
audition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323 experimental evidence for a Movement
Hierarchy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Physical Properties of sound Waves . . . . . . . . . . . . 323
Brainstem: species-Typical Movement . . . . . . . . . 361
Perception of sound . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
EXPERIMENT 11-1 Question: What are the effects
Properties of language and Music of brainstem stimulation under different
as sounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 conditions? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
10-2 functional anatomy CliniCal Focus 11-2 Cerebral Palsy . . . . . . . . . . . . . . . . . . . 363
of the auditory system . . . . . . . . . . . . . . . . . . . . . . 329
spinal Cord: executing Movement . . . . . . . . . . . . . . .364
structure of the ear . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
CliniCal Focus 11-3 Spinal Cord Injury . . . . . . . . . . . . . . 365
auditory receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
11-2 Motor system Organization . . . . . . . . . . . . 366
researCh Focus 10-2 Otoacoustic Emissions . . . . . . . 333
Motor Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Pathways to the auditory Cortex . . . . . . . . . . . . . . . . 333
Experiment 11-2 Question: How does the
auditory Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .334 motor cortex take part in the control of
researCh Focus 10-3 Seeing with Sound . . . . . . . . . . . . 335 movement? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .368
10-3 neural activity and Hearing . . . . . . . . . . . 336 Motor Cortex and skilled Movement . . . . . . . . . . . .368
Hearing Pitch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 Plasticity in the Motor Cortex . . . . . . . . . . . . . . . . . . . 369
detecting loudness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .338 Experiment 11-3 Question: What is the effect of
rehabilitation on the cortical representation
detecting location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .338
of the forelimb after brain damage? . . . . . . . . . . . 369
xiv
Corticospinal Tracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 370 12-3 evolution, environment,
Motor neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371 and Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .406
Control of Muscles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372 evolutionary Influences on Behavior . . . . . . . . . . .406
Basal Ganglia, Cerebellum, and
11-3 environmental Influences on Behavior . . . . . . . . .408
Movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 Inferring Purpose in Behavior:
Basal Ganglia and the force To Know a Fly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .409
of Movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 12-4 neuroanatomy of Motivated
CliniCal Focus 11-4 Tourette Syndrome . . . . . . . . . . . . . 374 and emotional Behavior . . . . . . . . . . . . . . . . . . . . . 410
Cerebellum and Movement skill . . . . . . . . . . . . . . . . . 375 regulatory and nonregulatory Behavior . . . . . . . .411
Experiment 11-4 Question: does the cerebellum regulatory function of the
help to make adjustments required to keep Hypothalamic Circuit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412
movements accurate? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377 Organizing function of the limbic Circuit . . . . . . 416
11-4 somatosensory system receptors executive function of the frontal lobes . . . . . . . 418
and Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379 CliniCal Focus 12-2 Agenesis of the
somatosensory receptors and Perception . . . . 379 Frontal Lobes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420
Posterior root Ganglion neurons . . . . . . . . . . . . . . . . 381 stimulating and expressing emotion . . . . . . . . . . . 421
somatosensory Pathways to the Brain . . . . . . . . . 382 amygdala and emotional Behavior . . . . . . . . . . . . . 422
spinal reflexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .384 Prefrontal Cortex and emotional Behavior . . . . 423
feeling and Treating Pain . . . . . . . . . . . . . . . . . . . . . . . . .385 emotional disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424
researCh Focus 11-5 Phantom Limb Pain . . . . . . . . . . .386 CliniCal Focus 12-3 Anxiety Disorders . . . . . . . . . . . . . . 425
Vestibular system and Balance . . . . . . . . . . . . . . . . .388 12-5 Control of regulatory and
exploring the somatosensory
11-5 nonregulatory Behavior . . . . . . . . . . . . . . . . . . . . . 426
Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .390 Controlling eating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 426
somatosensory Homunculus . . . . . . . . . . . . . . . . . . . .390 CliniCal Focus 12-4 Weight Loss Strategies . . . . . . . .428
researCh Focus 11-6 Tickling . . . . . . . . . . . . . . . . . . . . . . . . 392 Experiment 12-1 Question: does the hypothalamus
effects of somatosensory Cortex damage . . . . 392 play a role in eating? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .430
somatosensory Cortex and Complex Controlling drinking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .430
Movement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393 Controlling sexual Behavior . . . . . . . . . . . . . . . . . . . . . . 431
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395 CliniCal Focus 12-5 Androgen Insensitivity
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396 Syndrome and the Androgenital Syndrome . . .433
sexual Orientation, sexual Identity, and Brain
ChApter 12 Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .434
Katherine Streeter
What Causes Emotional Cognitive Influences on sexual Behavior . . . . . . .436
reward . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .436
and Motivated 12-6
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .439
Behavior? . . . . . . . . . . . . . . . . . . . . . 397 Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .440
researCh Focus 12-1 The Pain of Rejection . . . . . . . . . .398
12-1 Identifying the Causes ChApter 13
of Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Katherine Streeter
Behavior for Brain Maintenance . . . . . . . . . . . . . . . . .400
Why Do We Sleep
neural Circuits and Behavior . . . . . . . . . . . . . . . . . . . . . 401 and Dream? . . . . . . . . . . . . . . . . . . .441
12-2 The Chemical senses . . . . . . . . . . . . . . . . . . . . . 401 CliniCal Focus 13-1 Doing the Right Thing at the
Olfaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401 Right Time . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
Gustation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .404 13-1 a Clock for all seasons . . . . . . . . . . . . . . . . . . . 442
xv
Origins of Biological rhythms . . . . . . . . . . . . . . . . . . . . 442 ChApter 14
Katherine Streeter
Biological Clocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .443 How Do We Learn
Experiment 13-1 Question: Is plant movement
exogenous or endogenous? . . . . . . . . . . . . . . . . . . . . . .444 and Remember? . . . . . . . . . . . . 479
Measuring Biological rhythms . . . . . . . . . . . . . . . . . . .444 CliniCal Focus 14-1 Remediating Dyslexia . . . . . . . . . .480
free-running rhythms . . . . . . . . . . . . . . . . . . . . . . . . . . .445 14-1 Connecting learning
Zeitgebers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .446 and Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
CliniCal Focus 13-2 Seasonal Affective Disorder . . .448 studying learning and Memory
in the laboratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
13-2 neural Basis of the Biological
Experiment 14-1 Question: does an animal
Clock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .450
learn the association between emotional
suprachiasmatic rhythms . . . . . . . . . . . . . . . . . . . . . . .450 experience and environmental stimuli? . . . . . . . .482
Keeping Time . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .450 Two Categories of Memory . . . . . . . . . . . . . . . . . . . . . . .483
Pacemaking Circadian rhythms . . . . . . . . . . . . . . . . . 452 What Makes explicit and Implicit Memory
researCh Focus 13-3 Synchronizing different? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .485
Biorhythms at the Molecular Level . . . . . . . . . . . . . 453 What Is special about Personal
Pacemaking Circannual rhythms . . . . . . . . . . . . . . .454 Memories? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .486
Cognitive and emotional rhythms . . . . . . . . . . . . . . 455 14-2 dissociating Memory Circuits . . . . . . . . .488
13-3 sleep stages and dreaming . . . . . . . . . . . . 456 disconnecting explicit Memory . . . . . . . . . . . . . . . . . .489
Measuring How long We sleep . . . . . . . . . . . . . . . . . . . 456 disconnecting Implicit Memory . . . . . . . . . . . . . . . . .489
Measuring sleep in the laboratory . . . . . . . . . . . . . . 457 CliniCal Focus 14-2 Patient Boswell’s Amnesia . . . . .490
stages of Waking and sleeping . . . . . . . . . . . . . . . . . . 457 neural systems underlying explicit
14-3
a Typical night’s sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . .458 and Implicit Memories . . . . . . . . . . . . . . . . . . . . . . . 491
Contrasting nreM sleep and reM sleep . . . . . . . . 459 neural Circuit for explicit Memories . . . . . . . . . . . . 491
CliniCal Focus 13-4 Restless Legs Syndrome . . . . . . .460 CliniCal Focus 14-3 Alzheimer Disease . . . . . . . . . . . . . 492
dreaming . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461 CliniCal Focus 14-4 Korsakoff Syndrome . . . . . . . . . . . 496
What We dream about . . . . . . . . . . . . . . . . . . . . . . . . . . . . 461 Consolidation of explicit Memories . . . . . . . . . . . . . 497
13-4 What does sleep accomplish? . . . . . . . . .464 neural Circuit for Implicit Memories . . . . . . . . . . . .498
sleep as a Biological adaptation . . . . . . . . . . . . . . . .465 neural Circuit for emotional Memories . . . . . . . . .498
sleep as a restorative Process . . . . . . . . . . . . . . . . . .466 14-4 structural Basis
sleep and Memory storage . . . . . . . . . . . . . . . . . . . . . . . 467
of Brain Plasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . .500
long-Term Potentiation . . . . . . . . . . . . . . . . . . . . . . . . . .500
13-5 neural Bases of sleep . . . . . . . . . . . . . . . . . . . . 470
Measuring synaptic Change . . . . . . . . . . . . . . . . . . . . . . 502
reticular activating system and sleep . . . . . . . . . 470
enriched experience and Plasticity . . . . . . . . . . . . .504
neural Basis of eeG Changes associated
with Waking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471 sensory or Motor Training and Plasticity . . . . . . . 505
neural Basis of reM sleep . . . . . . . . . . . . . . . . . . . . . . . . 471 Experiment 14-2 Question: does the learning
of a fine motor skill alter the cortical
13-6 sleep disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472 motor map? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .506
disorders of nreM sleep . . . . . . . . . . . . . . . . . . . . . . . . . . 473 researCh Focus 14-5 Movement, Learning,
CliniCal Focus 13-5 Sleep Apnea . . . . . . . . . . . . . . . . . . . . . 474 and Neuroplasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507
disorders of reM sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . 474 experience-dependent Change
13-7 What does sleep Tell us about in the Human Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .508
Consciousness? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 476 epigenetics of Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . .509
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477 Plasticity, Hormones, Trophic factors,
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 478 and drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .509
xvi
Experiment 14-3 Question:
What effect do Mapping the Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 534
repeated doses of amphetamine, a Cognition and the Cerebellum . . . . . . . . . . . . . . . . . . . 535
psychomotor stimulant, have on neurons? . . . . .511
social neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 536
some Guiding Principles of Brain Plasticity . . . . .511
neuroeconomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .538
14-5 recovery from Brain Injury . . . . . . . . . . . . . 513
15-4 Cerebral asymmetry in Thinking . . . . . . 539
donna’s experience with Traumatic
Brain Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 513 anatomical asymmetry . . . . . . . . . . . . . . . . . . . . . . . . . . 539
Three-legged Cat solution . . . . . . . . . . . . . . . . . . . . . . . 514 functional asymmetry in neurological
Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .540
new-Circuit solution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
functional asymmetry in the Healthy Brain . . . 541
Experiment 14-4 Question: does nerve growth
factor stimulate recovery from stroke, functional asymmetry in the split Brain . . . . . . . 542
influence neural structure, or both? . . . . . . . . . . . . 515 explaining Cerebral asymmetry . . . . . . . . . . . . . . . . . 543
lost neuron replacement solution . . . . . . . . . . . . . 516 Experiment 15-3 Question: Will severing the corpus
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517 callosum affect the way in which the brain
responds? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 518
Experiment 15-4 (a) Question: How can the right
hemisphere of a split-brain subject show
ChApter 15
that it knows information? (B) Question:
Katherine Streeter
How Does the Brain What happens if both hemispheres are asked
to respond to competing information? . . . . . . . . .544
Think? . . . . . . . . . . . . . . . . . . . . . . . . . . .519 left Hemisphere, language, and Thought . . . . . 545
researCh Focus 15-1 Split Brain . . . . . . . . . . . . . . . . . . . . . . 520 15-5 Variations in Cognitive
15-1 The nature of Thought . . . . . . . . . . . . . . . . . . . 520 Organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .546
Characteristics of Human Thought . . . . . . . . . . . . . 521 sex differences in Cognitive Organization . . . . .546
neural unit of Thought . . . . . . . . . . . . . . . . . . . . . . . . . . . 522 Handedness and Cognitive Organization . . . . . . . 549
Comparative Focus 15-2 Animal Intelligence . . . . . . . 523 CliniCal Focus 15-5 Sodium Amobarbital Test . . . . . . 550
Experiment 15-1 Question:
How do individual synesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
neurons mediate cognitive activity? . . . . . . . . . . . 524 CliniCal Focus 15-6 A Case of Synesthesia . . . . . . . . . . 551
15-2 Cognition and the association 15-6 Intelligence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 552
Cortex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 525 Concept of General Intelligence . . . . . . . . . . . . . . . . . 553
Knowledge about Objects . . . . . . . . . . . . . . . . . . . . . . . . 526
Multiple Intelligences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553
Multisensory Integration . . . . . . . . . . . . . . . . . . . . . . . . . 527
divergent and Convergent Intelligence . . . . . . . . . 554
spatial Cognition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 527
Intelligence, Heredity, epigenetics, and the
attention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 528 synapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555
Experiment 15-2 Question: Can neurons learn to 15-7 Consciousness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 556
respond selectively to stimuli? . . . . . . . . . . . . . . . . . . 529
Why are We Conscious? . . . . . . . . . . . . . . . . . . . . . . . . . . . 556
Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
What Is the neural Basis of
Imitation and understanding . . . . . . . . . . . . . . . . . . . . 531 Consciousness? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557
researCh Focus 15-3 The Rise and Fall of Mirror Experiment 15-5 Question: Can people alter their
Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532 movements without conscious awareness? . . . 557
expanding frontiers of Cognitive
15-3 suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533 Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .560
CliniCal Focus 15-4 Neuropsychological
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533
xvii
ChApter 16 epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 581
Katherine Streeter
What Happens When Multiple sclerosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .583
neurodegenerative disorders . . . . . . . . . . . . . . . . . . .584
the Brain Misbehaves? . . .561 are all degenerative dementias
researCh Focus 16-1 Posttraumatic Stress aspects of a single disease? . . . . . . . . . . . . . . . . . . . . .589
Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562 age-related Cognitive loss . . . . . . . . . . . . . . . . . . . . . . 591
16-1 Multidisciplinary research understanding and Treating
16-4
on Brain and Behavioral disorders . . . . . . .564 Psychiatric disorders . . . . . . . . . . . . . . . . . . . . . . . . . 592
Causes of disordered Behavior . . . . . . . . . . . . . . . . . .564 schizophrenia spectrum and Other
Investigating the neurobiology of Behavioral Psychotic disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 592
disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565 Mood disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 594
Classifying and Treating Brain
16-2 researCh Focus 16-4 Antidepressant Action
and Behavioral disorders . . . . . . . . . . . . . . . . . . .568 and Brain Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 596
Identifying and Classifying anxiety disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 597
Behavioral disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .568
16-5 Is Misbehavior always Bad? . . . . . . . . . . . . 597
Treatments for disorders . . . . . . . . . . . . . . . . . . . . . . . . . 571
suMMary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .598
researCh Focus 16-2 Treating Behavioral
Key TerMs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 599
Disorders with Transcranial Magnetic
Stimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573 ansWers TO seCTIOn reVIeW self-TesTs . . . . . . . . .A-1
understanding and Treating
16-3 GlOssary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .G-1
neurological disorders . . . . . . . . . . . . . . . . . . . . . . . 577
referenCes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . R-0
Traumatic Brain Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577
naMe Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .N-1
CliniCal Focus 16-3 Concussion . . . . . . . . . . . . . . . . . . . . . . 578
stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .580 suBJeCT Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .S-1
xviii
prefACe
The fifth edition of An Introduction to Brain and Behavior continues to reflect fifth editioN updAtes
the evolution of behavioral neuroscience. In keeping with this evolution, we welcome
G. Campbell Teskey, whose fresh perspective—especially on topics related to neurophysiol- ChApter 1: ORIGINS
ogy and nervous system disorders—enhances our author team. NEW: locked-in syndrome in §1-1 features the
case of Martin Pistorius .
Other major changes in this edition include a deeper emphasis on genetics and epi-
genetics throughout. Epigenetics is especially important for understanding brain and be- NEW: Figure 1-12, Neanderthal Woman, and
havior because environmentally induced modifications in gene expression alter the brain NEW text describes H. sapiens sapiens–H.
and ultimately behavioral development. Thus, experience—especially early experience— neanderthalis intermingling .
modifies how brain development unfolds. These modifications—of at least some behavioral NEW discussion in §1-4 and Comparative Focus
traits—can be transferred across generations, a process known as epigenetic inheritance. We 1-3 explain brain cell packing density .
introduce it in the case study at the end of Section 3-3.
UPDATED coverage, Altered Maturation, in
This edition fully addresses advances in imaging technology, including techniques that §1-4, simplifies the concept neoteny .
are fueling the burgeoning field of connectomics and progress toward a comprehensive map
of neural connections—a brain connectome. These exciting advances are especially relevant NEW section, Acquisition of Culture, in §1-5,
introduces the concept memes .
in the second half of the book, where we review higher-level functions.
Imaging advances and epigenetics concepts and research continue as a prime focus in
this revision but are not our sole focus. In Chapter 2 we introduce the enteric nervous sys- ChApter 2: NEUROANATOMY
tem, which controls the gut, and later chapters elaborate on ENS functioning. Section 7-1 NEW: Research Focus 2-1, Agenesis of the
introduces the emerging field of synthetic neurobiology, elaborated in Section 16-2. Section Cerebellum .
5-2 adds new research on lipid neurotransmitters and detail on receptor subtypes. UPDATED Figure 2-2 charts ENS in anatomic
The range of updates and new coverage in the Fifth Edition text and Focus features is and functional nervous system organization .
listed, chapter by chapter, in the margins of these Preface pages. See for yourself the breadth
NEW: §2-5 introduces the enteric nervous sys-
and scope of the revision; then read on to learn more about the big-picture improvements
tem, diagrammed in NEW Figure 2-31 .
in the Fifth Edition.
With encouraging feedback from readers, the book’s learning apparatus continues to
feature sets of self-test questions at the end of the major sections in each chapter. These ChApter 3: NEURONAL ANATOMY
Section Reviews help students track their understanding as they progress. Answers appear UPDATED Focus 3-3 describes chlorotoxin-
based methods for identifying and treating brain
at the back of the book.
tumors .
We continue to expand the popular margin notes. Beyond offering useful asides to the
text narrative, these marginalia increase the reader’s ease in finding information, especially NEW photos: social roboticist Heather Knight
when related concepts are introduced early in the text then elaborated on in later chapters. with Marilyn Monrobot, Figure 3-6; Woody
Guthrie, Focus 3-4; Chris Burke, Figure 3-22 .
Readers can return quickly to an earlier discussion to refresh their knowledge or jump ahead
to learn more. The margin notes also help instructors move through the book to preview
later discussions. ChApter 4: NERVOUS SYSTEM
The illustrated Experiments, one of the book’s most popular features, show readers how ELECTRICAL ACTIVITY
researchers design experiments, that is, how they approach the study of brain–behavior UPDATED Focus 4-1, Epilepsy, details elec-
relationships. The Basics features let students brush up or get up to speed on their science trographic seizure and alternatives to drug
treatments .
foundation—knowledge that helps them comprehend behavioral neuroscience.
We have made some big changes, yet much of the book remains familiar. In shaping UPDATED: Multiple Sclerosis now Focus 4-2;
content throughout, we continue to examine the nervous system with a focus on function, Focus 4-4, ALS: Lou Gehrig’s Disease, profiles
on how our behavior and our brain interact, by asking key questions that students and Stephen Hawking’s 50-year-plus battle with
ALS .
neuroscientists ask:
• Why do we have a brain? CONDENSED: Myasthenia gravis coverage and
photos conclude §4-4 .
• How is the nervous system organized, functionally as well as anatomically?
• How do drugs and hormones affect our behavior?
• How does the brain learn?
• How does the brain think?
xix
Fifth edition updates Every chapter’s central question highlights the brain–behavior relationship. When we
first describe how neurons communicate in Section 5-4, for example, we also describe how
ChApter 5: NEUROTRANSMISSION synaptic plasticity serves as the basis of learning. Later, in Section 14-4, we expand on plas-
NEW in §5-2: Lipid Transmitters focuses on ticity as we explore learning and memory.
endocannabinoids; Varieties of Receptors
As it was when we wrote the First Edition, our goal in this new edition is to bring coher-
introduces subunits plus NEW Table 5-3, Small-
Molecule Transmitter Receptors . ence to a vast subject by helping students understand the big picture. Asking fundamental
questions about the brain has another benefit: it piques students’ interest and challenges
NEW in §5-3: enteric nervous system–CNS them to join us on the journey of discovery that is brain science.
autonomy .
Scientific understanding of the human brain and human behavior continues to grow at
REVAMPED: neural bases of habituation and an exponential pace. We want to communicate the excitement of recent breakthroughs in
sensitization responses in Aplysia, in §5-4 . brain science and to relate some of our own experiences from a combined 120+ years of
studying brain and behavior, both to make the field’s developing core concepts and latest
ChApter 6: DRUGS AND revelations understandable and to transport uninitiated students to the frontiers of physi-
HORMONES ological psychology.
STREAMLINED Table 6-1, Grouping Psychoactive
areas of emphasis
Drugs .
UPDATED coverage: endogenous opioid pep-
tides and anandamide psychedelics in §6-2 . To convey the excitement of neuroscience as researchers understand it, we interweave evolu-
tion, genetics, and epigenetics; psychopharmacology; and neural plasticity and connectivity,
UPDATED statistics in Figure 6-16, Drug Use in
the United States . including CNS and ENS interactions, throughout the book.
eVoLutioN Our perspective—neuroscience in an evolutionary context—recurs in almost
REVAMPED: Glucocorticoids and Stress in §6-5
features discrete sections on Activating a Stress every chapter. By focusing on comparative behavior and anatomy, we address nervous sys-
Response and on Ending one . tem evolution in depth in Chapters 1 and 2, evolution of the synapse in Section 5-1, and
evolution of visual pathways in Section 9-2. We add ideas about how natural selection might
promote overeating in Section 12-5 and evolutionary theories of sleeping and dreaming in
ChApter 7: RESEARCH METHODS
Section 13-3. We describe the evolution of sex differences in spatial cognition and language
REFOCUSED: Figure 7-5, Pathology in Parkinson
Disease, accompanies discussion of Brain in Section 15-5 and links between our evolved reactions to stress and anxiety disorders in
Lesions in §7-1 . Section 16-4.
NEW coverage: synthetic biology and chemoge- GeNetiCs ANd epiGeNetiCs We introduce the foundations of genetic and epigenetic
netics, including DREADD, and temporary and research in Sections 1-3 and 2-1 and begin to elaborate on them in Section 3-3. Chapter 5
reversible lesion techniques in §7-1 . includes discussions of metabotropic receptors and DNA and of learning and genes. The
REVAMPED: Single-Cell Recording begins §7-2, interplay of genes and drug action is integral to Chapter 6, as are the developmental roles of
including NEW Figure 7-8, Spatially Related genes and gene methylation to Chapter 8. Section 9-4 explains the genetics of color vision,
Cells . and the genetics of sleep disorders anchors Section 13-6. Section 14-4 now includes the role
of epigenetics in memory. Sections 16-1 and 16-3 consider the roles of genetics and of prions
NEW: Tables 7-1 and 7-2 summarize neuro-
science research methods that Measure and in understanding the causes of behavioral disorders.
Manipulate Brain–Behavior Relations, in §7-6 . psYChophArMACoLoGY Chapter 6 investigates how drugs and hormones affect behavior,
UPDATED in §7-7: Animal Models of topics we revisit often through the book. You will find coverage of drugs and information
Disease and Animal Welfare and Scientific transfer in Section 4-3, drugs and cellular communication in Section 5-3, and synthetic neu-
Experimentation . robiology in Section 7-1. Section 12-6 covers drugs and motivation; Section 13-6, drugs and
sleep disorders; and Section 14-4, neuronal changes with drug use. Section 16-2 discusses
ChApter 8: DEVELOPMENT the promise of the liposome as a delivery vehicle in pharmacological treatments, and Section
NEW Clinical Focus 8-1, Linking SES to Cortical 16-4, drugs used as treatments for a range of behavioral disorders.
Development, sets a chapterwide theme .
CoNNeCtiVit Y Neural plasticity is a hallmark of this book. We introduce the concept in
NEW in §8-4: infant sexual differentiation now Section 1-5, define it in Section 2-1, develop it in Section 2-6, and expand on it throughout.
introduces Hormones and Brain Development; At the conclusion of Section 14-4, we elaborate seven Guiding Principles of Brain Plasticity.
Gut Bacteria and Brain Development reveals the We describe the expanding boundaries of connectomics in Section 15-3. The new field of
microbiome’s influence .
psychotropics, which identifies the connection between the gut microbiome and its effects
UPDATED in §8-4: fetal exposure statistics in on the enteric nervous system—as well as on the central nervous system—appears in Sec-
Drugs and Brain Development; coverage of SIDS . tions 2-5 and 12-5.
xx
scientific Background Provided fifth editioN updAtes
We describe the journey of discovery that is neuroscience in a way that students just begin- SENSATION,
ChApter 9:
ning to study the brain and behavior can understand; then they can use our clinical examples PERCEPTION, AND VISION
to tie its relevance to the real world. Our approach provides the background students need NEW Focus 9-1 photo echoed chapterwide,
to understand introductory brain science. Multiple illustrated Experiments in 13 chapters illustrating receptive fields, §9-1; visual stream
functions, §9-2; neural spatial coding (§9-
help them visualize the scientific method and how scientists think. The Basics features
3), luminance contrast, §9-4; visual pathway
in 6 chapters address the fact that understanding brain function requires understanding injury, §9-5 .
information from all the basic sciences.
These encounters can prove both a surprise and a shock to students who come to the UPDATED: §9-2 introduces Müller cells’ role
in retinal function; discussion of photoreceptor
course without the necessary background. The Basics features in Chapters 1 and 2 address
luminance expanded .
the relevant evolutionary and anatomical background. In Chapter 3, The Basics provides a
short introduction to chemistry before the text describes the brain’s chemical activities. In NEW photos in Focus 9-3, Color-Deficient
Chapter 4 The Basics addresses electricity before exploring the brain’s electrical activity. Vision, contrast trichromatic vision to protano-
pia and deuteranopia .
Readers already comfortable with the material can easily skip it; less experienced read-
ers can learn it and use it as a context for neuroscience. Students with this background can NEW photo: the dress that sparked a contro-
tackle brain science with greater confidence. Similarly, for students with limited knowledge versy illustrates color constancy in §9-4 .
of basic psychology, we review such facts as stages of behavioral development in Chapter 8
and forms of learning and memory in Chapter 14. ChApter 10: AUDITION
Students in social science disciplines often remark on the amount of biology and chem- NEW: Clinical Focus 10-2, Otoacoustic
istry in the book, whereas an equal number of students in biological sciences remark on the Emissions .
amount of psychology. More than half the students enrolled in the Bachelor’s of Science in
NEW Figure 10-15 illustrates EXPANDED text
Neuroscience program at the University of Lethbridge have switched from a biochemistry
coverage of cochlear implants .
or psychology major after taking this course. We must be doing something right!
Chapter 7 showcases the range of methods behavioral neuroscientists use to measure and NEW photo in Figure 10-17: an owl skull
manipulate brain and behavior—traditional methods and such cutting-edge techniques as illustrates interaural intensity difference (IID).
optical tomography, resting-state fMRI, chemogenetics, and DREADD. Expanded discus- UPDATED coverage, Music as Therapy,
sions of techniques appear where appropriate, especially in Research Focus features, includ- concludes §10-4 .
ing Focus 3-2, Brainbow: Rainbow Neurons; Focus 4-3, Optogenetics and Light-Sensitive
UPDATED: Echolocation in Bats in §10-5 .
Channels; and Focus 16-1, Posttraumatic Stress Disorder, which includes treatments based
on virtual reality exposure therapies.
Finally, because critical thinking is vital to progress in science, select discussions through- ChApter 11: MOVEMENT AND
out the book center on relevant aspects. Section 1-2 concludes with The Separate Realms of SOMATOSENSATION
Science and Belief. Focus 15-3, The Rise and Fall of Mirror Neurons, demonstrates how the NEW photo: a robotic arm controlled by a brain–
media—and even scientists—can fail to question the validity of research results. Section 12-5 computer–brain interface in UPDATED Research
Focus 11-1, Neuroprosthetics .
introduces the idea that gender identity comprises a broad spectrum rather than a female–
male dichotomy. Section 7-7 considers issues of animal welfare in scientific research and NEW: Focus 11-2, Cerebral Palsy, introduces the
the use of laboratory animal models to mimic human neurologic and psychiatric disorders. connectome as an investigative tool .
NEW photo: wheelchair basketball team scrim-
Clinical focus Maintained
mage in Focus 11-3, Spinal Cord Injury .
NEW Figure 11-8 illustrates EXPANDED cover-
Neuroscience is a human science. Everything in this book is relevant to our lives, and every- age of Graziano’s movement categories .
thing in our lives is relevant to neuroscience. Understanding neuroscience helps us under-
stand how we learn, how we develop, and how we can help people with brain and behavioral
disorders. Knowledge of how we learn, how we develop, and the symptoms of brain and
behavioral disorders offer insights into neuroscience.
Clinical material also helps to make neurobiology particularly relevant to students who
are going on to a career in psychology, social work, or another profession related to mental
health, as well as to students of the biological sciences. We integrate clinical information
throughout the text and Clinical Focus features, and we expand on it in Chapter 16, the
book’s capstone, as well.
xxi
Fifth edition updates In An Introduction to Brain and Behavior, the placement of some topics is novel relative
to traditional treatments. We include brief descriptions of brain diseases close to discussions
EMOTION,
ChApter 12: of basic associated processes, as exemplified in the integrated coverage of Parkinson disease
MOTIVATION, CHEMICAL SENSES through Chapter 5, How Do Neurons Communicate and Adapt? This strategy helps first-
UPDATED estimates of the number of smells time students repeatedly forge close links between what they are learning and real-life issues.
humans can discriminate in §12-2 .
To provide a consistent disease nomenclature, the Fifth Edition follows the system advo-
UPDATED: Stimulating and Expressing Emotion cated by the World Health Organization for diseases named after their putative discoverers.
in §12-4 explains how the ENS interacts with Down syndrome, for example, has largely replaced Down’s syndrome in the popular and
other neural systems . scientific literature. We extend that convention to Parkinson disease and Alzheimer disease,
NEW: mindfulness training as a treatment strat- among other eponymous diseases and disorders.
egy for anxiety disorders in Clinical Focus 12-3 . The nearly 150 disorders we cover are cross-referenced in the Index of Disorders inside
the book’s front cover. Chapter 16 expands on the nature of neuroscience research and the
UPDATED: Clinical Focus 12-4 includes a
multidisciplinary treatment methods for neurological and psychiatric disorders described in
high-fiber food component in any weight
loss strategy; Figure 12-24 charts the ENS, preceding chapters. Its discussion of causes and classifications of abnormal behavior includes
hormones, and cognition as major factors in updated Table 16-3, now thoroughly revised to conform to the DSM-5 classification.
controlling eating . We emphasize questions that relate to the biological bases of behavior. For us, the excite-
ment of neuroscience lies in understanding how the brain explains what we do, whether it is
UPDATED in §12-5: the spectrum of gender
identity, including transgender identity, illus- talking, sleeping, seeing, or learning. Readers will therefore find nearly as many illustrations
trated by Bruce Jenner’s transition to Caitlyn about behavior as illustrations about the brain. This emphasis on explaining the biological
Jenner . foundation of behavior is another reason that we include a mix of Clinical, Research, and
Comparative Focus features throughout the text.
NEW Figure 12-30: mapped by rs-fMRI, areas
affected by nicotine illustrate the breadth of the
brain’s reward system .
abundant Chapter Pedagogy
ChApter 13: SLEEP Building on the innovative teaching devices described so far, numerous in-text pedagogi-
NEW photo: schoolchildren using light treat- cal aids adorn every chapter, beginning with an outline and an opening Focus feature that
ment to combat SAD in Focus 13-2 . draws students into the chapter’s topic. Focus features dot each chapter to connect brain
NEW table: Recommended Sleep Duration and behavior to relevant clinical or research experience. Within chapters, definitions of
times, by age group, in §13-3 . boldface key terms introduced in the text appear in the margins as reinforcement, margin
notes link topics together, and end-of-section Review self-tests help students check their
UPDATED: REM Sleep Disorders in §13-6
grasp of major points.
includes NEW subsections: Sleep Paralysis,
Cataplexy, and REM Sleep Behavioral Disorder . Each chapter ends with a Summary—several include summarizing tables or illustrations
to help students visualize or review big-picture concepts—and a list of Key Terms, each
referenced to the page number on which the term is defined. Following this Preface, the
ChApter 14: LEARNING
Media and Supplements section describes the wide array of supplemental materials designed
AND MEMORY
exclusively for students and teachers using the Fifth Edition.
NEW discussion: highly superior autobiographi-
cal memory (HSAM) in §14-1 .
NEW: Figure 14-12 illustrates EXPANDED dis-
cussion of spatially related cells that constitute
superb Visual reinforcement
our neural GPS . Our most important learning aid appears on nearly every page in the book: an expansive
and, we believe, exceptional set of illustrations. Overwhelmingly, readers agree that, hand
NEW neuroimages: Figure 14-6, impaired
in hand with our words, the diagrams describe and illuminate the nervous system. Impor-
autobiographical memory; Focus 14-3,
neurofibrillary tangle formed by misfolded tant anatomical illustrations are large-format to ease perusal. We have retained applications
tau proteins; Figure 14-26, brain sections photos that range from a dance class for Parkinson patients in Section 5-3 to a seniors’ bridge
show cortical stroke and repair via induced game in Section 16-3. New photos include, to illustrate color constancy in Section 9-4, the
neurogenesis . dress that inspired a social media controversy.
Illustrations are consistent from chapter to chapter so as to reinforce one another. We
consistently color-code diagrams that illustrate each aspect of the neuron, depict each struc-
tural region in the brain, and demark nervous system divisions. We include many varieties
of micrographic images to show what a particular neural structure actually looks like. These
xxii
illustrations and images are included on our PowerPoint presentations and integrated as Fifth edition updates
labeling exercises in our Study Guide and Testing materials.
ChApter 15: COGNITION
NEW: Hebb’s cell assembly diagram concludes
Teaching Through Metaphors, §15-1 .
examples, and Principles NEW: Research Focus 15-3, The Rise and Fall of
Mirror Neurons .
If a textbook is not enjoyable, it has little chance of teaching well. We heighten students’ UPDATED discussions: connectomics and the
interest through abundant use of metaphors and examples. Students read about patients Human Connectome Project in §15-3 .
whose brain injuries offer insights into brain function, and we examine car engines, robots,
NEW research: Cognition and the Cerebellum in
and prehistoric flutes for the same purpose. Frequent illustrated Experiments, comparative §15-3 .
biology examples, and representative Comparative Focus features help students understand
how much we humans have in common with creatures as far distant from us as sea slugs NEW: Figure 15-20 maps sex differences in
female–male hemispheric connectivity .
and as close to us as chimpanzees.
We also facilitate learning by reemphasizing main points and by distilling sets of prin- UPDATED: research in §15-5 on brain networks
ciples about brain function that offer a framework to guide students’ thinking. Thus, Sec- and gender identity .
tion 2-6 introduces ten key principles that explain how the parts of the nervous system work NEW research on bilingual brain connectivity
together. Section 14-4 summarizes seven guiding principles of neuroplasticity. These sets concludes §15-6 .
of principles form the basis of many discussions throughout the book. Frequently, marginal
notes remind readers when they encounter these principles again—and where to review
ChApter 16: DISORDERS
them in depth.
AND DYSFUNCTION
UPDATED Focus 16-1, PTSD, illustrates increas-
Big-Picture emphasis ingly effective VR exposure therapies .
UPDATED Table 16-3 thoroughly revised to con-
One challenge in writing an introductory book on any topic is deciding what to include and form to DSM-5 .
what to exclude. We organize discussions to focus on the bigger picture—a focus exempli-
NEW coverage, §16-2, diagrams a liposome for
fied by the ten principles of nervous system function introduced in Section 2-6 and echoed
drug delivery .
throughout the book. Any set of principles may be arbitrary yet nevertheless afford students
a useful framework for understanding the brain’s activities. NEW chart: in §16-3 F .A .S .T . test for spotting
In Chapters 8 through 16 we tackle behavioral topics in a more general way than most stroke .
contemporary books do. In Chapter 12, for instance, we revisit experiments and ideas from NEW discussion in §16-3: Are All Degenerative
the 1960s to understand why animals behave as they do, then we consider emotional and Dementias Aspects of a Single Disease? out-
motivated behaviors as diverse as eating and anxiety attacks in humans. In Chapter 14, the lines prion theory and its implications, and
larger picture of learning and memory is presented alongside a discussion of recovery from Figure 16-13 diagrams healthy and misfolded
proteins .
traumatic brain injury.
This broad focus helps students grasp the big picture that behavioral neuroscience paints.
While broadening our focus requires us to leave out some details, our experience with stu-
dents and teachers through four earlier editions confirms that discussing the larger problems
and issues in brain and behavior is of greater interest to students, especially those new to this
field, and is more often remembered than are myriad details without context.
As in preceding editions, we are selective in our citation of the truly massive literature on
the brain and behavior because we believe that too many citations can disrupt the text’s flow
and distract students from the task of mastering concepts. We provide citations to classic
works by including the names of the researchers and by mentioning where the research was
performed. In areas where controversy or new breakthroughs predominate, we also include
detailed citations—177 in all—to papers (especially reviews) from the years 2013 to 2016. An
end-of-book References section lists, by chapter, all the literature used in developing the
book, reflecting the addition of about 200 new citations total in this edition and elimination
of other, now superseded, research.
xxiii
acknowledgements
As in past editions of this text and Fundamentals of Human Neuropsychology, we have a
special debt to Barbara Brooks, our long-time development editor, who has left a strong
imprint on both books.
We sincerely thank as well the many people who also contributed to the development of
this edition. The staff at Worth Publishers is remarkable and makes revisions a joy to do. We
thank our sponsoring editor, Daniel DeBonis, more than ably assisted by Katie Pachnos; our
project editor, Edgar Doolan; and production manager Paul Rohloff.
We thank design manager Blake Logan for a striking cover and Charles Yuen for a fresh,
inviting, accessible new interior design. Thanks also to Cecilia Varas for coordinating photo
research and to Richard Fox, who found photographs and other illustrative materials that
we would not have found on our own. We are indebted to Macmillan art manager Matt
McAdams, illustration coordinator Janice Donnola, and medical illustrator Evelyn Pence
for their excellent work in creating new illustrations.
Our colleagues, too, have helped in the development of every edition. For their contribu-
tions in shaping the Fifth Edition, we are especially indebted to the reviewers who provided
extensive comments on selected chapters and illustrations: Nancy Blum, California State
University, Northridge; Kelly Bordner, Southern Connecticut State University; Benjamin
Clark, University of New Mexico; Roslyn Fitch, University of Connecticut; Trevor Gilbert,
University of Calgary; Nicholas Grahame, Indiana University–Purdue University Indianapolis;
Kenneth Troy Harker, University of New Brunswick; Jason Ivanoff, St. Mary’s University;
Dwight Kravitz, The George Washington University; Ralph Lydic, University of Tennessee,
Knoxville; Paul Meyer, The State University of New York at Buffalo; Jaime Olavarria, University
of Washington; Christopher Robison, Florida State University; Claire Scavuzzo, University of
Alberta; Sarah Schock, University of Ottawa; Robert Stackman, Florida Atlantic University;
Sandra Trafalis, San Jose State University; Douglas Wallace, Northern Illinois University;
Matthew Will, University of Missouri, Columbia; and Harris Philip Zeigler, Hunter College.
Likewise, we continue to be indebted to the colleagues who provided extensive comments
on selected chapters and illustrations during the development of the Fourth Edition: Mark
Basham, Regis University; Pam Costa, Tacoma Community College; Russ Costa, Westminster
College; Renee Countryman, Austin College; Kristen D’Anci, Salem State University; Trevor
James Hamilton, Grant MacGewn University; Christian Hart, Texas Woman’s University;
Matthew Holahan, Carleton University; Chris Jones, College of the Desert; Joy Kannarkat,
Norfolk State University; Jennifer Koontz, Orange Coast College; Kate Makerec, William
Paterson University of New Jersey; Daniel Montoya, Fayetteville State University; Barbara Os-
wald, Miami University of Ohio; Gabriel Radvansky, University of Notre Dame; Jackie Rose,
Western Washington University; Steven Schandler, Chapman University; Maharaj Singh,
Marquette University; Manda Williamson, University of Nebraska—Lincoln.
We’d also like to thank the reviewers who contributed their thoughts to the Third Edi-
tion: Chana Akins, University of Kentucky; Michael Anch, Saint Louis University; Maura
Mitrushina, California State University, Northridge; Paul Wellman, Texas A&M University;
and Ilsun White, Morehead State University. The methods chapter was new to the Third Edi-
tion and posed the additional challenge of taking what easily could read like a seed catalog
and making it engaging to readers. We therefore are indebted to Margaret G. Ruddy, The
College of New Jersey, and Ann Voorhies, University of Washington, for providing extensive
advice on the initial version of Chapter 7.
In addition, we thank the reviewers who provided their thoughts on the Second Edition:
Barry Anton, University of Puget Sound; R. Bruce Bolster, University of Winnipeg; James
Canfield, University of Washington; Edward Castañeda, University of New Mexico; Darragh
P. Devine, University of Florida; Kenneth Green, California State University, Long Beach;
Eric Jackson, University of New Mexico; Michael Nelson, University of Missouri, Rolla; Joshua
xxiv
S. Rodefer, University of Iowa; Charlene Wages, Francis Marion University; Doug Wallace,
Northern Illinois University; Patricia Wallace, Northern Illinois University; and Edie Woods,
Madonna University. Sheri Mizumori, University of Washington, deserves special thanks for
reading the entire manuscript for accuracy and providing fresh ideas that proved invaluable.
Finally, we must thank our tolerant wives for putting up with sudden changes in plans
as chapters returned, in manuscript or in proof, with hopes for quick turnarounds. We also
thank our colleague Robbin Gibb, who uses the book and has provided much feedback, in
addition to our undergraduate and graduate students, technicians, and postdoctoral fellows
who kept our research programs moving forward when we were engaged in revising the book.
Bryan Kolb, Ian Q. Whishaw, G. Campbell Teskey
xxv
this page left intentionally blank
MediA ANd suppL eMeNt s
An Introduction to Brain and Behavior, Fifth Edition, features a wide array of supplemental
materials designed exclusively for students and teachers of the text. For more information
about any of the items, please visit Worth Publishers’ catalog at www.macmillanhighered.com.
for students
launchPad with learningCurve Quizzing
A comprehensive Web resource for teaching and learning psychology
LaunchPad combines Worth Publishers’ award-winning media with an innovative plat-
form for easy navigation. For students, it is the ultimate online study guide, with rich interac-
tive tutorials, videos, interactive e-Book, and the LearningCurve adaptive quizzing system.
For instructors, LaunchPad is a full-course space where class documents can be posted,
quizzes are easily assigned and graded, and students’ progress can be assessed and recorded. to Accompany An
Whether you are looking for the most effective study tools or a robust platform for an online Introduction to Brain and Behavior,
course, LaunchPad is a powerful way to enhance your class. Fifth Edition, can be previewed
and purchased at http://www.
LaunchPad for An Introduction to Brain and Behavior, Fifth Edition, includes the following macmillanhighered.com/launchpad/
resources:
kolbintro5e.
• the LeArNiNGCurVe quizzing system, written by Carolyn Ensley of Wilfrid Laurier
University, is a new media component for this edition. LearningCurve combines adaptive
question selection, immediate and valuable feedback, and a gamelike interface to engage
students in a learning experience that is unique to them. Each LearningCurve quiz is
fully integrated with other resources in LaunchPad through the Personalized Study Plan,
so that students will be able to review with Worth’s extensive library of videos and activi-
ties. And state-of-the-art question analysis reports allow instructors to track the progress
of individual students as well as their class as a whole.
• suMMAtiVe Quizzes, another new media component to this edition, were written
by Linda Lockwood of the Metropolitan State University. Each quiz is written on the
topics discussed throughout each chapter and features a variety of multiple-choice ques-
tions presented to students randomly from question pools. Valuable to both student and
instructor, the summative quizzes are a useful learning tool to propel students’ under- An Introduction to Brain and Behavior,
standing of the information introduced in the book. Fifth Edition, and can be
• AN iNterACtiVe e-book allows students to highlight, bookmark, and make notes, just ordered together with
as they would with a printed textbook. The search function and in-text glossary defini- ISBN 10: 1-319-06192-3
tions make the text ready for the digital age. ISBN-13: 978-1-319-06192-0
• studeNt Video ACtiVities include engaging modules that instructors can easily as-
sign for student assessment. Videos cover a variety of topics and are sure to spark discus-
sion and encourage critical thinking.
• the SCIEnTIfIC AmErICAn Newsfeed delivers weekly articles, podcasts, and news
briefs on the very latest developments in psychology from the first name in popular sci-
ence journalism.
xxvii
• the NeurosCieNCe tooL kit is a powerful Web-based tool for learning the core con-
cepts of behavioral neuroscience—by witnessing them firsthand. These 30 interactive
tutorials allow students to see the nervous system in action via dynamic illustrations, ani-
mations, and models that demystify the neural mechanisms behind behavior. Carefully
crafted multiple-choice assessments make it easy to assign and assess each activity. Based
on Worth Publishers’ groundbreaking CD-ROM, Foundations of Behavioral Neuroscience,
the Neuroscience Tool Kit is a valuable accompaniment to any biopsychology course.
• PSyCHology And THE rEAl World: ESSAyS IlluSTrATIng fundAmEnTAl
ConTrIBuTIonS To SoCIETy, seCoNd editioN is a superb collection of essays by
major researchers describing their landmark studies. Published in association with the
not-for-profit FABBS Foundation, this engaging reader includes Bruce McEwen’s work
on the neurobiology of stress and adaptation, Jeremy Wolfe’s look at the importance of
xxviii
visual search, Elizabeth Loftus’s reflections on her study of false memories, and Daniel
Wegner’s study of thought suppression. A portion of the proceeds is donated to FABBS
to support societies of cognitive, psychological, behavioral, and brain sciences.
for Instructors
reVised! iNstruCtor’s resourCes This invaluable tool, for new and experienced
instructors alike, was revised by Catherine Smith of Carleton University. It includes chapter-
by-chapter learning objectives and chapter overviews, detailed lecture outlines, thorough
chapter summaries, chapter key terms, in-class demonstrations and activities, springboard
topics for discussion and debate, ideas for research and term paper projects, homework assign-
ments and exercises, and suggested readings from journals and periodicals. Course-planning
suggestions and a guide to videos and Internet resources also are included. The Instructor’s
Resources can be downloaded from Worth’s online catalog at www.macmillanhighered.com.
assessment Tools
Downloadable Diploma Computerized Test Bank Prepared and revised by Christopher
Striemer of Grant MacEwan University, the Test Bank includes a battery of more than 1300
multiple-choice and short-answer test questions, as well as diagram exercises. Each item is
keyed to the page in the textbook on which the answer can be found. All the questions have
been thoroughly reviewed and edited for accuracy and clarity. The Diploma software allows
users to add, edit, scramble, or reorder items. The Test Bank also allows you to export into a
variety of formats that are compatible with many Internet-based testing products. For more
information on Diploma, please visit https://blackboard.secure.force.com. The Test Bank
files can be downloaded from Worth’s online catalog at www.macmillanhighered.com.
Presentation
Illustration Slides and Lecture Slides Available for download from www.macmillanhigh-
ered.com, these slides can either be used as they are or customized to fit the needs of
your course. There are two sets of slides for each chapter. The Illustration slides feature
all the figures, photos, and tables. The Lecture slides, prepared and revised by Matthew
Holahan of Carleton University, feature main points of the chapter with selected figures
and illustrations.
xxix
this page left intentionally blank
ch a p te r
1 What Are the Origins CLINICAL FOCUS 1-1 Living with traumatic Brain injury
1-1 NeUrOSCIeNCe IN the tweNty-FIrSt CeNtUry
of Brain and Behavior? why Study Brain and Behavior?
what iS the Brain?
what iS Behavior?
1-2 PerSPeCtIveS ON BrAIN ANd BehAvIOr
ariStotLe and mentaLiSm
deScarteS and duaLiSm
darwin and materiaLiSm
COMPArAtIve FOCUS 1-2 the Speaking Brain
eXPerIMeNt 1-1 QueStion: how do parentS tranSmit heritaBLe
FactorS to oFFSpring?
contemporary perSpectiveS on Brain and Behavior
1-3 evOLUtION OF BrAINS ANd OF BehAvIOr
origin oF Brain ceLLS and BrainS
THE BASICS cLaSSiFication oF LiFe
evoLution oF nervouS SyStemS in animaLS
chordate nervouS SyStem
1-4 evOLUtION OF the hUMAN BrAIN ANd BehAvIOr
humanS: memBerS oF the primate order
AustrAlopithecus: our diStant anceStor
the FirSt humanS
reLating Brain Size and Behavior
COMPArAtIve FOCUS 1-3 the eLephant’S Brain
why the hominid Brain enLarged
1-5 MOderN hUMAN BrAIN SIze ANd INteLLIgeNCe
meaning oF human Brain Size compariSonS
acQuiSition oF cuLture
katherine Streeter
1
2 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
CliniCal F cus 1-1
Living with Traumatic Brain Injury
Fred Linge, a clinical psychologist with
a degree in brain research, wrote this
description 12 years after his head
injury occurred:
Susan Walsh/AP/Wide World Photos
In the second it took for my car to crash
head-on, my life was permanently
Valerie Macon/Getty Images
changed, and I became another statistic
in what has been called “the silent
epidemic.”
During the next months, my family
and I began to understand something
of the reality of the experience of head
Left: U.S. Representative Gabrielle Giffords (D-AZ) reenacts her swearing-in with House Speaker John
injury. I had begun the painful task of
Boehner in January 2011, days before a gunshot through the left side of her brain left her near death.
recognizing and accepting my physical,
Right: Giffords and husband, astronaut Mark Kelly, 16 months later: she had regained limited speech, but
mental, and emotional deficits. I couldn’t
mobility on her right side remained limited.
taste or smell. I couldn’t read even the
simplest sentence without forgetting the beginning before I got to the copied, and handed out to thousands of survivors and families. It brought
end. I had a hair-trigger temper that could ignite instantly into rage over me an enormous outpouring of letters, phone calls, and personal visits
the most trivial incident. . . . that continue to this day. Many were struggling as I had struggled, with
Two years after my injury, I wrote a short article: “What Does It Feel no diagnosis, no planning, no rehabilitation, and most of all, no hope. . . .
Like to Be Brain Damaged?” At that time, I was still intensely focusing The catastrophic effect of my injury was such that I was shattered and
on myself and my own struggle. (Every head-injured survivor I have then remolded by the experience, and I emerged from it a profoundly
met seems to go through this stage of narcissistic preoccupation, which different person with a different set of convictions, values, and priorities.
creates a necessary shield to protect them from the painful realities of (Linge, 1990)
the situation until they have a chance to heal.) I had very little sense of
In the years after his traumatic brain injury (TBI)—a wound to the
anything beyond the material world and could only write about things
brain that results from a blow to the head—Fred Linge made a journey.
that could be described in factual terms. I wrote, for example, about my
various impairments and how I learned to compensate for them by a
Before the car crash, he gave little thought to the relation between his
variety of methods. brain and his behavior. After the crash, adapting to his injured brain and
At this point in my life, I began to involve myself with other brain- behavior dominated his life. On his journey, Linge learned how his injured
damaged people. This came about in part after the publication of my brain affected his behavior, he relearned many skills, and he learned to
article. To my surprise, it was reprinted in many different publications, compensate for the impairments his changed brain imposed on him.
1-1 Neuroscience in the
Twenty-First Century
Fred Linge emerged profoundly changed from his journey of learning to live with traumatic
brain injury (TBI). The purpose of this book is to take you on a journey toward understand-
ing the link between brain and behavior: how the brain is organized to produce behavior.
Evidence comes from studying three sources: (1) the evolution of brain and behavior in
diverse animal species, (2) how the brain is related to behavior in typical people, and (3) how
the brain changes in people with brain damage or other brain dysfunction. The knowledge
Illustrated Experiments through the book emerging from these three lines of study is changing how we think about ourselves, how
reveal how neuroscientists conduct research, we structure education and our social interactions, and how we aid those with brain injury,
beginning with Experiment 1-1 in Section 1-2. disease, and disorder.
We will marvel at the potential for future discoveries. We will begin to understand how
genes influence the brain’s structure and activity. We will learn how our experience in
turn changes our genes. We will review developments in brain imaging techniques that
allow us to watch our own brain in action as we think and solve problems or sleep. We will
consider the goals of brain–behavior research in arresting the progress of brain disease and
1-1 • Neuroscience in the Twenty-First Century 3
finding cures for brain disease and injury. We will marvel at the injured brain interacting
traumatic brain injury (TBI) Wound to the
with machines that serve as prosthetics. We will consider the possibility of repairing and
brain that results from a blow to the head.
even replacing malfunctioning brains. We will also consider the possibility of interacting
with artificial brains—brains of our making that can, in principle, match our intelligence spinal cord Part of the central nervous
system encased within the vertebrae (spinal
or perhaps even surpass it. Our journey will broaden your understanding of what makes
column); provides most of the connections
us human.
between the brain and the rest of the body.
central nervous system (cNs) The brain
Why Study Brain and Behavior? and spinal cord, which together mediate
The brain is a physical object, a living tissue, a body organ. Behavior is action, momentarily behavior.
observable but fleeting. Brain and behavior differ greatly but are linked. They have evolved peripheral nervous system (PNs) All of
together: one is responsible for the other, which is responsible for the other, and so on. There the neurons in the body outside the brain
are three reasons for linking the study of the brain to the study of behavior: and spinal cord; provides sensory and motor
connections to and from the central nervous
1. How the brain produces behavior is a major unanswered scientific question. Scientists and
system.
students study the brain to understand humanity. Understanding brain function will allow
neuron Specialized nerve cell engaged in
improvements in many aspects of our world, including educational systems, economic
information processing.
systems, and social systems. Many chapters in this book touch on the relation between
psychological questions related to brain and behavior and philosophical questions related
to humanity. For example, in Chapters 14 and 15, we address how we become conscious,
how we speak, and how we remember.
2. The brain is the most complex living organ on Earth and is found in many groups of animals.
Students of the brain want to understand its place in the biological order of our planet.
This chapter describes the basic structure and evolution of brains, especially the human
brain. Chapter 2 surveys its functional anatomy, and Chapters 3 through 5 describe the
functioning of brain cells—the building blocks of every animal’s brain.
3. A growing list of behavioral disorders can be explained and treated as we increase our
Major Divisions of the
FIGUre 1-1
understanding of the brain. More than 2000 disorders may in some way be related to brain Human Nervous System The brain
abnormalities. As indexed inside the front cover of this book, we detail relations between and spinal cord together make up the central
brain disorders and behavioral disorders in every chapter, especially in the Focus features. nervous system. All of the nerve processes
radiating out beyond the brain and spinal
None of us can predict how the knowledge we gain about the brain and behavior may
cord and all of the neurons outside the CNS
prove useful. A former psychology major wrote to tell us that she took our course because she connect to sensory receptors, muscles, and
was unable to register in a preferred course. She felt that, although our course was interest- internal body organs to form the peripheral
ing, it was “biology, not psychology.” After graduating and getting a job in a nervous system.
social service agency, she has found to her delight that understanding the
Central nervous system (CNS)
links between brain and behavior is in fact a source of insight into many of The brain is encased by the skull; the spinal cord is
her clients’ disorders and the treatment options available for them. encased by the vertebrae.
Peripheral nervous system (PNS)
What Is the Brain? Neurons and nerve processes outside CNS
Brain, the Anglo-Saxon word for the tissue found within the skull, is but a
part of the human nervous system (Figure 1-1). Most connections between Sensory connections
to receptors in the
the brain and the rest of the body are made through the spinal cord, which
skin
descends from the brainstem through a canal in the backbone.
Together, the brain and spinal cord make up the central nervous system
Motor connections
(CNS). The CNS is encased in bone, the brain by the skull and the spinal to body muscles
cord by the backbone, or vertebrae. The CNS is called central both because
it is physically the nervous system’s core and is as well the core structure
Sensory and motor
mediating behavior. All of the processes radiating out beyond the brain and connections to internal
spinal cord constitute the peripheral nervous system (PNS). body organs and gut
The human nervous system is composed of cells, as is the rest of
the body, and these nerve cells, or neurons, control behavior most
directly. Neurons in the brain communicate with one another, with
4 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
(A) Cerebrum (forebrain) (B) Right hemisphere of cerebrum
Right Left
hemisphere hemisphere
Brainstem Brainstem
Cerebellum
FIGUre 1-2 The Human Brain (A) Shown head-on, as oriented within the human skull,
are the nearly symmetrical left and right hemispheres of the cerebrum. (B) A cut through
the middle of the brain from back to front reveals the right hemispheres of the cerebrum and
cerebellum and the right side of the brainstem. The spinal cord (not shown) emerges from
the base of the brainstem. Chapter 2 describes the brain’s functional anatomy.
sensory receptors in the skin, with muscles, and with internal body organs. As shown
in Figure 1-2, the human brain comprises two major sets of structures. The cerebrum
(forebrain), shown in Figure 1-2A, has two nearly symmetrical halves, called hemispheres,
one on the left and one on the right. The cerebrum is responsible for most of our con-
scious behaviors. It enfolds the brainstem (Figure 1-2B), a set of structures responsible
for most of our unconscious behaviors. The second major brainstem structure, the
cerebellum, is specialized for learning and coordinating our movements. Its conjoint
Focus 2-1 elaborates cerebellar function by evolution with the cerebrum suggests that it assists the cerebrum in generating many
describing a man born without one. behaviors.
For his postgraduate research, our friend Harvey chose to study the electrical activity
given off by the brain. He had decided that he wanted to live on as a brain in a bottle after
his body died. He expected that his research would allow his bottled brain to communi-
cate with others who could read its electrical signals. Harvey mastered the techniques
used to study the brain’s electrical activity but failed in his objective, not only because
the goal was technically impossible but also because he lacked a full understanding of
what brain means.
Harvey clearly wanted to preserve not just his brain but his self—his consciousness,
his language, and his memory. This meaning of brain refers to something other than the
organ found inside the skull. It refers to the brain as the body organ that exerts control over
behavior. It is what we intend when we talk of someone smart being a brain or speak of the
computer that guides a spacecraft as being the vessel’s brain. The term brain, then, signifies
both the organ itself and the fact that this organ produces behavior.
To return to Harvey’s experiment, the effect of placing even the entire CNS in a bottle
would be to separate it from the PNS and thus from the sensations and movements the PNS
mediates. Could the brain function without sensory information and without the ability to
move? Some evidence suggests that it could not.
One line of research and philosophical argument, called embodied behavior, proposes
that the movements we make and the movements we perceive in others are central to our
behavior (Prinz, 2008). That is, we understand one another not only by listening to words but
1-1 • Neuroscience in the Twenty-First Century 5
also by observing gestures and other body language. We think not only with silent language
but also with overt gestures and body language. Thus, the brain as an intelligent entity
cannot be divorced from the body’s activities.
In the 1920s, Edmond Jacobson wondered what would happen if our muscles completely
stopped moving, a question relevant to Harvey’s experiment. Jacobson believed that, even
when we think we are entirely motionless, we still make subliminal movements related to our
thoughts. The muscles of the larynx subliminally move when we think in words, for instance,
and we make subliminal eye movements when we imagine or visualize some action or a per-
son, place, or thing. In Jacobson’s experiment, then, people practiced “total” relaxation and
were later asked what the experience was like. They reported a condition of mental empti-
ness, as if the brain had gone blank (Jacobson, 1932).
In 1957, Woodburn Heron investigated another question related to Harvey’s experiment:
How would the brain cope without sensory input? He examined the effects of sensory
deprivation, including feedback from movement, by having participants each lie on a bed
in a bare, soundproof room and remain completely still. Padded tubes covered their arms
so that they had no sense of touch, and translucent goggles cut off their vision. The partici- Figure 12-1 illustrates Heron’s experimental
pants reported that the experience was extremely unpleasant, not just because of the social setting. Note: we refer to healthy people who
isolation but also because they lost their focus. Some even hallucinated, as if their brain was take part in research studies as participants
somehow trying to create the sensory experiences that they suddenly lacked. Most asked to and to those with brain or behavioral
be released from the study before it ended. impairments as subjects or as patients.
Findings from these lines of research suggest that (1) the CNS needs ongoing sensory
stimulation from the environment and from its own body’s movement and (2) the brain com-
municates by producing movement and observing others’ movements. Thus, when we use
the term brain to mean an intelligent, functioning organ, we are referring to an active brain
that is connected to the rest of the nervous system and producing behavior.
Yet other evidence suggests that the brain can produce levels of consciousness with
greatly reduced sensory and motor stimulation. When Martin Pistorius was 12 years old,
his health began to deteriorate. Eventually, he lapsed into a coma. His parents placed
Martin in a nursing home, where over a number of years he became conscious of his con-
dition, locked-in syndrome, although he remained completely paralyzed and unable to
communicate.
Martin’s condition persisted until, when he was 25, a nurse noticed him making some
small facial movements. He seemed to be trying to communicate. With rehabilitation, he cerebrum (forebrain) Major structure of
made excellent progress toward recovering movement, including using a voice synthesizer. the forebrain that consists of two mirror-
Pistorius has since married. His book Ghost Boy describes his frustration and helpless- image hemispheres (left and right) and is
ness during years of enduring locked-in syndrome. We return to this idea of the nature of responsible for most conscious behavior.
consciousness in Section 1-2. hemisphere Literally, half a sphere, referring
Patients such as Martin Pistorius reveal that the brain can be conscious to a great extent to one side of the cerebrum.
in the absence of overt behavior. Whether it can maintain consciousness in the absence of brainstem Central structure of the brain;
all movement and sensory experience, the goal of Harvey’s brain in a bottle experiment, responsible for most unconscious behavior.
remains unknown. cerebellum Major brainstem structure
specialized for learning and coordinating
movements; assists the cerebrum in
What Is Behavior? generating many behaviors.
Irenäus Eibl-Eibesfeldt began his textbook Ethology: The Biology of Behavior, published in embodied behavior Theory that the
1970, with the following definition: “Behavior consists of patterns in time.” These patterns movements we make and the movements
can be made up of movements, vocalizations, or changes in appearance, such as the facial we perceive in others are central to
movements associated with smiling. The expression patterns in time includes thinking. We communication with others.
cannot directly observe someone’s thoughts. The changes in the brain’s electrical and bio- locked-in syndrome Condition in which a
chemical activity that are associated with thought show, however, that thinking, too, is a patient is aware and awake but cannot move
behavior that forms patterns in time. or communicate verbally because of complete
The behavioral patterns of animals vary enormously. Animals produce behaviors that paralysis of nearly all voluntary muscles
consist of inherited responses, and they also produce learned behaviors. Most behaviors except the eyes.
6 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
consist of a mix of inherited and learned actions. Figure 1-3 illustrates the contributions of
A crossbill's beak is
specifically designed to mainly inherited and mainly learned behavior in the eating behavior of two animal species,
open pine cones. This crossbills and roof rats.
behavior is innate. A crossbill beak seems awkwardly crossed at the tip, yet it is exquisitely evolved to eat
pine cones. If its shape is changed even slightly, the bird is unable to eat the pine cones it
prefers until its beak grows back. For crossbills, eating is largely a fixed behavioral pattern: it
is inherited and does not require much modification through learning. Roof rats, in contrast,
are rodents with sharp incisor teeth that appear to have evolved to cut into anything. Pine
cones are an unusual food for the rats, although they have been found to eat them. But roof
rats can eat pine cones efficiently only if an experienced mother teaches them to do so. This
eating is not only learned, it is cultural in that parents teach it to offspring. We expand on
the concept of culture in Section 1-5.
A baby roof rat must The mixture of inherited and learned constraints on behavior varies considerably from
learn from its mother species to species. Generally, animals with smaller, simpler nervous systems exhibit a narrow
how to eat pine cones. range of behaviors that depend mainly on heredity. Animals with complex nervous systems
This behavior is learned.
have more behavioral options that depend on learning. We humans believe that we are the
animal species with the most complex nervous system and the greatest capacity for learning
new responses. Most of our most complex behaviors, including reading, writing, mathemat-
ics, and using smartphones, were learned long after our brain evolved its present form.
But most human behaviors retain some mixture of inheritance and learning, because we
humans have not thrown away our simpler nervous systems. Like other animals, we retain
FIGUre 1-3 Innate and Learned
many inherited ways of responding. The sucking response of a newborn human infant, for
Behaviors Some animal behaviors are
largely innate and fixed (top). Others are example, is an inherited eating pattern, but later in life eating is strongly influenced by learn-
largely learned (bottom). Learning is a ing and by culture.
form of cultural transmission. Top: Information
from J. Weiner (1995). The beak of the finch (p. 183). New 1-1 reVIeW
York: Vintage. Bottom: Information from J. Terkel (1995).
Cultural transmission in the black rat: Pinecone feeding. Neuroscience in the Twenty-First Century
Advances in the Study of Behavior, 24, p. 122. Before you continue, check your understanding.
1. is a wound to the brain that results from a blow to the head.
2. The brain and spinal cord together make up the . All of the nerve fibers
radiating out beyond the brain and spinal cord as well as all of the neurons outside the
brain and spinal cord form the .
3. One major set of brain structures, the , or , has nearly
symmetrical left and right enfolding the , which connects to
the spinal cord.
4. A simple definition of behavior is any kind of movement in a living organism. All behaviors
have both a cause and a function, but they vary in complexity and in the degree to
which they are , or automatic, and the degree to which they depend on
.
5. Explain the concept of embodied behavior in a statement or brief paragraph.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
1-2 Perspectives on Brain
and Behavior
Back to our central topic, how the study of brain and behavior are related. Many philosophers
have reasoned about the causes of behavior. Their speculations can be classified into three
broad approaches: mentalism, dualism, and materialism. After describing each, we explain
1-2 • Perspectives on Brain and Behavior 7
why contemporary brain investigators subscribe to the materialist view. In reviewing these
theories, you will recognize that some familiar “commonsense” ideas about behavior derive
from these long-standing perspectives.
Aristotle and Mentalism
The hypothesis that the mind (or soul or psyche) controls behavior can be traced back more
than 2000 years to ancient Greece. In classical mythology, Psyche, a mortal, became the
wife of the young god Cupid. Venus, Cupid’s mother, opposed his marriage, so she harassed
Psyche with almost impossible tasks.
Psyche performed the tasks with such dedication, intelligence, and compassion that she
was made immortal, thus removing Venus’s objection to her. The ancient Greek philosopher
Aristotle was alluding to this story when he suggested that all human intellectual functions
are produced by a person’s psyche. The psyche, Aristotle argued, is responsible for life, and
erich Lessing/art resource ny
its departure from the body results in death.
Aristotle’s account of behavior marks the beginning of modern psychology, but the brain
played no role in it. Aristotle thought the brain existed to cool the blood. Even if he had
thought that the brain ruled behavior, as did some other philosophers and physicians of his
time, it would have made little difference in the absence of any idea of how a body organ
could produce behavior (Gross, 1995). François Gérard, Psyche and
To Aristotle, the psyche was responsible for human consciousness, perceptions, and emo- Cupid (1798)
tions and for such processes as imagination, opinion, desire, pleasure, pain, memory, and
reason. The nonmaterial psyche was an entity independent of the body. In formulating the
concept of a soul, Christianity adopted Aristotle’s view that a nonmaterial entity governs our
behavior and that our essential consciousness survives our death.
Mind is an Anglo-Saxon word for memory, and when psyche was translated into English,
it became mind. The philosophical position that a person’s mind (psyche) is responsible
for behavior is mentalism. Mentalism has influenced modern behavioral science, because
many terms that originated with Aristotle—consciousness, sensation, perception, attention,
imagination, emotion, motivation, memory, and volition among them—survive today as
descriptions of behavior. Indeed, we use these terms in this book, and they frequently appear
as chapter titles in contemporary psychology and neuroscience textbooks.
Descartes and Dualism
In the first book on brain and behavior, René Descartes (1664), a French philosopher, pro-
posed a new explanation of behavior in which he retained the mind’s prominence but gave
the brain an important role. Descartes placed the seat of the mind in the brain and linked
the mind to the body. He stated in the first sentence of Treatise on Man (1664) that mind and
body “must be joined and united to constitute people.”
Descartes’s innovation was the insight into how body organs produce their actions. He
realized that mechanical and physical principles could explain most activities of body and
brain—motion, digestion, and breathing, for example. Descartes was influenced by complex
machines, including gears, clocks, and waterwheels, being built in Paris at the time. He saw
mechanical gadgets on public display. In the water gardens in Paris, one device caused a hid-
den statue to approach and spray water when an unsuspecting stroller walked past it. The
statue’s actions were triggered when the person stepped on a pedal hidden in the sidewalk.
Influenced by these clever devices, Descartes developed mechanical principles to explain psyche Synonym for mind, an entity once
bodily functions. proposed to be the source of human behavior.
But Descartes could not imagine how consciousness could be reduced to a mechanistic mind Proposed nonmaterial entity
explanation. He thus retained the idea that a nonmaterial mind governs rational behavior. responsible for intelligence, attention,
Descartes did, however, develop a mechanical explanation for how the mind interacts with awareness, and consciousness.
the body to produce movement, working through a small structure at the brain’s center, the mentalism Explanation of behavior as a
pineal body (pineal gland). He concluded that the mind instructed the pineal body, which function of the nonmaterial mind.
8 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
Pineal gland lies beside fluid-filled brain cavities called ventricles, to direct fluid from them through
nerves and into muscles (Figure 1-4). When the fluid expanded the muscles, the body
would move.
Descartes’s thesis that the mind directed the body was a serious attempt to give the brain
an understandable role in controlling behavior. This idea that behavior is controlled by two
entities, a mind and a body, is dualism (from Latin, meaning two). To Descartes, the mind
received information from the body through the brain. The mind also directed the body
through the brain. The rational mind, then, depended on the brain both for information
and to control behavior.
Ventricles
Problems plague Descartes’s dualistic theory. It quickly became apparent to scientists that
FIGUre 1-4 Dualist Hypothesis To people who have a damaged pineal body or even no pineal body still display typical intel-
explain how the mind controls the body, ligent behavior. Today, we understand that the pineal gland’s role in behavior is relegated
Descartes suggested that the mind resides to biological rhythms; it does not govern human behavior. We now know that fluid is not
in the pineal gland, where it directs the pumped from the brain into muscles when they contract. Placing an arm in a bucket of water
flow of fluid through the ventricles and
and contracting its muscles does not cause the water level in the bucket to rise, as it should
into the muscles to move the body. The
pineal gland actually influences daily and if the volume of the muscle increased because fluid had been pumped into it. We now also
seasonal biorhythms; see Section 13-2. know that there is no obvious way for a nonmaterial entity to influence the body: doing so
requires the spontaneous generation of energy, which violates the physical law of conserva-
tion of matter and energy.
The difficulty in Descartes’s theory of how a nonmaterial mind and a physical brain
might interact has come to be called the mind–body problem. Nevertheless, Descartes
proposed that his theory could be tested to determine whether an organism possessed a
mind, Descartes proposed the language test and the action test. To pass the language test,
an organism, or even an intelligent machine such as a robot, must use language to describe
and reason about things that are not physically present. The action test requires behavior
based on reasoning, not just an automatic response to a particular situation. Descartes pro-
posed that nonhuman animals and machines would be unable to pass the tests because they
lacked a mind.
A 2014 film, The Imitation Game, dramatizes The contemporary version of Descartes’ language test, the Turing test, is named for
Turing’s efforts during World War II to crack Alan Turing, an English mathematician. In 1950, Turing proposed that a machine could be
the Nazi’s Enigma code. judged conscious if a questioner could not distinguish its answers from a human’s. Machines
are close to passing the Turing test; some might argue that it’s happened. Experimental
dualism Philosophical position that both research also casts doubt on Descartes’s view that nonhuman animals cannot pass the
a nonmaterial mind and a material body language and action tests. Studies of language in apes and other animals partly seek to
contribute to behavior. discover whether other species can describe and reason about things that are not present.
Comparative Focus 1-2, The Speaking Brain, summarizes a contemporary approach to
mind–body problem Difficulty of explaining
how a nonmaterial mind and a material body studying language in animals.
interact. Descartes’s theory of mind led to bad results. Based on dualism, some people argued that
young children and the insane must lack minds, because they often fail to reason appro-
materialism Philosophical position that
priately. We still use the expression he’s lost his mind to describe someone who is mentally
behavior can be explained as a function of the
nervous system without recourse to the mind. ill. Some proponents of dualism also reasoned that, if someone lacked a mind, that person
was simply a machine, not due respect or kindness. Cruel treatment of animals, children,
natural selection Darwin’s theory for
and the mentally ill has for centuries been justified by Descartes’s theory. It is unlikely that
explaining how new species evolve and
Descartes himself intended these interpretations. Reportedly he was very kind to his own
how existing species change over time.
Differential success in the reproduction of dog, Monsieur Grat.
different characteristics (phenotypes) results
from the interaction of organisms with their Darwin and Materialism
environment. By the mid-nineteenth century, another brain–behavior theory emerged. Materialism
species Group of organisms that can advanced the idea that the workings of the brain and the rest of the nervous system alone
interbreed. fully explain rational behavior. The mind, literally, is immaterial. Materialism came to
phenotype Set of individual characteristics prominence when supported by the evolutionary theory of Alfred Russel Wallace and
that can be seen or measured. Charles Darwin.
1-2 • Perspectives on Brain and Behavior 9
COMPaR aTiVE F cus 1-2
The Speaking Brain
Language is such a striking characteristic of our species that it was once Imaging brain blood flow associated with the use of chimpanzeeish
thought unique to humans. Yet evolutionary theory finds it unlikely that indicates that humans and chimpanzees activate the same brain regions
language appeared full-blown in modern humans. Language does have when they speak (Taglialatela, 2011). Wild bonobos are found to use one
antecedents in other animals. Many species lacking a cerebral cortex, distinct call to attract others to feeding locations and another to initiate a
including fishes and frogs, are capable of elaborate vocalizations, and trip. The animals also use numerous gestures to signal intent to others.
vocalization is still more elaborate in species having a cerebral cortex, Stewart Watson and colleagues (2015) report that in two chimpanzee
such as birds, whales, and primates. But can nonhuman animals speak? colonies, the animals used different referential calls (names) for apples.
In language studies with chimpanzees, humans’ closest living rela- When the groups were combined, both modified their calls and adopted
tives, scientists have used two approaches: language training and ana- a common call, an example of gestural drift analogous to people adopting
lyzing spontaneous vocalizations and gestures (Gillespie-Lynch et al., the speech patterns of those around them. The study demonstrates that
2014). To show that nonverbal forms of language might have preceded chimpanzees can learn and share referential calls.
verbal language, Beatrice and Alan Gardner (1969) taught a version of
Laurentiu Garofeanu/Barcroft USA/Barcoft Media via Getty Images
American Sign Language (ASL) to a chimpanzee named Washoe. Sue
Savage-Rumbaugh and her coworkers (1999) taught a pygmy chimpan-
zee named Malatta the symbolic language Yerkish. (The pygmy chim-
panzee, or bonobo, is a species thought to be an even closer relative of
humans than other chimps.)
Malatta’s son Kanzi accompanied his mother to class and became
an excellent Yerkish student. Kanzi also displayed clear evidence of un-
derstanding complex human speech. While recording his vocalizations
when interacting with people and eating, Jared Taglialatela and cowork-
ers found that Kanzi made many sounds associated with their mean-
ings, or semantic context. For example, Kanzi associated various peeps
with specific foods. The research group also found that chimps use a
raspberry or extended grunt sound in a specific context to attract the
attention of others, including people. Kanzi
Evolution by Natural Selection
Wallace and Darwin independently arrived at the same conclusion—the idea that all living
things are related. Both outlined this view in papers presented at the Linnaean Society
of London in July 1858. Darwin further elaborated the topic in his book On the Origin of
Species by Means of Natural Selection, published in 1859. The Origin of Species presented
a wealth of supporting detail, which is why Darwin is regarded as the founder of modern
evolutionary theory.
Both Darwin and Wallace had looked carefully at the anatomy of animals and at animal
behavior. Both were struck by the myriad characteristics common to so many species despite
their diversity. For example, the skeleton, muscles, and body parts of humans, monkeys, and
other mammals are remarkably similar. So is their behavior: many animal species reach for
food with their forelimbs.
Such observations led first to the idea that living organisms must be related, an idea
widely held even before Wallace and Darwin. More important, these same observations led
Darwin to explain how the great diversity in the biological world could have evolved from
common ancestry. Darwin proposed that animals have traits in common because these traits
are passed from parents to their offspring.
Natural selection is Darwin’s theory for explaining how new species evolve and how
existing species change over time. A species is a group of organisms that can breed among
themselves. Individual organisms of any species vary extensively in their phenotype, the
characteristics we can see or measure. No two individuals of any species are exactly alike.
Some are big, some are small, some are fat, some are fast, some are light-colored, and some Figure 2-1 illustrates this principle of
have large teeth. phenotypic plasticity.
10 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
Individual organisms whose characteristics best help them to survive in their environ-
ment are likely to leave more offspring than are less-fit members. This unequal ability of in-
dividual members to survive and reproduce leads to a gradual change in a species’ population
over time, with characteristics favorable for survival in a particular habitat becoming more
prevalent in succeeding generations. Natural selection is nature’s blueprint for the methods
of artificial selection practiced for centuries by plant and animal breeders to produce organ-
isms with desirable traits.
Natural Selection and Heritable Factors
Neither Darwin nor Wallace understood the basis of the great variation in plant and animal
species they observed. Another scientist, the monk Gregor Mendel, discovered one principle
underlying phenotypic variation and how traits pass from parents to their offspring. Through
experiments he conducted on pea plants in his monastery garden beginning about 1857,
Mendel deduced that heritable factors, which we now call genes, govern various physical
traits displayed by the species.
Section 3-3 explains what constitutes a gene, Members of a species that have a particular genetic makeup, or genotype, are likely
how genes function, and how genes can to express (turn on) similar phenotypic traits, as posited in the Procedure section of
change, or mutate. Experiment 1-1. If the gene or combination of genes for a trait, say, flower color, is passed on
ExPERImENT 1-1
Question: How do parents transmit heritable factors to offspring?
Procedure
Mendel crossbred pea plants, then observed which traits parent plants passed to their offspring in successive generations.
Results
Parents × Parents ×
White flower Purple flower
crosses produce crosses produce
white flowers purple flowers
in the first in the first
generation (F1). generation.
F1 F1
First-generation white flower crossed
with first-generation purple flower F1 Parents ×
produces all purple flowers in the
second generation (F2).
F2 × Second-generation purple flowers
crossed with second- generation
purple flower produces, on
average, three purple flowers
and one white flower in the third
F3 generation (F3).
Conclusion: An individual inherits two factors (genes) for each trait, but the
effects of one gene may hide the other gene in the individual. The hidden gene can
resurface after crossbreeding.
1-2 • Perspectives on Brain and Behavior 11
to offspring, the offspring will express the same trait, as illustrated at the top of the Results
genotype Particular genetic makeup of an
section in Experiment 1-1. Two white-flowered pea plants produce white-flowered offspring
individual.
in the first generation, or F1, and purple-flowered parents produce purple-flowered offspring.
Observing this result, Mendel reasoned that two alternative heritable elements govern the epigenetics Differences in gene expression
trait flower color. related to environment and experience.
Mendel then experimented with crossbreeding F1 purple and white pea plant flowers.
The illustration at the bottom of the Results section in Experiment 1-1 shows that
second-generation (F2) offspring all express the purple phenotype. Had the element
that expresses white flowers disappeared? To find out, Mendel crossbred the F2 purple
flowers. The third generation, F3, produced flowers in the ratio of roughly 1 white to
3 purple blooms.
This result suggested to Mendel that the trait for white flowers had not disappeared but
rather was hidden by the trait for purple flowers. He concluded that individuals inherit two
factors, or genes, for each trait, but one may dominate and hide (suppress) the other in the
individual’s phenotype.
Thus, the unequal ability of individual organisms to survive and reproduce is related to
the different genes they inherit from their parents and pass on to their offspring. By the
same token, similar characteristics within or between species are usually due to similar
genes. For instance, genes that produce the nervous system in different animal species tend
to be very similar.
Interplay of Genes, Environment, and Experience
The principles of inheritance that Mendel demonstrated through his experiments have led
to countless discoveries about genetics. We now know that new traits appear because new
gene combinations are inherited from parents, existing genes change or mutate, suppressed
genes are re-expressed, expressed genes are suppressed, or genes or parts of genes are deleted
or duplicated.
But genes alone cannot explain most inherited traits. Mendel realized that environ-
ment participates in expression of traits: planting tall peas in poor soil reduces their
height, for example. Experience likewise plays a part. The experience of children who
attend a substandard school, for example, is far different from that of children who attend
a model school.
Epigenetics is the study of differences in gene expression related to environment and Consult Section 3-3 for details on genetic and
experience. Epigenetic factors do not change your genes, but they do influence how your epigenetic principles.
genes express the traits you’ve inherited from your parents. Epigenetic changes can persist
throughout a lifetime, and their cumulative effects can make dramatic differences in how
your genes work. Epigenetic factors described throughout this book are revolutionizing our
understanding of gene–brain interactions in typical brain development and in brain func-
tion. They will also help investigators understand, and develop new treatments for, some
neurological disorders.
Summarizing Materialism
Darwin’s theory of natural selection, Mendel’s discovery of genetic inheritance, and
the reality of epigenetics have three important implications for studying the brain and
behavior:
1. Because all animal species are related, their brains must be related. A large body of research
confirms first that all animals’ brain cells are so similar that these cells must be related
Section 3-1 describes the varieties of neurons
and second that all animal brains are so similar that they must be related as well. Brain and other brain cells.
researchers study the nervous systems of animals as different as slugs, fruit flies, rats, and
monkeys, knowing that they can extend their findings to the human nervous system.
2. Because all animal species are related, their behavior must be related. In his book The More on emotions and their expression in
Expression of the Emotions in Man and Animals, Darwin (1872) argued that emotional Sections 12-2, 12-4, and 14-3.
12 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
© robert harding picture Library Ltd/alamy
jerome tisne/getty images
a. cassidy/Stone images
o. Benn/Stone images
FIGUre 1-5 An Inherited Behavior
People the world over display the same
emotional expressions that they recognize
in others—these smiles, for example. This
evidence supports Darwin’s suggestion expressions are similar in humans and other animals because we inherited them from
that emotional expression is an inherited a common ancestor. Figure 1-5 offers evidence. That people the world over display the
behavior. same behavior suggests that the trait is inherited rather than learned.
3. Brain and behavior in complex animals such as humans evolved from simpler animals’
brains and behaviors and also depend on learning. Coming up in Section 1-3 we trace the
evolution of nervous systems and their increasingly complex repertoires of actions, from
a simple netlike arrangement to a multipart nervous system with a brain that controls
behavior.
Contemporary Perspectives on Brain
and Behavior
Where do modern students of the brain stand on the perspectives of mentalism, dual-
ism, and materialism? In his influential 1949 book, The Organization of Behavior, psy-
chologist Donald O. Hebb describes the scientific acceptance of materialism in a folksy
manner:
Modern psychology takes completely for granted that behavior and neural function are perfectly
correlated, that one is completely caused by the other. There is no separate soul or life force
to stick a finger into the brain now and then and make neural cells do what they would not
otherwise. (Hebb, 1949, p. iii)
Hebb’s claim dovetails with his theory of how the brain produces consciousness. He sug-
gested that learning is enabled by neurons forming new connections with one another in
the brain. He called the resulting neuronal network a cell assembly. As the neural substrate
for the learned experience, cell assemblies interact: one cell assembly becomes connected
to another. This linking of cell assemblies is thus the linking of memories, which to Hebb is
what consciousness is.
Hebb’s argument is materialistic. The contemporary philosophical school eliminative
materialism takes the position that if behavior can be described adequately without recourse
to the mind, then the mental explanation should be eliminated. Daniel Dennett (1978) and
other philosophers, who have considered such mental attributes as consciousness, pain, and
attention, argue that an understanding of brain function can replace mental explanations
of these attributes. Mentalism, by contrast, defines consciousness as an entity, attribute, or
thing. Let us use the concept of consciousness to illustrate the argument for eliminative
materialism.
1-2 • Perspectives on Brain and Behavior 13
Recovering Consciousness: A Case Study minimally conscious state (mcs)
Darwin offered no suggestion about how the brain produces consciousness, although his Condition in which a person can display some
theory predicted that it must. One patient’s case study offers insight into how the study of rudimentary behaviors, such as smiling or
brain and behavior begins to describe consciousness. The patient, a 38-year-old man, had uttering a few words, but is otherwise not
lingered in a minimally conscious state (MCS) for more than 6 years after an assault. He conscious.
was occasionally able to communicate with single words, occasionally able to follow simple persistent vegetative state (PVs)
commands. He was able to make a few movements but could not feed himself despite 2 years Condition in which a person is alive but
of inpatient rehabilitation and 4 years in a nursing home. unaware, unable to communicate or to
This patient is one of approximately 1.4 million people each year in the United States who, function independently at even the most
as described by Fred Linge in Clinical Focus 1-1, contend with TBI. Among them, as many basic level.
as 100,000 may become comatose; as few as 20 percent recover consciousness. Among the clinical trial Consensual experiment directed
remaining TBI patients, some are diagnosed as being in a persistent vegetative state (PVS), toward developing a treatment.
alive but unable to communicate or to function independently at even the most basic level. deep brain stimulation (DBs)
Their brain damage is so extensive that no recovery can be expected. Others, such as the MCS Neurosurgery in which electrodes implanted
assault victim described earlier, are so diagnosed because behavioral observation and brain in the brain stimulate a targeted area with
imaging studies suggest that they do have a great deal of functional brain tissue remaining. a low-voltage electrical current to facilitate
Adrian Owen (2015) and his colleagues have found that by imaging the brain of comatose behavior.
patients they can assess the extent to which the patients are conscious by the patterns of
activity in their brain. Using an imaging system that measures brain function in terms of
oxygen use, Owen’s group discovered that some comatose patients are actually locked in, as
was Martin Pistorius, whom you met in Section 1-1.
Furthermore, these investigators devised ways to communicate with conscious patients
by teaching them a language that signals changes in their brains’ activity patterns. For ex-
ample, while imaging the brain of control subjects, Owen’s group asks them to imagine hit-
ting a tennis ball with a racket. The group identifies the active brain region associated with
the imaginary act. They then ask patients to imagine hitting a tennis ball and so determine
from their brain images whether they understand. If the patient understands the instruction
and so demonstrates consciousness, procedures for further communication and rehabilita-
tion can begin. FIGUre 1-6 Deep Brain Stimulation
X-ray image showing electrodes implanted
On the rehabilitation front, Nicholas Schiff and his colleagues (Schiff & Fins, 2007)
in the thalamus, a structure deep in the
reasoned that, if they could stimulate their MCS patient’s brain by administering a small brain near the tip of the brainstem, for
electrical current, they could improve his behavioral abilities. As part of a clinical trial (a DBS. DBS can treat disorders such as
consensual experiment directed toward developing a treatment), they implanted thin wire Parkinson disease and depression (see
electrodes in his brainstem so they could administer a small electrical current. Section 16-3) and aid recovery from TBI
Through these electrodes, which are visible in the X-ray image shown (see Section 14-5).
in Figure 1-6, the investigators applied the electrical stimulation for 12
hours each day. The procedure is called deep brain stimulation (DBS).
The researchers found dramatic improvement in the patient’s behavior and
ability to follow commands. For the first time, he was able to feed himself
and swallow food. He could even interact with his caregivers and watch tele-
vision, and he showed further improvement in response to rehabilitation.
The experimenters’ very practical measures of consciousness are
formalized by the Glasgow Coma Scale (GCS), one indicator of the
degree of unconsciousness and of recovery from unconsciousness. The
GCS rates eye movement, body movement, and speech on a 15-point
scale. A low score indicates coma and a high score indicates conscious-
ness. Thus, the ability to follow commands, to eat, to speak, and even
zephyr/Science Source
to watch TV provide quantifiable measures of consciousness contrast-
ing sharply with the qualitative description that sees consciousness
as a single entity. Eliminative materialists would argue, therefore,
that the objective, measurably improved GCS score of behaviors in a
14 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
brain-injured patient is more useful than a subjective mentalistic explanation that con-
sciousness has “improved.”
People under the age of 19 can be especially vulnerable to head trauma and concussion
when they participate in recreational activities and sporting competitions. The Centers
for Disease Control and Prevention has cited bicycling and football injuries as leading
More research on and treatments for MCS causes of TBI in this population. TBI can also lead to accelerated brain aging, an area of
and TBI in Sections 7-3, 14-5, and 15-7. growing concern for participants in athletic competitions that lead to repeated concus-
Concussion is the topic of Focus 16-3. sion or other head trauma, and to military combatants.
The Separate Realms of Science and Belief
Contemporary brain theory is materialistic. Although materialists, your authors included,
continue to use subjective mentalistic words such as consciousness, pain, and attention to
describe more complex behaviors, at the same time they recognize that these words do not
describe mental entities. Materialism argues for objective, measurable descriptions of behav-
ior that can be referenced to brain activity.
Some people may question materialism’s tenet that only the brain is responsible for
behavior because they think it denies religion. But materialism is neutral with respect to
religion. Many of the world’s major religions accept both evolution and the brain’s centrality
in behavior as important scientific theories. Fred Linge, introduced in Clinical Focus 1-1,
has strong religious beliefs, as do the other members of his family. They used their reli-
gious strength to aid in his recovery. Yet despite their religious beliefs, they realize that
Linge’s brain injury caused his changed behavior and that learning to compensate for his
impairments caused his brain function to improve.
The four-step experimental procedure Indeed, many behavioral scientists hold religious beliefs and see no contradiction between
is (1) formulate a question (hypothesis), them and their engagement with science. Science is not a belief system but rather a set of
(2) design a procedure to test it, (3) evaluate procedures designed to allow investigators to confirm answers to a question independently.
the results, (4) confirm or modify the As outlined in Experiment 1-1, this four-step procedure allows anyone to replicate, or repeat,
hypothesis. their original conclusions—or find that they cannot.
1-2 reVIeW
Perspectives on Brain and Behavior
Before you continue, check your understanding.
1. The view that behavior is the product of an intangible entity called the mind (psyche) is
. The notion that the immaterial mind acts through the material brain to
produce language and rational behavior is . , the view that
brain function fully accounts for all behavior, guides contemporary research on the brain
and behavior.
2. The implication that the brains and behaviors of complex animals such as humans evolved
from the brains and behaviors of simpler animals draws on the theory of
advanced by .
3. The brain demonstrates a remarkable ability to recover, even after severe brain
injury, but an injured person may linger in a , occasionally able to
communicate or to follow simple commands but otherwise not conscious. Those
who have such extensive brain damage that no recovery can be expected remain in a
, alive but unable to communicate or to function independently at even
the most basic level.
4. Darwin and Mendel were nineteenth-century contemporaries. Briefly contrast the
methods they used to reach their scientific conclusions.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
1-3 • Evolution of Brains and of Behavior 15
1-3 Evolution of Brains and
of Behavior
Neither nervous system nor brain is common to all living organisms; rather, nervous systems
and behavior have built up and changed bit by bit as animals have evolved. We trace the
evolution of the human brain and behavior by describing (1) animals that first developed
a nervous system and muscles with which to move, (2) how the nervous system grew more
complex as the brain evolved to mediate complex behavior, and (3) how the human brain
evolved its present complexity.
The popular interpretation of human evolution is that we are descended from apes.
Actually, humans are apes. Other living apes are not our ancestors, although we are related
to them through a common ancestor, a forebear from which two or more lineages or family
groups arise. To demonstrate the difference, consider the following story.
Two people named Joan Campbell are introduced at a party, and their names provide a
rich conversation starter. Although both belong to the Campbell lineage (family line), one
Joan is not descended from the other. The two women live in different parts of North Amer-
ica, one in Texas and the other in Ontario, and both their families have been there for many
generations.
Nevertheless, after comparing family histories, the two Joans discover that they have
ancestors in common. The Texas Campbells are descended from Jeeves Campbell, brother
of Matthew Campbell, from whom the Ontario Campbells are descended. Jeeves and Mat-
thew both boarded the same fur-trading ship when it stopped for water in the Orkney Islands
north of Scotland before sailing to North America in colonial times.
The Joan Campbells’ common ancestors, then, were the mother and father of Jeeves and
Matthew. Both the Texas and the Ontario Campbell family lines are descended from this
man and woman. If the two Joan Campbells were to compare their genes, they would find
similarities that correspond to their common lineage.
In much the same way, humans and other apes are descended from common ancestors.
But unlike the Joan Campbells, we do not know exactly who those distant relatives were. By
comparing the brain and behavioral characteristics of humans and related animals and by
comparing their genes, however, scientists are tracing our lineage back farther and farther
to piece together the origins of our brain and behavior.
Some living animal species display characteristics more similar to those of a common
ancestor than do others. For example, in some ways chimpanzees are more similar to the
common ancestor of humans and chimpanzees than are modern humans. In the following
sections, we trace some major evolutionary events that led to human brains and human
behavior by looking at the nervous systems of living animal species and the fossils of extinct
animal species.
Origin of Brain Cells and Brains
Earth formed about 4.5 billion years ago, and the first life-forms arose about a billion years
later. About 700 million years ago, animals evolved the first brain cells, and by 250 million
years ago, the first brain had evolved. A humanlike brain first developed only about 6 mil-
lion years ago, and our modern human brain has been around for only the past 200,000
years or so.
Although life arose very early in our planet’s history, then, brain cells and brains evolved
comparatively recently. Large, complex brains, such as ours, appeared only an eyeblink ago
in evolutionary terms. If you are familiar with the principles of taxonomic classification,
which names and orders living organisms according to their evolutionary relationships, read common ancestor Forebear of two or more
on. If you prefer a brief review before you continue, turn first to The Basics: Classification lineages or family groups; ancestral to both
of Life on pages 16–17. groups.
16 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
THE BASICS
Classification of Life
Taxonomy classifies groups of
representative living organisms into
increasingly specific, subordinate groups.
Taxonomy is the branch of biology concerned
Living organisms
with naming and classifying species by group-
Classified in five main kingdoms:
ing representative organisms according to their
Monera (bacteria), Protista
common characteristics and their relationships (single cells), Plantae (plants),
to one another. Fungi (fungi), Animalia (animals)
As shown in the left column of the figure
Taxonomy of Modern Humans, which illus- Kingdom: Animals
trates the human lineage, the broadest unit of
Characteristics: Neurons and
classification is a kingdom, with more subordi- muscles used for locomotion
nate groups being phylum, class, order, family,
genus, and species. This taxonomic hierarchy is
useful in helping us trace the evolution of brain Phylum: Chordates
cells and the brain. Characteristics: Brain and
We humans belong to the animal kingdom, spinal cord
the chordate phylum, the mammalian class, the
primate order, the great ape family, the genus Class: Mammals
Homo, and the species sapiens. Animals are usu- Characteristics: Large brains
ally identified by their genus and species names. and social behavior
So we humans are called Homo sapiens sapiens,
meaning wise, wise human. Order: Primates
The branches in the figure Cladogram,
Characteristics: Visual control
which shows the taxonomy of the animal king- of hands
dom, represent the evolutionary sequence
(phylogeny) that connects all living organisms.
Cladograms are read from left to right: the most
recently evolved organism (animal) or trait (mus- Family: Great apes
cles and neurons) is farthest to the right. Characteristics: Tool use
Of the five kingdoms of living organisms rep-
resented in the cladogram, only the one most re-
cently evolved, Animalia, contains species with
muscles and nervous systems. It is noteworthy Genus: Human
that muscles and nervous systems evolved to- Characteristics: Language
gether to underlie the forms of movement (be-
havior) that distinguish members of the animal Modern humans are the only
kingdom. surviving species of the genus
The figure Evolution of the Nervous System Species: Modern human that includes numerous extinct
shows the taxonomy of the 15 groups, or phyla, species of humanlike animals.
Characteristics: Complex
of Animalia, classified according to increasing culture
complexity of nervous systems and movement. Taxonomy of Modern Humans
Evolution of Nervous Systems in Animals
A nervous system is not essential for life. In fact, most organisms both in the past and at
present have done without one. In animals that do have a nervous system, comparison of a
Evolution of the Nervous System on page 17 wide variety of species broadly outlines how the nervous system has evolved. We summarize
offers a visual recap. this evolution in the following general steps:
1. Neurons and muscles. Brain cells and muscles evolved first, allowing animals to move.
1-3 • Evolution of Brains and of Behavior 17
Brain cells, nervous systems, and
muscles first evolved in animals.
In proceeding to the right from the nerve net, we find that
nervous systems in somewhat more recently evolved phyla,
such as flatworms, have more complex structure. These
organisms have heads and tails, and their bodies show both
bilateral symmetry (one half of the body is the mirror image
of the other) and segmentation (the body is composed of sim-
Monera Protista Plantae Fungi Animalia ilarly organized parts). The structure of the human spinal
(bacteria) (single cells) (plants) (fungi) (animals) cord resembles this segmented nervous system.
Muscles
and neurons
Multicells
Common ancestor True cells
of animals (nuclei and organelles) Cladogram
Nerve net: Simple nervous system, Segmented nerve trunk: Bilaterally Ganglia: Structures that resemble Brain: True brain
organized as a net, with no brain symmetrical organization and function somewhat like a brain and spinal cord
Sea Flatworm Squid Frog
anemone
Ganglia
Common ancestor
of animals Complexity of movement Evolution of the Nervous System
2. Nerve net. The nervous system representative of evolutionarily older phyla, such as
jellyfishes and sea anemones, is extremely simple. It consists of a diffuse nerve net, which
has no structure that resembles a brain or spinal cord but consists entirely of neurons that nerve net Simple nervous system that has
receive sensory information and connect directly to other neurons that move muscles. no center but consists of neurons that receive
Look again at Figure 1-1 and imagine that the brain and spinal cord have been removed. sensory information and connect directly to
The human PNS is reminiscent of the nerve net in phylogenetically simpler animals. other neurons that move muscles.
18 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
In the context of the brain’s overall 3. Bilateral symmetry. In more complex animals such as flatworms, the nervous system is
bilateral symmetry, Section 15-4 examines more organized, and it features bilateral symmetry: the nervous system on one side of
asymmetries between its cerebral the animal mirrors that on the other side. The human nervous system is also bilaterally
hemispheres. symmetrical (see Figure 1-1).
4. Segmentation. The body of animals such as earthworms consists of a series of similar
muscular segments. Their nervous system has similar repeating segments. The human
Figure 2-28 maps the human spinal cord’s spinal cord and brain display such segmentation: the vertebrae contain the similar
segments. repeating nervous system segments of the spinal cord.
5. Ganglia. In still more recently evolved invertebrate phyla, including clams, snails,
and octopuses, are clusters of neurons called ganglia that resemble primitive brains
and function somewhat like them in that they are command centers. In some phyla,
bilateral symmetry Body plan in which encephalization, having the ganglia in the head, is distinctive. For example, insects’
organs or parts present on both sides of ganglia are sufficiently large to merit the term brain.
the body are mirror images in appearance.
For example, the hands are bilaterally 6. Spinal cord. In relatively highly evolved chordates—animals that have both a brain and a
symmetrical, whereas the heart is not. spinal cord—a single nervous system pathway connects the brain with sensory receptors
and muscles. Chordates get their name from the notochord, a flexible rod that runs the
segmentation Division into a number of
length of the back. In humans, the notochord is present only in the embryo; by birth, bony
parts that are similar; refers to the idea
that many animals, including vertebrates, vertebrae encase the spinal cord.
are composed of similarly organized body 7. Brain. The chordate phylum, of which amphibians, reptiles, birds, and mammals are
segments. class members, displays the greatest degree of encephalization: a true brain. Of all of the
ganglia Collection of nerve cells that function chordates, humans have the largest brain relative to body size, but many other chordates
somewhat like a brain. have large brains as well. Although built to a common plan, the brain of each chordate
chordate Animal that has both a brain and a species displays specializations related to the distinctive behaviors of that species.
spinal cord.
cladogram Phylogenetic tree that branches Chordate Nervous System
repeatedly, suggesting a taxonomy of
A chart called a cladogram (from the Greek word clados, meaning branch) displays groups of
organisms based on the time sequence in
related organisms as branches on a tree. The cladogram in Figure 1-7 represents seven of the
which evolutionary branches arise.
nine classes to which the approximately 38,500 chordate species belong. Wide variation exists
among the nervous systems of chordates, but common to all is the basic structural pattern of
bilateral symmetry, segmentation, and a spinal cord and brain encased in cartilage or bone.
As chordates evolved limbs and new forms of locomotion, their brain became larger. For
FIGUre 1-7 Representative Classes
of Chordates This cladogram example, all chordates have a brainstem, but only the birds and mammals have a large fore-
illustrates evolutionary relationships brain. The evolution of more complex behavior in chordates is closely related to the evolu-
among animals that have a brain and tion of the cerebrum and cerebellum. Their increasing size in various classes of chordates is
spinal cord. Brain size increased with the illustrated in Figure 1-8. These increases accommodate new behaviors, including new forms
evolution of limbs in Amphibia. Birds and of locomotion on land, complex movements of the mouth and hands for eating, improved
mammals are the most recently evolved
learning ability, and highly organized social behavior.
chordates, and both classes have large
brains relative to body size.
Agnatha Chondrichthyes Osteichthyes Amphibia Reptilia Aves Mammalia
(lampreys and hagfish) (sharks and rays) (bony fishes) (frogs and salamanders) (reptiles) (birds) (mammals)
Large brains
Limbs
Common ancestor
1-4 • Evolution of the Human Brain and Behavior 19
Brain
FIGUre 1-8
Cerebrum Cerebellum Cerebrum Cerebellum Cerebrum Cerebellum Cerebrum Cerebellum
Evolution The brains
of representative chordate
species have many structures
in common, illustrating a
single basic brain plan.
Fish Frog Bird Human
The cerebrum and the cerebellum are proportionately small and smooth in the earliest
evolved classes (e.g., fish, amphibians, and reptiles). In later-evolved chordates, especially
the birds and mammals, these structures are much more prominent. In many large-brained
mammals, both structures are extensively folded, which greatly increases their surface area
while allowing them to fit into a small skull, just as folding a large piece of paper enables it
to occupy a small envelope.
Increased size and folding are particularly pronounced in dolphins and primates, animals
with large brains relative to their body size. Because relatively large brains with a complex
cerebrum and cerebellum have evolved in a number of animal lineages, humans are neither
unique nor special in these respects. We humans are distinguished, however, in belonging to
the large-brained primate lineage and are unique in having the largest, most complex brain
in this lineage.
1-3 reVIeW
Evolution of Brains and of Behavior
Before you continue, check your understanding.
1. Because brain cells and muscles evolved only once in the animal kingdom, a similar basic
pattern exists in the of all animals.
2. Evolutionary relationships among the nervous systems of animal lineages are classified
by increasing complexity, progressing from the simplest to a
segmented nervous system to nervous systems controlled by to nervous
systems in the phylum , which feature a brain and spinal cord.
3. A branching diagram that represents groups of related animals is called a .
4. Given that a relatively large brain with a complex cerebrum and cerebellum has evolved in
a number of animal lineages, what if anything makes the human brain unique?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
1-4 Evolution of the Human Brain
and Behavior
Anyone can see similarities among humans, apes, and monkeys. Those similarities extend to
the brain as well. In this section, we consider the brain and behaviors of some more promi-
nent ancestors that link ancestral apes to our brain and our behaviors. Then we consider the
relation between brain complexity and behavior across species. We conclude by surveying
leading hypotheses about how the human brain evolved to become so large and the behavior
that it mediates so complex. The evolutionary evidence shows that we humans are specialized
in having an upright posture, making and using tools, and developing language but that we
are not special, because our ancestors also shared these traits, at least to some degree.
20 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
Lemurs Tarsiers New World Old World Gibbons Orangutans Gorillas Chimpanzees Humans
and lorises monkeys monkeys
Great apes
Common ancestor
of primates FIGUre 1-9 Representatives of the Primate Order This cladogram illustrates
hypothetical relationships among members of the primate order. Humans are members of
the great ape family. In general, brain size increases across the groupings, with humans
having the largest brain of all primates.
hominid General term referring to primates
that walk upright, including all forms of
Humans: Members of the Primate Order
humans, living and extinct. Humans are members of the primate order, a subcategory of mammals that includes apes,
Old World monkeys, New World monkeys, tarsiers, and lemurs as well (Figure 1-9). We hu-
mans are but one of about 275 primate species. Primates have excellent color vision, with the
eyes positioned at the front of the face to enhance depth perception. They use their highly
FIGUre 1-10 Australopithecus developed visual sense to deftly guide their hand movements.
africanus (A) The hominid Female primates usually have only one infant per pregnancy, and they spend a great deal
Australopithecus walked upright with free more time caring for their young than most other animals do. Primate brains are on average
hands, as do modern humans, but its brain larger than those of animals in other mammalian orders, such as rodents (mice, rats, beavers,
was about one-third the size of ours.
squirrels) and carnivores (wolves, bears, cats, weasels).
(B) Human and Australopithecus figures
compared on the basis of the most complete Humans are members of the great ape family, which includes orangutans, gorillas, and
Australopithecus skeleton yet found, a young chimpanzees. Apes are arboreal animals with limber shoulders that allow them to brachiate
female about 1 meter tall, popularly known in trees (swing from one handhold to another), a trait retained by humans, who generally do
as Lucy, who lived 3 million years ago. not live in trees these days. Nevertheless, freeing the arms at the shoul-
der is handy for all sorts of human activities, from traversing monkey
(A) (B)
bars on the playground to competing in the Olympic hammer toss to
raising a hand to ask a question in class. Apes are distinguished as well
by their intelligence and large brain, traits that humans exemplify.
Among the apes, we are most closely related to the chimpanzee, hav-
ing had a common ancestor between 5 million and 10 million years ago.
Between that common ancestor and us over the past 5 million years,
many hominids—primates that walk upright—in our lineage evolved.
Australopithecus
During most of this time, a number of hominid species coexisted. At
present, however, we are the only surviving hominid species.
Australopithecus:
Our Distant Ancestor
One of our hominid ancestors is probably an Australopithecus species
(from the Latin austral, meaning southern, and the Greek pithekos,
meaning ape.) Figure 1-10 shows reconstructions of the face and
body of one such animal, Australopithecus africanus. Many species of
Australopithecus lived, some at the same time, so it is uncertain which
Homo sapiens “Lucy” is our common ancestor.
1-4 • Evolution of the Human Brain and Behavior 21
These early hominids were among the first primates to show distinctly human traits, Australian Raymond Dart coined
including walking upright and using tools. Scientists have deduced their upright posture Australopithecus in naming the skull of a child
from the shape of their back, pelvic, knee, and foot bones and from a set of fossilized foot- he found among fossilized remains from a
prints that a family of australopiths left behind, walking through freshly fallen volcanic ash limestone quarry near Taung, South Africa, in
some 3.8 million years ago. These footprints feature impressions of a well-developed arch 1924. Choosing so to represent his native land
probably was no accident.
and an unrotated big toe—more like humans' than other apes'. (Nevertheless, australopiths
retained the ability to skillfully climb trees.) The bone structure of their hands evinces tool
use (Pickering et al., 2011).
The First Humans
One of the first finds to be designated as genus Homo (human) dates to about 2 million
years ago. The remains were found by Mary and Louis Leakey in the Olduvai Gorge in
Tanzania in 1964. The primates that left these skeletal remains had a strong resemblance
to Australopithecus but more closely resembled modern humans in one important respect:
they made simple stone tools. The Leakeys named the species Homo habilis (handy human)
to signify that its members were toolmakers. To date, the earliest member of the genus
Homo, found in Ethiopia, dates to about 2.8 million years ago. The fossils reveal a jaw
and teeth much smaller than in any Australopithecus species but characteristic to humans
(Villmoare et al., 2015).
The first humans who spread beyond Africa migrated into Europe and Asia. This spe-
cies was Homo erectus (upright human), so named because of the mistaken notion that its
predecessor, H. habilis, had a stooped posture. Homo erectus first shows up in the fossil
record about 1.6 million years ago. As shown in Figure 1-11, its brain was bigger than that
of any preceding hominid, overlapping in size the measurements of present-day human AFRICA
brains. The tools made by H. erectus were more sophisticated than those made by H. habilis.
Early humans may have followed such
An especially small subspecies of H. erectus, about 3 feet tall, was found on the Indonesian proposed routes out of Africa, first to Asia
island of Flores. Named Homo floresiensis, these hominids lived up to about 13,000 years and Europe, eventually to Australia, and
ago (Gordon et al., 2008). finally to the Americas.
As their brain size increased, the
Homo species developed
1600 increasingly sophisticated tools.
H. neanderthalensis
1400 H. sapiens
H. erectus
Brain size (in cubic centimeters)
1200
1000
800 H. habilis
600
Common A. africanus
ancestor
400
200
FIGUre 1-11 Increases in Hominid Brain Size The brain of Australopithecus was
about the same size as that of living nonhuman apes, but succeeding members of the human
lineage display increased brain size. Data from Johanson and Edey, 1981
22 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
Modern humans, Homo sapiens sapiens, appeared within about the past 200,000 years.
Most anthropologists think that they also migrated from Africa. Until about 30,000 years ago
in Europe and 18,000 years ago in Asia, H. sapiens sapiens coexisted and interbred with other
H. sapiens species, collectively called archaic humans. In Europe, for example, H. sapiens
sapiens lived alongside another subspecies of modern humans, H. neanderthalis, named for
the Neander Thal (Valley), Germany, where the first Neanderthal skulls were found. As the
first fossil ancestral humans to be discovered, Neanderthals have maintained a preeminent
place in the study of modern human ancestors.
Neanderthals had brains as large as or larger than those of modern humans, used similar
philippe plailly & atelier daynes/Science Source
tools, and wore jewelry and makeup. They lived in family groups similar to modern human
ones, made music, cared for their elders, and buried their dead. From these archeological
findings, we can infer that Neanderthals probably communicated using language and held
religious beliefs.
We do not know how modern humans completely replaced archaic human species, but
perhaps they had advantages in toolmaking, language use, or social organization. Contem-
porary genetic evidence shows that modern European humans who interbred with Nean-
derthals acquired genes that adapted them to the cold, to novel disease, and possibly to light
skin that better absorbs vitamin D (Sankararaman et al., 2014). Reconstructions such as that
FIGUre 1-12 Neanderthal Woman
in Figure 1-12 show how similar to us Neanderthals really were.
A facial reconstruction by Elisabeth
Daynes made from a casting of the skull. One possible human lineage is shown in Figure 1-13. A common ancestor gave rise to the
The female, whom the discoverers called Australopithecus lineage, and one member of this group gave rise to the Homo lineage. The
Pierrette, died a violent death between the bars in Figure 1-13 are not connected because many more hominid species have been dis-
ages of 17 and 20. Her 36,000-year-old covered than are shown, and exact direct ancestors are uncertain. The bars overlap because
remains were discovered in western
many hominid species coexisted until quite recently. The last of the australopith species
France in 1979, lying near tools from the
Neanderthal period. Focus 10-1 reports disappeared from the fossil record about 1 million years ago.
on the discovery of a flute made by
Neanderthals. Relating Brain Size and Behavior
A. robustus Scientists who study brain evolution propose that increased brain size and complexity
evolved in different species to enable more complex behavior. Having a large brain clearly
A. afarensis has been adaptive for humans, but many animals have large brains. Whales’ and elephants’
brains are much larger than ours. Of course, whales and elephants are much larger than
A. africanus
humans overall. How is relative brain size measured, and what does brain size signify? Two
Common ancestor ways of estimating relative brain size are to compare brain size to body size and to count
brain cells.
H. habilis
H. erectus Estimating Relative Brain–Body Size
Harry Jerison (1973) developed an index that compares the ratio of brain size to body size
H. neanderthalensis
across species. He calculated that as body size increases, brain size increases at about two-
H. sapiens thirds the increase in body weight. Jerison’s underlying assumption was that even if one knew
very little about an animal’s behavior, its brain size could provide some clues to its behavioral
4 3 2 1 0
Millions of years ago
complexity. The idea is that species exhibiting more complex behaviors must possess more
FIGUre 1-13 Human Origins The brain than species whose behaviors are fewer and less complex.
human lineage and a lineage of extinct Using the ratio of actual brain size to expected size, Jerison developed a quantitative
Australopithecus probably arose from a measure, the encephalization quotient (EQ). He defined an average animal (a domestic
common ancestor about 4 million years cat is Jerison’s pick) as having an EQ of 1. The diagonal trend line in Figure 1-14 plots the
ago. The ancestor of the human lineage
expected brain–body size ratio of animals with an EQ of 1. Some animals lie below the
Homo was probably an animal similar to
A. africanus. line: their brain size is smaller than would be expected for an animal of that size. Other
animals lie above the line: their brain size is larger than would be expected for an animal
encephalization quotient (EQ) Jerison’s of that size.
quantitative measure of brain size obtained The lower an animal’s brain falls below the trend line in Figure 1-14, the smaller its EQ. The
from the ratio of actual brain size to expected higher an animal’s brain lies above the trend line, the larger its EQ. Notice that the rat’s brain
brain size, according to the principle of proper is a little smaller (lower EQ) and the elephant’s brain a little larger (higher EQ) than the ratio
mass, for an animal of a particular body size. predicts. A modern human, farther above the line than any other animal, has the highest EQ.
1-4 • Evolution of the Human Brain and Behavior 23
Ratios of Brain to Body
FIGUre 1-14
The modern human brain has
10,000 Elephant Size in Common Mammals As
the largest size relative to
5,000 Homo sapiens represented logarithmically on this graph,
body weight.
Dolphin Blue average brain size relative to body weight
whale falls along a diagonal trend line, where you
1,000
Brain weight (in grams)
Gorilla find the cat. Data from Jerison, 1973.
500 Australopithecus Chimpanzee
Baboon
Lion
100 Wolf
50 Deviation from the trend line indicates
Cat either larger (above) or smaller (below)
10.0 brain size than average, relative to
5.0 body weight.
Vampire bat
1.0 Rat
0.5 Mole
0.001 0.01 0.1 1 10 100 1,000 10,000 100,000
Body weight (in kilograms)
Jerison’s EQ provides a rough estimate of comparative brain size, but body size and brain
size can vary independently (Figure 1-15, top). To get around this problem, scientists have
devised ways to count the cells in the brain.
Counting Brain Cells
Consider the roundworm Caenorhabditis elegans. C. elegans has 959 cells. Of these, 302 are
neurons. In contrast, the blue whale—the largest animal that has ever lived, weighing as
much as 200 tons—has a brain weighing 15,000 grams (33 lb). In cell number, 30 percent of
C. elegans is nervous system, whereas in terms of body weight, less than 0.01 percent of the FIGUre 1-15 Comparing EQs The EQs
blue whale is nervous system. of some familiar mammals are ranked at
Based on EQs, we would predict that C. elegans has a more complex behavioral repertoire the top of the chart, and members of the
primate lineage are ranked at the bottom.
than a blue whale. But it makes no sense to suggest that a worm’s behavior is more complex
Clearly, intelligence is widespread among
than a whale’s. Obviously a whale has a lot more neurons than a worm. Our estimate of brain animals.
size and behavioral complexity line up better if we simply compare cell counts.
Karina Fonseca-Azevedo and her colleagues (2012) have devised such a method, using a Rat
counting machine. Not only can they estimate the number of cells in a brain or a part of the
Cat
brain but they also can estimate the brain cells’ packing density. For example, two similar-
Familiar animals
sized brains could consist of either diffusely distributed large cells or closely packed small Elephant
cells. It turns out that the packing density of cells differs by a lot among species and brain
Crow
regions. Rodents have larger, more loosely packed cells, for example, and primates smaller
and more densely packed cells. Fruit bat
Packing density is relatively constant in the primate lineage, and so EQ provides a good
comparison of their brain sizes (Figure 1-15, bottom). Brain cell counts support the EQs Dolphin
Jerison calculated in the primate lineage: Australopithecus had about 50 billion to 60 billion
Monkey
neurons, Homo habilis about 60 billion, Homo erectus about 75 billion to 90 billion, and
modern humans have about 86 billion neurons.
Chimpanzee
In terms of brain size and cell counts, then, what makes us humans unusual (along with
Primate lineage
archaic humans such as Neanderthals) are our large brain and many neurons. Although Australopithecus
researchers have not made similar neuron counts in all other animal species with brains
larger than the humans', if neurons are not densely packed, resembling the somewhat less- Homo habilis
dense packing of a rodent, then they may well have far fewer neurons. For example, despite
their large brains, dolphins’ 30 billion neurons is similar to the number in chimpanzees, Homo erectus
many fewer than in humans, because dolphin neurons are not densely packed. As detailed
in Comparative Focus 1-3, The Elephant’s Brain, on page 24, pachyderms have an enormous Homo sapiens
number of brain cells, but most are in the cerebellum, while the number in the elephant 0 1 2 3 4 5 6 7
cerebrum is equivalent to that of dolphins and chimpanzees. Encephalization quotients
24 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
COMPaR aTiVE F cus 1-3
The Elephant’s Brain
The cerebrum and cerebellum have evolved into the human brain’s most The elephant’s cerebral cortex boasts more neurons than most
distinct and largest structures, larger than in any other primate brain. animals can boast but somewhat fewer than chimpanzees’ cerebrums.
Although the cerebellum appears smaller than the cerebrum physically, The elephant’s cognitive ability also ranks slightly lower than a chimp’s.
its small, tightly packed neurons are four times the number found in The Herculano-Houzel study offers a conclusion related to the func-
the cerebrum (about 68 billion vs. 16 billion), a 4:1 ratio that humans tion of the human cerebrum, as well. The remarkable cognitive abilities
share with all other primates. Typically, the cerebrum is described as of humans, which exceed those of all other animal species, are best
mediating cognitive functions, whereas the cerebellum mediates motor explained by the sheer number of cerebral neurons, which exceed the
function. In fact, both structures contribute to both kinds of functions in number found in all other animal species, even those with much larger
different ways. brains, including elephants.
African elephants are enormous animals. It is not surprising that they
have the largest brain of all terrestrial animals—three times the size of
a human’s. With such a large brain, why don’t elephants share humans’
intellectual abilities?
To investigate this question, Suzana Herculano-Houzel and her
colleagues (2014) made a neuronal count of an African elephant. They
found that its brain contains three times as many neurons as the human
brain (257 billion vs. 86 billion neurons). But remarkably, 251 billion of
those neurons (97.5 percent) reside in the elephant’s cerebellum. In con-
trast, the elephant’s cerebral cortex, with twice the mass of the human
cortex, contains only 5.6 billion neurons, about one-third the number
found in the human cerebrum. The elephant’s cerebellum contains nearly
45 times as many neurons as its cerebrum.
What do these numbers tell us about the elephant’s behavior? An An African Elephant’s Brain In this, the largest brain of all
elephant has almost infinite degrees of freedom in the use of its trunk: terrestrial animals, both the cerebrum (left) and the cerebellum (right)
are gigantic compared to those of the human brain. But the cerebellum
with it, it can bathe, lift a tree trunk, pick up a peanut, caress a baby, or
contains 97.5 percent of the neurons. Reproduced or adapted from our
paint a picture. The vast number of neurons in its cerebellum is probably websites at http://www.brains.rad.msu.edu and http://brainmuseum.org, supported by
requisite to controlling the trunk’s sensory and motor abilities. the U. S. National Science Foundation.
Why the Hominid Brain Enlarged
The evolution of modern humans—from when humanlike creatures first appeared
until humans like us emerged—spans more than 4 million years. As the relative
size differences of the hominid skulls pictured in Figure 1-16 illustrate, much of
this evolution was associated with increases in brain and body size and by changes
in behavior. These changes were probably driven by many influences. Among
the wide array of hypotheses that seek to explain why the modern human brain
enlarged so much and so rapidly, we examine four ideas.
One hypothesis suggests that numerous drastic climate changes drove
adaptation by hominids and led to more complex behavior. Another hypothesis
contends that the primate lifestyle favors an increasingly complex nervous sys-
tem that humans capitalize on. A third links brain growth to brain cooling. And
a fourth proposes that a changed rate of maturation favors larger brains. Likely, a
The Course of Human
FIGUre 1-16
combination of all of these factors was influential.
Evolution The hominid brain has
increased nearly threefold in relative
size, illustrated here by the skulls of
Climate and the Evolving Hominid Brain
Australopithecus afarensis (left), Homo Climate changes have driven many physical changes in hominids, ranging from brain
erectus (center), and modern Homo sapiens changes to the emergence of human culture. Evidence suggests that each new hominid
(right). Missing parts of the Australopithecus species appeared after climate changes devastated old environments and led to new ones.
skull, shown in blue, have been About 8 million years ago, a massive tectonic event (deformation of Earth’s crust) produced
reconstructed. The Origin of Modern Humans (p. 165),
by R. Lewin, 1998, New York: Scientific American Library.
the Great Rift Valley, which runs through the eastern part of Africa from south to north. The
Photo by Kevin O’Farrell/Concepts. reshaped landmass left a wet jungle climate to the west and a much drier savannah climate
1-4 • Evolution of the Human Brain and Behavior 25
to the east. To the west, the apes continued unchanged in their former habitat. But the fossil
record shows that in the drier eastern region, apes evolved rapidly into upright hominids in
response to the selective environmental pressures that formed their new home.
Thereafter, the climate in East Africa did not remain static. It underwent a number of AFRICA
alterations (Maslin et al., 2015). The appearance of Homo habilis 3 million years ago and that
of Homo erectus 1 million years ago were associated with these climatic alterations. Climatic
l ey
Great Rift Val
changes also track the disappearance of other members of the human family. The warm-
ing in Europe that ended the ice age as recently as 30,000 years ago contributed to modern
humans migrating to the continent and to the Neanderthal and other archaic European and Dry
Asiatic human species disappearing. Wet
What makes Homo sapiens the survivor? One suggestion is that we modern humans
evolved to adapt to change itself and that this adaptability has allowed us to populate every
region on Earth (Antón et al, 2014). The caution is that modern humans have been around
only a short time relative to the millions of years that other hominid species survived: our
adaptability has yet to be severely tested. Africa’s Great Rift Valley cut off ape species
living in a wetter climate to the west from
The Primate Lifestyle species that evolved into hominids, adapted
British anthropologist Robin Dunbar (1998) argues that a primate’s social group size, a to a drier climate to the east.
cornerstone of its lifestyle, is correlated with brain size. His conclusion: the average group size
of about 150 favored by modern humans explains their large brains. He cites as evidence that
150 is the estimated group size of hunter-gatherer groups and the average group size of many
contemporary institutions—a company in the military, for instance—and coincidentally, the
number of people that each of us can gossip about.
Consider how group size might affect how primates forage for food. Foraging is
important for all animals, but while some foraging activities are simple, others are com-
plex. Eating grass or vegetation is an individual pursuit: an animal need only munch and
move on. Vegetation eaters such as gorillas do not have especially large brains relative to
their body size. In contrast, apes that eat fruit, such as chimpanzees and humans, have
relatively large brains.
FIGUre 1-17 Picky Eaters Katharine
Katharine Milton (2003) documented the relation between fruit foraging and larger brains
Milton examined the feeding behavior and
by examining the feeding behavior and brain size of two South American (New World) monkeys
brain size of two New World monkeys that
of the same body size. As illustrated in Figure 1-17, spider monkeys obtain nearly three-quarters have the same body size but different brain
of their nutrients from fruit and have a brain twice as large as that of the howler monkey, which sizes and diets.
obtains less than half its nutrients from fruit.
Spider monkey diet
What is so special about eating fruit? Good sen-
sory skills such as color vision to see it, good motor
skills to reach and manipulate it, good spatial skills A spider monkey,
with a brain size
to find it, good memory to return to it, and having Fruit of 107 g, obtains
friends to help find it and ward off competitors are 72 percent of its
paul a. Souders/corbis
all useful fruit-harvesting skills. Having a parent who nutrients from fruit.
can teach fruit-finding skills and being a good learner F l ow
Leaves er
are also useful. The payoff in eating fruit is its nutri- s
tional value for nourishing a large, energy-dependent
brain that uses more than 20 percent of the body’s
resources. These same skills are useful for obtaining Howler monkey diet
other temporary and perishable types of food, such as
those obtained by scavenging, hunting, and gathering. A howler monkey,
Fruit with a brain size of
A neuron’s metabolic (energy) cost is estimated as
dc_columbia/getty images
50 g, obtains only
relatively constant across different species but also 42 percent of its
Flowers
high relative to that of other types of body cells. So nutrients from fruit.
any adaptive advantage to having more neurons Leaves
must support that energy cost. Fonseca-Azevedo and
Herculano-Houzel (2012) suggest that cooking food is a
26 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
unique contribution to hominid brain development. Gorillas must spend up to 8 hours of each
day foraging for vegetation and eating it. Chimps and early hominids, with a more varied diet,
could support more neurons provided that they also spent most of their waking time foraging.
The use of fire by Homo erectus and later hominids allowed for cooking, which predigests
food and thus maximizes caloric gain to the point that much less time need be devoted to
foraging. A high degree of male–male, female–female, and female–male cooperation in food
gathering and cooking, characteristic of the hominid lifestyle, further supported the evolu-
tion of a larger brain.
Changes in Hominid Physiology
Cooking might foster genetic mutations associated with marked size reductions in individual
muscle fibers in the face and entire masticatory muscles in hominids (Stedman et al., 2004).
The Stedman team speculates that smaller masticatory muscles paved the way for smaller,
A small jaw distinguishes the earliest Homo more delicate bones in the head. Smaller bones in turn allowed for changes in diet and access
fossils yet discovered. to more energy-rich food.
Another physiological adaptation may have given a special boost to greater brain size
in our human ancestors: changes in the morphology (form) of the skull. Dean Falk (Kunz
and Iliadis, 2007) developed the radiator hypothesis from her car mechanic’s remark that
to increase the size of a car’s engine, you also have to increase the size of the radiator that
cools it. Falk reasoned that if the brain’s radiator, the circulating blood, adapted into a more
effective cooling system, brain size could increase.
Brain cooling is so important because the brain’s metabolic activity generates a great deal
of heat and is at risk for overheating under conditions of exercise or heat stress. Falk argued
that, unlike australopith skulls, Homo skulls contain holes through which cranial blood vessels
pass. These holes suggest that, compared to earlier hominids, Homo species had a much more
widely dispersed blood flow from the brain, which would have greatly enhanced brain cooling.
Altered Maturation
All animal species’ life history can be divided into stages. Heterochrony (from the Greek
meaning different times) is the study of processes that regulate the onset and end of life
FIGUre 1-18 Neoteny The shape of stages and their developmental speed and duration. Several proposals suggest that altered
an adult human’s head more closely heterochronicity accounts for the large human brain and other distinctive human features.
resembles that of a juvenile chimpanzee’s In neoteny, juvenile stages of predecessors become adult features of descendants. Neoteny
head (left) than an adult chimp’s head is common in the animal world. Flightless birds are neotenic adult birds, domesticated dogs
(right). This observation leads to the
are neotenic wolves, and sheep are neotenic goats. Many anatomical features link us with
hypothesis that we humans may be
neotenic descendants of our more apelike the juvenile stages of other primates, including a small face, vaulted cranium, unrotated big
common ancestors. toe, upright posture, and primary distribution of hair on the head, armpits, and pubic areas.
Because a human infant’s head is large
relative to body size, neoteny has also led to
adults with proportionally larger bodies and
larger skulls to house larger brains. The shape
of a baby chimpanzee’s head is more similar
to the shape of an adult human’s head than
to an adult chimpanzee’s head (Figure 1-18).
Along with this physical morphology, human
adults also retain some behaviors of primate
infants, including play, exploration, and in-
tense interest in novelty and learning. The
brain processes that support learning thus
are retained in adulthood (Zollikofer, 2012).
photo24/getty images
Critics of neoteny offer an alternative view
FLpa/SuperStock
in which all of the stages of development still
occur, but their onset and duration change
(Workman et al., 2013). Evidence for this idea
1-5 • Modern Human Brain Size and Intelligence 27
is that each stage of human development—gestation, infancy, childhood, adulthood—is
neoteny Process in which juvenile stages
prolonged relative to such ancestral species as macaques and chimpanzees. Prolonged in-
of predecessors become adult features
fancy allows the birth and development of more neurons, more time for their growth to
of descendants; idea derived from the
produce a bigger brain. Prolonged childhood enhances learning time; and prolonged adoles- observation that more recently evolved
cence allows for the growth of a bigger body. species resemble the young of their common
ancestors.
1-4 reVIeW
Evolution of the Human Brain and Behavior
Before you continue, check your understanding.
1. Modern humans share a with the , our closest living relative.
2. Modern humans evolved from a lineage that successively featured
, , and , groups in which more than one species
existed concurrently.
3. The describes brain size relative to body size, but a complete comparison
of different species’ brains requires .
4. The large human brain evolved in response to a number of pressures and opportunities,
including , , , and .
5. One hypothesis proposes that Homo sapiens has evolved to adapt to change itself. Explain
the reasoning behind this hypothesis in a brief paragraph.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
1-5 Modern Human Brain Size
and Intelligence
In The Descent of Man, Charles Darwin detailed the following paradox:
No one, I presume, doubts the large proportion which the size of man’s brain bears to his body,
compared to the same proportion in the gorilla or orang, is closely connected with his higher
mental powers. . . . On the other hand, no one supposes that the intellect of any two animals or of
any two men can be accurately gauged by the cubic contents of their skulls. (Darwin, 1871, p. 37)
Ignoring Darwin, many have tried to tie individual intelligence to gross brain size. If the
functional unit of the brain is the brain cell and if larger human brains have more brain cells,
does it not follow that brain size and intelligence are related? It depends.
The evolutionary approach that we have been using to explain how the large human
brain evolved is based on comparisons between species. Special care attends the extension
of evolutionary principles to physical comparisons within species, especially biological com-
parisons within or among groups of modern humans. We now illustrate the difficulty of
within-species comparisons by considering the complexity of correlating human brain size
with intelligence (Deary, 2000). Then we turn to another aspect of studying the brain and
behavior in modern humans—the fact that unlike that of other animals, so much modern
human behavior is culturally learned.
Meaning of Human Brain Size Comparisons
Over a century ago some investigators promoted a simple conclusion: people with the largest
brains display the most intelligent behavior. The late Stephen Jay Gould, in his 1981 book The
Mismeasure of Man, reviews much of this early literature and criticizes the research on three
counts: brain measurement, correlating brain size and intelligence, and what intelligence is.
First, measuring a person’s brain is difficult. If a tape measure is simply placed around a
person’s head, factoring out skull thickness is impossible. There is also no agreement about
28 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
whether volume or weight is a better measure. And no matter which indicator we use, we
must consider body size. The human brain varies in weight from about 1000 grams to more
than 2000 grams, but people also vary in body mass. To what extent should we factor in body
mass in deciding whether a particular brain is large or small? And how should we measure
body mass, given that a person’s total weight can fluctuate widely over time?
Large differences between the brains of individual people do exist, but the reasons for
these differences are numerous and complex. Consider some examples. People may have
larger or smaller brain cells. Larger people are likely to have a larger brain than smaller
people. Men have a somewhat larger brain than women, but they are proportionately physi-
cally larger. Nevertheless, girls mature more quickly than boys, so in adolescence the brain
and body size differences may be absent. As people age, they generally lose brain cells, so
their brain shrinks.
To find information on specific conditions, Neurological diseases associated with aging accelerate the age-related decrease in brain
consult the Index of Disorders inside the front size. Brain injury near the time of birth often results in a dramatic reduction in brain size,
cover of this book. even in regions distant from the damage. Stress associated with physical or behavioral depri-
vation in infancy also reduces brain size (Herringa et al, 2013). Neurological disorders associ-
ated with a parent’s abuse of alcohol or other drugs are associated with conditions such as
fetal alcohol spectrum disorder (FASD), in which the brain can be greatly reduced in size.
Autism spectrum disorder (ASD), a largely genetic condition affecting development, produces
a wide variety of brain abnormalities, including either increases or decreases in brain size in
different individuals.
Brain size may also increase in individuals. For example, just as good nutrition in the early
years of life can be associated with larger body size, good nutrition can also be associated
Sections 2-1 and 2-6 elaborate on plasticity, with an increase in brain size. The brain’s plasticity—its ability to change—in response to an
Focus 8-1 and Section 8-4 on environment enriched environment is associated with growth of existing brain cells and thus an increase
and brain development, Section 11-3 on skilled in brain size. Furthermore, one way in which the brain stores new skills and memories is
movement, Section 14-1 on memory. to form new connections among brain cells, and these connections in turn contribute to
increased brain size.
Finally, we must also consider what is meant by intelligence. When we compare behavior
across species, we are comparing species-typical behavior—behavior displayed by all mem-
bers of a species. For example, lamprey eels do not have limbs and cannot walk, whereas
salamanders do have limbs and can walk: the difference in brain size between the two species
can be correlated with this trait. When we compare behavior within a species, however, we
are usually comparing how well one individual performs a certain task in relation to others—
how well one salamander walks relative to how well another salamander walks, for example.
We can make intraspecies comparisons for humans, but this likewise presents problems.
Sea lamprey Salamander
For one thing, individual performance on a task is influenced by many factors unrelated to
inherent ability, among them opportunity, interest level, training, motivation, and health.
For another, people vary enormously in their individual abilities, depending on the particu-
plasticity The nervous system’s potential for lar task. One person may have superior verbal skills but mediocre spatial abilities; another
physical or chemical change; enhances its person may be adept at solving spatial puzzles but struggle with written work; still another
adaptability to environmental change and its may excel at mathematical reasoning and be average in everything else. Which of these
ability to compensate for injury. (Also called people should we consider the most intelligent? Should certain skills carry greater weight as
neuroplasticity.) measures of intelligence? Clearly, it is difficult to say.
species-typical behavior Behavior that is Early in the twentieth century, Charles Spearman carried out the first formal perfor-
characteristic of all members of a species, mance analysis among various tests used to rate intelligence. He found a positive correlation
such as walking in amphibians. among tests and suggested that a single common factor explained them. Spearman named
culture Learned behaviors that are passed it g for general intelligence factor, but it turns out that g also varies. Many factors unrelated to
on from one generation to the next through inherent ability—among them opportunity, interest level, training, motivation, and health—
teaching and imitation. influence individual performance on a task.
meme An idea, behavior, or style that spreads For example, when IQ tests that were given to young adults of one generation are given
from person to person within a culture. to the next generation, scores increase by as much as 25 points, a phenomenon called
1-5 • Modern Human Brain Size and Intelligence 29
the Flynn effect (Flynn, 2012). Taken at face value—though it shouldn’t be—the increase
suggests that human g has risen to such a degree in two generations that most young adults
fall in the superior category relative to their grandparents. Obviously, the score change has
not been accompanied by a similar increase in brain size. It is more likely that education and
other life experiences explain the Flynn effect.
Howard Gardner (2006), furthermore, proposes that humans have a number of intelli-
gences—verbal, musical, mathematical, social, and so on. Each type of intelligence is depen-
dent on the function of a particular brain region or regions. Hampshire and colleagues (2012),
who presented participants with a battery of typical intelligence assessment tests, support
Gardner’s idea. As participants took the tests, their brain activity was imaged and recorded.
The study identified three separate abilities—reasoning, short-term memory, and verbal
ability—each associated with a different brain network. The experimenters argue that this Figure 15-9 illustrates the profusion of brain
finding provides little support for Spearman’s g. They further suggest that a wider array of networks; Section 15-6 relates network
assessments would reveal additional intelligence networks. efficiency to intelligence.
Given the difficulty in measuring brain size and in defining intelligence, it is not
surprising that scant research appears in the contemporary literature on the problem of
gross brain size and intelligence. If you are wondering whether having a larger brain might
mean you could study a little less, consider this. The brains of people who are widely
considered highly intelligent have been found to vary in size from the low end to the high Section 15-6 expands on theories of
end of the range for our species. The brain of the brilliant physicist Albert Einstein was intelligence. Einstein’s brain is pictured in
average in size. Figure 15-20.
Acquisition of Culture
In evolutionary terms, the modern human brain developed rapidly. Many behavioral changes
differentiate us from our primate ancestors, and these adaptations took place more rapidly
still, long after the modern brain had evolved. The most remarkable thing that our brains
have made possible is ever more complex culture—learned behaviors passed from generation
to generation through teaching and experience.
Cultural growth and adaptation render many contemporary human behaviors distinctly
different from those of Homo sapiens living 200,000 years ago. Only 30,000 years ago,
modern humans made the first artistic relics: elaborate paintings on cave walls and carved Saint Ambrose, who lived in the fourth
ivory and stone figurines. Agriculture appears still more recently, about 15,000 years ago, and century, is reportedly the first person who
reading and writing were invented only about 7000 years ago. could read silently.
Most forms of mathematics and many of our skills in using mechanical and digital
devices have still more recent origins. Early H. sapiens brains certainly did not evolve to
select smart phone apps or imagine traveling to distant planets. Apparently, the things that
the human brain did evolve to do contained the elements necessary for adapting to more
sophisticated skills.
Alex Mesoudi and his colleagues (2006) suggest that cultural elements, ideas, behaviors,
or styles that spread from person to person—called memes (after genes, the elements of
physical evolution)—can also be studied within an evolutionary framework. They propose
that individual differences in brain structure may favor the development of certain memes.
Once developed, memes would in turn exert selective pressure on further brain develop-
ment. For example, chance variations in individuals’ brain structure may have favored tool
use in some individuals. Tool use proved so beneficial that toolmaking itself exerted selective
pressure on a population to favor individuals well skilled in tool fabrication.
Similar arguments can be made with respect to other memes, from language to music,
from mathematics to art. Mesoudi’s reasoning supports neuroscience’s ongoing expansion
into seemingly disparate disciplines, including linguistics, the arts, business, and economics.
Studying the human brain, far from examining a body organ’s structure, means investigat-
ing how it acquires culture and fosters adaptation as the world changes and as the brain Section 15-3 explores some of psychology’s
changes the world. expanding frontiers.
30 Chapter 1 • WHAT ARE THE ORIGINS OF BRAIN AND BEHAVIOR?
1-5 reVIeW
Modern Human Brain Size and Intelligence
Before you continue, check your understanding.
1. Behavior that is displayed by all members of a species is called .
2. Some modern human behavior is inherent to our nervous system, but far more is
learned—passed generation to generation by . Ideas, behaviors, or styles
called may spread from person to person and culture to culture.
3. Spearman proposed a common intelligence factor he called . Gardner
supports the idea of .
4. Explain the reasoning behind the statement that what is true for evolutionary
comparisons across different species may not be true for comparisons within a single
species.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
SUMMarY
1-1 Neuroscience in the Twenty-First Century After severe TBI, the brain demonstrates a remarkable ability to
Studying the brain and behavior leads us to better understand our recover, but after either mild or severe injury, a person can be left
origins, our human nature, the causes of many behavioral disorders, with a permanent disability that prevents full recovery to former levels
and the rationale behind treatment for disorders. of function. Brain imaging techniques can confirm severe disabilities
The human nervous system is composed of the CNS, which such as the MCS, locked-in syndrome, and PVS.
includes the brain and the spinal cord, and the PNS, through which
the brain and spinal cord communicate with sensory receptors, with 1-3 Evolution of Brains and of Behavior
muscles and other tissues, and with the internal organs. The cerebrum Behavioral neuroscientists subscribe to the evolutionary principle that
and the cerebellum have undergone the most growth in large-brained all living organisms are descended from a common ancestor. Brain
animal species. cells and muscles are quite recent developments in the evolution of
We define behavior as any kind of movement, including mental life on Earth. Because they evolved only once, a similar basic pattern
processes such as thinking and imagining. In animals, behavior exists in the nervous systems of all animals.
is caused by nervous system activity. Behavioral flexibility and The nervous systems of some animal lineages have become more
complexity vary greatly across species, as does the nervous system. complex, with evolution featuring first a nerve net, followed by a
For some species, including humans, the brain is the organ that bilaterally symmetrical and segmented nervous system, a nervous
exerts control over behavior. The brain seems to need ongoing system controlled by ganglia, and eventually, in chordates, a nervous
sensory and motor stimulation to maintain its intelligent activity. system featuring a brain and spinal cord.
Mammals are a class of chordates characterized by a large brain
1-2 Perspectives on Brain and Behavior relative to body size. Modern humans belong to the primate order,
Mentalism views behavior as a product of an intangible entity called which is distinguished by especially large brains, and to the family of
the mind (psyche); the brain has little importance. Dualism is the great apes, whose members’ limber shoulders allow them to brachiate
notion that the immaterial mind acts through the material brain to (hang and swing by the arms).
produce language and rational behavior, whereas the brain alone is
responsible for the “lower” actions that we have in common with 1-4 Evolution of the Human Brain and Behavior
other animal species. One of our early hominid ancestors was probably an Australopithecus,
Materialism, the view that brain function fully accounts for all who lived in Africa several million years ago. It is from an australopith
behavior, language and reasoning included, guides contemporary species that Homo evolved through species such as Homo habilis and
research on the brain and behavior. Support for the materialistic view Homo erectus. Modern humans, Homo sapiens sapiens, appeared about
comes from the study of natural selection—the evolutionary theory 200,000 years ago.
that behaviors such as human language evolved from the simpler Since Australopithecus, the hominid brain has increased in size
language abilities of human ancestors—and from discoveries about almost threefold, as has its number of brain cells. The EQ describes
how genes function. Experiments follow the process of science: first, brain size relative to body size, but a complete comparison of
formulate a question (hypothesis), then design a procedure to test it, different species’ brains requires brain cell counts. Among the factors
evaluate the results, and confirm or modify the hypothesis. hypothesized to have stimulated brain evolution in human species are
Key Terms 31
environmental challenges and opportunities, such as climate changes brains were associated with more complex behavior. Yet within
that favored the natural selection of adaptability and more complex our species, the complexity of different brain regions is related to
behavior patterns. Also proposed are lifestyle changes such as social behavioral abilities. People vary widely in body size and in brain size
cooperation and cooking food, changes in physiology, and changed as well as in varying kinds of intelligence, making a simple comparison
maturation rate. of brain size and general intelligence unwise.
Recognizing the great extent to which modern human behavior,
1-5 Modern Human Brain Size and Intelligence rather than being inherent in our nervous systems, results from
Evolutionary principles learned from studying the brain and behavior cultural learning and transmission is paramount to understanding how
across species do not easily apply to the brain and behavior within our brains function. Memes may spread from person to person and
a single species, such as Homo sapiens. As animals evolved, larger culture to culture.
KeY terMS
bilateral symmetry, p. 18 deep brain stimulation (DBS), materialism, p. 8 peripheral nervous system
brainstem, p. 5 p. 13 meme, p. 28 (PNS), p. 3
central nervous system (CNS), dualism, p. 8 mentalism, p. 7 persistent vegetative state
p. 3 embodied behavior, p. 5 (PVS), p. 13
mind, p. 7
cerebellum, p. 5 encephalization quotient (EQ), phenotype, p. 8
mind–body problem, p. 8
cerebrum (forebrain), p. 5 p. 22 plasticity, p. 28
minimally conscious state
chordate, p. 18 epigenetics, p. 11 (MCS), p. 13 psyche, p. 7
cladogram, p. 18 ganglia, p. 18 natural selection, p. 8 segmentation, p. 18
clinical trial, p. 13 genotype, p. 11 neoteny, p. 27 species, p. 8
common ancestor, p. 15 hemisphere, p. 5 nerve net, p. 17 species-typical behavior, p. 28
culture, p. 28 hominid, p. 20 neuron, p. 3 spinal cord, p. 3
locked-in syndrome, p. 5 traumatic brain injury (TBI),
p. 3
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
this page left intentionally blank
RESEARCH FOCUS 2-1 Agenesis of the Cerebellum
ch a p te r 2-1 OvERviEw OF BRAin FUnCtiOn And StRUCtURE
2 What Is the Nervous PlAstiC PAtterns of neurAl orgAnizAtion
funCtionAl orgAnizAtion of the nervous system
System’s Functional
the brAin’s surfACe feAtures
THE BASICS finding your WAy Around the brAin
CLiniCAL FOCUS 2-2 meningitis And enCePhAlitis
Anatomy? the brAin’s internAl feAtures
CLiniCAL FOCUS 2-3 stroke
2-2 tHE nERvOUS SyStEm’S EvOLUtiOnARy dEvELOpmEnt
stAges in brAin evolution
the nervous system And intelligent behAvior
EXpERimEnt 2-1 Question: does intelligent behAvior reQuire
A vertebrAte nervous system orgAnizAtion?
2-3 tHE CEntRAL nERvOUS SyStEm: mEdiAting BEHAviOR
sPinAl Cord
brAinstem
forebrAin
CerebrAl Cortex
bAsAl gAngliA
limbiC system
olfACtory system
2-4 SOmAtiC nERvOUS SyStEm: tRAnSmitting inFORmAtiOn
CrAniAl nerves
sPinAl nerves
somAtiC nervous system ConneCtions
integrAting sPinAl funCtions
CLiniCAL FOCUS 2-4 mAgendie, bell, And bell PAlsy
2-5 AUtOnOmiC And EntERiC nERvOUS SyStEmS:
viSCERAL RELAtiOnS
Ans: bAlAnCing internAl funCtions
ens: Controlling the gut
2-6 tEn pRinCipLES OF nERvOUS SyStEm FUnCtiOn
PrinCiPle 1: the nervous system ProduCes movement in A
PerCePtuAl World the brAin ConstruCts
PrinCiPle 2: neuroPlAstiCity is the hAllmArk of nervous
system funCtioning
PrinCiPle 3: mAny brAin CirCuits Are Crossed
PrinCiPle 4: the Cns funCtions on multiPle levels
PrinCiPle 5: the brAin is symmetriCAl And AsymmetriCAl
PrinCiPle 6: brAin systems Are orgAnized
hierArChiCAlly And in PArAllel
PrinCiPle 7: sensory And motor divisions PermeAte
the nervous system
PrinCiPle 8: the brAin divides sensory inPut for objeCt
reCognition And motor Control
Katherine Streeter
PrinCiPle 9: brAin funCtions Are loCAlized And distributed
PrinCiPle 10: the nervous system Works by juxtAPosing
exCitAtion And inhibition
33
34 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
RESEARCH F cus 2-1
Agenesis of the Cerebellum
When an adult’s brain is damaged, as for example in traumatic brain injury,
we see a pattern of behavioral changes that offer insight into brain func-
tions, as described by Fred Linge in Clinical Focus 1-1, Living with Trau-
matic Brain Injury. Naturally occurring brain injuries rarely remove a single
structure completely, leaving the rest of the brain intact. However, agen-
esis, the failure of brain regions to develop, offers researchers a unique
Massachusetts General Hospital; Credit: Courtesy of Jeremy Schmahmann
window on the brain’s organization and function, because in rare cases
a complete structure is absent yet the rest of the brain appears normal.
Historically, the cerebellum was viewed as a motor structure, with
the most obvious sign of damage being ataxia, a failure of muscular
coordination and balance. But the cerebellum’s functions are much
more extensive than movement control (e.g., Schmahmann, 2010). Adult
patients with damage to the cerebellum do have motor disturbances, but
they also have cognitive deficits, for example, in abstract thinking and
language and in emotional control.
The cerebellum contains the most neurons of any brain region,
accounting for 80 percent of the neurons in humans and a whopping
97.5 percent of elephants’ neurons—believed to be related to the dexter-
ity of the elephant’s trunk. What would happen if the cerebellum failed
to develop but the rest of the brain developed apparently normally? We
MRI brain scans of a person with cerebellar agenesis (A, B)
humans would be missing 80 percent of our neurons! compared to a control person (C, D) of the same age. A and C
The accompanying images contrast the brain of a young man born are viewed in the coronal plane, B and D in the mid-sagittal
with agenesis of the cerebellum (A and B) to the brain of a person plane. For more about this condition:
whose brain developed normally (C and D). Even lacking 80 percent www.npr.org/blogs/health/2015/03/16/393351760
of his neurons, the young man’s behavioral capacities are remarkable,
but his behavior is not typical. Now in his thirties, he has an office job brain you see in images A and B had severe visuomotor spatial dis-
and lives alone. He has a distinctive speaking pattern, an awkward gait, abilities as a child and adolescent, but by age 30 he showed significant
and difficulties with balance, as well as deficits in planning and abstract improvement (Chheda et al., 2002; Schmahmann et al., 2007; Jeremy D.
thinking. His social skills and long-term memory are good, though, as is Schmahmann and Janet C. Sherman, personal communication). Other
his mastery of routine activities. patients’ language develops slowly.
Studies of other people with cerebellar agenesis reveal a hetero- In people with absence of the cerebellum it is thought that brain
geneous set of symptoms, but neuropsychological assessments show plasticity in response to early perturbations emerge as regions of the
behavioral deficits reminiscent of people with damage to frontal and cerebral cortex begin to function more efficiently. In fact, it has been
parietal cortical regions (e.g., Baumann et al., 2015), even though these reported that cerebellar agenesis patients appear to have some of the
cerebral regions are intact. Although people with cerebellar agenesis symptoms of autism early in life. This observation comports with evi-
develop slowly, they show remarkable improvement over time and seem dence that dysfunction (rather than absence) of the cerebellum is related
able to compensate for many of their symptoms. The individual whose to autism (detailed in Clinical Focus 8-2, Autism Spectrum Disorder).
throughout this book we examine the nervous system with a focus on function—
on how our behavior and our brain interact. In this chapter, we consider the human
nervous system’s organization and how its basic components function in the context
of plasticity, as illustrated in Research Focus 2-1, Agenesis of the Cerebellum. First, we
emphasize the brain’s biology. Then we elaborate on function—how the brain works in
concert with the rest of the nervous system. This focus on nervous system function and
plasticity suggests 10 principles of nervous system organization. We note each principle
through the chapter and in detail at its end, in Section 2-6. These big ideas apply equally
to the micro and macro views of the nervous system presented in this chapter and to the
broader picture of behavior that emerges in later chapters.
2-1 • Overview of Brain Function and Structure 35
2-1 Overview of Brain Function
and Structure
The brain’s primary function is to produce behavior, or movement. To produce behavior
as we search, explore, and manipulate our environment, the brain must absorb informa-
tion about the world—about the objects around us: their size, shape, and location. Without
stimuli, the brain cannot orient the body and direct it to produce an appropriate response.
The nervous system’s organs are designed to admit information from the world and to
convert this information into biological activity that produces perception, subjective experi- Principle 1: The nervous system produces
ences of reality. The brain thus produces what we believe is reality so that we can move. This movement in a perceptual world the brain
subjective reality is essential to carrying out any complex task. constructs.
When you answer the telephone, for example, your brain directs your body to reach for it as
the nervous system responds to vibrating air molecules by producing the subjective experience
of a ringtone. We perceive this stimulus as sound and react to it as if it actually exists, when
in fact the sound is merely a fabrication of the brain. That fabrication is produced by a chain
reaction that takes place when vibrating air molecules hit the eardrum. Without the nervous
system, especially the brain, sound does not exist—only the movement of air molecules.
But there is more to hearing a phone’s ringtone than vibrating air molecules. Our mental
construct of reality is based not only on the sensory information we receive but also on
the cognitive processes we might use to interact with that incoming information. Hearing
a ringtone when we are expecting a call has a meaning vastly different from its ringing at
three o’clock in the morning, when we are not expecting a call.
The subjective reality the brain constructs can be better understood by comparing the
sensory realities of two different kinds of animals. You are probably aware that dogs perceive
sounds that humans do not. This difference in perception does not mean that a dog’s ner-
vous system is better than ours or that our hearing is poorer. Rather, the perceptual world
constructed by a dog brain simply differs from that of a human brain. Neither experience is
“correct.” The difference in subjective experience is due merely to two differently evolved Section 9-1 elaborates on the nature of
systems for processing sensory stimuli. sensation and perception.
When it comes to visual perception, our world is rich with color, whereas dogs see very
little color. Human brains and dog brains construct different realities. Subjective differences
in brains exist for good reason: they allow different animals to exploit different features in
their environments. Dogs use their hearing to detect the movements of prey, such as mice in
the grass; early humans probably used color vision for identifying ripe fruit in trees. Evolution,
then, fosters adaptability, equipping each species with a view of the world that helps it survive.
Plastic Patterns of Neural Organization
The brain is plastic: neural tissue has the capacity to adapt to the world by changing how its
functions are organized. Just as the brain of the young man profiled in Research Focus 2-1
adapted to cerebellar agenesis, a person blind from birth has enhanced auditory capacities
because some of the brain’s visual regions have been co-opted for hearing. The brain is also
plastic in the sense that connections among neurons in a given functional system are con-
stantly changing in response to experience.
For us to learn anything new, neural circuits must change to represent and store this
knowledge. As we learn to play a musical instrument or speak a new language, the cortical
regions taking part can actually increase in size to accommodate the learning. An important
aspect of human learning and brain plasticity is related to the development of language and
to the expansion of the brain regions related to language. We have learned to read, to calcu-
late, to compose and play music, and to develop the sciences. Clearly, the human nervous
system evolved long before we mastered these achievements.
36 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
In turn, culture now plays a dominant role in shaping our behavior. Because we drive cars
and communicate electronically, we—and our nervous system—must differ from those of our
ancestors who did not engage in these activities. The basis for change in the nervous system is
Principle 2: Neuroplasticity is the hallmark of neuroplasticity, the nervous system’s fundamental potential for physical or chemical change
nervous system functioning. that enhances its adaptability to environmental change and its ability to compensate for injury.
Although it is tempting to see neuroplasticity as a trait unique to animals’ nervous sys-
tems, it is really part of a larger biological capacity called phenotypic plasticity, the indi-
vidual’s capacity to develop into more than one phenotype—the characteristics we can see or
measure. (See Gilbert & Epel, 2009, for a wonderful discussion of biological plasticity.) Stated
Section 1-2 introduces the genotype, simply, an individual’s genotype (genetic makeup) interacts with the environment to elicit a
phenotype, and epigenetics in an evolutionary specific phenotype. This phenotype emerges from a large genetic repertoire of possibilities,
context. a phenomenon that in turn results from epigenetic influences.
Epigenetic factors do not change genes but rather influence how genes inherited from
parents express specific traits. The two mice pictured in Figure 2-1 appear very different:
Randy L. Jirtle, Adjunct Professor of Epigenetics,
one is fat, one thin; one has dark fur, the other is light-colored. Yet these mice essentially
Department of Biological Sciences, NC State
are clones, genetically identical. They appear so different because their mothers were fed
different diets while pregnant. The diet supplements added chemical markers, or epigenetic
tags, on specific genes. The tags determine whether the gene is available to influence cells,
including neurons, leading to differences in body structure and eating behavior.
University, Raleigh, NC
Functional Organization of the
Nervous System
From an anatomical standpoint, the brain and spinal cord together make up the central
FIGUre 2-1 Phenotypic Plasticity
nervous system. The nerve fibers radiating out beyond the brain and spinal cord, as well
These two mice are genetically identical
but express very different phenotypes as all the neurons outside the brain and spinal cord, form the peripheral nervous system.
because their mothers were fed different Figure 2-2A charts this anatomical organization. PNS nerves carry sensory information into
supplements when pregnant. the CNS and carry motor instructions from the CNS to the body’s muscles and tissues,
including those that perform such functions as blood circulation and digestion.
Figure 2-2A restates Figure 1-1, the gross In a functional organization, little changes, but the focus turns to how the parts of the sys-
anatomy of the human CNS and PNS. tem work together. Neurons in the somatic division of the PNS connect through the cranial
and spinal nerves to receptors on the body’s surface and on its muscles. Somatic neurons gather
sensory information for the CNS and convey information from the CNS to move muscles of
the face, body, and limbs. Similarly, the autonomic division of the PNS enables the CNS to gov-
ern the workings of your body’s internal organs—your heartbeat, urination, pupillary response,
and the diaphragm movements that inflate and deflate your lungs. The enteric nervous system,
which is sometimes considered part of the ANS, controls digestion and stomach contractions.
And so, from a functional standpoint (Figure 2-2B), the major PNS divisions step up to
FIGUre 2-2 Parsing the Nervous
constitute, along with the CNS, an interacting four-part system:
System The nervous system can be
conceptualized (A) anatomically and • The CNS includes the brain and the spinal cord—the nervous system core, which
(B) functionally. The functional approach mediates behavior.
employed in this book focuses on how the
four parts of the nervous system interact.
(A) Anatomic Organization (B) Functional Organization
Nervous system
Nervous system
Central Somatic nervous system Autonomic nervous Enteric nervous
Central nervous Peripheral nervous nervous system (transmits sensation, system (balances system (controls
system (CNS) system (PNS) (mediates behavior) produces movement) internal functions) the gut)
Spinal Somatic Autonomic Enteric Spinal Cranial Spinal Sympathetic Parasympathetic
Brain Brain
cord nervous system nervous system nervous system cord nerves nerves division (arousing) division (calming)
2-1 • Overview of Brain Function and Structure 37
• The somatic nervous system (SNS) includes all the spinal and cranial nerves carrying Sensory (incoming)
sensory information to the CNS from the muscles, joints, and skin. It also transmits pathways are afferent.
outgoing motor instructions that produce movement.
• The autonomic nervous system (ANS) balances the body’s internal organs by producing
the rest-and-digest response through the parasympathetic (calming) nerves or the fight-or-
flight response or vigorous activity through the sympathetic (arousing) nerves.
• The enteric nervous system (ENS), formed by a mesh of neurons embedded in the
lining of the gut, controls the gut. The ENS communicates with the CNS via the ANS
Motor (outgoing)
but mostly operates autonomously.
pathways are efferent.
The directional flow of neural information is important. Afferent (incoming) information
Sensory
is sensory, coming into the CNS or one of its parts, whereas efferent (outgoing) information endings
is leaving the CNS or one of its parts. When you step on a tack, the afferent sensory signals
are transmitted from the body into the brain and felt as pain. Efferent signals from the brain FIGUre 2-3 Neural Information Flow
trigger a motor response: you lift your foot (Figure 2-3).
The Brain’s Surface Features
When buying a new car, people like to look under the hood and examine the engine, the part
of the car responsible for most of its behavior—and misbehavior. All most of us can do is gaze
at the maze of tubes, wires, boxes, and fluid reservoirs. What we see makes no sense except
in the most general way. We know that the engine somehow generates power to make the
car move and to run the sound system, lights, and wipers. But knowing this tells us nothing
about what all the many engine parts do.
When it comes to our behavior, the brain is the engine. In many ways, examining a brain
for the first time is similar to looking under the car hood. We have a vague sense of what
the brain does, but most of us have no sense of how its parts accomplish these tasks. We neuroplasticity The nervous system’s
may not even be able to identify those parts. If you are familiar with the anatomical terms potential for physical or chemical change
and orientations used in drawings and images of brains, read on. If you prefer to review this to adapt to environmental change and to
terminology before you continue, consult The Basics: Finding Your Way Around the Brain compensate for injury.
on pages 38–39. phenotypic plasticity An individual’s
capacity to develop into more than one
Protecting the Nervous System phenotype.
We start our functional overview by opening the hood and observing the brain snug in its
somatic nervous system (sNs) Part of
home in the skull. The first thing you encounter is not the brain but rather a tough triple- the PNS that includes the cranial and spinal
layered protective covering, the meninges (sing. meninx) (Figure 2-4). The outer dura mater nerves to and from the muscles, joints, and
(from Latin, meaning hard mother) is a tough double layer of fibrous tissue that encloses the skin, which produce movement, transmit
brain and spinal cord in a kind of loose sac. In the middle is the arachnoid layer (from Greek, incoming sensory input, and inform the CNS
meaning like a spider’s web), an ultrathin sheet of delicate connective tissue that follows the about the position and movement of body
brain’s contours. The inner layer, or pia mater (from Latin, meaning soft mother), is a moder- parts.
ately tough membrane of connective tissue fibers that cling to the brain’s surface. autonomic nervous system (ANs) Part
of the PNS that regulates the functioning of
internal organs and glands.
Skull enteric nervous system (ENs) Mesh of
Dura neurons embedded in the lining of the gut,
mater running from the esophagus through the
Arachnoid Meninges colon; controls the gut.
membrane
Pia mater afferent Conducting toward a CNS structure.
Subarachnoid space efferent Conducting away from a CNS
Brain (filled with CSF) structure.
FIGUre 2-4 Cerebral Protection A triple-layered covering, the meninges Three layers of protective tissue—
meninges, encases the brain and spinal cord, and cerebrospinal fluid dura mater, arachnoid, and pia mater—that
(CSF) cushions them. encase the brain and spinal cord.
38 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
THE BASICS
Finding Your Way Around the Brain
When the first anatomists began to examine the brain with the primitive Brain–Body Orientation
tools of their time, the names they chose for brain regions often manifested
their erroneous assumptions about how the brain works. They named one Structures atop the brain or a
brain region the gyrus fornicatus because they thought that it had a role Structures toward
structure within the brain are dorsal.
the brain’s midline
in sexual function, but most of this region actually has nothing to do with
are medial; those
sexual activity.
located toward the
sides are lateral.
A Wonderland of Nomenclature
As time went on, the assumptions and tools of brain research changed, but
naming continued to be haphazard and inconsistent. Many brain struc-
tures have several names, and terms are often used interchangeably. This
peculiar nomenclature arose because research on the brain and behavior
spans several centuries and includes scientists of many nationalities and
languages. Anterior is in
Early investigators named structures after themselves or objects or ideas. front; posterior
is at the back. Structures toward the bottom of the
They used various languages, especially Latin, Greek, and English. More
brain or one of its parts are ventral.
recently, investigators have often used numbers or letters, but even this sys-
tem lacks coherence, because the numbers may be Arabic or Roman and are
often used in combination with Greek or Latin letters.
Describing Locations in the Brain
Many names for nervous system structures reflect their anatomical locations • Spatial Orientation illustrates brain structure location in relation to other
with respect to other body parts of the animal, with respect to their relative body parts and body orientation.
spatial locations, and with respect to a viewer’s perspective: • Anatomical Orientation illustrates the direction of a cut, or section,
• Brain–Body Orientation illustrates brain structure location from the through the human brain (part A) from the perspective of a viewer
frame of reference of the human face. (part B).
Spatial Orientation
Animals’ brains are oriented similarly, but spinal-cord
orientations may differ because many animals stand on “all
Dorsal
fours.” Compared with the head orientation of a four-legged
Rostral (beak), caudal (tail), animal, “dorsal” and “ventral” take a 90° turn counter-
dorsal (back), and ventral clockwise when describing the human or the bird brain
(superior)
(stomach) parts of the brain
Dorsal
are located near those body
Dorsal
parts.
Rostral Caudal Anterior Posterior Anterior Posterior
Superior and inferior may be
used to refer to structures Posterior and caudal
Ventral
both mean “tail.”
(inferior)
located dorsally or ventrally.
Ventral
The terms have only to do
with location, not with
importance.
Ventral
2-1 • Overview of Brain Function and Structure 39
Anatomic Orientation
(A) Plane of section (B) View of brain
These orienting terms are derived from
Latin. Consult the accompanying Glossary
of Anatomical Location and Orientation for A coronal section is cut in
Living Art Enterprises/Science Source
easy reference. It is common practice to com- a vertical plane, from the
bine orienting terms. A structure described crown of the head down,
as dorsolateral, for example, means that it yielding a frontal view of
the brain’s internal
lies up and to the side.
structures.
Finally, the nervous system, like the body,
is bilaterally symmetrical: it has a left side
and a right side. Structures that lie on the
same side are ipsilateral; if they lie on oppo-
site sides, they are contralateral to each other. Coronal section Frontal view
Structures that occur in each hemisphere
are bilateral. Structures that are close to one
Living Art Enterprises/Science Source
another are proximal; those far from one an- A horizontal section,
other are distal. so-called because the view
or the cut falls along the
horizon, is usually viewed
looking down on the brain
from above—a dorsal
view.
Horizontal section Dorsal view
A sagittal section is cut
Living Art Enterprises/Science Source
lengthways from front to
back and viewed from
the side. (Imagine the
brain split by an arrow—in
Latin, sagitta.) Here, a cut
in the midsagittal plane
divides the brain into
symmetrical halves, a
medial view.
Sagittal section Medial view
glossary of Anatomical location and orientation
term Meaning with respect to the nervous system term Meaning with respect to the nervous system
Anterior Near or toward the front of the animal or the front of the head Lateral Toward the side of the body or brain
(see also frontal and rostral)
Medial Toward the middle, specifically the body’s midline; in reference
Caudal Near or toward the tail of the animal (see also posterior) to brain sections, a side view of the central structures
Coronal Cut vertically from the crown of the head down; used to Posterior Near or toward the animal’s tail (see also caudal); for human
reference the plane of a brain section that reveals a frontal view spinal cord, at the back
Dorsal On or toward the back of a four-legged animal (equivalent to Rostral Toward the beak (front) of the animal (see also anterior and
posterior for human spinal cord); in reference to human brain frontal)
nuclei, above, and to brain sections, viewed from above
Sagittal Cut lengthways from front to back of the skull to reveal a medial
Frontal Of the front (see also anterior and rostral); in reference to brain view into the brain from the side; a cut in the midsagittal plane
sections, a viewing orientation from the front divides the brain into symmetrical halves.
Horizontal Cut along the horizon; used to reference the plane of a brain Superior Above (see also dorsal)
section that reveals a dorsal view
Ventral On or toward the belly of four-legged animals (see also inferior);
Inferior Below (see also ventral) in reference to human brain nuclei, below.
40 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
Frontal view
Your right hand, if made into a
The brain is made up Cerebral cortex is the brain’s fist, represents the positions of
of two hemispheres, thin, outer “bark” layer. the lobes of the left hemisphere
left and right. of your brain.
Parietal lobe
Science Source
(knuckles) Occipital
Glauberman/
Frontal lobe lobe
(fingers) (wrist)
Parietal
lobe
Frontal
lobe Bumps in the brain’s
folded surface are
Occipital called gyri, and cracks
lobe Temporal lobe
are called sulci. (thumb)
Temporal
lobe FIGUre 2-5 The Cerebral Cortex Each cerebral hemisphere is
divided into four lobes: frontal, parietal, temporal, and occipital, shown
at left as oriented in the head. The brain surface, or cerebral cortex, shown
in the frontal view, is a thin sheet of nerve tissue, heavily folded to fit inside
Lobes define broad
divisions of the
the skull. Your right fist can map the orientation of the left hemisphere and
cerebral cortex. its lobes.
Between the arachnoid layer and the pia mater flows cerebrospinal fluid (CSF),
a colorless solution of sodium chloride and other salts. CSF cushions the brain so
that it can move or expand slightly without pressing on the skull. The symptoms
of meningitis, an infection of the meninges and CSF, are described in Clinical
Focus 2-2, Meningitis and Encephalitis, on page 42.
Cerebral Geography
After removing the meninges, we can examine the brain’s surface features, most promi-
nently its two nearly symmetrical left and right hemispheres. Figure 2-5 diagrams the left
hemisphere of a typical human forebrain oriented in the upright human skull. The outer
forebrain consists of a thin, folded film of nerve tissue, the cerebral cortex, detailed in the
frontal view in Figure 2-5. The word cortex, Latin for tree bark, is apt, considering the cortex’s
heavily folded surface and its location, covering most of the rest of the brain. Unlike the
bark on a tree, however, the brain’s folds are not random but rather demarcate its functional
cortical zones.
Make a fist with your right hand and hold it up, as shown on the right in Figure 2-5, to
represent the positions of the forebrain’s broad divisions, or lobes, in the skull. Each lobe is
named for the skull bone it lies beneath.
• The forward-pointing temporal lobe lies at the side of the brain, in approximately
the same place as the thumb on your upraised fist. The temporal lobe functions in
connection with hearing and with language and musical abilities.
• Immediately above your thumbnail, your fingers correspond to the location of the
frontal lobe, often characterized as performing the brain’s executive functions, such as
decision making.
• The parietal lobe is at the top of the skull, as represented by your knuckles, behind
the frontal lobe and above the temporal lobe. Parietal functions include directing our
movements toward a goal or to perform a task, such as grasping an object.
• The area at the back of each hemisphere, near your wrist, constitutes the occipital lobe,
where visual processing begins.
2-1 • Overview of Brain Function and Structure 41
Examining the Brain’s Surface from All Angles cerebrospinal fluid (csF) Clear solution
As we look at the dorsal view in Figure 2-6A, the brain’s wrinkled left and right hemispheres of sodium chloride and other salts that fills
resemble a walnut meat taken whole from its shell. These hemispheres constitute the the ventricles inside the brain and circulates
cerebrum, the major forebrain structure and most recently evolved feature of the CNS. around the brain and spinal cord beneath the
Visible from the opposite ventral view in Figure 2-6B are the brainstem, including the arachnoid layer in the subarachnoid space.
cerebral cortex Thin, heavily folded film of
nerve tissue composed of neurons that is
(A) Dorsal view the outer layer of the forebrain. Also called
Frontal Central sulcus neocortex.
Courtesy of Yakovlev Collection/National Museum
lobe Parietal
lobe temporal lobe Part of the cerebral cortex
that functions in connection with hearing,
language, and musical abilities; lies below the
lateral fissure, beneath the temporal bone at
the side of the skull.
of Health and Medicine.
frontal lobe Part of the cerebral cortex often
generally characterized as performing the
Longitudinal
Occipital brain’s executive functions, such as decision
lobe making; lies anterior to the central sulcus and
fissure
beneath the frontal bone of the skull.
(B) Ventral view
parietal lobe Part of the cerebral cortex
Temporal lobe Cerebellum that directs movements toward a goal or to
Courtesy of Yakovlev Collection/National Museum
Frontal perform a task, such as grasping an object;
lobe
lies posterior to the central sulcus and
beneath the parietal bone at the top of the
skull.
occipital lobe Part of the cerebral cortex
of Health and Medicine.
where visual processing begins; lies at the back
Occipital of the brain and beneath the occipital bone.
Olfactory lobe
bulbs Brainstem
Cranial nerves
(C) Lateral view
Courtesy of Yakovlev Collection/National Museum
Central sulcus
Parietal
lobe
Frontal
lobe
of Health and Medicine.
Lateral
fissure Temporal Occipital
lobe lobe
(D) Medial view
Central sulcus
Courtesy of Yakovlev Collection/National Museum
Frontal Parietal
lobe lobe
Occipital
lobe
FIGUre 2-6 Examining the Human
B
rain Locations of the lobes of the
of Health and Medicine.
cerebral hemispheres, shown in dorsal,
ventral, lateral, and medial (top, bottom,
side, and midline) views, as are the
Temporal
lobe
cerebellum, longitudinal and lateral
Brainstem Cerebellum
fissures, and the central sulcus.
42 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
CliniCAl F cus 2-2
Meningitis and Encephalitis
Harmful microorganisms can invade the layers of the meninges, particu-
larly the pia mater and the arachnoid layer, as well as the CSF flowing
between them, to cause a variety of infections that lead to meningitis.
One symptom of this condition, inflammation, places pressure on the
brain. Because the space between meninges and skull is slight, unre-
lieved pressure can lead to delirium and, if the infection progresses, to
drowsiness, stupor, and even coma.
Usually the earliest symptom of meningitis is severe headache
and a stiff neck (cervical rigidity). Head retraction (tilting the head
backward) is an extreme form of cervical rigidity. Convulsions,
a common symptom in children, indicate that the inflammation is
affecting the brain.
Infection of the brain itself is called encephalitis. Some of its many
forms have great historical significance. A century ago, during World
War I, a form of encephalitis called sleeping sickness (encephalitis
lethargica) reached epidemic proportions. Its first symptom is sleep dis-
turbance. People sleep all day and become wakeful, even excited, at
night. Subsequently they show symptoms of Parkinson disease, includ-
ing severe tremors, muscular rigidity, and difficulty in controlling body
CDC/Dr. Edwin P. Ewing, Jr.
movements. Many are completely unable to make voluntary movements,
such as walking or even combing their hair. Survivors of sleeping sick-
ness were immortalized by the neurologist Oliver Sacks in the book and
movie Awakenings. Sacks died in 2015 at age 82.
Encephalitis symptoms are caused by the death of an area deep in
the brain, the substantia nigra (black substance), which you will learn Pus is visible over the surface of this brain infected
about in Section 2-3. Other forms of encephalitis may have different with meningitis.
effects on the brain. For example, Rasmussen encephalitis attacks one Surprisingly, some young children who lose a hemisphere adapt
cerebral hemisphere in children. In most cases, the only effective treat- rather well. They may even complete college, literally with half a brain. But
ment is radical: hemispherectomy, surgical removal of the entire affected intellectual disabilities are a more common outcome of hemispherectomy
hemisphere. as a result of encephalitis.
wrinkly hemispheres of the smaller cerebellum (Latin for little brain). Both the cerebrum
and the brainstem are visible in the lateral and medial views in Figure 2-6C and D.
Much of the crinkled-up cerebral cortex is invisible from the brain’s surface. All we can
see are bumps, or gyri (sing. gyrus), and cracks, or sulci (sing. sulcus). Some sulci are so
deep that they are called fissures. The longitudinal fissure runs between the cerebral hemi-
spheres and the lateral fissure along the sides of the brain. Both are shown in various views
in Figure 2-6, along with the central sulcus that runs from the lateral fissures across the top
of the cerebrum.
Looking at the bottom of the brain, the ventral view in Figure 2-6B, we see in the midst
of the wrinkled cerebrum and ventral to the cerebellum a smooth, whitish structure with
little tubes attached. This central set of structures is the brainstem, the area responsible for
most unconscious behavior. The tubes mark out the cranial nerves that run to and from the
brain as part of the SNS.
Cerebral Circulation
The brain’s surface appears to be covered with blood vessels. As with the rest of the body, the
arteries feed blood to the brain and send it back through veins to the kidneys and lungs for
cleaning and oxygenation. The cerebral arteries emerge from the neck to wrap around the
2-1 • Overview of Brain Function and Structure 43
Anterior cerebral artery Middle cerebral artery Posterior cerebral artery FIGUre 2-7 Major Cerebral
Arteries Each of the three major
arteries that feed blood to the cerebral
hemispheres branches extensively to
supply the regions shaded in pink.
Dorsal view Lateral view Ventral view
Lateral view Medial view Medial view
outside of the brainstem, cerebrum, and cerebellum, finally penetrating the brain’s surface
to nourish its inner regions.
Three major arteries send blood to the cerebrum—the anterior, middle, and posterior
cerebral arteries, shown in Figure 2-7. Because the brain is highly sensitive to blood loss,
a blockage or break in a cerebral artery is likely to lead to the death of the affected region.
This condition, known as stroke, is the sudden appearance of neurological symptoms Section 16-3 elaborates on the effects of
as a result of severely interrupted blood flow. Because the three cerebral arteries supply stroke and its treatment.
different parts of the brain, strokes disrupt different brain functions, depending on the
artery affected.
Because the brain’s connections are crossed, stroke in the left hemisphere affects sen- Principle 3: Many brain circuits are crossed.
sation and movement on the right side of the body. The opposite is true for those with
strokes in the right hemisphere. Clinical Focus 2-3, Stroke, on page 45, describes some
disruptions that stroke causes, both to the person who has it and to those who care for
stroke victims.
The Brain’s Internal Features
The simplest way to examine the inside of something is to cut it in half. Of course, the
orientation of the cut affects what we see. Consider slicing through a pear. If we cut from
side to side, we cut across the core, providing a dorsal view; if we cut from top to bottom, we
cut parallel to the core, providing a medial view. Our impression of the inside of a pear is gyri (sing. gyrus) A small protrusion or
clearly influenced by how we slice it. The same is true of the brain. bump formed by the folding of the cerebral
cortex.
Macro View sulci (sing. sulcus) A groove in brain matter;
We can reveal the brain’s inner features by slicing it parallel to the front of the body, most are in the neocortex or cerebellum.
downward through the middle in a coronal section (Figure 2-8A). The resulting frontal stroke Sudden appearance of neurological
view, shown in Figure 2-8B, makes immediately apparent that the brain’s interior is not symptoms as a result of severely interrupted
homogeneous. Both dark and light regions of tissue are visible, and though these regions blood flow.
may not be as distinctive as car engine parts, they nevertheless represent different brain gray matter Areas of the nervous system
components. composed predominantly of cell bodies and
The darker regions are gray matter, largely composed of cell bodies and capillary blood capillary blood vessels that either collect and
vessels. Gray matter neurons either collect and modify information or support this activity. modify information or support this activity.
44 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
(A) Coronal section (B) Frontal view
White matter
Gray matter
Glauberman/Science Source
Corpus callosum
Lateral ventricles
Lateral sulcus
Temporal lobe
FIGUre 2-8 Coronal Brain Section (A) The brain is cut down the middle parallel to
the front of the body; then a coronal section is viewed at a slight angle. This frontal view
(B) displays white matter, gray matter, and the lateral ventricles. Visible above the ventricles,
a large bundle of fibers, the corpus callosum, joins the hemispheres.
The lighter regions are white matter, mostly nerve fibers with fatty coverings that produce
white matter Areas of the nervous system
the white appearance, much as fat droplets in milk make it appear white. White matter fibers
rich in fat-sheathed neural axons that form
form connections between and among the brain’s cells.
the connections between brain cells.
A second feature, apparent at the center of our frontal view in Figure 2-8B, are the
ventricle One of four cavities in the brain
ventricles—two wing-shaped cavities that contain cerebrospinal fluid. The brain’s
that contain CSF to cushion the brain; may
four ventricles, shown in place in Figure 2-9, are filled with CSF made by the cells
play a role in maintaining brain metabolism.
lining the ventricles. All four ventricles are connected, so CSF flows from the two lateral
corpus callosum Band of white matter ventricles to the third and fourth ventricles, which lie on the brain’s midline, and into the
containing about 200 million nerve fibers
cerebral aqueduct, a canal that runs down the length of the spinal cord. CSF is also found
that connects the two cerebral hemispheres
in the space between the lower layers of the meninges that wrap around the brain and
to provide a route for direct communication
spinal cord (see Figure 2-4).
between them.
Although the ventricles’ functions are not well understood, researchers think that they
play an important role in maintaining brain metabolism. CSF may allow certain compounds
access to the brain, and it probably helps the brain excrete metabolic wastes. In the event of
trauma to the brain or spinal cord, CSF cushions the blow.
(A) Lateral view of brain (B) Frontal view of brain
Left lateral Lateral
Right lateral
ventricle ventricle
ventricle
Cerebral Third
Third ventricle aqueduct ventricle
Fourth ventricle Fourth ventricle
FIGUre 2-9 Interconnected Cerebral Ventricles The lateral ventricles are
symmetrical, one in each hemisphere. The third and fourth ventricles lie in the brain’s midline
and drain into the cerebral aqueduct, which runs the length of the spinal cord.
2-1 • Overview of Brain Function and Structure 45
CliniCAl F cus 2-3
Stroke
Approximately every minute in the United States, someone has a stroke
with obvious visible symptoms—more than a half million every year.
Worldwide, stroke is the second leading cause of death. Acute symp-
toms include facial droop, motor weakness in limbs, visual disturbance,
speech difficulties, and sudden onset of severe headache.
In addition to visible strokes, at least twice as many silent strokes may
occur each year. These ministrokes occur primarily in the white matter
and do not produce obvious symptoms. (To view a brief video on silent
stroke, go to https://www.youtube.com/watch?v=J3fb0CaDpEk).
Even with the best, fastest medical attention, most stroke patients
have some residual motor, sensory, or cognitive deficit. According to
the Canadian Stroke Network, for every 10 people who have a stroke,
2 die, 6 are disabled to varying degrees, and 2 recover to a degree but
still have a diminished quality of life. Of those who survive, 1 in 10 risk
further stroke.
The consequences of stroke are significant for those who have them,
Simon Fraser/Science Source
their family, and their lifestyle. Consider Mr. Anderson, a 45-year-old
electrical engineer, who took his three children to the movies one Sat-
urday afternoon in 1998 and collapsed. He had a massive stroke of the
middle cerebral artery in his left hemisphere. The stroke has impaired
Mr. Anderson’s language ever since, and because the brain’s connec-
tions are crossed, his right-side motor control as well. Dorsal view of a brain with a stroke, imaged by computed tomography
Seven years after his stroke, Mr. Anderson remained unable to speak, (CT). The dark area in the right hemisphere has been damaged by the
but he understood simple conversations. Severe difficulties in moving his loss of blood flow.
right leg required him to use a walker. He could not move the fingers of
his right hand and so had difficulty feeding himself, among other tasks. When patients receive t-PA within 3 hours of an ischemic stroke,
Mr. Anderson will probably never return to his engineering career or the number who make a nearly complete recovery increases by about
drive or get around on his own. 25 percent compared with those who receive a placebo (Hatcher and
Like him, most stroke survivors require help to perform everyday Starr, 2011). In addition, impairments are reduced in the remaining patients
tasks. Caregivers are often female relatives who give up their own who survive the stroke. The risk of hemorrhage is about 6 percent in
career and other pursuits. Half of the caregivers develop emotional t-PA–treated patients relative to no risk in placebo-treated patients.
illness, primarily depression or anxiety or both, in a year or so. Lost Many people are unable to reach a hospital soon enough for treatment
income and stroke-related medical bills significantly affect the family’s with t-PA. Most stroke victims do not visit an emergency department
living standard. until about 24 hours after symptoms appear, too late for the treatment.
We tend to speak of stroke as a single disorder, but two major types of Apparently, most people fail to realize that stroke is an emergency.
strokes have been identified. In the more common and often less severe By taking advantage of developments in neuroimaging, research
ischemic stroke, a blood vessel is blocked, as by a clot. The more severe has shown that it is possible to remove clots from cerebral vessels
hemorrhagic stroke results from a burst vessel bleeding into the brain. mechanically (Appireddy et al., 2015). Although quick treatment with t-PA
The hopeful news is that ischemic stroke can be treated acutely is still preferred, these new procedures have expanded the window of
with a drug called tissue plasminogen activator (t-PA), which breaks benefit to as long as 8 hours post stroke. There is also intense interest
up clots and allows normal blood flow to return to an affected region. in developing treatments that will stimulate the brain to initiate reparative
Unfortunately, there is no treatment for hemorrhagic stroke, for which processes during the postacute period. Such treatment will facilitate the
the use of clot-preventing t-PA would be disastrous. patient’s functional improvement (see a review by Langhorne et al., 2011).
Cutting through the brain vertically from front to back produces a sagittal section
( Figure 2-10A). If we make our cut down the brain’s midline, that is, in the midsagittal
plane, we divide the cerebrum into its two hemispheres, revealing several distinctive struc-
tures in the resulting medial view (Figure 2-10B). One feature is a long band of white matter
that runs much of the length of the cerebral hemispheres. This band, the corpus callosum,
contains about 200 million nerve fibers that join the two hemispheres and allow them to
communicate.
46 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
FIGUre 2-10 Sagittal Brain Section Cortex
Corpus
(A) (B)
(A) A section in the midsagittal plane callosum
separates the hemispheres, allowing (B) a
medial view of the brain’s midline structures,
including the subcortical structures that lie
ventral to the corpus callosum.
Third
Plane ventricle
of cut
Fourth
ventricle
Cerebellum
Brainstem
Figure 2-10B clearly shows that the cortex covers the cerebral hemispheres above the cor-
pus callosum; below it are various internal subcortical regions. The brainstem is a subcortical
structure that generally controls basic physiological functions. But many subcortical regions
are forebrain structures intimately related to the cortical areas that process motor, sensory,
perceptual, and cognitive functions. This relation between the cortex and the subcortex
Principle 4: The CNS functions on multiple alerts us to the concept that redundant functions exist at many levels of nervous system
levels. organization.
If you were to compare medial views of the left and right hemispheres, you would be
struck by their symmetry. The brain, in fact, has two of nearly every structure, one on
each side. The few one-of-a-kind structures, such as the third and fourth ventricles, lie
along the brain’s midline (see Figure 2-9B). Another one-of-a-kind structure is the pineal
Principle 5: The brain is symmetrical and gland, which Descartes declared the seat of the mind in his dualistic theory of how the
asymmetrical. brain works.
Microscopic Inspection: Cells and Fibers
The brain’s fundamental units—its cells—are so small that they can be viewed only with the
Human brains contain about 86 billion aid of a microscope. A microscope quickly reveals that the brain has two main types of cells,
neurons and 87 billion glia. Section 3-1 illustrated in Figure 2-11. Neurons carry out the brain’s major functions, whereas glial cells
examines their structures and functions aid and modulate the neurons’ activities—for example, by insulating them. Both neurons and
in detail. glia come in many forms, each marked by the work that they do.
We can see the brain’s internal structures in even greater detail by dyeing their cells with
special stains (Figure 2-12). For example, if we use a dye that selectively stains cell bodies,
we can see that the neurons in the cortical gray matter lie in layers, revealed by the bands of
Cell body
Cell body
FIGUre 2-11 Brain Cells Branches
Nancy Kedersha/Science Photo Library Science
emanate from the cell bodies of a
prototypical neuron (left) and a glial
cell (right). This branching organization
Kasthuri and Lichtman, Harvard
increases the cell’s surface area. This
type of neuron is called a pyramidal cell
because the cell body is shaped somewhat
like a pyramid; the glial cell is called an
University
astrocyte because of its star-shaped Neuron Glial cell
Source
appearance. (pyramidal cell) (astrocyte)
2-2 • The Nervous System’s Evolutionary Development 47
tissue in Figure 2-12A and C. Each layer contains cells that stain characteristi-
cally. Figure 2-12A and B shows that stained subcortical regions are composed (A) (B)
of clusters, or nuclei, of similar cells.
Although layers and nuclei appear very different, both form functional units
in the brain. Whether a particular brain region has layers or nuclei is largely an Subcortical
nuclei
accident of evolution. By using a stain that selectively dyes neuronal fibers, as
shown in Figure 2-12B and D, we can see the borders of the subcortical nuclei
more clearly. In addition, we can see that the stained cell bodies lie in regions
adjacent to those with most of the fibers.
A key feature of neurons is that they are connected to one another by Gray-matter layers White matter
(C) (D)
fibers known as axons. When axons run along together, much like the wires
Photos courtesy of bryan kolb
that run from a car engine to the dashboard, they form a nerve or tract
( Figure 2-13). By convention, a tract is a collection of nerve fibers in the
brain and spinal cord, whereas bundles of fibers outside of the CNS are typi-
cally called nerves. Thus, the pathway from the eye to the brain is the optic
nerve, whereas the pathway from the cerebral cortex to the spinal cord is the
corticospinal tract. FIGUre 2-12 Cortical Layers and Glia
Brain sections from the left hemisphere of a
monkey (midline is to the left in each image),
2-1 reVIeW viewed through a microscope. Cells are
stained with (A and c) a selective cell body
Overview of Brain Function and Structure stain for neurons (gray matter) and (B and D)
Before you continue, check your understanding. a selective fiber stain for insulating glial cells,
or myelin (white matter). The images reveal
1. The nervous system’s function is to produce movement, or , in a perceptual
very different views of the brain at the macro
world constructed by the . (A and B) and microscopic (c and D) levels.
2. The left and right cerebral hemispheres are each divided into four lobes: ,
, , and .
Neuron 1
3. The human nervous system has evolved the potential to change, for example, to adapt to
changes in the world or to compensate for injury. This attribute is called . Neuron 2
Axon
4. Neural tissue is of two main types: (1) forms the connections among cells,
and (2) collects and processes incoming (afferent) sensory or outgoing
(efferent) information.
5. The nerve fibers that lie in the brain form . Outside the brain they are called Cell body Terminal
.
Several axon fibers running together
6. Chart the human nervous system’s functional organization.
form a nerve when outside the CNS or
Answers appear at the back of the book. a tract within the CNS.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
2-2 The Nervous System’s FIGUre 2-13 Neuronal Connections
Evolutionary Development
The developing brain, which is less complex than the mature adult brain, provides a clear nuclei (sing. nucleus) A group of cells
picture of its basic structural plan. The striking biological similarity of embryos as diverse as forming a cluster that can be identified with
amphibians and mammals is evident in the earliest stages of development. In the evolution special stains to form a functional grouping.
of complex nervous systems in vertebrate species, simpler and evolutionarily more primitive nerve Large collection of axons coursing
forms have not been discarded and replaced but rather added to. As a result, all anatomical together outside the CNS.
and functional features of simpler nervous systems are present in and form the base for the tract Large collection of axons coursing
most complex nervous systems, including ours. together in the CNS.
48 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
The bilaterally symmetrical nervous system of simple worms, for example, is common
to complex nervous systems. Indeed, we can recognize in humans the spinal cord that
Section 1-3 outlines nervous system evolution constitutes most of the simplest fishes’ nervous system. The same is true of the brainstem
and Section 8-1, developmental similarities of more complex fishes, amphibians, and reptiles. The neocortex, although particularly
among humans and other species. complex in humans, is clearly the same organ found in other mammals.
Stages in Brain Evolution
In a vertebrate embryo, the nervous system begins as a sheet of cells. This sheet folds into a
hollow tube and develops into three regions, forebrain, midbrain, and hindbrain, recogniz-
able as a series of three enlargements at the end of the embryonic spinal cord (Figure 2-14A).
The adult brain of a fish, amphibian, or reptile is roughly equivalent to this three-part
brain. The prosencephalon (front brain) is responsible for olfaction, the sense of smell; the
mesencephalon (middle brain) is the seat of vision and hearing; and the rhombencephalon
(hindbrain) controls movement and balance. The spinal cord is part of the hindbrain.
In mammals (Figure 2-14B), the prosencephalon develops further to form the subcor-
tical structures known collectively as the diencephalon (between brain) and the cerebral
hemispheres and cortex, or telencephalon (endbrain). The mammalian hindbrain devel-
ops further into the metencephalon (across brain), which includes the cerebellum, and the
myelencephalon (spinal brain), including the spinal cord.
The human brain is particularly complex, possessing especially large cerebral hemi-
spheres but retaining most other mammalian brain features (Figure 2-14C). Various human
cerebral areas—regions in the frontal, temporal, and parietal lobes—are larger than those
of other primates’ brains—necessary to produce language. Language is thought to have fos-
tered a novel worldview—in the way we think, reflect on our own thoughts, and imagine.
The Nervous System and Intelligent
Behavior
Most behaviors are the product not of a single locus in the brain but rather of many interacting
brain areas and levels. These several nervous system layers do not simply replicate function;
rather, each region adds a different dimension to the behavior. This hierarchical organization
FIGUre 2-14 Stages in Brain Evolution
affects virtually every human behavior. Abnormalities associated with brain injury and brain dis-
and Development Over the evolution
ease that seem bizarre in isolation are but the normal manifestation of parts of a hierarchically
of the mammalian brain, the forebrain has
grown dramatically.
(A) Vertebrate embryo (B) Mammalian embryo (C) Fully developed human brain
Telencephalon Telencephalon
Diencephalon
Prosencephalon (forebrain) Mesencephalon
Mesencephalon (midbrain)
Myelencephalon
Spinal cord Diencephalon
Rhombencephalon Mesencephalon
(hindbrain) Metencephalon
Spinal cord Metencephalon
Myelencephalon
Spinal cord
Neocortex, basal ganglia, limbic system
Telencephalon (endbrain) Forebrain
olfactory bulb, lateral ventricles
Prosencephalon (forebrain)
Thalamus, hypothalamus, pituitary gland,
Diencephalon (between brain)
pineal body, third ventricle
Mesencephalon (midbrain) Mesencephalon Tectum, tegmentum, cerebral aqueduct Brainstem
Metencephalon (across brain) Cerebellum, pons, fourth ventricle
Rhombencephalon (hindbrain)
Myelencephalon (spinal brain) Medulla oblongata, fourth ventricle
Spinal cord Spinal cord Spinal cord Spinal cord
2-2 • The Nervous System’s Evolutionary Development 49
organized brain. Our evolutionary history, our developmental history, and our own personal Principle 6: Brain systems are organized
history are integrated at the various anatomical and functional levels of the nervous system. hierarchically and in parallel.
Is the vertebrate nervous system the only path to evolving intelligent behavior? Inverte-
brate animals, such as the octopus, have traveled on an evolutionary pathway separate from
that of vertebrates for over 700 million years. The octopus nervous system, while strikingly
different from ours, is complex. Might the octopus learn much as vertebrate animals do?
Italian biologists Graziano Fiorito and Pietro Scotto (1992) placed individuals of Octopus
vulgaris (the common octopus) in separate tanks, each with an independent water sup-
ply, and allowed them to interact visually for 2 hours. As shown in the Procedure section of
Experiment 2-1, the observer octopus watched the demonstrator octopus from an adjacent tank
through a transparent wall. The demonstrator was being conditioned to learn that a red ball
was associated with a reward, whereas a white ball was associated with a weak electric shock.
As noted in the Results section, the demonstrator animals quickly learned to distinguish
between the colored balls. The observers then were placed in isolation. When tested later,
they selected the same object the demonstrators had, responded faster than the demon-
strators did during their conditioning, and performed the task correctly for 5 days without
significant error or further conditioning.
ExpErimENt 2-1
Question: Does intelligent behavior require a vertebrate nervous system organization?
Procedure
Transparent wall
between tanks
Demonstrator octopus,
conditioned to associate a
red ball with a reward
Observer octopus watches and a white ball with a
the demonstrator from an weak shock.
adjacent tank through a
transparent wall.
Results
1. The demonstrator animal quickly learns to distinguish between the colored balls.
2. When placed in isolation and tested later, the observer animals selected the same object as the demonstrators,
responded faster, and performed the task correctly for 5 days without significant error.
Conclusion: Invertebrates display intelligent behavior, such as learning by observation.
Research from G. Fiorito and P. Scotto (1992). Observational learning in Octopus vulgaris. Science, 256, 545–547.
50 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
2-2 reVIeW
The Nervous System’s Evolutionary Development
Before you continue, check your understanding.
1. The brains of vertebrate animals have evolved into three regions: ,
, and .
2. The functional levels of the nervous system interact, each region contributing different
aspects, or dimensions, to produce .
3. In a brief paragraph, explain how the evolution of the forebrain in mammals reinforces the
principle that the CNS functions on multiple levels.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
2-3 The Central Nervous System:
Mediating Behavior
When we look under the hood, we can make some pretty good guesses about what each
part of a car engine does. The battery must provide electrical power to run the radio and
lights, for example, and because batteries have to be charged, the engine must contain some
brainstem Central structure of the brain, mechanism for charging them. We can take the same approach to deduce how the parts of
including the hindbrain, midbrain, thalamus, the brain function. The part connected to the optic nerve coming from each eye must have
and hypothalamus, that is responsible for something to do with vision. Structures connected to the auditory nerve coming from each
most unconscious behavior. ear must have something to do with hearing.
From such simple observations, we can begin to understand how the brain is organized.
The real test comes in analyzing actual brain function: how this seeming jumble of parts
produces behaviors as complex as human thought. The place to start is the brain’s functional
anatomy: learning the name of a particular CNS structure is pointless without also learning
something about what it does. We focus now on the names and functions of the three major
CNS components: spinal cord, brainstem, and forebrain.
Spinal Cord
Although producing movement is the brain’s principal function, ultimately the spinal
cord executes most body movements, usually following instructions from the brain
but at times acting independently via the somatic nervous system. To understand how
important the spinal cord is, think of the old saying “running around like a chicken with
its head cut off.” When a chicken’s head is lopped off for the farmer’s family dinner,
the chicken is still capable of running around the barnyard until it collapses from loss
of blood. The chicken accomplishes this feat because the spinal cord is acting indepen-
dently of the brain.
Grasping the spinal cord’s complexity is easier once you realize that it is not a single
structure but rather a set of segmented switching stations. As detailed in Section 2-4, each
spinal segment receives information from a discrete part of the body and sends out com-
Patellar
tendon
mands to that area. Spinal nerves, which are part of the SNS, carry sensory information to
the cord from the skin, muscles, and related structures and in turn send motor instructions
to control each muscle.
You can demonstrate movement controlled by the spinal cord in your own body by tap-
ping your patellar tendon, just below your kneecap (the patella). The sensory input causes
2-3 • The Central Nervous System: Mediating Behavior 51
your lower leg to kick out, and try as you might, it is very hard to prevent the movement. Your
brain, in other words, has trouble inhibiting this spinal reflex: it is automatic. We explain reflexes in Section 11-4.
Brainstem
The brainstem begins where the spinal cord enters the skull and extends upward into the
lower areas of the forebrain. The brainstem receives afferent nerves coming in from all of
the body’s senses, and it sends efferent nerves out to the spinal cord to control virtually all Alphabetically, afferent comes before efferent:
of the body’s movements except the most complex movements of the fingers and toes. The sensory signals must enter the brain before
brainstem, then, both directs movements and creates a sensory world. an outgoing signal triggers a motor response.
In some vertebrates, such as frogs, the entire brain is largely equivalent to the mamma-
lian or avian brainstem. And frogs get along quite well, demonstrating that the brainstem is
a fairly sophisticated piece of machinery. If we had only a brainstem, we would still be able
to construct a world, but it would be a far simpler sensorimotor world, more like the world a
frog experiences.
The brainstem, which is responsible for most unconscious behavior, can be divided into
three regions: hindbrain, midbrain, and diencephalon, meaning between brain because it
borders the brain’s upper and lower parts. In fact, the between-brain status of the dien-
cephalon can be seen in a neuroanatomical inconsistency: some anatomists place it in the
brainstem and others place it in the forebrain. Figure 2-15A illustrates the location of these
three brainstem regions under the cerebral hemispheres. Figure 2-15B compares the shape
of the brainstem regions to the lower part of your arm when held upright. The hindbrain is
long and thick like your forearm, the midbrain is short and compact like your wrist, and the
diencephalon at the end is bulbous like a fist.
The hindbrain and midbrain are essentially extensions of the spinal cord; they
developed first as vertebrate animals evolved a brain at the anterior end of the body.
It makes sense, therefore, that these lower brainstem regions should retain a division
between structures having sensory functions and those having motor functions, with
sensory structures lying dorsal and motor ones ventral, or in upright humans, posterior Principle 7: Sensory and motor divisions
and anterior. permeate the nervous system.
Each brainstem region performs more than a single task. Each contains various group-
ings of nuclei that serve various purposes. All three regions, in fact, have both sensory and
motor functions. However, the hindbrain is especially important in motor functions, the
midbrain in sensory functions, and the diencephalon in integrative sensorimotor tasks. Here
we consider the central functions of these three regions; later chapters contain more detailed
information about them.
FIGUre 2-15
Brainstem
(A) (B) Structures (A) Medial
Diencephalon Fist view shows the relation of
(analogous to the brainstem to the cerebral
diencephalon)
hemispheres. (B) The shapes and
Midbrain Wrist relative sizes of the brainstem’s
(analogous
three parts are analogous to your
to midbrain)
fist, wrist, and forearm.
Forearm
(analogous
Hindbrain to hindbrain)
Cerebellum
52 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
(A) (B)
Three-
toed sloth
White matter
Leopard (cerebellar cortex)
Hawk
Subcortical
nuclei
Gray matter
(cerebellar cortex)
FIGUre 2-16 The Cerebellum and Movement (A) Their relatively large cerebellum
hindbrain Evolutionarily the oldest part of enables finely coordinated movements such as flying and landing in birds and pouncing on
the brain; contains the pons, medulla, reticular prey in cats. Slow-moving animals such as the sloth have a smaller cerebellum relative to
formation, and cerebellum, structures that brain size. (B) Like the cerebrum, the human cerebellum has left and right hemispheres, an
coordinate and control most voluntary and extensively folded cortex with gray and white matter, and subcortical nuclei.
involuntary movements.
reticular formation Midbrain area in which Hindbrain
nuclei and fiber pathways are mixed, producing The hindbrain controls motor functions ranging from breathing to balance to fine move-
a netlike appearance; associated with sleep– ments, such as those used in dancing. Its most distinctive structure, and one of the largest
wake behavior and behavioral arousal. in the human brain, is the cerebellum. Its relative size increases with the physical speed and
midbrain Central part of the brain; contains dexterity of a species, as shown in Figure 2-16A.
neural circuits for hearing and seeing as well Animals that move relatively slowly (such as a sloth) have a relatively small cerebellum for
as orienting movements. their body size. Animals that can perform rapid acrobatic movements (such as a hawk or a
tectum Roof (area above the ventricle) cat) have a very large cerebellum relative to overall brain size. The human cerebellum, which
of the midbrain; its functions are sensory resembles a cauliflower in the medial view in Figure 2-16B, likewise is important in control-
processing, particularly visual and auditory, ling complex movements. But cerebellar size in humans is also related to cognitive capacity.
and the production of orienting movements. Relative to other mammals, apes show an expansion of the cerebellum that correlates with
tegmentum Floor (area below the ventricle) increased capacity for planning and executing complex behavioral sequences, including tool
of the midbrain; a collection of nuclei with use and language (see Barton, 2012).
movement-related, species-specific, and pain As we look beyond the cerebellum at the rest of the hindbrain, shown in Figure 2-17, we
perception functions. find three subparts: the reticular formation, the pons, and the medulla. Extending the length
orienting movement Movement related to of the entire brainstem at its core, the reticular formation is a netlike mixture of neurons
sensory inputs, such as turning the head to (gray matter) and nerve fibers (white matter). This nerve net gives the structure the mottled
see the source of a sound. appearance from which its name derives (from Latin rete, meaning net). The reticular forma-
diencephalon The between brain, which tion’s nuclei are localized into small patches along its length. Each has a special function in
integrates sensory and motor information on stimulating the forebrain, such as in waking from sleep.
its way to the cerebral cortex.
Pons
FIGUre 2-17 Hindbrain The principal
hindbrain structures integrate voluntary and Reticular
formation
involuntary body movements. The reticular
formation is sometimes called the reticular Medulla Cerebellum
activating system.
2-3 • The Central Nervous System: Mediating Behavior 53
The pons and medulla contain substructures that control many
vital body movements. Nuclei in the pons receive inputs from the cer- (B) Substantia Periaqueductal
nigra gray matter
ebellum and actually form a bridge from it to the rest of the brain (in
Ante
Latin, pons means bridge). At the rostral tip of the spinal cord, the me- rior Cerebral
dulla’s nuclei regulate such vital functions as breathing and the cardio- aqueduct
vascular system. For this reason, a blow to the back of the head can kill
Pos
you: your breathing stops if the hindbrain control centers are injured. terio
r
Midbrain Red Reticular Superior
nucleus formation colliculus
In the midbrain, a sensory component, the tectum (roof), is dorsal (pos-
terior in upright humans), whereas a motor structure, the tegmentum
(floor), is ventral (anterior in humans; Figure 2-18A). The tectum
(A)
receives a massive amount of sensory information from the eyes and Superior colliculus
ears. The optic nerve sends a large bundle of fibers to the superior (receives visual
input)
colliculus, whereas the inferior colliculus receives much of its input Tectum
from auditory pathways. The colliculi function not only to process Inferior colliculus
sensory information but also to produce orienting movements related Tegmentum (receives auditory
input)
to sensory inputs, such as turning your head to see a sound’s source.
This orienting behavior is not as simple as it may seem. To produce
it, the auditory and visual systems must share a map of the external Cerebellum
world so that the ears can tell the eyes where to look. If the audi-
tory and visual maps differed, it would be impossible to use the two
together. In fact, the colliculi also have a tactile map. After all, if you
want to look at what’s making your leg itch, your visual and tactile FIGUre 2-18 Midbrain (A) Structures in the midbrain are critical
systems need a common representation of where that place is so you for producing orienting movements, species-specific behaviors,
can scratch the itch by moving your arm and hand. and pain perception. (B) The tegmentum in cross section, revealing
Lying ventral to the tectum, the tegmentum (shown in Figure 2-18B various nuclei. Colliculus comes from collis, Latin for hill. The colliculi
resemble four little hills on the midbrain’s posterior surface.
in cross section) is composed of many nuclei, largely with movement-
related functions. Several tegmental nuclei control eye movements. The red nucleus controls
limb movements, and the substantia nigra connects to the forebrain, a connection especially Principle 8: The brain divides sensory input
important in initiating movements. (Recall from Clinical Focus 2-2 that the symptoms of for object recognition and motor control.
Parkinson disease are related to the destruction of the substantia nigra.) The periaqueductal
gray matter (PAG), made up of cell bodies that surround the aqueduct joining the third and
fourth ventricles, contains circuits controlling species-typical behaviors (e.g., female sexual
behavior). These nuclei also play an important role in the modulation of pain by opioid drugs.
FIGUre 2-19 Diencephalon The
diencephalon (center) is composed of
Diencephalon the thalamus, shown at right, and the
hypothalamus and other structures,
The diencephalon, shown in sagittal section in the center of Figure 2-19, integrates sensory shown at left. Thalamic regions connect
and motor information on its way to the cerebral cortex. Its two principal structures are to discrete cortical regions. Below the
the hypothalamus and the thalamus. The thalamus—one in each hemisphere—lies just thalamus, at the base of the brain, the
to the left of the brainstem’s tip, and the hypothalamus lies below the thalamus in each hypothalamus (hypo-, below) and pituitary
lie above the roof of the mouth. The
hemisphere.
hypothalamus is composed of many nuclei,
each with distinctly different functions.
Hypothalamus and pituitary gland Diencephalon Right thalamus
Dorsomedial nucleus
Hypothalamus to frontal lobe
Lateral geniculate nucleus
to visual cortex
Medial geniculate nucleus
Pituitary stalk
to auditory cortex
Auditory input Visual input
Pituitary gland
54 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
The hypothalamus in each hemisphere lies along the brain’s midline; it is composed of
hypothalamus Diencephalon structure
about 22 small nuclei and the nerve fiber systems that pass through it. Its critical function is to
that contains many nuclei associated with
control the body’s production of hormones, accomplished via its interactions with the pituitary
temperature regulation, eating, drinking, and
sexual behavior. gland, shown at left in Figure 2-19. Although constituting only about 0.3 percent of the brain’s
weight, the hypothalamus takes part in nearly all aspects of behavior, including feeding, sleep-
thalamus Diencephalon structure through
ing, temperature regulation, sexual and emotional behavior, hormone function, and move-
which information from all sensory systems is
ment. The hypothalamus is organized and functions more or less similarly across mammals.
integrated and projected into the appropriate
region of the neocortex. But sex differences have been found in the structures of some of its parts, owing probably to
differences between males and females in activities such as sexual behavior and parenting.
forebrain Evolutionarily the newest part of
The other principal structure of the diencephalon, the thalamus, is much larger than the
the brain; coordinates advanced cognitive
hypothalamus, as are its 20-odd nuclei. Perhaps the most distinctive thalamic function, shown
functions such as thinking, planning, and
language; contains the limbic system, basal at the right in Figure 2-19, is its role as a gateway for channeling sensory information traveling
ganglia, and neocortex. to the cerebral cortex from all sensory systems. The thalamus integrates information from
sensory inputs and relays it to the appropriate cortical area. The optic tract, for example, sends
neocortex (cerebral cortex) Most recently
information through a large fiber bundle to a thalamic region called the lateral geniculate nu-
evolved outer layer (new bark) of the
forebrain, composed of about six layers of cleus (LGN), shown at the right tip of the thalamus in Figure 2-19. In turn, the LGN processes
gray matter; constructs our reality. some of this information, then sends it to the visual region of the cortex in each hemisphere.
The routes to the thalamus may be indirect. For example, the route for olfaction traverses
several synapses before entering the dorsomedial thalamic nucleus on its way to the forebrain.
We examine how thalamic sensory nuclei Analogous sensory regions of the thalamus receive auditory and tactile information, which
process incoming information in Sections 9-2, is subsequently relayed to the respective auditory and tactile cortical regions in each hemi-
10-2, 11-4, 12-2, and in Section 14-3, memory sphere. Some thalamic regions have motor functions or, like its dorsomedial nucleus, which
pathways. connects to most of the frontal lobe, perform integrative tasks.
Forebrain
The largest and most recently evolved region of the mammalian brain is the forebrain. Its major
internal and external structures are shown in Figure 2-20. Each of its three principal structures
has multiple functions. To summarize briefly, the cerebral cortex regulates a host of mental
FIGUre 2-20 Forebrain Structures activities ranging from perception to planning; the basal ganglia control voluntary movement;
The major internal and external forebrain
structures integrate sensation, motivation and the limbic system regulates emotions and behaviors that produce and require memory.
and emotion, and memory to enable such Extending our analogy between the brainstem and your forearm, imagine that the fist—
advanced cognitive functions as thinking, the diencephalon—is thrust inside a watermelon—the forebrain, with the cortex as the rind
planning, and using language. and the subcortical limbic system and basal ganglia as the fruit inside. Just as watermelons
come in sizes, so do brains, which in a sense is what evolution has done:
Cerebral the forebrain varies considerably in size across species.
cortex
Cerebral Cortex
Basal ganglia The forebrain contains two types of cortex, three- or four-layered and
six-layered. The six-layered neocortex (new bark) is the tissue visible when
we view the brain from the outside, as in Figure 2-5. The more recently
evolved neocortex is unique to mammals; its primary function is to con-
struct a perceptual world and respond to that world. The older, more
Hippocampus
Limbic primitive three- or four-layered cortex, sometimes called allocortex, lies
structures adjacent to the neocortex. Allocortex is found in the brains of other chor-
Amygdala
dates in addition to mammals, especially in birds and reptiles.
The allocortex plays a role in controlling motivational and emotional
states as well as in certain forms of memory. Although neocortex and
allocortex have anatomical and functional differences, those distinctions
are not critical for most discussions in this book. Therefore, we usually
refer to both types of tissue simply as cortex.
Measured by volume, the cortex makes up most of the forebrain, con-
stituting 80 percent of the human brain overall. It is the brain region that
2-3 • The Central Nervous System: Mediating Behavior 55
has expanded the most in the course of mammalian evolution. The human neocortex Monkey Chimpanzee Human
Reproduced or adapted from our websites at
http://www.brains.rad.msu. edu and http://
has a surface area as large as 2500 square centimeters but a thickness of only 1.5 to
brainmuseum.org, supported by the U. S.
3.0 millimeters, an area equivalent to about four pages of this book. By contrast, a
chimpanzee has a cortical area equivalent to about one page.
National Science Foundation.
The pattern of sulci and gyri formed by the folding of the cortex varies across spe-
cies. Some, such as rats, have no sulci or gyri, whereas in carnivores, such as cats, the
gyri form a longitudinal pattern. In primates, the sulci and gyri form a more diffuse
pattern.
The brains of a monkey, chimpanzee,
Cortical Lobes and human, shown here to scale, differ
To review, the human cortex consists of the nearly symmetrical left and right hemispheres, dramatically in size and in surface
which are separated by the longitudinal fissure, shown at left in Figure 2-21. As shown at appearance. With an encephalization
right, each hemisphere is subdivided into four lobes corresponding to the skull bones overly- quotient of 2.0, the monkey’s brain is just
over one-quarter the size of a human’s
ing them: frontal, temporal, parietal, and occipital. Unfortunately, bone location and brain
(EQ 7.0). The chimp’s brain, EQ 2.5,
function are unrelated. As a result, the cortical lobes are rather arbitrarily defined anatomical is a bit more than one-third as large
regions that include many functional zones. (see Figure 1-15).
Nevertheless, we can attach some gross functions to each lobe. The three posterior lobes
have sensory functions: the occipital lobe is visual; the parietal lobe is tactile; and the tem-
poral lobe is visual, auditory, and gustatory. In contrast, the frontal lobe is motor and is Principle 9: Brain functions are localized and
sometimes called the brain’s executive because it integrates sensory and motor functions and distributed.
formulates plans of action. We can also predict some effects of injuries to each lobe:
• People with an injured occipital lobe have deficits in processing visual information.
Although they may perceive light versus dark, they may be unable to identify either the
shape or the color of objects.
• Injuries to the parietal lobe make it difficult to identify or locate stimulation on the
skin. Deficits in moving the arms and hands to points in space may occur.
• Temporal lobe injuries result in difficulty recognizing sounds, although unlike people
with occipital injuries, those with temporal injury can still recognize that they are
hearing something. Temporal lobe injuries can also produce difficulties in processing
complex visual information, such as faces.
• Individuals with frontal lobe injuries may have difficulties organizing and evaluating
their ongoing behavior as well as planning for the future.
Fissures and sulci often establish the boundaries of cortical lobes (Figure 2-21, right).
For instance, in humans, the central sulcus and lateral fissure form the boundaries of each
frontal lobe as well as the boundaries of each parietal lobe lying posterior to the central
sulcus. The lateral fissure demarcates each temporal lobe, forming its dorsal boundary. The
occipital lobes are not so clearly separated from the parietal and temporal lobes because no Anatomical features presented in Section 9-2
large fissure marks their boundaries. define occipital lobe boundaries.
Dorsal view of brain Lateral view of brain
Central
Frontal lobe (motor and sulcus
executive functions) Parietal lobe
(tactile functions)
Right
hemisphere
Longitudinal
fissure Lateral
Left
fissure
hemisphere
Temporal lobe (visual, auditory, Occipital lobe
(visual functions)
and gustatory functions) FIGUre 2-21 Cortical Boundaries
56 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
cytoarchitectonic map Map of the
Cortical Layers
neocortex based on the organization, In the neocortex, six layers of gray matter sit atop a layer of white matter. The allocortex,
structure, and distribution of the cells. by contrast, has three or four layers of gray matter. The six layers of the neocortex have
basal ganglia Subcortical forebrain nuclei distinct characteristics:
that coordinate voluntary movements of the • Different layers have different types of cells.
limbs and body; connected to the thalamus
• The cell density varies from layer to layer, ranging from virtually no cells in layer I (the
and to the midbrain.
top layer) to very dense cell packing in layer IV of the neocortex (Figure 2-22).
parkinson disease Disorder of the motor
system correlated with a loss of dopamine • Other differences in appearance are both regional and functional.
from the substantia nigra and characterized These visible differences led neuroanatomists to map the cortex a century ago. Korbinian
by tremors, muscular rigidity, and a reduction
Brodmann developed the map in Figure 2-23 around 1905. Because these maps are based
in voluntary movement.
on cell characteristics, the subject of cytology, they are called cytoarchitectonic maps. For
tourette syndrome Disorder of the basal
example, viewed through a microscope, sensory cortex in the parietal lobe, shown in red in
ganglia characterized by tics, involuntary
Figure 2-22, has a distinct layer IV. Motor cortex in the frontal lobe, shown in blue in Figure
vocalizations (including curse words and animal
2-22, has a distinctive layer V. Layer IV is afferent; layer V is efferent. It makes sense that a
sounds), and odd, involuntary movements of the
body, especially of the face and head. sensory region has a large input layer, whereas a motor region has a large output layer.
Staining cortical tissue can reveal chemical differences between cells and layers. Some
limbic system Disparate forebrain
structures lying between the neocortex and regions are rich in one chemical, others rich in another. These differences presumably relate
the brainstem that form a functional system to functional specialization of cortical areas.
controlling affective and motivated behaviors The one significant difference between the organization of the cortex and the orga-
and certain forms of memory; includes nization of other brain parts is its range of connections. Unlike most structures, which
cingulate cortex, amygdala, and hippocampus, connect only to certain brain regions, the cortex is connected to virtually all other parts of
among other structures. the brain. The cortex, in other words, is the ultimate meddler. It takes part in everything.
This fact not only makes it difficult to identify specific cortical functions but also com-
FIGUre 2-22 Neocortical plicates our study of the rest of the brain, because we must always consider the cortex’s
Layering Layer IV is relatively thick in role in other brain regions.
the sensory cortex and relatively thin in the Consider your perception of clouds. You have no doubt gazed up at clouds on a summer
motor cortex. Afferents from the thalamus day and imagined sailing ships, elephants, faces, and countless other objects. Although a cloud
connect to layer IV and to layers II and III.
does not really look like an elephant, you can concoct an image of one if you impose your
Efferents in layers V and VI connect to
other cortical areas and motor structures. frontal cortex—that is, your imagination—on the sensory inputs. This kind of cortical activity
Motor layers V and VI are thicker and is top-down processing because the top level of the nervous system, the cortex, is influencing
denser than sensory layers V and VI. how information is processed in lower regions of the hierarchy—in this case, the midbrain
and hindbrain.
Motor Sensory
cortex cortex
The cortex influences many behaviors besides object perception. It influences our crav-
ings for foods, our lust for things (or people), and how we interpret the meaning of abstract
concepts, words, and images. The cortex ultimately creates our reality, and one reason it
serves this function is that it is so well-connected.
FIGUre 2-23
Early 4 31
Motor cortex Sensory cortex 6 25
8
Brain Map In his 7
cytoarchitectonic map 9
I I
of the cortex, Brodmann 19
II Integrative II (1909) defined areas by
46 18
functions the organization and 40
39
III characteristics of the 10
III 45 44 43
cells he examined. The 42
Sensory 47 22 17
IV input (afferent) regions shown in color are
IV 11 21
associated with the simplest
37 19 18
V Output to
sensory perceptions of touch 38
V (red), vision (purple), and 20
other parts of
brain (efferent) VI hearing (orange). As we shall
VI see, the cortical areas that
process sensory information
are far more extensive than
Brodmann’s basic areas.
2-3 • The Central Nervous System: Mediating Behavior 57
Thalamus Corpus callosum FIGUre 2-24 Basal Ganglia A coronal
Lateral ventricle section through the cerebral hemispheres
reveals a frontal view of the basal ganglia
Caudate relative to surrounding forebrain structures.
nucleus Two associated structures likewise
Basal instrumental in controlling and coordinating
Putamen ganglia movement, the substantia nigra and
Globus subthalamic nucleus, also are shown.
pallidus
Basal
ganglia Subthalamic
nucleus
Substantia
nigra
Basal Ganglia
A collection of nuclei that lie in the forebrain just below the white matter of the cortex, the
basal ganglia consist of three principal structures: the caudate nucleus, the putamen, and
the globus pallidus, all shown in Figure 2-24. Together with the thalamus and two closely
associated nuclei, the substantia nigra and subthalamic nucleus, the basal ganglia form a
system that functions primarily to control voluntary movement.
We can observe the functions of the basal ganglia by analyzing the behavior resulting
from the many diseases that interfere with their healthy functioning. Parkinson disease, a Details on Parkinson disease appear in Focus
motor system disorder characterized by severe tremors, muscular rigidity, and a reduction in boxes 5-2, 5-3, and 5-4, Sections 11-3 and
voluntary movement, is among the most common movement disorders among the elderly. 16-3. Focus 11-4 details Tourette syndrome.
People with Parkinsonism take short, shuffling steps; display bent posture; and may need
a walker to get around. Many have almost continuous hand tremors and sometimes head
tremors as well. Another disorder of the basal ganglia is Tourette syndrome, characterized
by various motor tics; involuntary vocalizations (including curse words and animal sounds);
and odd, involuntary body movements, especially of the face and head.
Neither Parkinsonism nor Tourette syndrome is a disorder of producing movements, as in
paralysis. Rather, they are disorders of controlling movements. The basal ganglia, therefore,
must play a critical role in controlling and coordinating movement patterns rather than in
FIGUre 2-25 Limbic System This
activating the muscles to move. medial view of the right hemisphere
illustrates the principal structures
proposed by Papez to constitute the limbic
Limbic System system. This structure participates in
In the 1930s, psychiatry was dominated by the theories of Sigmund Freud, who emphasized emotional and sexual behaviors, motivation,
the roles of sexuality and emotion in human behavior. At the time, the brain regions and memory. For a contemporary view of
limbic anatomy, see Figure 12-18.
controlling these behaviors had not been identified, and coincidentally, a group of
brain structures collectively called the limbic lobe had no known function. It was Cingulate cortex
a simple step to thinking that perhaps the limbic structures played a central role in (allocortex)
sexuality and emotion.
One sign that this hypothesis might be correct came from James Papez (1937),
who discovered that people with rabies have infection in the limbic structures,
and one symptom of rabies is heightened emotionality. We now know that such a
simple view is inaccurate. In fact, the limbic system is not a unitary system at all.
And although some limbic structures have roles in emotional and sexual behaviors,
limbic structures serve other functions too, including contributing to memory and
motivation. Temporal
Figure 2-25 diagrams the principal limbic structures Papez proposed. The hippo- lobe
campus, cingulate cortex (a type of allocortex), and associated structures participate
Amygdala
in certain memory functions as well as in controlling navigation in space. Many
limbic structures, in particular the amygdala, are also believed to contribute to the Hippocampus
58 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
All sorts of behaviors can prove addictive—
eating, shopping, sex, video gaming,
gambling, even Twitter! How else to explain
these Canadian coeds tweeting all bundled
up when they could be defrosting on the
beach in the Florida sun? More on the
Photo via Newscom
limbic system and addiction in Section
6-3; motivation and emotion, Sections 12-3
and 12-4; memory, Section 14-3; and brain
disorders, Focus 16-1 and Section 16-4.
rewarding properties of psychoactive drugs and other potentially addictive substances and
behaviors. Repeated exposure to drugs such as amphetamine or nicotine produces both
chemical and structural changes in the cingulate cortex and hippocampus, among other
structures.
Olfactory bulb
Removal of the amygdala produces truly startling changes in emotional be-
havior. A cat with the amygdala removed will wander through a colony of mon-
To pyriform
keys, completely undisturbed by their hooting and threats. No self-respecting cat
cortex
would normally be caught anywhere near such bedlam.
Olfactory System
At the very front of the brain lie the olfactory bulbs, the organs responsible for our
Pyriform sense of smell. The olfactory system is unique among human senses, as Figure 2-26
cortex
shows, because it is almost entirely a forebrain structure. The other sensory systems
project most of their inputs from the sensory receptors to the midbrain and thala-
Sensory input from nose mus. Olfactory input takes a less direct route: the olfactory bulb sends most of its
inputs to a specialized region, the pyriform cortex, on the brain’s ventral surface.
FIGUre 2-26 Sense of Smell Our From there, sensory input progresses to the amygdala and the dorsomedial thalamus
small olfactory bulb lies at the base of the (see Figure 2-19, right), which routes it to the frontal cortex.
forebrain, connects to receptor cells that
Smell is one of the first senses to have evolved in animals, yet curiously, the olfactory
lie in the nasal cavity, and sends most of
this input to the pyriform cortex en route to system lies at the front of the human brain and is considered part of the forebrain (see the
the amygdala and thalamus. ventral view in Figure 2-6). This is partly an accident of evolution. The olfactory bulbs lie
near the olfactory receptors in the nasal cavity. Although they send their inputs to the
pyriform cortex in mammals, their input to the brainstem is more direct in simpler brains.
Compared with the olfactory bulbs of animals such as rats, cats, and dogs, which depend
Section 12-2 considers the chemical senses more heavily on smell than we do, the human olfactory bulb is relatively small. Nonetheless,
smell and taste in the context of emotional it is very sensitive, allowing us to distinguish a surprisingly large number of odors. Smell
and motivated behavior. plays important roles in various aspects of our feeding and sexual behavior.
2-3 reVIeW
The Central Nervous System: Mediating Behavior
Before you continue, check your understanding.
1. The three functionally distinct sections of the CNS—spinal cord, brainstem, and
forebrain—represent the evolution of multiple .
2. The can perceive sensations from the skin and muscles and produce
movements independent of the brain.
3. The brainstem includes three functional regions. The is an extension of the
spinal cord; the is the first brain region to receive sensory inputs; and the
integrates sensory and motor information on its way to the cerebral cortex.
2-4 • Somatic Nervous System: Transmitting Information 59
4. The coordinates fine motor movements and various cognitive functions.
5. The forebrain’s subcortical regions include the , which control voluntary
movement, and the , which controls mood, motivation, and some forms of
memory.
6. The two types of cerebral cortex are the older and the ,
which features layers that vary in density to perform , , and
functions.
7. Briefly describe the functions performed by the forebrain.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
2-4 Somatic Nervous System:
Transmitting Information
The SNS is monitored and controlled by the CNS—the cranial nerves by the brain and the
spinal nerves by the spinal cord segments.
Cranial Nerves
The linkages provided by the cranial nerves between the brain and various parts of
the head and neck as well as various internal organs are illustrated and tabulated in
Figure 2-27. Cranial nerves can have afferent functions, such as sensory inputs to the
brain from the eyes, ears, mouth, and nose, or they can have efferent functions, such
as motor control of the facial muscles, tongue, and eyes. Some cranial nerves have both
sensory and motor functions, such as modulation of both sensation and movement in
the face.
The 12 pairs of cranial nerves are known both by their numbers and by their names,
as listed in Figure 2-27. One set of 12 controls the left side of the head, whereas the other
set controls the right side. This arrangement makes sense for innervating duplicated
parts of the head (such as the eyes), but why separate nerves should control the right
and left sides of a singular structure (such as the tongue) is not so clear. Yet that is how
the cranial nerves work. If you have ever received lidocaine (often called Novocaine) for
dental work, you know that usually just one side of your tongue becomes numb because
the dentist injects the drug into only one side of your mouth. The rest of the skin and
muscles on each side of the head are similarly controlled by cranial nerves located on
the same side.
We consider many cranial nerves in detail in later chapters’ discussions on topics such
as vision, hearing, olfaction, taste, and stress responses. For now, you simply need to know
that cranial nerves form part of the SNS, providing inputs to the brain from the head’s sen-
sory organs and muscles and controlling head and facial movements. Some cranial nerves
also contribute to maintaining autonomic functions by connecting the brain and internal
organs (the vagus, cranial nerve 10) and by influencing other autonomic responses, such as
salivation.
cranial nerve One of a set of 12 nerve pairs
that control sensory and motor functions of
Spinal Nerves the head, neck, and internal organs.
The spinal cord lies inside the bony spinal column, which is made up of a series of small vertebrae (sing. vertebra) The bones that
bones called vertebrae (sing. vertebra), categorized into five anatomical regions from form the spinal column.
60 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
cranial
nerve Name Function
1 Olfactory Smell
1 2
3 2 Optic Vision
4 3 Oculomotor Eye movement
5 4 Trochlear Eye movement
5 Trigeminal Masticatory movements and
12 facial sensation
6 6 Abducens Eye movement
11
7 7 Facial Facial movement and
sensation
8 Auditory vestibular Hearing and balance
9 Glossopharyngeal Tongue and pharynx
8 movement and sensation
10
10 Vagus Heart, blood vessels, viscera,
9 movement of larynx and
pharynx
11 Spinal accessory Neck movement
12 Hypoglossal Tongue movement
FIGUre 2-27 Cranial Nerves Each
of the 12 pairs of cranial nerves has a
different function. A common mnemonic top to bottom: cervical, thoracic, lumbar, sacral, and coccygeal, as diagrammed in Fig-
device for learning the order of the cranial ure 2-28A. You can think of each vertebra in these five groups as a short segment of the
nerves is “On old Olympus’s towering top, spinal column. The corresponding spinal cord segment in each vertebral region functions
a Finn and German view some hops.” The as that segment’s minibrain.
first letter of each word is, in order, the
This arrangement may seem a bit odd, but it has a long evolutionary history. Think of a
first letter of the name of each nerve.
simpler animal, such as a snake, that evolved long before humans did. A snake’s body is a
segmented tube. In that tube is another tube, the spinal cord, which also is segmented. Each
of the snake’s nervous system segments receives nerve fibers from sensory receptors in the
part of the body adjacent to it, and that nervous system segment sends fibers back to the
muscles in that body part. Each segment, therefore, works independently.
A complication arises in animals such as humans, whose limbs may originate at one spi-
nal segment level but extend past other segments of the spinal column. Your shoulders, for
example, may begin at C5 (cervical segment 5), but your arms hang down well past the sacral
segments. So unlike the snake, which has spinal cord segments that connect to body seg-
Sections 11-1 and 11-4 review the spinal ments fairly directly adjacent to them, human body’s segments fall schematically into more
cord’s contributions to movement and to of a patchwork pattern, as shown in Figure 2-28B. This arrangement makes sense if the arms
somatosensation. are extended as they are when we walk on all fours.
Regardless of their complex pattern, however, our body segments still correspond to
the spinal cord segments. Each of these body segments is called a dermatome (mean-
ing skin cut). A dermatome has both a sensory nerve to send information from the skin,
joints, and muscles to the spinal cord and a motor nerve to control the muscle movements
in that particular body segment.
These sensory and motor nerves, known as spinal (or peripheral) nerves, are function-
dermatome Body segment corresponding to ally equivalent to the cranial nerves of the head. Whereas the cranial nerves receive
a segment of the spinal cord. information from sensory receptors in the eyes, ears, facial skin, and so forth, the spinal
law of Bell and magendie The principle that nerves receive information from sensory receptors in the rest of the body—that is, in the
sensory fibers are dorsal and motor fibers PNS. Similarly, whereas the cranial nerves move the muscles of the eyes, tongue, and
are ventral. face, the peripheral nerves move the muscles of the limbs and trunk.
2-4 • Somatic Nervous System: Transmitting Information 61
Somatic Nervous System (A)
Spinal cord Vertebrae
(B) Dermatomes
C3
Connections C1
(spinal column)
C2
C4
C5
C6
Like the CNS, the SNS is bilateral (two-sided). Just as the cranial C2 C7
C3 C8
nerves control functions on the side of the head where they are Cervical C4 T1
C5
found, the spinal nerves on the left side of the spinal cord control nerves C6 T2
C7 T3
the left side of the body, and those on the right side of the spinal C8 T4
T1 T5
cord control the body’s right side. T2 T6
Figure 2-29A on page 62 shows the spinal column in cross T3 T7
T4 T8
section. Look first at the nerve fibers entering its posterior side. T5 T9
Thoracic T6 C7 T10
These posterior fibers (dorsal in four-legged animals) are afferent: T7 T11
nerves T8 T12
they carry in information from the body’s sensory receptors. The T9 L1
fibers gather as they enter a spinal cord segment, and this collec- T10 L2
T11 L3
tion of fibers is called a posterior root in humans (dorsal root in L4
T12 L5
four-legged animals). L1 S1
Fibers leaving the spinal cord’s anterior side are efferent, S2
L2 S3
carrying information out from the spinal cord to the muscles. S4
Lumbar L3 S5
They, too, bundle together as they exit the spinal cord and so nerves S2
L4
form an anterior root (ventral root in four-legged animals). The S1
outer part of the spinal cord, pictured in Figure 2-29B, consists L5
of white matter, or CNS nerve tracts. These tracts are arranged S1
so that with some exceptions posterior tracts are sensory and S2
anterior tracts are motor. The inner part of the cord, which Sacral
nerves S3 Coccygeal
has a butterfly shape, is gray matter composed largely of cell segment
S4 L5
bodies. L5
S5
The observation that the dorsal spinal cord is sensory and
the ventral side is motor in four-legged animals is one of the FIGUre 2-28 Spinal Segments and
nervous system’s very few established laws, the law of Bell and Magendie. Combined D
ermatomes (A) Medial view showing
with an understanding of the spinal cord’s segmental organization, this law enables neu- the five spinal cord segments: cervical (C),
rologists to make accurate inferences about the location of spinal cord damage or disease thoracic (T), lumbar (L), sacral (S), and
on the basis of changes in sensation or movement. For instance, if a person has numbness coccygeal. (B) Each segment corresponds
to a region of body surface (a dermatome)
in the fingers of the left hand but can still move the hand fairly normally, one or more
identified by the segment number (e.g., C5
of the posterior (dorsal) nerves in spinal cord segments C7 and C8 must be damaged. at the base of the neck and L2 in the lower
In contrast, if sensation in the hand is normal but the person cannot move the fingers, back).
the anterior (ventral) roots of the same segments must be damaged. Clinical Focus 2-4,
Magendie, Bell, and Bell Palsy, on page 62, further explores diagnosing spinal cord injury Sections 11-1 and 11-4 explore spinal cord
or disease. injuries and treatments, and Section 12-3, the
link between spinal injury and loss of emotion.
Integrating Spinal Functions
So far we have emphasized the spinal cord’s segmental organization, but the spinal cord
must also somehow coordinate inputs and outputs across different segments. For example,
many body movements require coordinating muscles controlled by different segments, just
as many sensory experiences require coordinating sensory inputs to different parts of the
spinal cord. How is this coordination accomplished? The answer is that the spinal cord seg-
ments are interconnected in such a way that adjacent segments can operate together to direct
rather complex coordinated movements.
Integrating spinal cord activities does not require the brain’s participation, which is why
the headless chicken can run around. Still, a close working relation must exist between the
brain and the spinal cord. Otherwise, how could we consciously plan and execute our vol-
untary actions?
62 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
3 Collateral branches of
sensory neurons may cross to
(A) the other side and influence (B)
motor neurons there.
1 Fibers entering the Posterior root
posterior root bring (sensory)
sensory information Sensory
from sensory receptors. neuron
Motor
neuron Anterior
VideoSurgery/Getty Images
root (motor)
Gray White
matter matter
2 Fibers leaving the anterior
root carry motor information 4 White-matter fiber tracts carry
to the muscles. information to and from the brain.
FIGUre 2-29 Spinal Nerve
Connections (A) A cross section of
the human spinal cord, viewed from the Somehow information must be relayed back and forth, and examples of this infor-
front. The butterfly-shaped inner regions
mation sharing are numerous. For instance, tactile information from sensory nerves in
consist of neural cell bodies (gray matter),
and the outer regions consist of nerve the skin travels not just to the spinal cord but also to the cerebral cortex through the
tracts (white matter) traveling to and from thalamus. Similarly, the cerebral cortex and other brain structures can control movements
the brain. (B) A posterior view shows the through their connections to the spinal cord’s anterior roots. So even though the brain
intact human spinal cord exposed. and spinal cord can function independently, the two are intimately connected in their
CNS functions.
CliniCAl F cus 2-4
Magendie, Bell, and Bell Palsy
François Magendie, a volatile and committed French experimental physi- In 1811, a Scot named Charles Bell proposed functions for these nerve
ologist, reported in a three-page paper in 1822 that he had succeeded roots on the basis of anatomical information and the results of somewhat
in cutting the dorsal and ventral roots of puppies, animals in which the inconclusive experiments on rabbits. Although Bell’s findings were not
roots are sufficiently segregated to allow such surgery. Magendie found identical with those of Magendie, they were similar enough to ignite a
that cutting the dorsal roots caused loss of sensation, whereas cutting controversy. Bell hotly disputed Magendie’s claim to the discovery of
the ventral roots caused loss of movement. dorsal and ventral root functions. As a result, the principle of sensory
and motor segregation in the nervous system has been named after both
researchers: the law of Bell and Magendie.
Dr. P. Marazzi/Science Photo Library/Science Source
Magendie’s conclusive experiment on puppies was considered ex-
tremely important because for the first time it enabled neurologists to
localize nervous system damage from the symptoms that a patient dis-
plays. Bell went on to describe an example of such localized cranial
motor nerve dysfunction, and it still bears his name—Bell palsy, a facial
paralysis that develops when the motor part of the facial nerve on one
side of the head becomes inflamed (see the accompanying photograph).
The onset of Bell palsy is typically sudden. Often the stricken person
wakes up in the morning and is shocked to discover the face paralyzed
A young man with Bell palsy, a paralysis of the facial nerve
on one side. He or she cannot open the mouth or completely close the
(cranial nerve 7) that causes weakness over one side of eye on that side of the head. Most people fully recover from Bell palsy,
the face. He was photographed during an involuntary tic although it may take several months. But in rare instances, such as that
(a nervous reaction) that affects the right side of the face, of Jean Chrétien, a former prime minister of Canada, partial paralysis of
causing his right eye to close tightly. the mouth is permanent.
2-5 • Autonomic and Enteric Nervous Systems: Visceral Relations 63
2-4 reVIeW
Somatic Nervous System: Transmitting Information
Before you continue, check your understanding.
1. Two sets of SNS nerves, the and the , receive sensory
information or send motor signals to muscles or both.
2. Both sets of SNS nerves are symmetrically organized, and each set controls functions on
the side of the body.
3. The cranial nerves have both sensory and motor functions, receiving and sending
information to the and to the .
4. Define the law of Bell and Magendie and explain why it is important.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
2-5 Autonomic and Enteric Nervous
Systems: Visceral Relations sympathetic division Part of the autonomic
nervous system; arouses the body for
Control of the viscera (internal organs), including the heart, gut, liver, and lungs, requires
action, such as mediating the involuntary
complex neural systems. Yet the ANS and ENS are hidden partners, functioning in the back-
fight-or-flight response to alarm by increasing
ground as the CNS controls our perceptions and behaviors. If we had to focus consciously heart rate and blood pressure.
on visceral activities, we would do little else. The ANS and ENS interact with the CNS, but
parasympathetic division Part of the
each has distinctive anatomy and functions.
autonomic nervous system; acts in opposition to
the sympathetic division—for example, preparing
ANS: Balancing Internal Functions the body to rest and digest by reversing the
Without our conscious awareness, the ANS stays on the job to keep the heart beating, the alarm response or stimulating digestion.
liver releasing glucose, the pupils of the eyes adjusting to light, and so forth. Without the
ANS, which regulates the internal organs and glands via connections through the SNS to the
CNS, life would quickly cease. Although learning to exert some conscious control over some
of these vegetative activities is possible, such conscious interference is normally unneces- Section 5-3 explains CNS–ANS
sary. An important reason is that the ANS must keep working during sleep, when conscious communication, Figure 6-22 diagrams the
awareness is off duty. But gastrointestinal disorders are common, and stress is often a factor. stress response, and Section 16-4 discusses
Psychological therapies are often effective in treating such disorders. how mood affects reactivity to stress.
It is tempting to think that the ANS’s organization must be pretty simple because it func-
tions outside our conscious awareness. Yet, like the SNS, we can think about the ANS as a col-
lection of minibrains with a surprisingly complex organization. The two ANS divisions work
in opposition. The sympathetic division arouses the body for action, for example, by stimu-
lating the heart to beat faster and inhibiting digestion when we exert ourselves during exer- Principle 10: The nervous system works
cise or times of stress—the familiar fight-or-flight response. The parasympathetic division by juxtaposing excitation (increased neural
calms the body down, for example, by slowing the heartbeat and stimulating digestion to activity) and inhibition (decreased neural
allow us to rest and digest after exertion and during quiet times. activity).
Like the SNS, the ANS interacts with the rest of the nervous system, and like the SNS,
ANS connections are ipsilateral. Activation of the sympathetic division starts in the thoracic
and lumbar spinal cord regions. But the spinal nerves do not directly control the target
organs. Rather, the spinal cord is connected to autonomic control centers—collections of
neural cells called ganglia. The ganglia control the internal organs, and each acts as a mini-
brain for specific organs.
The sympathetic ganglia are near the spinal cord on each side, forming chains that run par-
allel to the cord, as illustrated at left in Figure 2-30 for one set of ganglia. The parasympathetic
64 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
division also is connected to the spinal cord—specifically, to the sacral region—but the greater
part of it derives from three cranial nerves: the vagus nerve, which calms most of the inter-
nal organs, and the facial and oculomotor nerves, which control salivation and pupil dilation,
respectively (review Figure 2-27). In contrast with the sympathetic division, the parasympathetic
division connects with ganglia that are near the target organs, as shown at right in Figure 2-30.
ENS: Controlling the Gut
The ENS is sometimes considered part of the ANS, but it functions largely independently.
Digestion is complicated, and evolution has provided this dedicated nervous system to control it.
Some scientists have even proposed that the CNS evolved from the gut of very simple organisms.
In fact, the ENS is sometimes called the second brain because, like the CNS, it con-
FIGUre 2-30
Autonomic Nervous
System The two ANS pathways exert tains a diversity of neuron types, the same chemical transmitters, a profusion of glial cells,
opposing effects. All fibers connect at and complex integrated neural circuits. Its estimated 200 million to 500 million neurons
“stops” formed by ganglia en route from roughly equals the number in the spinal cord. The gut reacts to a range of hormones and
the CNS to target ANS organs. Left: other chemicals with exquisite neural responses. The ENS functions to control bowel motil-
Arousing sympathetic fibers connect to a
ity, secretion, and blood flow to permit fluid and nutrient absorption and to support waste
chain of ganglia near the spinal cord. Right:
Calming parasympathetic fibers connect to elimination (see Avetisyan et al., 2015). This is no simple task, given the number and balance
individual ganglia near target organs. of nutrients needed to support the body.
Sympathetic division Parasympathetic division
Stimulatory: “fight or flight” Inhibitory: “rest and digest”
upil
tes p Contracts
pupil
Dila Oculomotor
nerve
toino Stimulat
ivati es s
aliv
ivla
sasla
ati
Constric on
iitbsits
els ay ts ai
ss irw rwa
hInibh
In esa y
lax
ve
Re
od
Lungs Facial nerve
blo
Cranial Cranial
icts
Sympathetic
str
Con
chain Vagus
ganglion nerve
at Slows heartbeat
Cervical tes heartbe Cervical
elera
Acc Heart
Stomach
tion
n Stimulates di ges
tio
i ges
s d
bit
Inhi
Thoracic Pancreas Thoracic
Liver
Stimulate
s glu
c
rele ose
ase
Secretion of Gall bladder
adrenalin
Lumbar Adrenal gland Lumbar
Kidney Intestines
Dilates blood
vessels
Sacral Rectum Sacral
Con
tract
s bladd adder
Sympathetic t im er Stimulates bl
S
ula
prevertebral ganglia tes
eja
cul
atio erection
n Stimulates
Genitals
2-5 • Autonomic and Enteric Nervous Systems: Visceral Relations 65
ENS neurons are located in a sheet of tissue (plexus) lining the esophagus, stomach, small
intestine, and colon. As shown in Figure 2-31, ENS neurons and glia form ganglia connected
by nerve fibers found in two layers of gut tissue. The brain and ENS connect extensively
through the ANS, especially via the vagus nerve. Although we are not conscious of our gut
“thinking,” the ENS sends information directly to the brain—information that affects our
mental state—and the brain can modify gut function. Indeed, a growing body of evidence Section 12-4 expands on how emotions and
implicates the ENS in many behavioral disorders, and stress and anxiety commonly modify the ENS interact, Section 12-5 on the ENS
gut function, leading to such symptoms as nausea and diarrhea. and eating.
The ENS interacts with gut bacteria, known collectively as the microbiome. About 1014
microbiota populate the adult gut, outnumbering the host cells by a factor of 10 (Farmer et al.,
2014). The microbiota influence nutrient absorption and are a source of neurochemicals that
regulate an array of physiological and psychological processes. This relationship has inspired
the development of a class of compounds known as psychobiotics, live microorganisms used
to treat behavioral disorders. Thus, the microbiota can influence both the CNS and ENS,
leading to changes in behavior.
Gastrointestinal FIGUre 2-31 Enteric Nervous
tract System The ENS is formed by a
network of neurons embedded in the lining
of the gastrointestinal tract. Congregations
of neurons form ganglia that send
projections to the ANS and CNS, in part
through the vagus nerve (cranial nerve 10),
to control gut function.
Nerve
Artery
Vein
Mesentery attaches
the gut to the
internal body wall.
Submucosal plexus
(ganglia)
Lumen, where digestion
occurs. No nerves enter
this area.
Myenteric plexus
(ganglia)
66 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
2-5 reVIeW
Autonomic and Enteric Nervous Systems: Visceral Relations
Before you continue, check your understanding.
1. The ANS interacts with the CNS and SNS via sets of autonomic control centers called
, which act as minibrains to control the internal organs.
2. The division of the ANS arouses the body for action, and the
division calms the organs. The two divisions work to
allow for quick defensive responses (fight or flight) or to induce a calming (rest
and digest) state.
3. Why is the ANS essential to life?
4. The ENS is often called a second brain because of the it contains.
5. The ENS interacts with bacteria that form the , which absorbs
and produces that can regulate CNS and ENS activity.
6. What are psychobiotics?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
2-6 Ten Principles of Nervous System
Function
The balance of the whole nervous system, of the functioning brain, and of individual cells
works in concert to produce behavior. Knowing the parts of the nervous system and some
general notions about what they do is only the beginning. Learning how the parts work
together allows us to proceed to a closer look, in the chapters that follow, at how the brain
produces behavior.
Thus far, we have identified 10 principles related to the nervous system’s functioning.
Here we elaborate each one. As you progress through the book, review these ideas regularly
with an eye toward understanding the concept rather than simply memorizing the principle.
Soon you will find yourself applying the principles of function as you encounter new infor-
mation about the brain and behavior.
Principle 1: The Nervous System Produces
Movement in a Perceptual World the Brain
Constructs
The nervous system’s fundamental function is to produce behavior, or movement.
Movements are not made in a vacuum but are related to objects, places, memories, and
myriad other forces and factors. Your mental representation of the world depends on the
information sent to your brain. People who are color-blind perceive the world very differently
from those who perceive color. The perceptual world of people who have perfect pitch is
different from that of those who do not.
Although we tend to think that the world we perceive is what is actually there, individual
realities, both between and within species, clearly are just rough approximations of what is
actually present. The brain of each animal species produces a reality that is adaptive for that
species to survive. The behavior that the brain produces, in other words, is directly related
to the world that the brain has constructed.
2-6 • Ten Principles of Nervous System Function 67
Principle 2: Neuroplasticity Is the Hallmark
of Nervous System Functioning
Experience alters the brain’s organization, and this neuroplasticity is requisite to learning
and memory as well as to survival. In fact, the nervous system stores information only if
neural connections change. Forgetting is presumably due to a loss of the connections that
represented the memory.
As Experiment 2-1 on page 49 demonstrates, neuroplasticity is a characteristic not just
of the mammalian brain; it is found in the nervous system of all animals, even the simplest
worms. Nonetheless, larger brains have more capacity for change, and thus their neural
organization is likely to show more plasticity.
Plasticity can be beneficial in recovering from disorders, such as brain injuries and dis-
eases, as well as in coping with aging. Plasticity also allows the brain to compensate for
developmental abnormalities, an extreme example being agenesis of brain structures, as dis-
cussed in Research Focus 2-1. Although beneficial in such circumstances, neuroplasticity has Detail on plasticity and drug addiction in
drawbacks. Brain analyses of animals given addicting doses of drugs such as cocaine or mor- Section 14-4, on feeling and treating pain
phine reveal broad changes in neural connectivity suspected of underlying some maladaptive in Section 11-4, on epilepsy in Focus 4-1.
behaviors related to addiction. Among many other examples of pathological neuroplasticity Section 16-3 details diagnosis and treatment
are those associated with pain, epilepsy, and dementia. of epilepsy and dementias.
Principle 3: Many Brain Circuits Are Crossed
Most brain inputs and outputs are crossed, that is, serve the opposite side of the body. Each
hemisphere receives sensory stimulation from the opposite (contralateral) side of the body
and controls muscles on the contralateral side. Crossed organization explains why people
who have a stroke or other damage to the left cerebral hemisphere may have difficulty in
sensing stimulation to the right side of the body or in moving body parts on the right side.
The opposite is true of people whose stroke occurs in the right cerebral hemisphere.
A crossed nervous system must somehow join both sides of the perceptual world together. Figure 9-10 illustrates how the human visual
To do so, innumerable neural connections link the brain’s left and right sides. The most system represents the world seen through
prominent connecting cable is the corpus callosum. Its roughly 200 million nerve fibers join two eyes as a single perception: both eyes
the left and right cerebral hemispheres, allowing them to interact. connect with both hemispheres.
Four important exceptions to the crossed-circuit principle are olfactory sensation and the
somatic, autonomic, and enteric PNS connections. Olfactory information does not cross but
rather projects directly into the same (ipsilateral) side of the brain. The cranial and spinal
nerves that constitute the SNS are connected ipsilaterally, as are the sympathetic and para-
sympathetic ANS division connections. Likewise, ipsilateral ENS connections link to the
ANS on both sides.
Principle 4: The CNS Functions on
Multiple Levels
In simple animals such as worms the spinal cord essentially constitutes the nervous system.
More complex animals, such as fishes, have a brainstem as well, and yet more complex
animals have also evolved a forebrain. Each new addition to the CNS has added a new level
of behavioral complexity without discarding previous levels of control. As animals evolved
legs, for example, brain structures evolved to move the legs. Later, the development of inde-
pendent digit movements required even more brainpower. Thus, new brain areas add new
levels of nervous system control. The new levels are not autonomous but rather must be
integrated into existing neural systems as refinements and elaborations of the control earlier
levels provided.
Multiple levels of function can be seen not only in the addition of forebrain areas to refine
brainstem control but also in the forebrain itself. As mammals evolved, they developed an
68 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
increased capacity to represent the world in the cortex, an ability related to the addition of
more maps. The new maps must be related to the older ones, however, and again are simply
an elaboration of the perceived sensory world that existed before.
Principle 5: The Brain Is Symmetrical and
Asymmetrical
The left and the right hemispheres look like mirror images, but they have some dissimilar
features. Cortical asymmetry is essential for integrative tasks, language and body control
among them.
Consider speaking. If a language zone existed in both hemispheres, each connected to
one side of the mouth, we would actually be able to talk out of both sides of our mouth at
once. That would make talking awkward, to say the least. One solution is to locate language
control of the mouth on one side of the brain. Organizing the brain in this way allows us to
speak with a single voice.
A similar problem arises in controlling body movements in space. We would not want the
left and the right hemispheres each trying to take us to a different place. Again, if a single
brain area controls this sort of spatial processing, problem solved.
Language control is typically situated on the left side, and spatial functions are typically
on the right. The brains of many species have such symmetrical and asymmetrical features.
In the bird brain, the control of singing is in one hemisphere, usually on the left side, as
is human language. It is likely that birds and humans evolved the same solution indepen-
dently—namely, to assign the control to only one side of the brain.
Principle 6: Brain Systems Are Organized
Hierarchically and in Parallel
When we consider the multiple levels of CNS function, it becomes apparent that these levels
(A) must be extensively interconnected to integrate their processing and produce unified percep-
Primary
tions or movements. The nature of neural connectivity leads to the principle that the brain
has both serial (or hierarchical) and parallel circuitry.
Secondary A hierarchical circuit hooks up a linear series of all regions concerned with a particular
function. Consider vision. In a serial system, the information from the eyes goes to regions
that detect the simplest properties, such as color or brightness. This information is passed
Tertiary along to another region that determines shape, then to another that measures movement,
and so on until at the most complex level the information is understood to be, say, your
(B) grandmother. Information therefore flows sequentially from simpler to more complex re-
gions in the hierarchy, as illustrated in Figure 2-32A.
Primary
However, functionally related brain structures are not always linked linearly. Although
the brain has many serial connections, many expected connections are missing. In the visual
system, not all cortical regions are connected to one another. The simplest explanation is
Level 2 Level 2
that the unconnected regions must have widely differing functions.
Parallel circuits operate on a different principle, also illustrated by the visual system.
Level 3 Level 3 Level 3 Imagine looking at a car. As we look at a car door, one set of visual pathways processes infor-
mation about its nature, such as color and shape, whereas another set of pathways processes
information about movements such as those necessary to open the door.
Level 4 Level 4 Level 4 Level 4 These two visual systems are independent of each other, yet they must interact somehow.
When you pull the car door open, you do not perceive two different representations—the
FIGUre 2-32 Models of Neural door’s size, shape, and color on the one hand and the opening movements on the other.
I nformation Processing (A) Simple When you open the door, you have the impression of unity in your conscious experience.
hierarchical model of serial cortical
Figure 2-32B illustrates the information flow in such a distributed hierarchy. If you trace
processing. (B) In a distributed
hierarchical processing model each of the flow from the primary area to levels 2, 3, and 4, you follow the parallel pathways. And
several processing streams has multiple while these multiple parallel pathways are also connected to one another, those connections
levels. Areas at each level interconnect. are more selective than connections in a purely serial circuit.
2-6 • Ten Principles of Nervous System Function 69
The brain’s subsystems are organized into multiple parallel pathways, yet our conscious
experiences are always unified. As we explore this conundrum throughout the book, keep in
mind that your commonsense impressions of how the brain works may not always be correct.
Principle 7: Sensory and Motor Divisions
Permeate the Nervous System
The segregation of SNS sensory and motor functions described by the Bell and Magendie
law exists throughout the nervous system. Distinctions between motor and sensory functions
become subtler in the forebrain.
Sensory and Motor Divisions in the SNS
Spinal nerves are either sensory or motor. Some cranial nerves are exclusively sensory; some
are exclusively motor; and some have two parts, one sensory and one motor, much like spinal Review cranial nerve and spinal nerve
nerves serving the skin and muscles. connections in Figures 2-27 and 2-28.
Sensory and Motor Divisions in the CNS
The lower brainstem regions—hindbrain and midbrain—are essentially extensions of the spi- Figures 2-15 through 2-19 illustrate brainstem
nal cord. They retain the spinal cord’s division, with sensory structures posterior and motor structures.
structures anterior in humans. An important midbrain function is orienting the body to
stimuli. Orienting movements require sensory input and motor output. The midbrain’s col-
liculi, posterior in the human tectum, are the sensory component, whereas the tegmentum,
which is anterior, is a motor structure that participates in controlling various movements,
including orienting.
Distinct sensory nuclei are present in the thalamus, too, although their positions are
not segregated, as they are in lower structures. Because all sensory information reaches the
forebrain through the thalamus, to find separate nuclei associated with vision, hearing, and
touch is not surprising. Separate thalamic nuclei also control movements. Other nuclei have
neither sensory nor motor functions but rather connect to cortical areas, such as the frontal
lobe, that perform more integrative tasks.
Finally, sensory and motor functions are divided in the cortex in two ways:
1. Separate sensory and motor cortical regions process a particular set of sensory inputs,
such as vision, hearing, or touch. Others control fine movements of discrete body parts,
such as the fingers.
2. The entire cortex is organized around the sensory and motor distinction. As diagrammed
in Figure 2-22, layer IV of the cortex always receives sensory inputs, layers V and VI
always send motor outputs, and layers I, II, and III integrate sensory and motor operations.
Principle 8: The Brain Divides Sensory Input
for Object Recognition and Motor Control Parietal
Sensory systems evolved first for controlling motion, not for recognizing things. Simple or- lobe
ganisms can detect stimulation such as light and move to or from it. It is not necessary to Occipital
perceive an object to direct movements toward or away from it. Animals only began to evolve lobe
Do
rsa
ways of representing their environment as their behaviors became more complex. Animals ls
tr e
with a complex brain evolved separate systems for recognizing objects and for moving toward am
them. The human visual system exemplifies this separation.
Ventral stream
Visual information travels from the eyes to the thalamus to visual regions of the occipital
lobe. From the occipital cortex it follows one of two routes: the ventral stream leads to the Temporal
temporal lobe for object identification, whereas the dorsal stream goes to the parietal lobe to lobe
Striate
guide movements relative to objects (Figure 2-33). People with ventral stream injuries are cortex (region V1)
blind for object recognition. They cannot distinguish a cup from a spoon. Nevertheless, they FIGUre 2-33 Neural Streams The
shape their hands appropriately when asked to reach for objects that they cannot identify. dorsal and ventral streams mediate vision
In contrast, people with dorsal stream injuries can recognize objects, but they make clumsy for action and recognition, respectively.
70 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
reaching movements because they do not form appropriate hand postures until they contact
objects. Only then do they shape the hand on the basis of tactile information.
Recognizing that perception for movement and perception for object recognition are
independent processes has three important implications for understanding brain organization:
1. The dorsal and ventral visual systems exemplify parallel information processing in the
brain.
2. Although we may think we are aware of our entire sensory world, the sensory analysis
required for some movements clearly is not conscious.
3. Unconscious and conscious brain processing underlies an important difference in our
cognitive functions. The unconscious movement system is always acting in the present
Sections 9-2 and 9-3 review evidence that led and in response to ongoing sensory input. In contrast, the conscious object recognition
to understanding the visual streams’ functions system allows us to escape the present and bring to bear information from the past, thus
and visual information processing. forming the neural basis of enduring memory.
Principle 9: Brain Functions Are Localized
and Distributed
A great debate in the history of brain research has concerned what aspects of different
functions are actually localized in specific brain regions. Perhaps the fundamental prob-
lem is defining a function. Language, for example, includes the comprehension of spoken
words, written words, signed words (as in American Sign Language), and even touched
words (as in Braille). Language also includes production of words orally, in writing, and
by signing, as well as constructing whole linguistic compositions, such as stories, poems,
songs, and essays.
Because the function that we call language has many aspects, it is not surprising that
these aspects reside in widely separated areas of the brain. We see evidence of this wide-
spread distribution in language-related brain injuries. People with injuries in different loca-
tions may selectively lose the abilities to produce words, to understand words, to read words,
to write words, and so forth. Specific language-related abilities, therefore, reside in specific
locations, but language as a whole is distributed throughout a wide brain region.
Memory provides another example of this same distributed pattern. Memories can
Figure 14-5 illustrates the extensive be richly detailed and can include sensual feelings, words, images, and much more. Like
distribution of memory areas through language, then, aspects of memory are located in many brain regions distributed throughout
the brain. a vast area of the brain.
Because many functions are both localized and distributed in the brain, damage to a
small brain region produces only focal (specific) symptoms. Massive brain damage is re-
quired to obliterate some functions. A small injury could impair some aspect of language
functioning, such as naming objects, but it would take widespread injury to remove all lan-
For Alzheimer neurochemistry, see Section guage abilities. In fact, one characteristic of dementing diseases is that people can endure
5-3; for incidence and possible causes, widespread deterioration of the cortex yet maintain remarkably normal language functions
Section 14-3; for treatments, Section 16-4. until late stages of the disease. Alzheimer disease is a degenerative brain disorder related
to aging that first appears as progressive memory loss and only much later develops into
generalized dementia.
Alzheimer disease Degenerative brain
disorder related to aging that first appears as
Principle 10: The Nervous System Works by
progressive memory loss and later develops Juxtaposing Excitation and Inhibition
into generalized dementia. We have emphasized the brain’s role in making movements, but we must also recognize that
excitation Increase in the activity of a the brain prevents movements. To make a directed movement, such as picking up a glass
neuron or brain area. of water, we must refrain from other movements, such as waving the hand back and forth.
inhibition Decrease in the activity of a In producing movement, then, the brain uses both excitation (increased neural activity) to
neuron or brain area. produce some action and inhibition (decreased neural activity) to prevent other actions.
Summary 71
Brain injury or disease can produce either a loss or a release of behavior by changing the
balance between excitation and inhibition. A brain injury in a region that normally initiates
speech may render a person unable to talk—a loss of behavior. A person with an abnormality
in a region that inhibits inappropriate language (such as swearing) may be unable to inhibit
this form of speech. Such a release of behavior can be seen in Tourette syndrome. Tourette syndrome and Parkinsonism are
Patients with Parkinson disease may have uncontrollable shaking of the hands because dysfunctions of the basal ganglia, which
the neural system that inhibits such movements has failed. Paradoxically, they often have coordinates voluntary movement.
difficulty initiating movements and appear frozen because they cannot generate the excita-
tion needed to produce deliberate movements.
The juxtaposition of excitation and inhibition, central to the way the brain produces
behavior, can be seen at the level of individual neurons. All neurons evince a spontaneous Chapter 3 details nervous system cell
activity rate that can be either increased (excitation) or decreased (inhibition). Some neu- structure; Chapter 4, how neurons transmit
rons excite others; some inhibit. Both effects are produced by neuronal communication via and integrate information; and Chapter 5,
specific neurochemicals. neuronal communication and adaptation.
2-6 reVIeW
Ten Principles of Nervous System Function
Before you continue, check your understanding.
1. Many of the brain’s input and output circuits are crossed. In the nervous system, four
exceptions to this principle are the , the , the ,
and the .
2. The vertebrate brain has evolved three regions—hindbrain, midbrain, and forebrain—
leading to and flexibility in controlling behavior.
3. One aspect of neural activity that resembles the on–off language of digital devices is the
juxtaposition of and .
4. Explain this statement: Perception is not reality.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
SUMMarY
2-1 Overview of Brain Function and Structure forms have not been replaced but rather have been adapted and
The brain’s primary function is to produce behavior, or movement, in a modified as new structures have evolved.
perceptual world the brain constructs. This perceptual world is ever- The principles of nervous system organization and function generalize
changing. To adapt, the brain must also change, a property referred across the three vertebrate brain regions—hindbrain, midbrain, and
to as neuroplasticity. forebrain—leading to multiple levels of functioning. The evolution of
To study how the nervous system functions, we abandon neural levels of control thus adds flexibility to behavioral control.
the anatomical divisions between the central nervous system and the
peripheral nervous system to focus instead on function—on how the 2-3 Central Nervous System: Mediating Behavior
CNS interacts with the divisions of the PNS: the somatic, autonomic, The CNS includes the brain and the spinal cord. The spinal cord
and enteric nervous systems. can perceive sensations from the skin and muscles and produce
movements independent of the brain. The brain can be divided into
2-2The Nervous System’s Evolutionary the brainstem and forebrain, each made up of hundreds of parts.
Development The brainstem both directs movements and constructs a sensory
The vertebrate nervous system evolved from a relatively simple world through its connections with the sensory systems, spinal
structure mediating reflexlike behaviors to the complex human brain cord, and forebrain. The forebrain modifies and elaborates basic
mediating advanced cognitive processes. To allow for more complex sensory and motor functions; regulates cognitive activity, including
behavior in an increasingly sophisticated perceptual world, primitive thought and memory; and ultimately controls movement. The most
72 Chapter 2 • WHAT IS THE NERVOUS SYSTEM’S FUNCTIONAL ANATOMY?
elaborate parts of the brain, the cerebral cortex and cerebellum, grow is affected by the microbiome, the roughly 100 trillion bacteria that
disproportionately large in the human brain. inhabit our gut.
2-4 Somatic Nervous System: Transmitting 2-6 Ten Principles of Nervous System Function
Information Ten principles listed in the right column below form the basis for
The SNS consists of two sets of spinal nerves that enter and leave the discussions throughout this book. Understanding them fully will
spinal column, connecting with muscles, skin, and joints in the body, enhance your study of brain and behavior.
and the cranial nerves that link the facial muscles and some internal
organs to the brain. Both sets of SNS nerves are symmetrical: one ten Principles of nervous system function
set controls each side of the body. Some cranial nerves are sensory,
1 The nervous system produces movement in a perceptual
some are motor, and some combine both functions. The spinal cord world the brain constructs.
acts as a minibrain for the peripheral (spinal) nerves that enter and
2 Neuroplasticity is the hallmark of nervous system
leave its five segments. Each spinal segment works independently, functioning.
although CNS fibers interconnect them and coordinate their activities.
3 Many brain circuits are crossed.
2-5 Autonomic and Enteric Nervous 4 The CNS functions on multiple levels.
Systems: Visceral Functions 5 The brain is symmetrical and asymmetrical.
The ANS controls the body’s glands and internal organs and operates 6 Brain systems are organized hierarchically and in parallel.
largely outside conscious awareness. Its sympathetic (arousing) 7 Sensory and motor divisions permeate the nervous system.
and parasympathetic (calming) divisions work in opposition. The
8 The brain divides sensory input for object recognition and
parasympathetic division directs the organs to rest and digest, motor control.
whereas the sympathetic division prepares for fight or flight.
9 Brain functions are localized and distributed.
The ENS controls the gut over its entire length, from the
esophagus to the colon, interacting with the brain via the ANS. ENS 10 The nervous system works by juxtaposing excitation and
inhibition.
activity can affect our behavior and mental state. In turn, the ENS
KeY terMS
afferent, p. 37 enteric nervous system (ENS), neocortex (cerebral cortex), stroke, p. 43
Alzheimer disease, p. 70 p. 37 p. 54 sulci (sing. sulcus), p. 43
autonomic nervous system excitation, p. 70 nerve, p. 47 sympathetic division, p. 63
(ANS), p. 37 forebrain, p. 54 neuroplasticity, p. 37 tectum, p. 52
basal ganglia, p. 56 frontal lobe, p. 41 nuclei (sing. nucleus), p. 47 tegmentum, p. 52
brainstem, p. 50 gray matter, p. 43 occipital lobe, p. 41 temporal lobe, p. 41
cerebral cortex, p. 41 gyri (sing. gyrus), p. 43 orienting movement, p. 52 thalamus, p. 54
cerebrospinal fluid (CSF), p. 41 hindbrain, p. 52 parasympathetic division, p. 63 Tourette syndrome, p. 56
corpus callosum, p. 44 hypothalamus, p. 54 parietal lobe, p. 41 tract, p. 47
cranial nerve, p. 59 inhibition, p. 70 Parkinson disease, p. 56 ventricle, p. 44
cytoarchitectonic map, p. 56 law of Bell and Magendie, p. 60 phenotypic plasticity, p. 37 vertebrae (sing. vertebra),
dermatome, p. 60 limbic system, p. 56 reticular formation, p. 52 p. 59
diencephalon, p. 52 meninges, p. 37 somatic nervous system (SNS), white matter, p. 44
efferent, p. 37 midbrain, p. 52 p. 37
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
3 What Are the Nervous ReseaRch Focus 3-1 A Genetic DiAGnosis
3-1 cells oF the NeRvous system
System’s Functional ReseaRch Focus 3-2 BrAinBow: rAinBow neurons
neurons: the BAsis of informAtion ProcessinG
Units? five tyPes of GliAl cells
expeRimeNt 3-1 Question: cAn the PrinciPles of
neurAl excitAtion AnD inhiBition control the
Activity of A simPle roBot?
cliNical Focus 3-3 BrAin tumors
3-2 iNteRNal stRuctuRe oF a cell
the cell As A fActory
The Basics chemistry review
cell memBrAne: BArrier AnD GAtekeePer
the nucleus AnD Protein synthesis
the enDoPlAsmic reticulum AnD Protein mAnufActure
Proteins: the cell’s ProDuct
GolGi BoDies AnD microtuBules: Protein
PAckAGinG AnD shiPment
crossinG the cell memBrAne: chAnnels, GAtes, AnD PumPs
3-3 GeNes, cells, aNd BehavioR
menDeliAn Genetics AnD the Genetic coDe
APPlyinG menDel’s PrinciPles
cliNical Focus 3-4 huntinGton DiseAse
Genetic enGineerinG
PhenotyPic PlAsticity AnD the ePiGenetic coDe
Katherine Streeter
73
74 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
ReseaRch F cus 3-1
A Genetic Diagnosis
Fraternal twins Alexis and Noah Beery seemingly acquired cerebral In searching the literature for similar cases, Retta found a photocopy
palsy perinatally (at or near birth). They had poor muscle tone and of a 1991 news report that described a child first diagnosed with cerebral
could barely walk or sit. Noah drooled and vomited, and Alexis had palsy, then found to have a rare condition, dopa-responsive dystonia.
tremors. (Dystonia means abnormal muscle tone.) It stems from a deficiency of a
Typically, children with cerebral palsy, a condition featuring perinatal neurochemical, dopamine, produced by a relatively small cluster of cells
brainstem damage, do not get worse with age, but the twins’ condition in the midbrain.
deteriorated. Their mother, Retta Beery, observed as well that Alexis’s When Alexis and Noah received a daily dose of l-dopa, a chemical
symptoms fluctuated: they improved after she slept or napped, for that some brain cells convert to dopamine, they displayed remarkable
example. improvement. “We knew that we were witnessing a miracle,” Retta recalled.
A few years later, in 2005, Alexis began to have new symptoms
marked by breathing difficulties. At this time the twins’ father, Joe,
worked for Life Technologies, a biotech company that makes equipment
used for sequencing DNA, the genetic coding molecule found in the
nucleus of every cell. Joe arranged for samples of the twins’ blood to be
sent to the Baylor College of Medicine’s DNA sequencing center.
The twins’ genome was sequenced and compared with that of their
parents and close relatives. The analysis showed that the twins had an
abnormality in a gene on chromosome 2 for an enzyme that enhances
not only dopamine production but also the production of serotonin,
another neurochemical made by brainstem cells (Bainbridge et al., 2011).
Courtesy of Retta Beery
When the twins’ doctors added tryptophan, the enzyme that is
converted to serotonin, to the l-dopa, both twins showed remarkable
improvement. Alexis competed in junior high school track, and Noah
played volleyball in the Junior Olympics. This is the first diagnosis
Noah, Retta, Joe, and Alexis Beery at Baylor College with the Solid established through genome sequencing that led to a treatment success,
Sequencer, which decoded the genomes of twins Noah and Alexis. a scientific miracle indeed.
the Beery twins’ remarkable story highlights how neuroscientists are applying advances
in genetics to treat brain disorders. Understanding genes, proteins, and cellular function
allows us to understand healthy brain functioning as well.
We begin this chapter by describing nervous system cell structure and relating structure
to functions. Brain cells not only give the nervous system its structure but also mediate
its moment-to-moment activity, the activity that underlies our behavior. We conclude the
chapter by elaborating on Mendelian genetics and how the science of epigenetics completes
Mendel’s theory.
3-1 Cells of the Nervous System
Cells have been likened to factories in that they make a product, proteins, the building
blocks of our bodies. But cells are more than factories. Cells use the proteins they produce
to participate in orchestrating our behavior.
Nervous system cells are small, are packed tightly together, and have the consistency
of jelly. To see a brain cell, the observer must distinguish it from surrounding cells, magni-
fied under a microscope. The first anatomists to study brain cells developed methods of
highlighting individual cells in nervous system tissue. To make the tissue firm, they soaked
it in formaldehyde to preserve and fix the tissue by binding together its constituent protein
3-1 • Cells of the Nervous System 75
ReseaRch F cus 3-2
Brainbow: Rainbow Neurons
Were it not for the discovery of stains that can highlight brain cell extent to which each gene is activated varies. As the mice develop,
features, their complexity and connections would remain unknown. Jean the variable expression of the color-coding genes results in cells
Livet (2007) and his colleagues at Harvard University developed a trans- that fluoresce in at least a hundred hues. When viewed through a
genic technique that labels different neurons by highlighting them with fluorescent microscope sensitive to these wavelengths, individual
distinct colors, a technique called Brainbow, a play on the word rainbow. brain cells and their connections can be visualized because they
(Transgenic techniques are a form of genetic engineering discussed in have slightly different hues, as illustrated in the accompanying
Section 3-3.) micrographs.
In the same way a television monitor produces the full range of colors Because individual cells can be visualized, Brainbow offers a
that the human eye can see by mixing only red, green, and blue, the way to describe where each neuron sends its processes and how it
Brainbow scientists introduced genes that produce cyan (blue), green, interconnects with other neurons. You have probably seen an elec-
and red fluorescent proteins into mice cells. The red gene is obtained trical power cord in which the different wires have different colors
from coral, and the blue and green genes are obtained from jellyfish. (black, white, red) that signify what they do and how they should
(The 2008 Nobel Prize in chemistry was awarded to Roger Tsien, Osamu be connected. By visualizing living brain tissue in a dish, Brainbow
Shimomura, and Martin Chalfie for their discovery and development of provides a method for examining changes in neural circuits with the
fluorescent proteins in coral and jellyfish.) passage of time.
The mice also received a bacterial gene called Cre. Cre activates In the future, Brainbow will prove useful for examining populations
the color genes inside each cell, but owing to chance factors, the of cells and their connections—for example, cells implicated in spe-
cific brain diseases. In principle, Brain-
bow could be turned on at specific times,
Livet, Draft, Sanes, and Lichtman, Harvard
as an individual ages or solves prob-
lems, for example (Rojczyk-Gołȩbiewska
et al., 2015). Despite Brainbow’s promise,
challenges remain. Even the simplest brain
contains extraordinary numbers of neu-
rons and fibers. Modifications in Brainbow
University
that restrict visualization to only a few
cells and fibers at a time are necessary
Cell bodies Axons Terminal buttons for their connections to be understood.
molecules. The fixed tissue was then sliced in thin sheets (sectioned), colored (stained) with
various dyes, and placed under a microscope for viewing.
Scientists continue to fix, slice, and stain brain tissue and to improve on ways of visual-
izing cells to provide insights into what cells do. Visualization is aided not only by using dyes
that either color an individual cell completely; color some cellular components. such as its
proteins; or as described in Research Focus 3-2, Brainbow: Rainbow Neurons, color the cell
only when it is engaged in a particular activity.
Scientists have developed other techniques of viewing living cells in the nervous system
or viewing cells that are cultured in a dish with nurturing fluids. In doing so, they use stain-
ing techniques to produce an image of the cell and to allow its activity to be viewed and
controlled. Investigators even implant tiny microscopes in the brain to view the activity
of its neurons (Chen et al., 2013). There remains, however, the problem of making sense of
what you see. Different brain samples can yield different images, and different people can
interpret the images in different ways.
So began a controversy between two great scientists—the Italian Camillo Golgi and
the Spaniard Santiago Ramón y Cajal—that resulted in defining neurons. Both men were
awarded the Nobel Prize for medicine in 1906. Imagine that you are Camillo Golgi, hard
at work in your laboratory staining and examining nervous system cells. You immerse
a thin slice of brain tissue in a solution containing silver nitrate and other chemicals,
76 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
FIGUre 3-1 Two Views of a Cell (A) (B)
(A) Tissue preparation revealing human
pyramidal cells stained using the Golgi
Biophoto Associates/Science Source/
technique. (B) Cajal’s drawing of a single
Purkinje neuron made from Golgi-stained
tissue. (B) Drawing from Histologie du système
nerveux de l’homme et des vertèbres, by S. Ramón y Cajal,
Photo Researchers
1909–1911, Paris: Maloine.
a technique used at the time to produce black-and-white photographs. A contemporary
Golgi never revealed just how he came to method, shown in Figure 3-1A, produces a color-enhanced microscopic image that
develop his staining technique. resembles the images Golgi saw.
The image is beautiful and intriguing, but what do you make of it? To Golgi, this struc-
ture suggested that the nervous system is an interconnected network of fibers. He thought
that information flowed around this “nerve net,” like water running through pipes, and so
produced behavior. His theory was reasonable, given what he saw.
But Santiago Ramón y Cajal came to a different conclusion. He used Golgi’s stain to
study chick embryos’ brain tissue. He assumed that their developing nervous system would
be simpler and easier to understand than an adult’s. Figure 3-1B shows an image he rendered
from the neural cells using the Golgi stain. Cajal concluded that the nervous system is made
up of such discrete cells, which begin life as a rather simple structure that becomes more
complex with age. When mature, each cell consists of a main body with many extensions
projecting from it.
Dendrites The structure looks something like a plant, with branches coming out of the top and
roots coming out of the bottom. Cajal showed that neurons come in many shapes and sizes.
Cajal’s neuron theory—that neurons are the nervous system’s functional units—is now uni-
versally accepted. The neuron theory includes the ideas that the interactions between these
discrete cells enable behavior and that the more neurons an animal has, the more complex
its behavior.
Figure 3-2 shows the three basic subdivisions of a neuron. The core region is called
the cell body, or soma (Greek, meaning body; the root of words such as somatic). A neu-
Cell body
ron’s branching extensions, or dendrites (from Greek for tree), collect information from
(soma)
other cells, and its main root is the single axon (Greek for axle), which carries messages
to other neurons. A neuron has only one axon, but most have many dendrites. Some
neurons have so many dendrites that they look like a garden hedge, as Cajal’s drawing in
Figure 3-1B illustrates.
The human nervous system contains 86 billion neurons (Herculano-Houzel et al., 2014).
Axon
How can 86 billion cells cooperate, make connections, and produce behavior? Fortunately,
neurons have a common plan: examining how one neuron works offers insights that we can
generalize to other neuron types. As you learn to recognize different types of nervous sys-
tem cells, you will begin to understand how their specialized structures contribute to their
functions in your body.
FIGUre 3-2 Basic Structure of a
Neuron Dendrites gather information Neurons: The Basis of Information
from other neurons, the cell body (soma)
integrates the information, and the axon
Processing
sends the information to other cells. As the information-processing units of the nervous system, neurons acquire information,
Although a neuron may have many interpret it, and pass the information along to other neurons that initiate a behavior. In
dendrites, it has only one axon. engaging in this activity, neurons also encode memories and produce our thoughts and
3-1 • Cells of the Nervous System 77
emotions. At the same time, they regulate body processes such as breathing, heartbeat, and
body temperature, to which we seldom give a thought.
Some scientists think that a specific function can be assigned to an individual
neuron. For example, many birds learn to sing during the breeding season, and this
learning is associated with the seasonal development of new neurons (Bertram et al.,
2014). To produce most behaviors in most species, however, scientists think that neurons
work together in groups of many hundreds to many thousands. It is important, then, to
understand not only how neurons function but also how they interconnect and influ-
ence one another.
Functional groups of neurons, or neural networks, connect wide areas of the brain and
spinal cord. The loss of a neuron or two from a network is no more noticeable than the
loss of one or two voices from a cheering crowd. It is the crowd that produces the overall
sound, not each person. In much the same way, although neuroscientists call neurons the
information-processing units of the brain, they really mean that neural networks serve this
function. An ongoing effort aims to map the structural connectivity—the physical wiring,
or connectome—of the entire human brain.
Scientists also speak informally about a particular neuron’s structure as if that structure
never changes. But neurons are the essence of plasticity. If you view fresh brain tissue
through a microscope, the neurons reveal themselves to be surprisingly active, produc-
ing new branches, losing old ones, and making and losing connections with each other as
you watch. This dynamic activity underlies both the constancies and the changes in our
behavior.
Another important property of most neurons is their longevity. At a few locations in the
human nervous system, ongoing production of new neurons does take place throughout life,
and some behavior does depend on the production of new neurons. But most of our CNS cell body (soma) Core region of the cell
neurons are with us for life. Although they change, they are not replaced when lost. For this containing the nucleus and other organelles
reason, if the brain or spinal cord is damaged, functional recovery is often poor. In some for making proteins.
nonhuman animal species, neurons can be replaced. The variability in neuronal longevity dendrite Branching extension of a neuron’s
and replacement are important properties to scientists who study diseases of aging, disorders cell membrane; greatly increases the cell’s
associated with age-related changes in the nervous system, and diseases or injuries that dam- surface area; collects information from other
age the nervous system. cells.
axon Root, or single fiber, of a neuron that
Structure and Function of the Neuron carries messages to other neurons.
Figure 3-3 on page 78 details the external and internal features common to neurons. The
neural network Functional group of neurons
cell’s surface area is increased immensely by its extensions into dendrites and an axon
that connects wide areas of the brain and
(Figure 3-3A and B). The dendritic area is further increased by many small protrusions spinal cord.
called dendritic spines (Figure 3-3C). A neuron may have up to 20 dendrites, each may
connectome Comprehensive map of all
have one to many branches, and the spines on the branches may number in the thousands.
structural connectivity (the physical wiring) in
Dendrites collect information from other cells, and the spines are the points of contact
an organism’s nervous system.
with those neurons. The extent of a cell’s branches and its spine number correspond to its
dendritic spine Protrusion that greatly
information-processing capacity.
increases the dendrite’s surface area; typical
Each neuron has but a single axon to carry messages to other neurons. The axon begins
point of dendritic contact with the axons of
at one end of the cell body at an expansion known as the axon hillock (little hill), shown in
other cells.
Figure 3-3D. The axon may branch out into one or many axon collaterals, which usually
axon hillock Juncture of soma and axon.
emerge from it at right angles, as shown at the bottom of Figure 3-3B.
The axon’s lower tip may divide into multiple smaller branches (telodendria, axon collateral Branch of an axon.
or end branches). At the end of each telodendrion is a knob called an end foot, or terminal button (end foot) Knob at the tip
terminal button. The terminal button sits very close to but usually does not touch a of an axon that conveys information to other
dendritic spine or some other part of another cell (Figure 3-3C). This near-connection, neurons.
called a synapse, includes the surfaces of the end foot and the neighboring dendritic synapse Spatial junction between one
spine as well as the space between them. The synapse is the information transfer site neuron and another; forms the information
between neurons. transfer site between neurons.
78 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
Major Parts
FIGUre 3-3 (A) (B)
Axon from another neuron
(C)
of a Neuron (A) Typical
End foot
neuron Golgi-stained to reveal Dendrites
Synapse
its dendrites and cell body. Dendritic spine
(B) The neuron’s basic structures
Ian Whishaw
identified. (c) An electron
micrograph captures the synapse
between an axon from another
neuron and a dendritic spine. (D)
(D) High-power light microscopic Dendrite
view inside the cell body. Note the
axon hillock at the junction of the Ian Whishaw
soma and axon.
Nucleus
Cell body (soma) Nucleolus
Cell body
Axon
hillock
Ian Whishaw
Axon
Nucleus
Axon
Axons from
other neurons Teleodendria Axon collateral
Terminal button (end foot)
Collecting
information
Dendrites from neighboring neuron
Dendrites
Information
from other
neurons is Chapter 4 describes how neurons transmit information; here, we simply generalize
collected
at dendrites,… about neuronal function by examining shape. Imagine looking down on a river system
Integrating Cell
information body from an airplane. You see many small streams merging to make creeks, which join to
…processed form tributaries, which join to form the main river channel. As the river reaches its
Flow of in the cell delta, it breaks up into many smaller channels again before discharging its contents
information Axon body,… into the sea.
…and passed on The general shape of a neuron suggests that it works in a broadly similar way to a river.
Sending
information to the axon… As illustrated in Figure 3-4, the neuron collects information from many sources on its
dendrites. It channels the information to its axon, which can send out only a single mes-
sage. The eventual branching of the axon then allows the message to be sent to many
targets.
Terminal button
Dendrites …and then to the Three Functions of Neurons
of target terminal, where it Neurons of varying shapes and sizes are structured to perform specialized functions.
neuron is passed on to its Sensory neurons (Figure 3-5A) conduct information from the sensory receptors in or on
target.
the body into the spinal cord and brain. Interneurons (Figure 3-5B) associate sensory and
FIGUre 3-4 Information Flow Through a motor activity in the CNS, and motor neurons (Figure 3-5C) carry information from the
Neuron brain and spinal cord out to the body’s muscles.
3-1 • Cells of the Nervous System 79
(A) Sensory neurons (B) Interneurons (C) Motor neurons
Bring information to the central nervous Associate sensory and motor activity in the central Send signals from the brain and spinal
system nervous system cord to muscles
Dendrites
Dendrite Dendrites
Dendrites
Axon
Bipolar Somatosensory Axon
neuron neuron Axon
(retina) (skin, muscle) Axon
Stellate cell Pyramidal cell Purkinje cell Motor neuron
(thalamus) (cortex) (cerebellum) (spinal cord)
FIGUre 3-5 Neuron Shape and
Function (A) Sensory neurons
SenSory neuronS Sensory neurons are the simplest structurally. A bipolar neuron of many types detect stimulation or
found in the retina of the eye, for example, has a single short dendrite on one side of its cell collect information and pass it on to
(B) an interneuron. The multibranched
body and a single short axon on the other side. Bipolar neurons transmit afferent (incoming)
interneuron dendrites collect information
sensory information from the retina’s light receptors to the neurons that carry information from varied sources and link to (c) motor
into the brain’s visual centers. neurons, which are distinctively large and
A bit more structurally complicated is the somatosensory neuron, which brings sensory which pass on commands to muscles to
information from the body into the spinal cord, a long distance. Structurally, the somato- move. Cells are not drawn to scale.
sensory dendrite connects directly to its axon, so the cell body sits to one side of this long
pathway.
InterneuronS Also called association cells because they link up sensory and motor neu-
rons, interneurons branch extensively, the better to collect information from many sources.
Animals with large brains have more interneurons, and their interneurons have more
branches, than those of small-brained animals. A specific type of interneuron, the stellate
(star-shaped) cell, is characteristically small, with many dendrites extending around the cell
body. Its axon is difficult to see in the maze of dendrites.
A pyramidal cell has a long axon, a pyramid-shaped cell body, and two sets of dendrites.
The apical set projects from the cell body apex, the basal set from the base of its cell body.
Pyramidal interneurons carry information from the cortex to the rest of the brain and spinal
cord. A Purkinje cell (named for its discoverer) is a distinctive interneuron with extremely
branched dendrites that form a fan shape. It carries information from the cerebellum to the sensory neuron Cell that detects or carries
rest of the brain and spinal cord. sensory information into the spinal cord and
brain.
Motor neuronS To collect information from many sources, motor neurons have exten-
sive dendritic networks, large cell bodies, and long axons that connect to muscles. Motor interneuron Association cell interposed
neurons reside in the lower brainstem and spinal cord. All efferent (outgoing) neural informa- between a sensory neuron and a motor
tion must pass through them to reach the muscles. neuron; in mammals, interneurons constitute
most of the brain’s neurons.
Neuronal Networks motor neuron Cell that carries efferent
information from the brain and spinal cord to
Sensory neurons collect afferent (incoming) information from the body and connect to
make muscles contract.
interneurons that process the information and pass it on to motor neurons. The motor
neurons’ efferent connections move muscles and so produce behavior. These three orga- bipolar neuron Sensory neuron with one
axon and one dendrite.
nizational aspects of neurons are thus features of neuronal networks: input, association,
and output. somatosensory neuron Brain cell that
Neurons that project for long distances, such as somatosensory neurons, pyramidal neu- brings sensory information from the body into
rons, and motor neurons, are relatively large. In general, neurons with a large cell body have the spinal cord.
long extensions, whereas neurons with a small cell body, such as stellate interneurons, have pyramidal cell Distinctively shaped
short extensions. interneuron found in the cerebral cortex.
Long extensions carry information to distant parts of the nervous system; short exten- Purkinje cell Distinctively shaped
sions are engaged in local processing. For example, the dendrite tips of some somatosensory interneuron found in the cerebellum.
80 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
neurons are in your big toe, whereas the target of their axons is at the base of your brain.
These sensory neurons send information over as much as 2 meters, even more in very large
animals. The axons of some pyramidal neurons must reach from the cortex as far as the lower
spinal cord, a distance that can be as long as a meter. The imposing size of this pyramidal
cell body therefore accords with the work it must do in providing nutrients and other cellular
supplies for its axons and dendrites.
The Language of Neurons: Excitation and Inhibition
Neurons are networkers with elaborate interconnections, but how do they communicate?
Simply put, neurons either excite other neurons (turn them on) or inhibit other neurons (turn
them off). Like digital computers, neurons send yes or no signals to one another; the yes sig-
nals are excitatory, and the no signals are inhibitory. Each neuron receives up to thousands
of excitatory and inhibitory signals every second.
Principle 10: The nervous system works by The neuron’s response to all those inputs is reasonably democratic: it sums them. A neu-
juxtaposing excitatory and inhibitory signals. ron is spurred into action and sends messages to other neurons if its excitatory inputs exceed
Section 4-3 explains how neurons summate its inhibitory inputs. If the reverse occurs and inhibitory inputs exceed excitatory inputs, the
excitatory and inhibitory signals. neuron does not communicate.
By exciting or inhibiting one another, a neuronal network can detect sensory informa-
tion and “decide” what kind of motor response to make to that information. To confirm
whether they understand how an entire neural network produces behavior, scientists might
make a model, such as a robot, intended to function in the same way. Robots, after all,
glial cell Nervous system cell that provides engage in goal-oriented actions, just as animals do. A robot’s computer must somehow sense
insulation, nutrients, and support and that aids the world, coordinate its actions in response, and perform much as an animal’s nervous
in repairing neurons and eliminating waste system performs.
products.
Constructing humanlike machines is one scientific objective of artificial intelligence (AI)
research. Barbara Webb’s cricket robot, constructed from Lego blocks, wires, and a motor
FIGUre 3-6 Nervous System Mimics (Figure 3-6, left), is designed to mimic a female cricket, which listens for the source of a
Left: Barbara Webb programmed rules
male’s chirping song and travels to it (Reeve et al., 2007). This is the beginning step in con-
she developed from studying cricket
behavior into her Lego cricket robot. Right: structing intelligent robots (Figure 3-6, right).
Social roboticist Heather Knight conducts In approaching a male, a female cricket must avoid open, well-lit places where a predator
research on robot body language with her could detect her. The female must often choose between competing males, preferring, for
companion, Marilyn Monrobot. example, the male that makes the longest chirps. All of these behaviors must be wired into
a successful cricket robot, making sure that one behavior does not interfere with another. In
simulating cricket behavior in a robot, Webb is duplicating the rules of a cricket’s nervous
system, which are programmed by its genes.
The Procedure sections of Experiment 3-1 illustrate
some ways that neural inhibition and excitation might
produce the cricket robot’s behavior. The Results sec-
tion confirms that this hypothetical arrangement mim-
ics the functions of sensory and motor neurons and
the principle of summating excitatory and inhibitory
signals—but with only six neurons and each neuron
connected to only one other neuron! Today, anthro-
pomimetic robots, so-called because their parts are
constructed to mimic the parts of a human body, in-
James King-Holmes/Science Photo Library
cluding its billions of neurons, are being designed to
model complex behavior ( Wittmeier et al., 2013).
Five Types of Glial Cells
Kike Calvo via AP Images
Another group of nervous system cell aids neurons in
processing information. Glial cells (from the Greek
for glue) are the nervous system’s support cells. The
3-1 • Cells of the Nervous System 81
ExPErimEnt 3-1
Question: Can the principles of neural excitation and inhibition control the
activity of a simple robot?
Procedure A
If we insert sensory neurons between the microphone for sound detection on each side
of this hypothetical robot and the motor on the opposite side, we need only two rules to
instruct the female robot to seek out a chirping male cricket.
Excitatory inputs from
the chirping of a male
cricket...
Cricket
...are picked up
by the cricket robot's +
microphone... Microphones
+
Cricket ...and activate the
robot robot’s wheels (at
plus signs) to orient
+ + toward the chirp.
Sensory neurons
rule 1 When a microphone detects a male cricket’s song, an excitatory message is sent
to the opposite wheel’s motor, activating it so the robot turns toward the cricket.
rule 2 If the chirp is coming from the robot’s left side, it will be detected as being
louder by the microphone on the left, which will make the right wheel turn a little faster,
swinging the robot to the left.
Procedure B
We add two more sensory neurons, coming from photoreceptors on the robot. When
activated, these light-detecting sensory neurons inhibit the motor neurons leading to the
wheels and prevent the robot from moving toward a male cricket. Now the female cricket
robot will move only when it is dark and “safe.”
In a slightly more
complex cricket robot...
...sensory neurons (red) Microphones Photoreceptor
from the microphone cells
excite motor neurons ...but input from
(blue) at the plus signs... photoreceptors
inhibits them at the
Wheel minus signs.
+ +
– –
+ +
+ +
Motor neurons
Result
This hypothetical arrangement illustrates the biological function of sensory and motor
neurons and the neural principle of summating excitatory and inhibitory signals.
Conclusion: A simple robot will operate on the principles of neural excitation and
inhibition. More neurons are necessary to make the robot more “intelligent.”
82 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
human brain’s estimated 87 billion glial cells reflect the typical nervous system ratio of
roughly 1:1 between neurons and glial cells (Herculano-Houzel et al., 2014). Although they
Glia form the fatty coverings around do not transmit information themselves, glial cells help neurons carry out this task, bind-
neurons—the white matter in brain images ing them together (some do act as glue) and providing support, nutrients, and protection,
such as Figure 2-12B and D. among other functions.
Table 3-1 lists the five major types of glia along with their characteristic structures and
functions. Glial cells are different from neurons in that new glial cells are produced, and
errors in replication can result in abnormal growths: brain tumors. Clinical Focus 3-3, Brain
Tumors, describes the results of such uncontrolled glial cell growth.
Ependymal Cells
On the walls of the ventricles, the fluid-filled cavities inside your brain, are ependymal cells,
which produce and secrete the cerebrospinal fluid that fills the ventricles. CSF is constantly
being secreted, and it flows through the ventricles toward the base of the brain, where it is
absorbed into the blood vessels. CSF serves several purposes. It acts as a shock absorber when
the brain is jarred, carries away waste products, assists the brain in maintaining a constant
temperature, and is a source of nutrients for parts of the brain adjacent to the ventricles.
As CSF flows through the ventricles, it passes through some narrow passages, especially
Figure 2-9 shows the location of the cerebral from the cerebral aqueduct into the fourth ventricle, which runs through the brainstem. If
aqueduct and the four ventricles. these passages are fully or partly blocked, fluid flow is restricted. Because CSF is continu-
ously being produced, this blockage causes a buildup of pressure that begins to expand the
ventricles, which in turn push on the surrounding brain.
If such a blockage develops in a newborn infant, before the skull bones are fused, the pres-
sure on the brain is conveyed to the skull, and the baby’s head swells. This condition, called
hydrocephalus (literally, water brain), can cause severe intellectual impairment, even death.
To treat it, doctors insert one end of a tube, called a shunt, into the blocked ventricle and the
other end into a vein, allowing excess CSF to drain into the bloodstream.
taBLe 3-1 types and functions of Glial cells
type appearance Features and function
Ependymal cell Small ovoid; secretes CSF
Astrocyte Star shaped; contributes to neuronal nutrition, support, and
repair; contributes to forming blood–brain barrier and to
ependymal cell Glial cell that makes and
healing scarring after injury
secretes CSF; found on the walls of the
brain’s ventricles.
hydrocephalus Buildup of fluid pressure in
the brain and, in infants, swelling of the head, Microglial cell Small, derived from blood; defensive function to remove
if the flow of CSF is blocked; can result in dead tissue
intellectual impairment.
tumor Mass of new tissue that grows
uncontrolled and independent of surrounding
structures. Oligodendroglial cell Forms myelin around CNS axons in brain and spinal cord
astrocyte Star-shaped glial cell that provides
structural support to CNS neurons and
transports substances between neurons and
blood vessels.
blood–brain barrier Tight junctions between Schwann cell Wraps around peripheral nerves to form myelin
the cells that compose blood vessels in the
brain, providing a barrier to the entry of an
array of substances, including toxins, into the
brain.
3-1 • Cells of the Nervous System 83
clinical F cus 3-3
Brain Tumors
One day while watching a movie in a neuropsychology class, R. J., a after treatment. U.S. Senator Edward Kennedy was diagnosed with a
19-year-old college sophomore, collapsed on the floor, displaying symp- malignant glioma in 2008 and died a year later. As with R. J., his first
toms of a seizure. The instructor helped her to the university clinic, symptom was an epileptic seizure.
where she recovered except for a severe headache. She reported that
2. Meningiomas, such as R. J.’s, attach to the meninges and so grow
she had repeated severe headaches.
entirely outside the brain, as shown in the accompanying CT scan.
A few days later, a computed tomography (CT) scan showed a tumor over
These tumors are usually encapsulated (contained), and if the tumor
her left frontal lobe. The tumor was removed surgically, and R. J. returned
is accessible to surgery, chances of recovery are good.
to classes after an uneventful recovery. Her symptoms have not recurred.
A tumor is an uncontrolled growth of new tissue that is independent 3. Metastatic tumors become established when cells from one region of
of surrounding structures. No region of the body is immune, but the the body transfer to another area (which is what metastasis means).
brain is a site for the more than 120 kinds of Typically, metastatic tumors are present in
tumors. They are a common cause of brain multiple locations, making treatment difficult.
Library/Science Source
Dept. of Clinical Radiology, Salisbury District Hospital/Science Photo
cancer in children. Symptoms of the underlying condition often
The incidence of brain tumors in the first appear when the tumor cells reach the
United States is about 20 per 100,000, brain.
according to the Central Brain Tumor Regis-
Treatment for brain tumors is usually sur-
try of the United States (Quinn et al., 2014). In
gical, and surgery also remains a main diag-
adults brain tumors grow from glia or other
nostic tool. Chemotherapy is less successful in
supporting cells rather than from neurons,
treating brain tumors than tumors elsewhere
but in infants, tumors may grow from de-
in the body, because the blood–brain barrier
veloping neurons. Rate of tumor growth de-
blocks the chemicals’ entry. Radiation therapy
pends on the type of cell affected.
(X-ray treatment) is more useful for destroying
Some tumors are benign, as R. J.’s was,
brain tumor cells. Nevertheless, radiation has
and not likely to recur after removal. Others
negative effects especially on the developing
are malignant, likely to progress, to invade
brain and chemotherapy can affect brain func-
other tissue, and apt to recur after removal.
The red area in this false-color CT scan is a tion, a condition referred to as Chemo Brain.
Both kinds can pose a risk to life if they
meningioma, a noncancerous tumor arising Recent approaches to treating brain
develop in sites from which they are difficult from the meninges, which cover the brain. tumors exploit biochemical differences
to remove. Large meningiomas may compress the brain between tumors and healthy tissue, for ex-
The earliest symptoms usually result but usually do not invade brain tissue. ample to visualize a tumor for surgical re-
from increased pressure on surrounding
moval. Chlorotoxin, a scorpion venom that
brain structures. They can include headaches, vomiting, mental dullness,
selectively binds to chloride channels in tumor cell membranes, com-
changes in sensory and motor abilities, and seizures such as R. J. had.
bined with a fluorescent dye, forms a tumor paint (Butte et al., 2014).
Many symptoms depend on the tumor’s location. The three major types of
Injected into a vein, the paint crosses the blood–brain barrier and coats
brain tumors are classified according to how they originate:
a tumor, which then glows when exposed to light in near-infrared wave-
1. Gliomas arise from glial cells. They are slow growing, not often malig- lengths. Human trials began in 2015.
nant, and relatively easy to treat if they arise from astrocytes. Gliomas Nonsurgical tumor removal might also replace or aid chemotherapy
that arise from the precursor blast or germinal cells that grow into and radiation therapy. It combines chlorotoxin with a poison to form a
glia are more often malignant, grow more quickly, and often recur drug that kills tumor cells (Wang and Guo, 2015).
Astroglia
Astrocytes (star-shaped glia, shown in Table 3-1), also called astroglia, provide structural sup-
port to the CNS. Their extensions attach to blood vessels and to the brain’s lining, forming a
scaffolding that holds neurons in place. These same extensions provide pathways for certain
nutrients to move between blood vessels and neurons. Astrocytes also secrete chemicals that
keep neurons healthy and help them heal if injured.
At the same time, astrocytes contribute to the structure of a protective partition between
blood vessels and the brain, the blood–brain barrier. As shown in Figure 3-7, the end feet of
84 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
Blood-vessel Astrocyte astrocytes attach to blood vessel cells, causing the vessels to bind tightly together.
Blood vessel cells end feet
These tight junctions prevent an array of substances, including many toxins, from
entering the brain through the blood vessel walls.
The molecules (smallest units) of these substances are too large to pass between
the blood vessel cells unless the blood–brain barrier is somehow compromised. The
downside is that many useful drugs, including antibiotics used to treat infections
Astrocyte Neuron cannot pass through the blood–brain barrier to enter the brain. As a result, brain
infections are very difficult to treat. Scientists can bypass the blood–brain barrier
Tight and introduce drugs into the brain by inserting small tubes that allow the delivery
junctions
of a drug directly to a targeted brain region.
Yet another important function of astrocytes is to enhance brain activity.
When you engage in any behavior, whether it’s reading or running, the neuronal net-
work responsible for that behavior requires more fuel in the form of oxygen and glucose.
Myelinated axon In response to neuron activity, the blood vessels that supply it expand, allowing greater
oxygen- and glucose-carrying blood flow. What triggers the blood vessels to dilate? This
FIGUre 3-7 Blood–Brain Barrier
is where astrocytes come in. They receive signals from the neurons, pass them on to the
Astrocyte processes attach to neurons
and to blood vessel cells to stimulate them blood vessels, and so contribute to increased blood flow and fuel supply (Rosenegger and
to form tight junctions and so form the Gordon, 2015).
blood–brain barrier. Astrocytes also move Astrocytes also contribute to healing damaged brain tissue. If the brain is injured by a
nutrients and other chemicals between blow to the head or penetrated by some object, astrocytes form a scar to seal off the dam-
blood vessels and neurons, support
aged area. Although the scar tissue is beneficial in healing the injury, it can also act as a
brain structures, and stimulate repair of
damaged brain tissue. barrier to the regrowth of damaged neurons. One experimental approach to repairing brain
tissue seeks to get the axons and dendrites of CNS neurons to grow around or through a
glial scar.
Microglia
Unlike other glial cells, which originate in the brain, microglia originate in the blood as an
offshoot of the immune system and migrate throughout the nervous system, where they
make up about 20% of all glial cells. The brain is largely immune privileged, because the
blood–brain barrier prevents most immune system cells from entering. Microglia monitor
the health of brain tissue and play the role of its immune system. They identify and attack
foreign tissue, as illustrated in Figure 3-8. When brain cells are damaged, microglia invade
Growth factors, described Section 8-2, are the area to provide growth factors that aid in repair.
chemicals that stimulate and support growth, There are several kinds of microglia, which take different shapes depending upon the
survival, and perhaps even brain cell plasticity role they are performing. Microglia engulf any foreign tissue and dead brain cells, an
(see Section 14-4). immune process called phagocytosis. When full they take on a distinctive appearance. The
stuffed and no-longer-functioning microglia can be detected as small dark bodies, shown in
Figure 3-8C, in and near damaged brain regions.
Because microglia are frontline players in protecting the nervous system and removing
its waste, considerable research is directed toward the extent to which microglia are involved
(A) (B) (C)
FIGUre 3-8 Detecting Brain Damage
(A) Arrows indicate the red nucleus in a rat
brain. (B) Close-up of cresyl violet–stained
neurons, the large dark bodies, in the
healthy red nucleus. (c) After exposure to
Ian Whishaw
a neurotoxin, only microglia, the small dark
objects in the micrograph, survive.
3-1 • Cells of the Nervous System 85
in protecting the nervous system from disease. A characteristic of Alzheimer disease, the More on understanding and treating
degenerative brain disorder commonly associated with aging, is the deposit of distinctive Alzheimer disease in Section 16-3.
bodies called plaques in regions of damage. Microglia may also play a harmful role, consum-
ing inflamed tissue rather than protecting it. They also interact with astrocytes in brain
healing. Although small, as their name suggests, microglia play a mighty role in maintaining
the brain’s health (Casano & Peri, 2015).
Oligodendroglia and Schwann Cells
Two kinds of glial cells insulate neuronal axons. Like the plastic insulation on electrical
wires, myelin prevents adjacent neurons from short-circuiting. Myelinated neurons send in-
formation much faster than neurons without myelin. Neurons that send messages over long Section 4-2, describes how myelin speeds
distances quickly, including sensory and motor neurons, are heavily myelinated to increase up the neuron’s information flow. Focus 4-2
their messaging speed. describes effects of myelin damage.
Oligodendroglia myelinate axons in the brain and spinal cord by sending out large, flat
branches that enclose and separate adjacent axons (the prefix oligo- means few and here refers
to the fact that these glia have few branches in comparison with astrocytes; see Table 3-1).
microglia Glial cells that originate in the
Schwann cells myelinate axons in the PNS. Each Schwann cell wraps itself repeatedly
blood, aid in cell repair, and scavenge debris
around a part of an axon, forming a structure somewhat like a bead on a string. In addition
in the nervous system.
to myelination, Schwann cells and oligodendroglia contribute to a neuron’s nutrition and
functioning by absorbing chemicals that the neuron releases and releasing chemicals that myelin Glial coating that surrounds axons in
the central and peripheral nervous systems;
the neuron absorbs.
prevents adjacent neurons from short-
Glial Cells and Neuron Repair circuiting.
The multifaceted relations among neurons and glia provide insights into nervous system oligodendroglia Glial cells in the CNS that
diseases and into brain injury and recovery from brain injury. Diseases that damage myelin myelinate axons.
impair a neuron’s ability to send information. The consequences of damage to oligodendrog- schwann cell Glial cell in the PNS that
lia and Schwann cells can be as debilitating as damage to neurons themselves. Damage to myelinates sensory and motor axons.
areas rich in neuron cell bodies can also be different from damage to fiber pathways, because paralysis Loss of sensation and movement
pathway damage includes both neurons and myelin cells. due to nervous system injury.
Glia can also aid in nervous system repair. A deep cut on your body—on your arm or
leg for instance—may cut the axons connecting your spinal cord to muscles and to sensory
receptors. Severing of motor neuron axons will render you unable to move the affected part
FIGUre 3-9 Neuron Repair Schwann
of your body, whereas severing of sensory fibers will result in loss of sensation from that
cells aid the regrowth of axons in the
body part. Cessation of both movement and sensation is paralysis. Weeks to months after somatic nervous system.
motor and sensory axons are severed, movement and sensation will return. What mediates
this recovery?
Both microglia and Schwann cells participate in 1 When a peripheral axon is Axon Cut Schwann cell
repairing damage to the peripheral nervous system. cut, the axon dies.
When a PNS axon is cut, it dies back to the cell body, Cell body
as shown at the top of Figure 3-9. Microglia remove all
Axon Degenerating
of the debris left by the dying axon. Meanwhile, the sprouts
2 Schwann cells first shrink and axon
Schwann cells that provided the axon’s myelin shrink then divide, forming glial cells
and divide to form numerous smaller glial cells along the along the axon’s former path.
path the axon formerly took. The cell body then sends Dividing Schwann cells
out axon sprouts that search for and follow the path
formed by the Schwann cells. 3 The neuron sends out axon
Eventually, one sprout reaches the intended target sprouts, one of which finds the
and becomes the new axon; all other sprouts retract. Schwann-cell path and
The Schwann cells envelop the new axon, forming becomes a new axon.
Schwann cells form myelin
new myelin and restoring function. In the PNS, then,
Schwann cells serve as signposts to guide axons to 4 Schwann cells envelop the Axon
their appropriate end points. Axons can get lost, how- new axon, forming new myelin.
ever, as sometimes happens after surgeons reattach a Myelin
86 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
severed limb. If axons destined to innervate one finger end up innervating another finger
instead, the wrong finger will move when a message is sent along that axon.
Sections 11-1 and 11-4 detail causes of and When the CNS is damaged, as happens, for example, when the spinal cord is cut,
treatments for spinal cord injury. regrowth and repair do not occur, even though the distance that damaged fibers must bridge
is short. The oligodendrocytes that myelinate CNS cells do not behave like PNS Schwann
cells to encourage brain repair. They may actually play a role in inhibiting neuron regrowth
(Rusielewicz et al., 2014). That recovery should take place in the PNS but not in the CNS is
puzzling. Regrowth in the CNS may not occur in part because as neuronal circuits mature,
they become exquisitely tuned to mediate individualized behavior and so are protected from
the proliferation of new cells or the regrowth of existing cells.
3-1 revIew
Cells of the Nervous System
Before you continue, check your understanding.
1. The two classes of nervous system cells are , which in humans number
around , and , which in humans number about ,
reflecting the typical ratio.
2. Neurons, the information-conducting units of the nervous system, act either by
or by one another through their connecting synapses.
3. The three types of neurons and their characteristic functions are ,
which ; , which ; and , which
.
4. The five types of glial cells are , , ,
, and . Their functions include , ,
, , and neurons.
5. What is the main obstacle to producing a robot with all of the behavioral abilities displayed
by a mammal?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
3-2 Internal Structure of a Cell
What is it about the structure of neurons that generates the remarkable ability to receive,
process, store, and send a seemingly limitless amount of information? To answer this ques-
tion, we must look inside a neuron to see what its components are and understand what they
do. Although neurons are minuscule, when we view them with an electron microscope, we
find packed inside hundreds of interrelated parts that do the cell’s work.
To a large extent, a cell’s proteins determine its characteristics and functions. Each cell
can manufacture thousands of proteins, which variously take part in building the cell and in
communicating with other cells. When a neuron malfunctions or contains errors, proteins
are implicated and so are involved in many kinds of brain disease. In this section, we explain
how the different parts of a cell contribute to protein manufacture, describe what a protein
is, and detail some functions of proteins.
Water, salts, and ions play prominent parts in the cell’s functions, as you will learn in this
and the next few chapters. If you already understand the structure of water and you know
what a salt is and what ions are, read on. If you prefer a brief chemistry review first, turn to
The Basics: Chemistry Review, on pages 88–89.
3-2 • Internal Structure of a Cell 87
The Cell as a Factory
We began Section 3-1 by comparing a cell to a miniature factory, with work centers that
cooperate to make and ship the cell’s products—proteins. To investigate the cell’s internal
parts—the organelles—and how they function, we begin with a quick overview of the cell’s
internal structure.
Figure 3-10 displays many external and internal cellular components. A factory’s outer
wall separates it from the rest of the world and affords some security. Likewise, a cell’s dou-
ble-layered outer wall, or cell membrane, separates the cell from its surroundings and allows
it to regulate what enters and leaves its domain. The cell membrane envelopes the neuron’s
contents and contributes to forming its cell body, its dendrites and their spines, and its axon
and terminals. It thus forms the boundary around a continuous intracellular compartment.
Very few substances can enter or leave a cell spontaneously, because the cell membrane
is virtually impermeable (impenetrable). Some proteins made by the cell are embedded in
the cell membrane, where they facilitate the transport of substances into and out of the cell.
FIGUre 3-10 Typical Nerve Cell This
These proteins thus serve as the cellular factory’s gates. view of the outside and inside of a neuron
reveals its overall structure and internal
organelles and other components.
Dendrite: Cell extension that collects Dendritic spine: Small protrusion on
information from other cells dendrites that increases surface area
Nucleus: Structure containing
the chromosomes and genes
Nuclear membrane: Membrane
surrounding the nucleus
Mitochondrion: Structure that
gathers, stores, and releases
energy
Endoplasmic reticulum: Folded
layers of membrane where
proteins are assembled
Intracellular fluid: Fluid in which
Golgi body: Membranous
the cell’s internal structures
structure that packages protein
are suspended
molecules for transport
Tubule: Tiny tube that transports
Lysosomes: Sacs containing
molecules and helps give the
enzymes that break down wastes
cell its shape
Microfilaments: Threadlike fibers
Cell membrane: Membrane
making up much of the cell’s
surrounding the cell
“skeleton”
Axon: Extension that transmits
information from cell body to
other cells
88 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
The Basics
Chemistry Review
The smallest unit of a protein or any other chemical substance is the mol- The smallest quantity of an element that retains the properties of that
ecule. Molecules and the even smaller atoms of elements that constitute element is an atom. Ordinarily, as shown opposite in part A of the figure Ion
them are the cellular factory’s raw materials. Formation, atoms are electrically neutral: their total positive and negative
charges are equal.
Elements, Atoms, and Ions Atoms of chemically reactive elements such as sodium and chlorine
Chemists represent each element, a substance that cannot be broken down can easily lose or gain negatively charged particles, or electrons. When an
into another substance, by a symbol—for example, O for oxygen, C for car- atom gives up electrons, it becomes positively charged; when it takes on
bon, and H for hydrogen. The 10 elements listed below in the table Chemi- extra electrons, it becomes negatively charged, as illustrated in part B of
cal Composition of the Brain constitute virtually the entire makeup of an Ion Formation. Either way, the charged atom is now an ion. Ions’ positive
average living cell. Many other elements are vital to the cell but present only or negative charges allow them to interact. This property is central to cell
in minute quantities. function.
chemical composition of the Brain
percentage element name, atomic structure percentage element name, atomic structure
of weight symbol (not to scale) of weight symbol (not to scale)
– –
– – – – –
65.0 Oxygen, O – –
–
– – – – – –
–
Together, – –
oxygen, – 0.4 Potassium, K –
– – – –
carbon, and – –
18.5 Carbon, C – –
hydrogen –
– – –
account for
more than 90
percent of a 9.5 Hydrogen, H Some symbols
– –
cell’s makeup. – – derive from an
– – – – – element’s Latin
– 0.2 Sulfur, S –– –– name—K for
3.5 Nitrogen, N – – – – –
– – – kalium (Latin
– – for potassium)
and Na for
– natrium (Latin
– –
– – – – for sodium),
– – – – for example.
– – –
1.5 Calcium, Ca – – – – – –
– 0.2 Sodium, Na
– – – – –
– –
– – –
–
– –– –
– – –– – – –
– – – – –– –
1.0 Phosphorus, P 0.2 Chlorine, Cl
– – – –– –
– – – – – –
–
ions critical to neuronal communication
Na1 Sodium
Ions formed by loss of electrons are represented by an
element’s symbol followed by one or more plus signs. K1 Potassium
Ca21 Calcium
Ions formed by gain of electrons are represented by
an element’s symbol followed by a minus sign. Cl2
Chloride
3-2 • Internal Structure of a Cell 89
Ion Formation Chemistry of Water
(A) Atoms (A) Water molecule (B) Hydrogen bonds
Total positive (+) and negative (–) charges in atoms Two hydrogen atoms share electrons Hydrogen bonds
are equal. The nucleus contains neutrons (no unequally with one oxygen atom, join water molecules
+
charge) and protons (positive charge). Orbiting the creating a polar water molecule + to a maximum of
nucleus are electrons (negative charge). –
positively charged on the hydrogen four partners.
end and negatively charged on the
– – oxygen end.
Outer orbit contains Outer orbit – – H H H
7 electrons – contains
– – – – – – H O + –
– – 1 electron – – H H
– – –– – +
–– – – –
– – – – –– – +
– – – + –
– – – – + +
Cl atoms have 17 protons Na atoms have 11 protons – – – –
– – –
and 17 electrons. and 11 electrons. –
– – O
(B) Ions O H2O H+ and O2– ions in each water molecule are
attracted to nearby water molecules.
The outer orbit gains The outer orbit
an electron. disappears
because it lost its
– only electron.
– – – – Because water molecules are polar, they are attracted to other elec-
– – – – trically charged substances and to one another. Part B of Chemistry of
– –
– – Water illustrates this attracting force, called a hydrogen bond. Hydrogen
– – – –
– –
– – bonding enables water to dissolve electrically neutral salt crystals into
– – – – – their component ions. Salts thus cannot retain their shape in water: they
–
– dissolve. As illustrated in the figure Salty Water, the polar water mol-
Charged chloride ion (Cl–) Charged sodium ion (Na+) ecules muscle their way into the Na1 and Cl2 lattice, surrounding and
separating the ions.
Essentially, it is salty water that bathes our brain cells, provides the
medium for their activities, supports their communications, and constitutes
the brain’s CSF. Sodium chloride and many other dissolved salts, including
KCl (potassium chloride) and CaCl2 (calcium chloride) are among the con-
stituents of the brain’s salty water.
Molecules: Salts and Water
Salt crystals form bonds via the electrical attraction between ions. The for-
mula for table salt, NaCl (sodium chloride), means that this molecule con- Salty Water
sists of one sodium ion and one chloride ion. KCl, the formula for the salt
potassium chloride, is composed of one potassium ion (K1) and one chloride Negative Cl– ions attract the positive
ion (Cl2). poles of water molecules. Positive
Atoms bind together to form molecules, the smallest units of a substance Na+ ions attract the negative poles
that contain all of its properties. A water molecule (H2O) is the smallest unit Salt (NaCl) of water molecules.
of water that retains the properties of water. Breaking down water any fur- –
+
ther would release its component elements, the gases hydrogen and oxygen. + + +
The symbol H2O indicates that a water molecule is the union of two hydro- –
Water (H2O) –
gen atoms and one oxygen atom. +
– +
Ionic bonds hold salt molecules together, but the atoms of water mole- – – –
+
cules share electrons and electron sharing is not equal: H electrons spend + + +
– + –
more time orbiting the O atom than orbiting each H atom. As shown + + +
–
above in part A of Chemistry of Water, this structure gives the oxygen + + +
Polar water molecules + – – –
+ +
region of the water molecule a slight negative charge and leaves the hy- surround Na+ and Cl– +
– + – +
drogen regions with a slight positive charge. Like atoms, most molecules ions in a salt crystal, + + +
are electrically neutral, but water is polar: it carries opposite charges on dissolving it. – + –
opposite ends, just as Earth does at the North and South Poles. –
90 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
Although neurons and glia appear to be packed tightly together, like all cells, they are
In the CNS, the extracellular fluid is CSF. separated by extracellular fluid composed mainly of water with dissolved salts and many
other chemicals. A similar intracellular fluid is found inside a cell. What’s important is the
cell membrane’s relative impermeability, which ensures that concentrations of substances
inside and outside the cell are different.
Within the cell shown in Figure 3-10 are membranes that surround its organelles, similar to
the work areas demarcated by a factory’s interior walls. Each organelle membrane is also rela-
tively impermeable and so concentrates needed chemicals while keeping out unneeded ones.
The prominent nuclear membrane surrounds the cell’s nucleus. Within the nucleus the
genetic blueprints for the cell’s proteins are stored, copied, then sent to the “ factory floor,”
the endoplasmic reticulum. The ER is an extension of the nuclear membrane, and here the
cell’s protein products are assembled in accordance with instructions from the nucleus. Once
those proteins are assembled, many are packaged and sent throughout the cell. The Golgi
bodies are “mailrooms,” where proteins are wrapped, addressed, and shipped.
Other cell components are tubules of several kinds. Some (microfilaments) reinforce the
cell’s structure; others aid in the cell’s movements. Still others (microtubules) form the trans-
portation network that carries proteins to their destinations, much as roads allow a factory’s
trucks and forklifts to deliver goods to their destinations.
Two other important parts of the cellular factory shown in Figure 3-10 are the mitochondria
(sing. mitochondrion), the cell’s power plants, which supply its energy needs, and lysosomes,
vesicles that transport incoming supplies and remove and store wastes. Interestingly, more
lysosomes are found in old cells than in young ones. Cells apparently have trouble disposing
of all of their garbage, just as societies do.
Cell Membrane: Barrier and Gatekeeper
The cell membrane separates the intracellular from the extracellular fluid, allowing
the cell to function as an independent unit. The membrane’s double-layered structure,
shown in Figure 3-11A, regulates the movement of substances into and out of the cell.
Cell (B) Representation of a (C) Space-filling model of phospholipid
membrane phospholipid molecule molecular structure
+ +
The hydrophilic
head has –
polar regions. –
(A) Phospholipid bilayer The phosphate
groups will bind
The cell membrane is a to water.
phospholipid bilayer Extracellular fluid
that separates
extracellular fluid Fatty acid tails
(outside the cell)… have no binding
The hydrophobic
sites for water.
tails have no
polar regions.
…from intracellular Intracellular fluid
fluid (inside the cell).
FIGUre 3-11 Bilayer Cell Membrane Structure (A) Double-layered cell membrane
close up. (B) Detail of a phospholipid molecule’s polar head and electrically neutral tails.
(c) Space-filling model shows why the phosphate head’s polar regions (positive and negative
poles) are hydrophilic, whereas its nonpolar fatty acid tail is hydrophobic.
3-2 • Internal Structure of a Cell 91
One regulated substance is water. If too much water enters a cell, it will burst; if too
gene DNA segment that encodes the
much water leaves a cell, it will shrivel. The cell membrane’s structure helps ensure that
synthesis of a particular protein.
neither happens.
The cell membrane also regulates the differing concentrations of salts and other chemi-
cals on its inner and outer sides. This regulation is important because, if its concentrations
of chemicals are unbalanced, the cell will not function normally. What properties of a cell
membrane allow it to regulate water and salt concentrations? One property is its special
molecular construction. These molecules, called phospholipids, are named for their struc-
ture, shown close up in Figure 3-11B.
Figure 3-11C shows a space-filling chemical model of the phospholipid molecule’s
structure. The molecule has a head containing the element phosphorus (P) bound to
some other atoms, and it has two tails, which are lipids, or fat molecules. The head has
a polar electrical charge, with a positive charge in one location and a negative charge
in another, as do water molecules. The tails consist of hydrogen and carbon atoms that
tightly bind to one another by their shared electrons; hence, the fatty tail has no polar
regions.
The polar head and the nonpolar tails are the underlying reasons that a phospholipid
molecule can form cell membranes. The heads are hydrophilic (Greek hydro, meaning water,
and philia, meaning love) and so are attracted to one another and to polar water molecules.
The nonpolar lipid tails have no such attraction for water. They are hydrophobic, or water
hating (from the Greek word phobia, meaning fear).
Quite literally, then, the head of a phospholipid loves water and the tails hate it. To avoid
water, the tails of phospholipid molecules point toward each other, and the hydrophilic heads
align with one another and point outward to the watery intracellular and extracellular fluid.
In this way, the cell membrane consists of a bilayer (two layers) of phospholipid molecules
(see Figure 3-11A).
The bilayer cell membrane is flexible even as it forms a formidable barrier to a wide
variety of substances. It is impenetrable to intracellular and extracellular water, because
polar water molecules cannot pass through the hydrophobic tails on the membrane’s inte-
FIGUre 3-12 Chromosome The
rior. Ions in the extracellular and intracellular fluid also cannot penetrate this membrane,
nerve cell’s nucleus contains paired
because they carry charges and thus cannot pass by the polar phospholipid heads. In fact,
chromosomes of double-stranded DNA
only a few small molecules, such as oxygen (O2), carbon dioxide (CO2), and the sugar glucose, molecules bound together by a sequence
can traverse a phospholipid bilayer. of nucleotide bases.
Chromosome
The Nucleus and Protein Each chromosome is
a double-stranded
Synthesis molecule of DNA.
In our factory analogy, the nucleus is the cell’s executive DNA
office, where the blueprints for making proteins are stored,
copied, and sent to the factory floor. These blueprints are
called genes, segments of DNA that encode the synthesis of
particular proteins. Genes are contained within the chromo-
somes, the double-helix structures that hold an organism’s
AC
entire DNA library. T G
The chromosomes have been likened to a book of blueprints. Each chromosome con-
tains thousands of genes. Each gene is the blueprint, or code, for making one protein. The
location of the chromosomes in the cell nucleus, the appearance of a chromosome, and the Adenine (A) binds
structure of the DNA within a chromosome are shown in Figure 3-12. with thymine (T).
This static picture of chromosomes does not represent the way they look in living cells. Guanine (G) binds
with cytosine (C).
Videos of the cell nucleus show that chromosomes are constantly changing shape and mov-
ing in relation to one another, jockeying to occupy the best locations within the nucleus.
92 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
Chromosome means colored body; they are so By changing shape, chromosomes expose different genes to the surrounding fluid, thus
named because chromosomes can be readily allowing the gene to begin the process of making a protein.
stained with certain dyes. A human somatic (body) cell has 23 pairs of chromosomes, or 46 chromosomes in all (in
contrast, the 23 chromosomes within a reproductive cell are not paired). Each chromosome
is a double-stranded molecule of deoxyribonucleic acid (DNA). The two strands of a DNA
molecule coil around each other, as shown in Figure 3-12.
Each strand possesses a variable sequence of four nucleotide bases, the constituent
molecules of the genetic code: adenine (A), thymine (T), guanine (G), and cytosine (C).
Adenine on one strand always pairs with thymine on the other, whereas guanine on one
strand always pairs with cytosine on the other. The two strands of the DNA helix are bound
together by the attraction between the two bases in each pair, as illustrated in Figure 3-12.
Sequences of hundreds of nucleotide bases within the chromosomes spell out the genetic
code. Scientists represent this code by the letters of the nucleotide bases, for example
ATGCCG and so forth.
A gene is a segment of a DNA strand. A gene’s code is its sequence of thousands of
nucleotide bases. Much as a sequence of letters spells out a word, the sequence of ACTG
base pairs spells out the order in which amino acids, the constituent molecules of proteins,
should be assembled to construct a certain protein. To begin to make a protein, the ap-
propriate gene segment of the DNA strands first unwinds to expose its bases. The exposed
sequence of nucleotide bases on one of the DNA strands then serves as a template to
attract free-floating molecules called nucleotides. The nucleotides, once attached, form
a complementary strand of ribonucleic acid (RNA), the single-stranded nucleic acid mol-
ecule required for protein synthesis. This process, called transcription, is shown in steps
1 and 2 of Figure 3-13. (To transcribe means to copy, as in copying part of a message you
receive in a text.)
Nucleus 1 DNA uncoils to expose
Gene
Nucleus a gene, a sequence of
nucleotide bases that
Endoplasmic encodes a protein.
reticulum
DNA mRNA
2 One strand of the gene
serves as a template for
Endoplasmic
reticulum transcribing a molecule
of mRNA.
mRNA
Ribosomes
3 The mRNA leaves the
nucleus and comes in
contact with ribosomes
in the endoplasmic
reticulum.
mRNA
Amino 4 As a ribosome moves
acid along the mRNA, it
translates the bases into
a specific amino acid
Ribosome
Protein chain, which
forms the protein.
protein Folded-up polypeptide chain that FIGUre 3-13 Protein Synthesis Information in a cell flows from DNA to mRNA to protein
serves a particular function in the body. (peptide chain).
3-2 • Internal Structure of a Cell 93
The Endoplasmic Reticulum and Protein Template strand
Manufacture DNA
G C C A A A C C G A G T
C G G T T T G G C T C A
RNA produced through transcription is much like a single strand of DNA except that the
base uracil (U), which also is attracted to adenine, takes the place of thymine. The tran-
TRANSCRIPTION
scribed strand of RNA is called messenger RNA (mRNA) because it carries the protein
code (the message) out of the nucleus to the endoplasmic reticulum, where proteins are
manufactured. mRNA C G G U U U G G C U C A
Steps 3 and 4 in Figure 3-13 show that the ER consists of membranous sheets folded to
Codon
form numerous channels. A distinguishing feature of the ER is that it may be studded with
TRANSLATION
ribosomes, protein structures that act as catalysts to facilitate the building of proteins. When
an mRNA molecule reaches the ER, it passes through a ribosome, where its genetic code is
Polypeptide
read. In this process of translation, a particular sequence of nucleotide bases in the mRNA Arg Phe Gly Ser
chain
is transformed into a particular sequence of amino acids. Transfer RNA (tRNA) assists in Amino acids
translating nucleotide bases into amino acids.
FIGUre 3-14 Transcription and
As shown in Figure 3-14, each group of three consecutive nucleotide bases along an
Translation In protein synthesis (see
mRNA molecule encodes one particular amino acid. These sequences of three bases are Figure 3-13), a particular sequence of
called codons. For example, the codon uracil, guanine, guanine (UGG) encodes the amino nucleotide bases in a strand of DNA (top)
acid tryptophan (Trp), whereas the codon uracil, uracil, uracil (UUU) encodes the amino acid is transcribed into mRNA (center). Each
phenylalanine (Phe). The sequence of codons on the mRNA strand determines the sequence sequence of three nucleotide bases in the
mRNA strand (a codon) encodes one amino
of the resulting amino acid chain.
acid. In translation, the amino acids, directed
Humans utilize 20 different amino acids, all structurally similar, as illustrated in by the codons, link together to form a
Figure 3-15A. Each consists of a central carbon atom (C) bound to a hydrogen atom (H), polypeptide chain (bottom). The amino acids
an amino group (NH31), a carboxyl group (COO2), and a side chain (represented by the are tryptophan (Trp), phenylalanine (Phe),
letter R). The side chain varies in chemical composition from one amino acid to another. glycine (Gly), and serine (Ser).
Each amino group (NH31) is bound to the carboxyl group (COO2) of the adjacent amino
(A) Amino acid structure
acid by a peptide bond, which gives amino acid chains their alternative name, polypeptide
chain (Figure 3-15B). The chemical
Just as a remarkable number of words can be made from the 26 letters of the English composition
of the R group
alphabet, a remarkable number of polypeptide (meaning many peptides) chains can be made distinguishes one
from the 20 amino acids. These amino acids can form 400 (20 3 20) dipeptides (two-peptide amino acid from
combinations), 8000 (20 3 20 3 20) tripeptides (three-peptide combinations), and almost another.
countless polypeptides.
In summary, the information flow driven by the genetic code is conceptually quite simple:
R
a gene (portion of a DNA strand) is transcribed into a strand of mRNA, and ribosomes
NH 3+
C COO–
translate the mRNA into a molecular chain of amino acids, a polypeptide chain. Thus the
Amino H Carboxyl
sequence of events in building a protein:
group group
DNA S mRNA S protein
(B) Polypeptide chain
Proteins: The Cell’s Product Peptide
A chain of amino acids
forms a protein.
A polypeptide chain and a protein are related, but they are not the same. The relation is bond
analogous to the relation between a length of ribbon and a bow that can be made from the
ribbon. Long polypeptide chains have a strong tendency to twist into a helix (a spiral) or to
form pleated sheets, which in turn have a strong tendency to fold together to form more
complex shapes, as shown in Figure 3-16. A protein is a folded-up polypeptide chain that
serves a particular function in the body. Properties of Amino
FIGUre 3-15
Any one neuron contains as many as 20,000 genes, and it can, in principle, produce as Acids (A) Each amino acid consists
of a central carbon atom (C) attached to
many as 20,000 different protein molecules. The number of proteins that can ultimately be
an amine group (NH31), a carboxyl group
produced by a neuron is far larger than the number of its genes, however. Although each (COO2), and a distinguishing side chain (R).
gene codes for one protein, a protein can be cleaved into pieces—by enzymes, for example— (B) The amino acids are linked by peptide
or combined with other proteins in a variety of cellular processes to form still other proteins. bonds to form a polypeptide chain.
94 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
Primary structure Secondary structures Tertiary structure Quaternary structure
Pleated sheet Helix
Amino acid …form pleated sheets Sheets and helices fold A number of proteins combine to
chains… or helices. to form a protein. form a more complex protein.
Four Levels of Protein
FIGUre 3-16
Structure Whether a polypeptide chain
A protein’s shape and its ability to change shape and to combine with other proteins are
forms a pleated sheet or a helix and what
its three-dimensional shape ultimately central to its function. Through their shapes and changes in shape, proteins can combine
will be are determined by the amino acid with other proteins in chemical reactions. They can modify the length and shape of other
sequence in the primary structure. In rare proteins and so act as enzymes. Proteins embedded in a cell membrane form passageways
circumstances, prion proteins can misfold called channels, gates, and pumps that regulate the flow of substances through the mem-
and wreak havoc; see Section 16-3.
brane. And proteins can be exported through the axon terminal to travel to other cells and
so act as messenger molecules.
Golgi Bodies and Microtubules: Protein
Packaging and Shipment
Getting proteins to the right destination is the task of cellular components that package,
label, and ship them. These components operate much like a postal or shipping service.
To reach their appropriate destinations, protein molecules that have been synthesized
in the cell are wrapped in membranes and marked with addresses to indicate where they
are to go. This wrapping and labeling take place in the organelles called Golgi bodies. The
packaged proteins are then loaded onto motor molecules that move along the many micro-
tubules radiating through the cell, carrying each protein to its destination. Protein export is
illustrated in Figure 3-17.
If a protein is destined to remain within the cell, it is unloaded into the intracellular fluid.
If it is to be incorporated into the cell membrane, it is carried to the membrane, where it
inserts itself. Some proteins are expelled from the cell. In this process, called exocytosis, the
membrane, or vesicle, in which the protein is wrapped fuses with the cell membrane, and
the protein is excreted into the extracellular fluid. The roles proteins play when embedded
1 Proteins formed in the ER enter 2 Each protein package is 3 A protein may
the Golgi bodies, where they are attached to a motor molecule be incorporated
wrapped in a membrane and and moves along a into the
given a shipping address. microtubule to its destination. membrane,…
4 …remain
within the cell
Vesicle to act as an
Nucleus enzyme,...
FIGUre 3-17 Protein
Export Exporting
a protein entails Microtubule 5 …or be
Golgi bodies excreted
packaging, transport, Endoplasmic reticulum from the cell
and assigning its fate
by exocytosis.
at the destination.
3-2 • Internal Structure of a Cell 95
in the cell membrane or exported from the cell are central to understanding how neurons Protein
process information and determine behavior. Glucose
molecule
Receptor
Crossing the Cell Membrane: Channels, site
Gates, and Pumps
Proteins embedded in the cell membrane serve many functions. One is transporting
substances across the membrane. We now consider how three such membrane proteins—
channels, gates, and pumps—perform the transport function. In each case, the particular
Protein has a receptor
protein’s function is an emergent property of its shape. site for glucose.
A protein’s shape and its ability to change shape both derive from the precise amino acid
sequence that composes the protein molecule. Some proteins change shape when other
chemicals bind to them; others change shape as a function of temperature; and still others Glucose bound
to receptor
change shape in response to changes in electrical charge. The protein molecule’s ability to site
change shape is analogous to a lock in a door. When a key of the appropriate size and shape
is inserted into the lock and turned, the locking device activates and changes shape, allowing
the door to be closed or opened.
Such a shape-changing protein is illustrated in Figure 3-18. The surface of this protein
molecule has a groove, called a receptor, analogous to a keyhole. Small molecules, such as
glucose, or other proteins can bind to a protein’s receptors and cause the protein to change
shape. Changes in shape allow the proteins to serve some new function.
Protein changes shape
Some membrane proteins form channels through which substances can pass. Different- when glucose docks
sized channels regulate the passage of different-sized substances. Figure 3-19A illustrates a with the receptor.
protein with a particular shape forming a channel large enough to pass potassium (K1) but
not other ions. Other protein channels allow sodium ions or chloride ions to pass into or out FIGUre 3-18 Receptor Binding When
of the cell. Still others allow the passage of various other substances. substances bind to a protein’s receptors,
the protein changes shape, which may
Figure 3-19B shows a protein molecule that acts as a gate to regulate the passage of sub-
change its function.
stances. Like the protein in Figure 3-18, gates change their shape in response to some trigger.
The protein allows substances to pass through when its shape forms a channel and prevents
passage when its shape leaves the channel closed.
Changes in protein shape can also allow it to act as a pump. Figure 3-19C shows a protein channel Opening in a protein embedded in
that changes its shape to pump Na1 and K1 across the membrane, exchanging the Na1 on the cell membrane that allows the passage
of ions.
one side for the K1 on the other.
Channels, gates, and pumps play an important role in allowing substances to enter and gate Protein embedded in a cell membrane
leave a cell. This passage of substances is critical in explaining how neurons send messages. that allows substances to pass through the
Chapter 4 explores how neurons use electrical activity to communicate. membrane on some occasions but not on
others.
pump Protein in the cell membrane that
(A) Channel (B) Gated channel (C) Pump actively transports a substance across the
Gates open Gate closed Extracellular fluid membrane.
K+ Na+
K+ Na+
Intracellular fluid
Na+ K+
Ions can cross a A gated channel …and to prevent A pump …to carry
cell membrane changes shape to passage when transporter substances
through the allow the passage one or both changes across a cell FIGUre 3-19 Transmembrane
appropriately of substances gates are closed. shape… membrane.
Proteins Channels, gates, and pumps
shaped when gates are
are proteins embedded in the cell
channel. open…
membrane.
96 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
3-2 revIew
Internal Structure of a Cell
Before you continue, check your understanding.
1. The constituent parts of the cell include the , , ,
, , and .
2. The product of the cell is . They serve many functions, including acting
at the cell membrane as , , and to regulate
movement of substances across the membrane.
3. The basic sequence of events in building a protein is that makes
makes .
4. Once proteins are formed in the , they are wrapped in membranes by
and transported by to their designated sites in the neuron or
its membrane or exported from the cell by .
5. Why is a cell more than a protein factory?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
3-3 Genes, Cells, and Behavior
Your genotype (genetic makeup) influences your physical and behavioral traits, which com-
bine to form your phenotype (individual characteristics). Genetic analysis conducted by the
Human Genome Project has cataloged the human genome—all 20,000 or so genes in our
species—and today individual genomes are routinely sequenced. (Recall the Beery twins
in Research Focus 3-1.) James Watson, the codiscoverer of DNA, was the first to have his
genome sequenced.
Researchers have succeeded in sequencing the long-extinct Neanderthal genome as well.
The genomes of James Watson and the Neanderthal are surprisingly similar, as you’d expect for
close hominid relatives. You can have your genome sequenced to reveal many aspects of its cod-
Figure 1-12 shows how a Neanderthal woman ing functions, including your relationship to Neanderthals. The cost is about $100. (Before you
might have looked. decide, you may want to check on any required information sharing with employers and insurers.)
Studying how genes influence our traits is the objective of Mendelian genetics, named for
Gregor Mendel, whose research led to the concept of the gene. Studying how the environ-
ment influences gene expression is the objective of epigenetics. In this section we describe
how both factors influence our phenotypes.
Mendelian Genetics and the Genetic Code
The nucleus of each human somatic cell contains 23 pairs of chromosomes, or 46 in all. One
member of each pair comes from the mother, and the other member comes from the father.
The chromosome pairs are numbered from 1 to 23, roughly according to size, with chromo-
some 1 being the largest (Figure 3-20).
Chromosome pairs 1 through 22 are called autosomes, and they contain the genes that
contribute most to our physical appearance and behavior. The twenty-third pair are the sex
chromosomes, which contribute to our physical and behavioral sexual characteristics. The
two mammalian sex chromosomes are referred to as X and Y because of their appearance,
shown at the right in Figure 3-20. Ordinarily, female mammals have two X chromosomes,
whereas males have an X and a Y.
Because all but your sex chromosomes are matched pairs, each cell contains two copies
of every gene, one inherited from your mother, the other from your father. These two copies
3-3 • Genes, Cells, and Behavior 97
Nucleus FIGUre 3-20 Human Chromosomes
The nucleus of a human cell contains
23 chromosomes derived from the
father and 23 from the mother. Sexual
CNRI/Science Photo Library/
characteristics are determined by the
twenty-third pair, the X and Y (sex)
chromosomes.
Science Source
x y
of a gene are called alleles. The term matched here does not necessarily mean identical.
The nucleotide sequences in a pair of alleles may be either identical or different. If they are
identical, the two alleles are homozygous (homo- means the same). If they are different, the
two alleles are heterozygous (hetero- means different).
The nucleotide sequence most common in a population is called the wild-type allele,
whereas a less frequently occurring sequence is called a mutation. Any wild-type allele may
have a number of mutations, some beneficial, some neutral and some harmful.
Dominant and Recessive Alleles
If both alleles in a gene pair are homozygous, the two encode the same protein, but if the
two alleles in a pair are heterozygous, they encode somewhat different proteins. Three pos-
sible outcomes attend the heterozygous condition when these proteins express a physical or
behavioral trait: (1) only the allele from the mother may be expressed, (2) only the allele from
the father may be expressed, or (3) both alleles may be expressed simultaneously.
A member of a gene pair that is routinely expressed as a trait is called a dominant allele; a
unexpressed allele is recessive. Alleles can vary considerably in their dominance. In complete
dominance, only the allele’s own trait is expressed in the phenotype. In incomplete domi-
nance, the allele’s own trait is expressed only partially. In codominance, both the allele’s own
trait and that of the other allele in the gene pair are expressed completely.
Each gene makes an independent contribution to the offspring’s inheritance, even though
the contribution may not always be visible in the offspring’s phenotype. When paired with
a dominant allele, a recessive allele is often not expressed. Still, it can be passed on to future
generations and influence their phenotypes when not masked by the influence of some
dominant trait.
Genetic Mutations
The mechanism described in Section 3-2 for reproducing genes and passing them on to
offspring is fallible. Errors can arise in the nucleotide sequence when reproductive cells
make gene copies. The altered alleles are mutations.
A mutation may be as small as a change in a single nucleotide base, or single nucleotide
polymorphism (SNP, pronounced snip). This one base change results in a change in a codon
and a resulting change in one amino acid in a protein. A single amino acid change is a muta-
tion and is often sufficient to alter the protein’s function.
allele Alternative form of a gene; a gene pair
Because the average gene has more than 1200 nucleotide bases, an enormous number of
contains two alleles.
SNPs as well as more complex losses and changes in bases can occur on a single gene. For
example, the BRCA1 (breast cancer) gene, found on chromosome 17, is a caretaker gene that homozygous Having two identical alleles for
contributes to preventing breast cancer and other cancers in both men and women. More a trait.
than 1000 mutations of this gene have already been found. Thus, in principle, there are more heterozygous Having two different alleles
than 1000 ways in which to inherit a predisposition to a cancer just from this gene. for the same trait.
A mutation in a nucleotide or the addition of a nucleotide to a gene sequence can be bene- mutation Alteration of an allele that yields a
ficial or disruptive or both. For example, a SNP in which a T base is substituted for an A base different version of its protein.
98 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
in the HBB (hemoglobin) gene on chromosome 11 causes sickle-cell anemia, a condition in
which blood cells take on an abnormal sickle shape. The sickle shape offers some protection
against malaria, but sickle cells also have poor oxygen-carrying capacity, which weakens the
person who possesses them. Sickle-cell anemia is the most common genetic blood disease,
affecting millions of people worldwide, including 80,000 people in the United States.
Al Lamme/Phototake
Each of us carries a surprisingly large number of genetic mutations. Because of cell divi-
sion, different mutations may be localized in different parts of our body and brain and may
contribute to individual variations in our organs, including the brain (Charney, 2012). While
mutations may be beneficial or seemingly neutral to the functioning of the organism that
In this micrograph a sickle cell is surrounded carries them, most mutations have negative effects. If not lethal, they produce in their car-
by healthy blood cells. rier debilitating physical and behavioral abnormalities.
Neuroscientists cannot yet explain human behavior in relation to genes and neurons, but
we know the severe behavioral consequences of about 2000 genetic abnormalities that affect
the nervous system. For example, an error in a gene could produce a protein that should be
an ion channel but will not allow the appropriate substance to pass. It may produce a pump
that will not pump or a protein that the cell’s transportation system refuses to transport.
Applying Mendel’s Principles
Experiment 1-1 describes one of Mendel’s Gregor Mendel introduced the concept of dominant and recessive alleles in the nineteenth
experiments. century, when he studied pea plants. Today, scientists study genetic variation to gain insight
into how genes, neurons, and behaviors are linked. This knowledge is directed toward
explaining healthy behavior and helping reduce the negative effects of genetic abnormali-
ties, perhaps someday even eliminating them.
Allele Disorders That Affect the Brain
Some disorders caused by mutant genes illustrate Mendel’s principles of dominant and
Scientists Warren Tay and Bernard Sachs recessive alleles. One is Tay-Sachs disease, caused by a dysfunctional protein that acts as
first described the disorder. the enzyme HexA (hexosaminidase A). The outcome is that it fails to break down a class of
lipids (fats) in the brain.
Symptoms usually appear a few months after birth and rarely at later ages. The baby
begins to have seizures, deteriorating eyesight, and degenerating motor and mental abilities.
Inevitably, the child dies within a few years. Tay-Sachs mutations appear with high frequency
among certain ethnic groups, including Jews of European origin and French Canadians, but
the mutation in different populations can be different.
The dysfunctional Tay-Sachs HexA enzyme is caused by a recessive allele of the HEXA
(hexosaminidase) gene on chromosome 15. Distinctive inheritance patterns result from reces-
sive alleles, because two copies (one from the mother and one from the father) are needed
for the disorder to develop. A baby can inherit Tay-Sachs disease only when both parents
carry the recessive allele. However, a number of causative alleles exist, and even inheriting
different mutant alleles, one from each parent, can cause Tay-Sachs disease.
Because both parents have survived to adulthood, both must also possess a correspond-
tay-sachs disease Inherited birth defect ing dominant wild-type HEXA allele for that particular gene pair. The egg and sperm cells
caused by the loss of genes that encode the produced by this man and woman will therefore contain a copy of the wild type or the
enzyme necessary for breaking down certain mutation of these two alleles. Which allele is passed on is determined completely by chance.
fatty substances; appears 4 to 6 months In any child born of two Tay-Sachs carriers, then, this situation gives rise to three possible
after birth and results in intellectual disability, gene combinations, as shown in Figure 3-21A. The child may have two wild-type alleles, in
physical changes, and death by about age 5. which case he or she will be spared the disorder and cannot pass it on. The child may have one
wild type Typical allele (most common in a normal and one Tay-Sachs allele, in which case he or she, like the parents, will be a carrier.
population). Or the child may have two Tay-Sachs alleles, in which case he or she will develop the disease.
Huntington disease Hereditary disease The chance of a child of two carriers being normal is 25 percent, the chance of being a
characterized by chorea (ceaseless carrier is 50 percent, and the chance of having Tay-Sachs disease is 25 percent. If one parent
involuntary jerky movements) and is a Tay-Sachs carrier and the other is normal, any child has a 50-50 chance being normal or
progressive dementia, ending in death. a carrier. Such a couple has no chance of conceiving a baby with Tay-Sachs disease.
3-3 • Genes, Cells, and Behavior 99
(A) Recessive gene carries Tay-Sachs allele (B) Dominant gene carries Huntington’s allele
Parents Parents Parents Parents
huntingtin
HexA Normal allele
Normal
allele allele
allele
= = = =
Carrier Normal Carrier Carrier Carrier Normal Carrier Carrier
Two copies required Only one copy required
to exhibit trait to exhibit trait
Offspring Offspring Offspring Offspring
Carrier Normal Tay-Sachs Normal Huntington’s Huntington’s Huntington’s Huntington’s
Carrier Normal Carrier Carrier Normal Normal Normal Huntington’s
FIGUre 3-21 Inheritance Patterns
(A) Recessive condition: If a parent has
one mutant allele, the parent will not show
The Tay-Sachs allele operates independently of the dominant allele. As a result, it still pro- symptoms of the disease but will be a
duces the defective HexA enzyme, so the person who carries it has a higher than normal lipid carrier. If both parents carry a mutant
accumulation in the brain. Because this person also has a normal allele that produces a func- allele, each of their offspring stands a 25
tional enzyme, the abnormal lipid accumulation is not enough to cause Tay-Sachs disease. percent chance of developing the disease.
Fortunately, a blood test can detect whether a person carries the Tay-Sachs allele. People (B) Dominant condition: A person with a
single allele will develop the disease. If this
who find that they are carriers can make informed decisions about conceiving children. If
person mates with a noncarrier, offspring
they avoid having children with another Tay-Sachs carrier, none of their children will have have a 50-50 chance of developing the
the disorder, although some will probably be carriers. Where genetic counseling has been disease. If both parents are carriers, both
effective, the disease has been eliminated. will develop the disease, and offspring
The normal dominant allele that a carrier of Tay-Sachs possesses produces enough have a 75 percent chance of developing it.
functional enzyme to enable the brain to operate in a satisfactory way. That would not be
the case if the normal allele were recessive, however, as happens with the genetic disorder
Huntington disease. Here, the buildup of an abnormal version of the huntingtin protein kills
brain cells, especially in the basal ganglia and the cortex.
Symptoms can begin at any time from infancy to old age, but they most often start in
midlife and include abnormal involuntary movements, which is why the disorder was once
called a chorea (from the Greek meaning dance). Other symptoms are memory loss and even-
tually a complete deterioration of behavior, followed by death. The abnormal HTT (hunting-
tin) allele is dominant, the recessive allele normal, so only one defective allele is needed to
cause the disease.
Figure 3-21B illustrates the inheritance patterns associated with a dominant allele on
chromosome 4 that produces Huntington disease. If one parent carries the defective allele,
offspring have a 50 percent chance of inheriting the disorder. If both parents have the
defective allele, the chance of inheritance increases to 75 percent. As discussed further in
Clinical Focus 3-4, Huntington Disease, on page 100, because the abnormal huntingtin allele
usually is not expressed until midlife, after the people who possess it have had children, it is
passed down even though it is lethal.
As with the allele causing Tay-Sachs disease, a genetic test can determine whether a
person carries the allele that causes Huntington disease. If so, the person can elect not
to procreate. A decision not to have children in this case will reduce the incidence of the
abnormal huntingtin allele in the human gene pool.
100 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
clinical F cus 3-4
Huntington Disease
Woody Guthrie, whose protest songs made him a spokesman for farm non-Europeans have fewer repeats than do Europeans, among whom
workers during the Great Depression of the 1930s, is revered among the the disease is more common. The number of repeats can also increase
founders of American folk music. His best-known song is “This Land Is with transmission from the father but not from the mother.
Your Land.” Singer and songwriter Bob Dylan was instrumental in reviv- Investigations into why brain cells change in Huntington disease and
ing Guthrie’s popularity in the 1960s. into potential treatments use transgenic animal models. Mice, rats, and
Guthrie died in 1967 after struggling with what was eventually diag- monkeys that have received the HTT gene feature the abnormal hunting-
nosed as Huntington disease. His mother had died of a similar condition, tin protein and display symptoms of Huntington disease (Gu et al., 2015).
although her illness was never diagnosed. Two of Guthrie’s five children
from two marriages developed the disease, and his second wife, Marjo-
rie, became active in promoting its study.
Huntington disease is devastating, characterized by memory
impairment; choreas (abnormal, uncontrollable movements); and marked
changes in personality, eventually leading to nearly total loss of healthy
behavioral, emotional, and intellectual functioning. Even before the onset
of motor symptoms, Huntington disease impairs theory of mind, a per-
son’s ability to assess the behavior of others (Eddy and Rickards, 2015).
The symptoms of Huntington disease result from neuronal degenera-
tion in the basal ganglia and cortex. Symptoms can appear at any age but
typically start in midlife. In 1983, the HTT (huntingtin) gene responsible for
forming the abnormal huntingtin protein was found on chromosome 4.
The HTT gene has been a source of insights into the transmission
of genetic disorders. Part of the gene contains repeats of the base
sequence CAG. The CAG codon encodes the amino acid glutamine. If the
© MixPix/Alamy
number of CAG repeats exceeds about 40, then the carrier, with 40 or
more glutamine amino acids in the huntingtin protein, has an increased
likelihood of Huntington symptoms.
As the number of CAG repeats increases, the onset of symptoms Woody Guthrie, whose unpublished lyrics and
occurs earlier in life, and the disease progresses more rapidly. Typically, artwork are archived at woodyguthrie.org.
Chromosome Abnormalities
Genetic disorders are not caused solely by single defective alleles. Some nervous system
disorders are caused by copy number variations, that is, aberrations in a part of a chromosome
or even an entire chromosome. Copy number variations are related to a variety of disorders,
including autism, schizophrenia, and learning disabilities. Often though, copy number varia-
tion has little obvious consequence or is beneficial. For example, humans average about
6 copies of the AMY1 (amylase) gene but may have as many as 15 copies. The gene is an
adaptation that improves the ability to digest starchy foods (Mimori et al., 2015).
One condition due to a change in chromosome number in humans is Down syndrome,
which affects approximately 1 in 700 children. Down syndrome is usually the result of an
extra copy of chromosome 21. One parent (usually the mother) passes on two copies of
chromosome 21 to the child rather than the normal single chromosome. Combining these
two with one chromosome from the other parent yields three chromosomes 21, an abnormal
number called a trisomy (Figure 3-22).
Although chromosome 21 is the smallest human chromosome, its trisomy can dramatically
alter a person’s phenotype. People with Down syndrome have characteristic facial features
and short stature. They are susceptible to heart defects, respiratory infections, and intellecutal
Down syndrome Chromosomal abnormality impairment. They are prone to developing leukemia and Alzheimer disease. Although people
resulting in intellecutal impairment and other with Down syndrome usually have a much shorter than normal life span, some live to middle
abnormalities, usually caused by an extra age or beyond. Improved educational opportunities for children with Down syndrome shows
chromosome 21. that they can learn to compensate greatly for their mental disabilities.
3-3 • Genes, Cells, and Behavior 101
Chromosome
FIGUre 3-22
Aberration Left: Down syndrome, also
known as trisomy 21, is caused by an extra
chromosome 21 (colored red, bottom row
at left). Right: Chris Burke, the first person
with Down syndrome to play a leading role,
on the television series Life Goes On in the
1990s, is now in his fifties. He performs as
a lead singer in a band.
© Everett Collection Inc/Alamy
BSIP/Getty Images
Genetic Engineering
Despite advances in understanding gene structure and function, the gap in understanding
how genes produce behavior remains wide. To investigate gene structure and behavior rela-
tions, geneticists have invented methods to influence the traits genes express. This approach
collectively defines the science of genetic engineering. In its simplest forms, genetic engineer-
ing entails manipulating a genome, removing a gene from a genome, or modifying or adding
a gene to the genome. Its techniques include selective breeding, cloning, and transgenics.
Selective Breeding
The oldest means of influencing genetic traits is the selective breeding of animals and plants.
Beginning with the domestication of wolves into dogs more than 30,000 years ago, humans
have domesticated many animal species by selectively breeding males and females that dis-
play particular traits. The selective breeding of dogs, for example, has produced the species
with the most diverse traits of all animal species: breeds that can run fast, haul heavy loads,
retrieve prey, dig for burrowing animals, climb rocky cliffs in search of sea birds, herd sheep
and cattle, or sit on an owner’s lap and cuddle. Selective breeding especially influences dogs’
sociability with humans (Persson et al., 2015).
Maintaining spontaneous mutations is one objective of selective breeding. Using this
method, researchers produce whole populations of animals possessing some unusual trait
that originally arose as an unexpected mutation in only one individual or in a few animals.
In laboratory colonies of mice, for example, multiple spontaneous mutations have been dis-
covered and maintained to produce over 450 different mouse strains.
Some strains of mice make abnormal movements, such as reeling, staggering, and jump-
ing. Other strains have diseases of the immune system; others are blind or cannot hear. Some Unlike other animals, humans can consent
mice are smart; some mice are not; some have big brains;, some, small; and many display to experimental procedures. Section 7-7
distinctive behavioral traits. Many such genetic variations can also be found in humans. frames debates on the benefits and ethics
As a result, the neural and genetic bases of the altered behavior in the mice can be studied of conducting research using nonhuman
systematically to understand and treat human disorders. animals.
Cloning
More direct approaches to manipulating the expression of genetic traits include altering
early embryonic development. One such method is cloning—producing an offspring that is Sections 7-1 and 7-5 review genetic methods
genetically identical to another animal. used in neuroscience research.
102 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
To clone an animal, scientists begin with a cell nucleus containing DNA, usually from a
living animal donor, place it in an egg cell from which the nucleus has been removed, and
after stimulating the egg to start dividing, implant the new embryo in the uterus of a female.
Because each individual animal that develops from these cells is genetically identical to the
A team of researchers in Scotland cloned donor, clones can be used to preserve valuable traits, to study the relative influences of hered-
Dolly in 1996. As an adult, she mated and ity and environment, or to produce new tissue or organs for transplant to the donor. Dolly, a
bore a lamb. female sheep, was the first cloned mammal.
Cloning has matured from an experimental manipulation to a commercial enterprise.
The first horse to be cloned was Charmayne James’s horse Scamper, the mount she rode
to 11 world championships in barrel racing. The first cat to be cloned,
shown in Figure 3-23, was called Copycat. The first rare species cloned
was an Asian gaur, an animal related to the cow. Investigators anticipate
that cloning will be used to reanimate extinct animals, a process called
de-extinction. They propose using preserved cells from the extinct pas-
Photos used with permission from Texas A&M College of
senger pigeon or from frozen carcasses of the mastodon (an enclosure
to house a de-extinct mastodon has been prepared in Russia), an extinct
Veterinary Medicine & Biomedical Sciences.
elephant species, to clone those animals.
Transgenic Techniques
Transgenic technology enables scientists to introduce genes into an embryo
or remove genes from it. For example, introducing a new gene can enable
cows or goats to produce medicines in their milk. The medicines can be
extracted from the milk to treat human disease. Transgenic techniques
used to take a mouse gene that affords resistance to tuberculosis and insert
it into cows has increased their resistance to TB (Wu et al., 2015).
FIGUre 3-23 A Clone and Her Mom Chimeric animals are composites formed when an embryo of one
Copycat (left) and Rainbow (right), the cat
species receives cells from a different species. The resulting animal has cells with genes from
that donated the cell nucleus for cloning.
Although the cats’ genomes are identical, both parent species and behaviors that are a product of those gene combinations. The chi-
their phenotypes, including fur color, meric animal may display an interesting mix of the parent species’ behaviors. For example,
differ. One copy of the X chromosome is chickens that received Japanese quail cells in early embryogenesis display some aspects of
randomly inactivated in each cell, which quail crowing behavior rather than chicken crowing behavior—evidence for the genetic basis
explains the color differences. Even clones
of the bird’s vocalization (Balaban, 2005). The chimeric preparation provides an investigative
are subject to phenotypic plasticity: they
retain the capacity to develop into more tool for studying the neural basis of crowing, because quail neurons can be distinguished
than one phenotype. from chicken neurons when examined under a microscope.
Chimerism is common in humans (Giorgi, 2015). Twin zygotes (fertilized eggs) may fuse
into a single individual, twins may exchange cells through placental circulation, and the
fetus and the mother may exchange cells with one another. Even organ transplant or stem
cell recipients may incorporate transplanted cells into other organs.
In knock-in technology, a number of genes or a single gene from one species is added to
the genome of another species, passed along, and expressed in subsequent generations of
transgenic animals. Brainbow technology, described in Research Focus 3-2, applies the knock-
in technique. Another application is in the study and treatment of human genetic disorders.
For instance, researchers have introduced into a line of mice and a line of Rhesus monkeys
transgenic animal Product of technology in
the human HTT gene that causes Huntington disease (Gill and Rego, 2009; see Focus 3-4).
which one or more genes from one species
The mice express the abnormal allele and display humanlike Huntington symptoms. This
is introduced into the genome of another
species to be passed along and expressed in mouse line is being used to study possible therapies for Huntington disease in humans.
subsequent generations. Knockout technology is used to inactivate a gene, for example so that a line of mice fails
to express it. The mouse line can then be examined to determine whether the targeted gene
is responsible for a specific function or a human disorder and to examine possible therapies.
It may be possible to knock out genes related to certain kinds of memory, such as emotional
memory, social memory, or spatial memory. Knockout technology is a useful way of inves-
The neural basis of memory is the topic of tigating the neural basis of memory as well as clinical conditions associated with learning
Section 14-3. impairments (Kusakari et al., 2015).
3-3 • Genes, Cells, and Behavior 103
Phenotypic Plasticity and the (A) Corpus callosum
Advances in Behavioral Biology Volume 42, 1994, pp. 125–133; Defects of the
Fetal Forebrain in Acallosal Mice; Douglas Wahlsten, Hiroki S. Ozaki, © 1994
Plenum Press, New York, figure 1, with permission of Springer Science1Busi-
Epigenetic Code
Our genotype is not sufficient to explain our phenotype. We all know that if we expose our-
selves to the sun, our skin darkens; if we exercise, our muscles enlarge; if we study, we learn.
Our phenotype also changes with our diet and as we age. In short, the extent of phenotypic
variation, given the same genotype, is remarkable.
Anterior commissure
Every individual has a capacity to develop into more than one phenotype. This phenotypic
plasticity is due in part to the genome’s capacity to express a large number of phenotypes and (B)
in part to epigenetics, the influence of environment and experience in phenotypic expression.
Seemingly puzzling features in the expression of genomes in relation to phenotypes are
illustrated in strains of genetically identical mice, some of which develop a brain with no
ness Media
corpus callosum (Figure 3-24). The absence of this hemispheric connector results from an
epigenetic influence on whether the trait is expressed in a particular mouse. It occurs in the
embryo at about the time the corpus callosum should form. This lack of concordance (inci-
FIGUre 3-24 Gene Expression
dence of similar behavioral traits) is also observed in patterns of disease incidence in human Identical coronal sections through the
identical twins, who share the same genome. brain of mice with identical genotypes
The concordance rate between identical twins for a vast array of diseases—including reveal frontal views of distinctly different
schizophrenia, Alzheimer disease, multiple sclerosis, Crohn disease (a form of inflammatory phenotypes. (A) This mouse had a corpus
bowel disease), asthma, diabetes, and prostate cancer—is between 30 and 60 percent. For callosum. (B) This mouse did not.
cleft palate and breast cancer, identical twins’ concordance rate is about 10 percent. The
expectation from Mendelian genetics is 100 percent concordance. These less than perfect
concordance rates point to other contributing factors.
Phenotypic plasticity is in evidence not only in adult organisms but also in cells. In The cloned mice shown in Figure 2-1
Section 3-1, we described the variety of neurons and glia found in the nervous system. Each exemplify phenotypic plasticity.
of these cells usually has the same genotype. So also do the 248 other cell types of our body.
How then do they become so different?
Applying the Epigenetic Code
The genes expressed in a cell are influenced by factors within the cell and in the cell’s
environment. Once a fertilized egg begins to divide, each new cell finds itself in a somewhat
different environment from that of its parent cell. The cell’s environment will determine The International Human Epigenome
which genes are expressed and so what kind of tissue it becomes, including what kind of Consortium (IHEC) mandate is to describe
nervous system cell it becomes. Environmental influences do not end at birth, of course. the epigenetic code, as the Human Genome
Our environment changes daily throughout our lives, as does its influence on our genes. Project has described the genetic code.
Epigenetic mechanisms create phenotypic variation without altering the base pair nucleo-
tide sequence of the genes. Through these mechanisms, experience and the environment
can allow a gene to be expressed or prevent its expression. Epigenetics is viewed as a second
code; the first code is the genome. Epigenetics describes how a single genetic code produces
each somatic cell type, explains how a single genome can code for many phenotypes, and
describes how cell functions go astray to produce diseases ranging from cancer to brain
dysfunction.
Epigenetic mechanisms can influence protein production either by blocking a gene to
prevent transcription or by unlocking a gene so that it can be transcribed. This is where
experiential and environmental influences come into play. To review, each of your chromo-
somes consists of a long, double-stranded chain of nucleotide bases that forms your DNA.
Each gene on a chromosome is a segment of DNA that encodes the synthesis of a particular
protein (see Figure 3-13).
Chromosomes are wrapped around supporting molecules of a protein called histone.
Histone wrapping allows the many yards of a chromosome to be packaged in a small space,
as yards of thread are wrapped around a spool. For any gene to be transcribed into messenger
RNA, its DNA must be unspooled from the histones. Once unspooled, each gene must be
instructed to transcribe mRNA. Then the mRNA must be translated into an amino acid
104 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
Blocked Open
1 Histone modification
A methyl group (CH3) or
other molecules bind to the
tails of histones, either
blocking them from opening
DNA (orange circles) or allowing
Histone them to open for transcription
M M (green squares).
M M
2 Gene (DNA) methylation
A C G A A A C G A
Methyl groups (M) bind to
CG base pairs to block
T G C T T T G C T
transcription.
DNA
M M
ncRNA 3 mRNA modification
block ncRNA binds to mRNA,
mRNA
preventing translation.
Ribosome
FIGUre 3-25 Epigenetic Mechanisms
chain that forms the protein. Figure 3-25 illustrates some ways that each step can be either
enabled or blocked:
1. Histone modification. DNA may unwrap or be stopped from unwrapping from the histone.
At the top of Figure 3-25, a methyl group (CH3) or other molecule binds to the tails of
histones to block DNA from unspooling. Its genes cannot be exposed for transcription
with the block in place (left), but it can be opened for transcription (right) if the block is
absent or removed.
Methylation dramatically alters gene expression 2. Gene (DNA) methylation. Transcription of DNA into mRNA may be enabled or blocked.
during brain development (see Sections 8-2 In Figure 3-25 at center, one or more methyl groups bind to CG base pairs to block
and 12-5) and can affect memory and brain transcription.
plasticity (see Section 14-4).
3. mRNA modification. mRNA translation may be enabled or blocked. In Figure 3-25,
bottom, noncoding RNA (ncRNA) binds to mRNA, blocking translation.
An environmental influence can either induce or remove one or more blocks, thus allow-
ing the environment to regulate gene expression (Charney, 2012). It is through these epigen-
etic mechanisms that cells are instructed to differentiate into various body tissues and that
our unique environment and experience induce changes in our brain that make us a unique
individual. Some experientially induced events can also be passed from one generation to
the next, as the following case study illustrates.
gene (DnA) methylation Epigenetic process
in which a methyl group attaches to the DNA A Case of Inheriting Experience
sequence, suppressing or enabling gene The idea that traits are passed from parent to child through genes is a cornerstone of
expression. Mendelian genetics. Mendel’s theory also predicts that individual life experience cannot be
3-3 • Genes, Cells, and Behavior 105
inherited. Lars Olov Bygren and colleagues (Kaati et al., 2007) found, however, that individu-
als’ nutritional experiences can affect their offspring’s health.
The investigators focused on Norrbotten, a sparsely populated northern Swedish region.
In the nineteenth century, Norrbotten was virtually isolated from the outside world. If
the harvest there was bad, people starved. According to historical records, the years 1800,
1812, 1821, 1836, and 1856 saw total crop failure. The years 1801, 1822, 1828, 1844, and 1863
brought good harvests and abundance.
Bygren and colleagues identified at random individuals who had been subjected to famine
or to plenty in the years just before they entered puberty. Then the researchers examined the
health records and longevity of these people’s children and grandchildren.
The findings seem to defy logic. The descendants of the plenty group had higher rates of
cardiovascular disease and diabetes and had a life expectancy more than seven years shorter
than that of the famine group! Notably, these effects were found only in male offspring of
males and female offspring of females.
Bygren and colleagues propose that diet during a critical period can modify the genetic
expression of sex chromosomes—the Y chromosome in males and the X chromosome in
females. Further, this change can be passed on to subsequent generations. Dietary experi- Section 8-4 examines critical periods, limited
ence in the prepubertal period, just before the onset of sexual maturity, is important: this is time spans during which events have long-
the time at which gene expression on the sex chromosomes begins. lasting influences on development.
Many other studies support Bygren and coworkers’ seminal findings. Together, this
body of research makes a strong argument for epigenetics and for the idea that some epi-
genetic influences can be passed on for at least a few generations. Evidence that epigenetic
influences play a demonstrable role in determining gene expression is disclosing how our
experiences shape our brains to influence whom we become and how our current envi-
ronment might influence our descendants’ epigenetic inheritance (Guerrero-Bosagna and
Jensen, 2015).
3-3 revIew
Genes, Cells, and Behavior
Before you continue, check your understanding.
1. Each of our chromosome pairs contains thousands of genes, and each
gene contains the code for one .
2. The genes we receive from our parents may include slightly different of
particular genes, which will be expressed in slightly different .
3. Abnormalities in a gene, caused by a(n) , can result in an abnormally
formed protein, hence in abnormal cell function. Chromosome abnormality can result in
abnormal functioning of many genes. , for example, is caused by an extra
copy of chromosome 21, a .
4. Tay-Sachs disease results from a(n) allele being expressed; Huntington
disease results from the expression of a(n) allele.
5. is the oldest form of genetic manipulation. Genetic engineering manipulates
or alters the genome of an animal. produces an animal that is genetically
identical to a parent or sibling; animals contain new, altered, or inactivated
genes.
6. is an epigenetic mechanism that either enables or blocks transcription.
7. What distinguishes Mendelian genetics from epigenetics?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
106 Chapter 3 • WHAT ARE THE NERVOUS SYSTEM’S FUNCTIONAL UNITS?
SuMMary
3-1 Cells of the Nervous System A gene is a segment of a DNA molecule made up of a sequence of
The nervous system is composed of two kinds of cells: neurons, nucleotide bases. Through transcription, a copy of a gene is produced
which transmit information, and glia, which support neuronal function. in a strand of messenger RNA. The mRNA travels to the endoplasmic
Sensory neurons may act as receptors to convey information from the reticulum, where a ribosome moves along the mRNA molecule, translating
body to the brain; motor neurons command muscles to move; and it into a sequence of amino acids. The resulting amino acid chain is a
interneurons link up sensory and motor neuron activities. polypeptide. Polypeptides fold and combine to form protein molecules
Like neurons, glial cells can be grouped by structure and function. with distinctive shapes that serve specific purposes in the body.
Ependymal cells produce CSF. Astrocytes structurally support
neurons, help to form the blood–brain barrier, and seal off damaged 3-3 Genes, Cells, and Behavior
brain tissue. Microglia aid in brain cell repair and waste removal. From each parent, we inherit one of each chromosome in the 23
Oligodendroglia and Schwann cells myelinate axons in the CNS and in chromosome pairs that constitute the human genotype. Because
the somatic division of the PNS, respectively. all but the sex chromosomes are matched pairs, a cell contains two
A neuron is composed of three parts: a cell body, or soma; multiple alleles of every gene. Sometimes the paired alleles are homozygous
branching extensions called dendrites, designed to receive information; and (the same), and sometimes they are heterozygous (different).
a single axon that passes information along to other neurons. Numerous An allele may be dominant and expressed as a trait, recessive
dendritic spines greatly increase a dendrite’s surface area. An axon may and not expressed, or codominant and expressed along with the
have branches (axon collaterals), which further divide into telodendria, other allele in the organism’s phenotype. One allele of each gene is
each ending at a terminal button (end foot). A synapse is the almost designated the wild type—the most common in a population—whereas
connection between a terminal button and another cell’s membrane. the other alleles are called mutations. A person might inherit any of
these alleles from a parent, depending on the parent’s genotype.
3-2 Internal Structure of a Cell Genes have the potential to undergo many mutations—of a single
A surrounding cell membrane protects the cell and regulates what enters base pair, part of the chromosome, or the entire chromosome.
and leaves it. Within the cell are a number of organelles, also enclosed Mutations can be beneficial, harmful, or neutral in their effects on
in membranes. These compartments include the nucleus (containing nervous system structure and behavioral function. Genetic research
the cell’s chromosomes and genes), the endoplasmic reticulum (where seeks to prevent the expression of genetic and chromosomal
proteins are manufactured), the mitochondria (where energy is gathered abnormalities and to find cures for those that are expressed.
and stored), the Golgi bodies (where protein molecules are packaged for Selective breeding is the oldest form of genetic manipulation. In
transport), and lysosomes (which break down wastes). A cell also contains genetic engineering, an animal’s genome is artificially altered. The
a system of tubules (microfilaments) that aid its movements, provide genetic composition of a cloned animal is identical to that of a parent
structural support, and act as highways for transporting substances. or sibling. In transgenic animals, a new or altered gene may be added
To a large extent, the work of cells is carried out by proteins. The or a gene removed.
nucleus contains chromosomes—long chains of genes, each encoding The genome encodes a range of phenotypes. The phenotype
a specific protein the cell needs. Proteins perform diverse tasks by eventually produced is determined by epigenetics and further
virtue of their diverse shapes. Some act as enzymes to facilitate influenced by experience and the environment. Epigenetic mechanisms
chemical reactions; others serve as membrane channels, gates, and such as DNA methylation can influence whether genes are transcribed
pumps; still others are exported for use in other parts of the body. or transcription is blocked without changing the genetic code itself.
Key terMS
allele, p. 97 dendritic spine, p. 77 interneuron, p. 79 pyramidal cell, p. 79
astrocyte, p. 82 Down syndrome, p. 100 microglia, p. 85 Schwann cell, p. 85
axon, p. 77 ependymal cell, p. 82 motor neuron, p. 79 sensory neuron, p. 79
axon collateral, p. 77 gate, p. 95 mutation, p. 97 somatosensory neuron, p. 79
axon hillock, p. 77 gene, p. 91 myelin, p. 85 synapse, p. 77
bipolar neuron, p. 79 gene (DNA) methylation, p. 104 neural network, p. 77 Tay-Sachs disease, p. 98
blood–brain barrier, p. 82 glial cell, p. 80 oligodendroglia, p. 85 terminal button (end foot), p. 77
cell body (soma), p. 77 heterozygous, p. 97 paralysis, p. 85 transgenic animal, p. 102
channel, p. 95 homozygous, p. 97 protein, p. 92 tumor, p. 82
connectome, p. 77 Huntington disease, p. 98 pump, p. 95 wild type, p. 98
dendrite, p. 77 hydrocephalus, p. 82 Purkinje cell, p. 79
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
4 How Do Neurons Use 4-1
CLINICAL FOCUS 4-1 EpilEpsy
SeArChINg FOr eLeCtrICAL ACtIvIty IN the
Electrical Signals to
NervOUS SyStem
Early CluEs ThaT linkEd ElECTriCiTy and nEuronal aCTiviTy
Transmit Information?
The Basics ElECTriCiTy and ElECTriCal sTimulaTion
Tools for mEasuring a nEuron’s ElECTriCal aCTiviTy
how ion movEmEnT produCEs ElECTriCal ChargEs
4-2 eLeCtrICAL ACtIvIty OF A membrANe
rEsTing poTEnTial
mainTaining ThE rEsTing poTEnTial
gradEd poTEnTials
aCTion poTEnTial
nErvE impulsE
rEfraCTory pEriods and nErvE aCTion
salTaTory ConduCTion and ThE myElin shEaTh
CLINICAL FOCUS 4-2 mulTiplE sClErosis
4-3 hOw NeUrONS INtegrAte INFOrmAtION
ExCiTaTory and inhibiTory posTsynapTiC poTEnTials
eXPerImeNt 4-1 QuEsTion: how doEs sTimulaTing a nEuron
influEnCE iTs ExCiTabiliTy?
summaTion of inpuTs
volTagE-sEnsiTivE ChannEls and ThE aCTion poTEnTial
ThE vErsaTilE nEuron
reSeArCh FOCUS 4-3 opTogEnETiCs and lighT-sEnsiTivE
ion ChannEls
4-4 INtO the NervOUS SyStem ANd bACk OUt
how sEnsory sTimuli produCE aCTion poTEnTials
how nErvE impulsEs produCE movEmEnT
CLINICAL FOCUS 4-4 als: lou gEhrig’s disEasE
Katherine Streeter
107
108 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
CLINICAL F cus 4-1
Epilepsy
J. D. worked as a disc jockey for a radio station and at parties in his off- When the electrical activity in J. D.’s brain was recorded while a
hours. One evening, he set up on the back of a truck at a rugby field to strobe light was flashed before his eyes, an electroencephalogram, or
emcee a jovial and raucous rugby party. Between musical sets, he made EEG, displayed a series of abnormal electrical patterns characteristic
introductions, told jokes, and exchanged toasts. of epilepsy. The doctor prescribed Dilantin (diphenylhydantoin), an anti-
About one o’clock in the morning, J. D. suddenly collapsed, making seizure drug, and advised J. D. to refrain from drinking alcohol. He was
unusual jerky motions, then passed out. He was rushed to a hospital required to give up his driver’s license to prevent the possibility of an
emergency room, where he gradually recovered. The attending physi- attack while driving. And he lost his job at the radio station.
cian noted that he was not intoxicated, released him to his friends, and After 3 uneventful months, medication was stopped and his driver’s
recommended a series of neurological tests for the next day. Neuroimag- license was restored. J. D. convinced the radio station that he could
ing with state-of-the-art brain scans can usually reveal brain abnormali- resume work, and subsequently he has remained seizure free.
ties (Bano et al., 2011), but it did not do so in J. D. ’s case. Epilepsy is a common neurological disease marked by periods of
excessive neural synchrony called electrographic seizures. The dis-
ease is electrical in nature. Electrographic seizures often follow innocu-
ous stimuli—events that would not typically cause seizures in people
who do not have epilepsy. The core concept is that the brain of a person
with epilepsy has a chronically low seizure threshold and so is sub-
ject to recurrent seizures. About 4 in 10 cases of epilepsy have been
linked to specific neural causes, among them infections, trauma, tumors,
structural abnormalities, or genetic mutations in the proteins that make
up ion channels (Bhalla et al., 2011). But that leaves the remaining 60%
without a clear cause.
If seizures occur repeatedly and cannot be controlled by drug
AJPhoto/Science Source
treatment, as occurs in about 30% of people with epilepsy, other options
may include the high-fat–low-carbohydrate ketogenic diet, deep brain
stimulation, and surgical resection of the seizure focus (Duncan et al.,
2006). Removing this small area of brain tissue may prevent seizures and
The EEG detects electrical signals given off by the brain in various keep them from spreading to other brain regions. The brain is normally
states of consciousness, as explained in Sections 7-2 and 13-3. Section electrically active. If this activity becomes abnormal, even infrequently,
16-3 details the diagnosis and treatment of epilepsy. the consequences can be severe.
the most reproduced drawing in behavioral neuroscience is nearly 350 years old,
predating our understanding of the electrical basis of epilepsy by centuries. Taken from René
Descartes’s book Treatise on Man and reproduced in Figure 4-1, it illustrates the first serious
attempt to explain how information travels through the nervous system. Descartes proposed
that the carrier of information was cerebrospinal fluid flowing through nerve tubes.
Descartes reasoned that when the fire burns the man’s toe, it stretches the skin, which
tugs on a nerve tube leading to the brain. In response to the tug, a valve in a brain ventricle
opens, and CSF flows down the tube, filling the leg muscles and causing them to contract
Descartes proposed the idea behind and pull the toe back from the fire. The flow of fluid through other tubes to other muscles
dualism—that the nonmaterial mind controls of the body (not shown in Figure 4-1) causes the head to turn toward the painful stimulus
body mechanics; see Section 1-2. and the hand to rub the injured toe.
Descartes’s theory was incorrect, yet it is remarkable because he isolated the three basic
questions that underlie a behavioral response to stimulation:
1. How do our nerves detect a sensory stimulus and inform the brain about it?
2. How does the brain decide what response to make?
3. How does the brain command muscles to move?
Descartes was trying to explain the very same things that scientists have sought to explain
in the intervening centuries. If not by stretched skin tugging on a nerve tube initiating the
4-1 • Searching for Electrical Activity in the Nervous System 109
message, the message must still be initiated somehow. If not by opening valves to initiate
the flow of CSF to convey information, the information must still be sent. If not by filling
the muscles with fluid that produces movements, the muscles must contract by some other
mechanism.
These mechanisms are the subject of this chapter. We examine how neurons convey
information from the environment throughout the nervous system and ultimately activate
muscles to produce movement. We begin by describing the clues and tools that explained
the nervous system’s electrical activity.
Print Collector/Getty Images
4-1 Searching for Electrical Activity
in the Nervous System
The first hints about how the nervous system conveys its messages came in the eighteenth
century, following the discovery of electricity. Early discoveries about the nature of electric- FIGUre 4-1 Descartes’s Theory of
ity quickly led to proposals that it plays a role in conducting information in the nervous
Information Flow
system. We describe a few milestones that led from this idea to an understanding of how the
nervous system really conveys information. If you have a basic understanding of how elec-
tricity works and how it is used to stimulate neural tissue, read on. If you prefer to brush up
on electricity and electrical stimulation first, turn to The Basics: Electricity and Electrical
Stimulation on page 110.
Early Clues That Linked Electricity
and Neuronal Activity
In a dramatic demonstration in 1731, Stephen Gray, an amateur English scientist, rubbed a
rod with a piece of cloth to accumulate electrons on the rod. Then he touched the charged
Gray’s experiment resembles accumulating
rod to the feet of a boy suspended on a rope and brought a metal foil to the boy’s nose. The
electrons by combing your hair. Hold a piece
foil was attracted to the boy’s nose and bent on approaching it, and as foil and nose touched,
of paper near the comb, and the paper bends
electricity passed from the rod through the boy to the foil. toward it. Negative charges on the comb push
Yet the boy felt nothing. Therefore, Gray speculated that electricity might be the messen- negative charges on the paper to its backside,
ger that spreads information through the nervous system. Two other lines of evidence, drawn leaving the front side positively charged.
from electrical stimulation and electrical recording studies, implicated electrical activity in Because opposite charges attract, the paper
the nervous system’s flow of information. bends toward the comb.
Electrical Stimulation Studies
When the Italian scientist Luigi Galvani, a contemporary of Gray, observed that frogs’ legs
hanging on a wire in a market twitched during a lightning storm, he surmised that sparks of
electricity from the storm were activating the leg muscles. Investigating this possibility, he
found that if an electrical current is applied to a dissected nerve, the muscle connected to
that nerve contracts. While it was unclear how the process worked, Galvani had discovered
electrical stimulation: passing an electrical current from the uninsulated tip of an electrode
onto a nerve to produce behavior—a muscular contraction.
Among the many researchers who used Galvani’s technique to produce muscle contrac-
tion, two mid-nineteenth-century Prussian scientists, Gustave Theodor Fritsch and Eduard
Hitzig, demonstrated that electrical stimulation of the neocortex causes movement. They electrographic seizures Abnormal rhythmic
studied several animal species, including rabbits and dogs, and may even have stimulated neuronal discharges; may be recorded by an
the neocortex of a person whom they were treating for head injuries sustained on a Prussian electroencephalogram.
battlefield. They observed their subjects’ arm and leg movements in response to the stimula- electrical stimulation Passage of an
tion of specific parts of the neocortex. electrical current from the uninsulated tip
In 1874, Roberts Bartholow, a Cincinnati physician, first described the effects of human of an electrode through tissue, resulting in
brain stimulation. His patient, Mary Rafferty, had a skull defect that exposed part of her changes in the electrical activity of the tissue.
110 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
The Basics
Electricity and Electrical Stimulation
Electricity powers the lights in your home and the batteries that run so many electronic gadgets,
from smartphones to electric cars. Electricity is the flow of electrons from a body that contains Because electrons carry a negative charge, the
a higher charge (more electrons) to a body that contains a lower charge (fewer electrons). This negative pole has a higher electrical charge (more
electron flow can perform work—lighting an unlit bulb, for instance. When biological tissue con- electrons) than the positive pole.
tains an electrical charge, the charge can be recorded; if living tissue is sensitive to an electrical
Negative
charge, the tissue can be stimulated. Positive
pole
pole
How Electricity Works + –
In Power Source, negatively charged electrons are attracted to the positive pole because
opposite charges attract. The electrons on the negative pole have the potential to flow to the Battery
positive pole. This electrical potential, or electrical charge, is the ability to do work using stored
electrical energy.
Electrical potential is measured in volts, the difference in charge between the positive and
the negative poles. These poles are separated by an insulator. Thus, when not connected, the Uninsulated
switch
positive and negative poles in a battery, like the poles in each wall socket in your home, hold
voltage between the poles.
Electrical Activity in Cells
If the bare tip of an insulated wire, or electrode, from each pole of a battery comes into contact
with biological tissue, current will flow from the electrode connected to the negative pole into
the tissue and from the tissue into the electrode connected to the positive pole. The stimulation
comes from the electrode’s uninsulated tip. Microelectrodes can record from or stimulate tissue
as small as parts of a single living cell.
Electrical stimulation, illustrated in part A of Studying Electrical Activity in Animal Tissue, Light bulb
is most effective when administered in brief pulses. A timer in the stimulator turns the cur-
rent on and off to produce the pulses. In electrical recording, voltage can be displayed by the 1 The battery will
light the bulb only 2 …and a flow, or
dial on a voltmeter, a recording device that measures the voltage of a battery or of biological
when the switch is current, of electrons
tissue (part B). closed. A conducting streams through the
medium, such as an bulb from the negative
uninsulated wire, (–) to the positive (+)
connects the pole, lighting up the
two poles… bulb.
Power Source
(A) Electrical stimulation (B) Electrical recording
Current leaves the stimulator through a wire lead (red) that attaches to an The difference in voltage between the tip
electrode. From the uninsulated tip of the electrode, the current enters of a recording electrode and a reference
the tissue and stimulates it. The current flows back to the stimulator electrode deflects a needle that indicates
through a second lead (green) connected to a reference electrode. the current’s voltage.
Stimulator Voltmeter
Reference Reference
1 A stimulating electrode delivers electrode electrode
current (electrons) ranging from
2 to 10 millivolts, intensities
Stimulating
sufficient to produce a response Recording
electrode
without damaging cells. Nerve electrode
Uninsulated tip
2 The reference electrode contacts a large surface
area that spreads out the current and thus does
Current flow Current flow
not excite the tissue here.
Studying Electrical Activity in Animal Tissue
4-1 • Searching for Electrical Activity in the Nervous System 111
neocortex. Bartholow stimulated her exposed brain tissue to examine the effects. In one of
voltmeter Device that measures the flow and
his observations he wrote:
the strength of electrical voltage by recording
Passed an insulated needle into the left posterior lobe so that the non-insulated portion rested
the difference in electrical potential between
entirely in the substance of the brain. The reference was placed in contact with the dura mater.
When the circuit was closed, muscular contraction in the right upper and lower extremities two bodies.
ensued. Faint but visible contraction of the left eyelid, and dilation of the pupils, also ensued. electroencephalogram (EEG) Graph that
Mary complained of a very strong and unpleasant feeling of tingling in both right extremities,
records electrical activity from the brain and
especially in the right arm, which she seized with the opposite hand and rubbed vigorously.
Notwithstanding the very evident pain from which she suffered, she smiled as if much amused. mainly indicates graded potentials of many
(Bartholow, 1874) neurons.
As you might imagine, Bartholow’s report was not well received! The uproar after its By the 1960s, the scientific community
publication forced him to leave Cincinnati. Despite the questionable ethics of his experi- had established ethical standards for
ment, Bartholow had demonstrated that the brain of a conscious person could be stimulated research on human and nonhuman subjects
electrically to produce movement of the body. (see Section 7-7). Today, brain stimulation is
standard in many neurosurgical procedures
Electrical Recording Studies (see Section 16-2).
A less invasive line of evidence that information flow in the brain is partly electrical came
from the results of electrical recording experiments. Richard Caton, a Scottish physician who
lived a century ago, was the first to measure the brain’s electrical currents with a sensitive
voltmeter, a device that measures the flow and the strength of electrical voltage by recording
the difference in electrical potential between two bodies. When he placed electrodes on a
human subject’s skull, Caton reported fluctuations in his voltmeter recordings. Today, this
type of brain recording, the electroencephalogram (EEG), is a standard tool used, among
other things, to monitor sleep stages and to detect the excessive neural synchrony that char- Detail on these EEG applications appears in
acterizes electrographic seizures, as described in Clinical Focus 4-1, Epilepsy. Sections 7-2, 13-3, and 16-3.
These pioneering studies provided evidence that neurons send electrical messages, but
concluding that nerves and tracts carry the kind of electrical current that powers your phone
would be incorrect. Hermann von Helmholtz, a nineteenth-century German scientist, stimu-
lated a nerve leading to a muscle and measured the time the muscle took to contract. The
nerve conducted information at only 30 to 40 meters per second, whereas electricity flows
along a wire about a million times faster.
Information flow in the nervous system, then, is much too slow to be a flow of electricity
(based on electrons). To explain the electrical signals of a neuron, Julius Bernstein suggested
in 1886 that neuronal chemistry (based on ions) produces an electrical charge. He also pro-
posed that the charge can change and so act as a signal. Bernstein’s idea was that successive
waves of electrical change constitute the message conveyed by the neuron.
Moreover, it is not the ions themselves that travel along the axon but rather a wave of
charge. To understand the difference, consider other kinds of waves. If you drop a stone into
a pool of still water, the contact produces a wave that travels away from the site of impact, FIGUre 4-2 Wave Effect Waves formed
as shown in Figure 4-2. The water itself does not travel. Only the change in pressure moves, by dropping stones into still water do not
shifting the height of the water surface and producing the wave effect. entail the water’s forward movement but
Similarly, when you speak, you induce pressure waves in air, and these waves rather pressure differences that change
the height of the water surface.
carry the sound of your voice to a listener. If you flick a towel, a wave travels
to the other end of the towel. Just as waves through the air send a spoken mes-
sage, Bernstein’s idea was that waves of chemical change travel along an axon
to deliver a neuron’s message.
Tools for Measuring a Neuron’s
© Fotosearch/Age Fotostock, Inc.
Electrical Activity
Waves that carry nervous system messages are minute and are restricted to the
surfaces of neurons. Still, we can produce these waves using conventional elec-
trical stimulation and measure them using electrical recording techniques to
determine how they are produced. When a single axon is stimulated, it produces
112 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
Voltmeter
Incoming
signal Outgoing
– signal
– –– –– –– ––
– –– –– –– ––
–
Electrical
charge
FIGUre 4-3 Wave of Information
Neurons can convey information as a wave
induced by stimulation on the cell body a wave of excitation. If an electrode connected to a voltmeter is placed on a single axon, as
traveling down the axon to its terminal. illustrated in Figure 4-3, the electrode can detect a change in electrical charge on that axon’s
A voltmeter detects the wave’s passage.
membrane as the wave passes.
As simple as this process may seem, recording a wave and explaining how it is pro-
duced require a neuron large enough to record, a recording device sensitive enough
to detect a tiny electrical impulse, and an electrode small enough to be placed on the
surface of a single neuron. The fortuitous discovery of the giant axon of the squid, the
invention of the oscilloscope, and the development of microelectrodes met all these
requirements.
Giant Axon of the Squid
The neurons of most animals, including humans, are tiny, on the order of 1 to 20 micrometers
(mm) in diameter, too small to be seen by the naked eye. The British zoologist J. Z. Young,
when dissecting the North Atlantic squid, Loligo vulgaris, noticed that it has giant axons, as
much as a millimeter (1000 mm, or about a twenty-fifth of an inch) in diameter. Figure 4-4
1 micron (mm) 5 one-millionth of a meter or illustrates Loligo and the giant axons leading to its body wall, or mantle, which contracts to
one-thousandth of a millimeter (mm). propel the squid through the water.
Loligo is not a giant squid. It is only about a foot long. But its axons are giant, as axons
go. Each is formed by the fusion of many smaller axons. Because larger axons send mes-
sages faster than smaller axons do, these giant axons allow the squid to jet-propel away from
predators.
In 1936, Young suggested to Alan Hodgkin and Andrew Huxley, neuroscientists at
Cambridge University in England, that Loligo’s axons were large enough to be used for
electrical recording studies. A giant axon could be dissected out of the squid and kept func-
tional in a bath of salty liquid that approximates body fluids. In this way, Hodgkin and
Huxley (1939) described the neuron’s electrical activity. In 1963 they received the Nobel Prize
for their accomplishment.
(A) (B)
Water forced
Mantle Stellate out for propulsion
Giant axon axons ganglion
© Age Fotostock/Alamy
FIGUre 4-4 Laboratory Specimen (A) The North
Atlantic squid propels itself both with fins and by contracting
its mantle to force water out for propulsion. (B) The stellate
ganglion projects giant axons to contract the squid’s mantle.
4-1 • Searching for Electrical Activity in the Nervous System 113
30
Voltage (mV)
0
GIPhotostock/Science Source
–70
Time (ms)
S
(A) (B)
FIGUre 4-5 Oscilloscope Recording
Oscilloscope (A) Basic wave shapes are displayed on a
digital oscilloscope, a versatile electronic
Hodgkin and Huxley’s experiments were made possible by the invention of the
instrument used to visualize and measure
oscilloscope, a voltmeter with a screen sensitive enough to display the minuscule electrical signals as they change. (B) On
electrical signals emanating from a nerve or neuron over time (Figure 4-5A). As graphed the graph of a trace produced by an
in Figure 4-5B, the units used when recording the electrical charge from a nerve or neuron oscilloscope, S stands for stimulation.
are millivolts (mV; 1 mV is one-thousandth of a volt) and milliseconds (ms; 1 ms is one- The horizontal axis measures time, and
thousandth of a second). the vertical axis measures voltage. By
convention, the axon voltage is represented
as negative, in millivolts (mV). On the right,
Microelectrodes one trace of two action potentials from an
The final device needed to measure a neuron’s electrical activity is an electrode small individual neuron as displayed on a digital
enough to place on or in an axon—a microelectrode. Microelectrodes can deliver an oscilloscope screen.
electrical current to a single neuron or record from it. One way to make a microelectrode
is to etch the tip of a piece of thin wire to a fine point about 1 mm in size and insulate
the rest of the wire. The tip is placed on or in the neuron, as shown in the image at left oscilloscope Device that serves as a
in Figure 4-6A. sensitive voltmeter by registering changes in
Microelectrodes can also be made from a thin glass tube tapered to a very fine tip voltage over time.
(Figure 4-6A, right image). The tip of a hollow glass microelectrode can be as small as 1 mm. microelectrode A microscopic insulated
When the glass tube is filled with salty water, a conducting medium (through which an electri- wire or a saltwater-filled glass tube whose
cal current can travel), it acts as an electrode. A wire in the salt solution connects the electrode uninsulated tip is used to stimulate or record
to either a stimulating or a recording device. from neurons.
Microelectrodes can record from axons in many ways. The tip of a microelectrode placed
on an axon provides an extracellular measure of the electrical current from a tiny part of the
axon. The tip of one electrode can be placed on the
surface of the axon and the tip of a second electrode (A) (B)
Microelectrode
can be inserted into the axon. This technique mea-
To stimulation Ion
sures voltage across the cell membrane.
or recording channel
A still more refined use of a glass microelectrode is device
to place its tip on the neuron’s membrane and apply
a little suction until the tip is sealed to a patch of the Wire
Membrane
membrane, as shown in Figure 4-6B. This technique,
Insulation
analogous to placing the end of a soda straw against a FIGUre 4-6 Uses of
piece of plastic wrapping and sucking, allows a record- Microelectrodes (A) A squid
Conducting axon is larger than the tip of either
ing to be made from only the small patch of membrane
fluid such a wire (left) or a glass (right)
sealed to the microelectrode tip. Uninsulated
as salt
wire tip
water
microelectrode. Both can be placed
Using the giant axon of the squid, an oscilloscope,
on an axon or in it. (Drawings are
and microelectrodes, Hodgkin and Huxley recorded Glass not to scale.) (B) A microelectrode
Squid axon
the electrical voltage on an axon’s membrane and ex- can record from only a small area of
plained the nerve impulse as changes in ion concentra- an axon by suctioning the membrane
tion across the cell membrane. The basis of electrical up into the glass electrode.
activity in nerves is the movement of intracellular Open tip
114 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
and extracellular ions, which carry positive and negative charges across the cell membrane.
To understand Hodgkin and Huxley’s results, you first need to understand the principles
underlying the movement of ions.
How Ion Movement Produces
Electrical Charges
The intracellular fluid within a neuron and the extracellular fluid surrounding it contain
various ions, including Na1 (sodium) and K1 (potassium)—positively charged, as the plus
signs indicate—and negatively charged Cl2 (chloride). These fluids also contain numer-
ous negatively charged protein molecules (A2). Positively charged ions are cations, and
negatively charged ions, including protein molecules, are anions. Three factors influence
the movement of anions and cations into and out of cells: diffusion, concentration gradient,
and charge.
Because molecules move constantly, they spontaneously spread out from a point of con-
centration. This spreading out is diffusion. Requiring no work, diffusion results from the
random motion of molecules as they move and bounce off one another to gradually disperse
in a solution. When diffusion is complete, a dynamic equilibrium, with an equal number of
molecules everywhere, is the result.
Smoke from a fire gradually diffuses through the air in a room until every bit of air
contains the same number of smoke molecules. Dye poured into water diffuses in the same
way—from its point of contact to every part of the water in the container. Salts placed in
The Basics, pp. 88–89, covers ions. The water dissolve into ions surrounded by water molecules. Carried by the random motion of
illustration, Salty Water, shows how water the water molecules, these ions diffuse throughout the solution to equilibrium, when every
molecules dissolve salt crystals. part of the container has the same salt concentration.
Concentration gradient describes the relative abundance of a substance in space or in a
solution. As illustrated in Figure 4-7A, when you drop a little ink into a beaker of water, the
diffusion Movement of ions from an area dye starts out concentrated at the site of contact, then diffuses. The ink spreads out from
of higher concentration to an area of lower a point of concentration until it is equally distributed and all the water in the beaker is the
concentration through random motion. same color. A similar process takes place when a salt is put into water. The salt is initially
concentration gradient Difference in the concentrated where it enters the water, but it diffuses from that location until its ions are in
relative abundance of a substance among equilibrium.
regions of a container; allows the substance to Because ions carry an electrical charge and because like charges repel one another, ion
diffuse from an area of higher concentration movement can be described either by a concentration gradient, the difference in the number
to an area of lower concentration. of ions between two regions, or by a voltage gradient, the difference in charge between two
voltage gradient Difference in charge regions. Ions will move down a voltage gradient from an area of higher charge to an area of
between two regions that allows a flow of lower charge, just as they move down a concentration gradient from an area of higher con-
current if the two regions are connected. centration to an area of lower concentration.
(A) Concentrating gradient (B) Voltage gradient
1 Ink dropped into 2 …until it is equally 3 If a salty solution 4 …the positive and
water diffuses from distributed through- is poured into negative ions will flow
the initial point of out the water. water,… down their electrostatic
contact… gradients until positive
and negative charges
are everywhere equal.
Salt water
Ink
²
²
²
²²²
² ² ² ²
²²²²²
² ² ²²²²
Time ² ² Time ²²²²²
² ²² ²²²²
FIGUre 4-7 Moving to Equilibrium ²² ²²²
4-1 • Searching for Electrical Activity in the Nervous System 115
Figure 4-7B illustrates this process. When salt is dissolved in water, its diffusion can
be described either as movement down a concentration gradient (for sodium and chloride
ions) or movement down a voltage gradient (for the positive and negative charges). In a
container that allows unimpeded movement of ions, the positive and negative charges
eventually balance.
A thought experiment will illustrate how a cell membrane influences ion movement. The cell membrane is an insulator
Figure 4-8A shows a container of water divided in half by a solid, impermeable membrane. impermeable to salty solutions: salt ions,
If we place a few grains of table salt (NaCl) in the left half of the container, the salt dissolves. surrounded by water molecules, will not pass
The ions diffuse down their concentration and voltage gradients until the water in the left through the membrane’s hydrophobic tails
compartment is in equilibrium. (review Figure 3-11).
In the left side of the container, there is no longer a gradient for either sodium or chloride
ions because the water everywhere is equally salty. There are no gradients for these ions on
the other side of the container either, because the solid membrane prevents the ions from
entering that side. But there are concentration and voltage gradients for both sodium and
chloride ions across the membrane—that is, from the salty side to the freshwater side.
Transmembrane protein molecules embedded in a cell membrane form channels, some
with gates, and pumps that allow certain kinds of ions to pass through the membrane. Re-
turning to our thought experiment, we place a few chloride channels in the membrane that
divides the container of water, making the membrane semipermeable, as illustrated at the
left in Figure 4-8B. Chloride ions will now diffuse across the membrane and move down their Dissolved sodium ions are smaller than
concentration gradient on the side of the container that previously had no chloride ions, chloride ions but more likely to stick to water
shown in the middle of Figure 4-8B. The sodium ions, in contrast, cannot cross through the molecules and so are bulkier and will not
chloride channels or the cell membrane. pass through a small chloride channel.
If the only factor affecting the movement of chloride ions were the chloride concentration
gradient, the efflux (outflow) of chloride from the salty to the freshwater side of the container
would continue until chloride ions were in equilibrium on both sides. But this is not what
happens. Because opposite charges attract, the chloride ions, which carry a negative charge,
are attracted to the positively charged sodium ions they left behind. Because they are pulled
back toward the sodium ions, the chloride ions cannot diffuse completely. Consequently, the
concentration of chloride ions remains higher in the left side of the container than in the
right, as illustrated at the right in Figure 4-8B.
In other words, the efflux of chloride ions down the chloride concentration gradient is
counteracted by the influx (inflow) of chloride ions down the chloride voltage gradient. At
some point, equilibrium is reached: the chloride concentration gradient on the right side of
the beaker is balanced by the chloride voltage gradient on the left. In brief:
concentration gradient 5 voltage gradient
(A) Impermeable membrane (B) Semipermeable membrane
1 Salt placed in one 2 Positive and negative 3 If the barrier has a 4 Cl– will not be equally FIGUre 4-8 Modeling the
side of a beaker of ions distribute channel through which distributed on the Cell Membrane
water that is divided themselves evenly Cl– can pass but Na+ two sides, because of
by a barrier dissolves. throughout half of the cannot, Cl– will diffuse the voltage gradient
container but cannot from the side of high pulling them back
cross the barrier. concentration through toward the positve 5 At equilibrium, one
the hole in the barrier. sodium ions. half of the container will
be positively charged,…
Salt (NaCl)
Cell membrane
6 …the other half will be
–+ –+ ++ – + –
negatively charged, and
+–+ +–+ + – – +–
–+– –+– + – ++ the voltage difference
––++ +–+ +–+ + –+ – – +– ++ –
––+–++–
Time –+– –+– Time –+ Time – + will be greatest close
–+ +++ +–+ +–+ +– – +–
––+– –+– –+– – ++ – – + – to the membrane.
116 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
At this equilibrium, the differential concentration of the chloride ions on the two sides
of the membrane produces a difference in charge—voltage. The left side of the container
is positively charged because some chloride ions have migrated, leaving a preponderance of
positive (Na1) charges. The right side of the container is negatively charged because some
chloride ions have entered that chamber, where none were before. The charge is highest on
the surface of the semipermeable membrane, the area at which positive and negative ions
accumulate. Much the same process happens in a real cell.
4-1 reVIeW
Searching for Electrical Activity in the Nervous System
Before you continue, check your understanding.
1. Although he was incorrect, was the first to seriously attempt to explain
how information travels through the nervous system.
2. Experimental results obtained over hundreds of years from electrical and
more recently from electrical implicated electrical activity in the nervous
system’s flow of information.
3. By the mid-twentieth century, scientists had solved three technical problems in
measuring the changes in electrical charge that travel like a wave along an axon’s
membrane: , , and .
4. The electrical activity of neuronal axons entails the diffusion of ions. Ions may move
down a(n) and down a(n) .
5. In what three ways does the semipermeable cell membrane affect the movement of ions
in the nervous system?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
4-2 Electrical Activity of a
Membrane
Specific aspects of the cell membrane’s electrical activity interact to convey information
throughout the nervous system. The movement of ions across neuronal membranes pro-
duces the electrical activity that enables this information flow.
Resting Potential
Figure 4-9 shows how the voltage difference is recorded when one microelectrode is placed
on the outer surface of an axon’s membrane and another is placed on its inner surface. In the
absence of stimulation, the difference is about 70 mV. Although the charge on the outside of
the membrane is actually positive, by convention it is given a charge of zero. Therefore, the
inside of the membrane at rest is 270 mV relative to the extracellular side.
If we were to continue to record for a long time, the charge across the unstimulated
resting potential Electrical charge across membrane would remain much the same. The charge can change, given certain changes
the insulating cell membrane in the absence of in the membrane, but at rest the difference in charge on the inside and outside of the
stimulation; a store of potential energy produced membrane produces an electrical potential—the ability to use its stored power, analogous
by a greater negative charge on the intracellular to a charged battery. The charge is thus a store of potential energy called the membrane’s
side relative to the extracellular side. resting potential.
4-2 • Electrical Activity of a Membrane 117
…while another records By convention, the extracellular
the inner surface. 0 side of the membrane is given a
charge of 0 mV;…
Voltage (mV)
Axon
…therefore the intracellular
One electrode side of the membrane is –70 mV
records the relative to the extracellular
–70
outer surface side. This measurement is the
of an axon… Time (ms) membrane’s resting potential.
FIGUre 4-9 Resting Potential The electrical charge across a resting cell membrane
stores potential energy.
We might use the term potential in the same way to talk about the financial
A– ions and K+ ions have …whereas Cl– ions
potential of someone who has money in the bank—the person can spend the higher concentration and Na+ ions are
money at some future time. The resting potential, then, is a store of energy inside the axon relative more concentrated
that can be used later. Most of your body’s cells have a resting potential, but to the outside,... outside the axon.
it is not identical on every axon. Resting potentials vary from 240 to 290 mV,
Axon
depending on neuronal type and animal species.
Four charged particles take part in producing the resting potential: ions A– K+ Na+ Cl–
1 1 2
of sodium (Na ), potassium (K ), chloride (Cl ), and large protein molecules Intracellular
(A2). These are the cations and anions, respectively, defined in Section 4-1. As Extracellular
Figure 4-10 shows, these charged particles are distributed unequally across the
axon’s membrane, with more protein anions and potassium ions in the intracellular fluid and FIGUre 4-10 Ion Distribution Across
more chloride and sodium ions in the extracellular fluid. How do the unequal concentrations the Resting Membrane The number
arise, and how does each contribute to the resting potential? of ions distributed across the resting cell
membrane is unequal. Protein ions are
represented by the label, A2.
Maintaining the Resting Potential
The cell membrane’s channels, gates, and pumps maintain the resting potential. Figure 4-11,
which shows the resting membrane close up, details how these three features contribute to
the cell membrane’s resting charge:
1. Because the membrane is relatively impermeable to large molecules, the negatively
charged proteins remain inside the cell.
2. Ungated potassium and chloride channels allow potassium and chloride ions to pass more
freely, but gates on sodium channels keep out positively
charged sodium ions. Na+ channels are Na+–K+ pumps
K+ is free to
1 1 1
3. Na –K pumps extrude Na from the intracellular fluid and enter and leave ordinarily closed to out three Na+
the cell. prevent entry of Na+. for two K+.
inject K1.
Extracellular fluid
Inside the Cell K+ 2 K+
Large protein anions are manufactured inside cells. No mem- Na+
brane channels are large enough to allow these proteins to leave
the cell, and their negative charge alone is sufficient to produce
transmembrane voltage, or a resting potential. Because most
cells in the body manufacture these large, negatively charged
protein molecules, most cells have a charge across the cell K+ 3 Na+
membrane. A–
Intracellular fluid
To balance the negative charge produced by large protein
anions in the intracellular fluid, cells accumulate positively FIGUre 4-11 Maintaining the Resting Potential Channels, gates,
charged potassium ions to the extent that about 20 times as and pumps in the cell membrane contribute to the transmembrane charge.
118 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
many potassium ions cluster inside the cell as outside it. Potassium ions cross the cell
membrane through open potassium channels, as shown in Figure 4-11. With this high con-
centration of potassium ions inside the cell, however, the potassium concentration gradient
across the membrane limits the number of potassium ions entering the cell. In other words,
not all the potassium ions that could enter do enter. Because the internal concentration of
potassium ions is much higher than the external potassium concentration, potassium ions
are drawn out of the cell by the potassium concentration gradient.
A few residual potassium ions on the outside of the membrane are enough to contribute
to the charge across the membrane. They add to the negative charge on the intracellular side
of the membrane relative to the extracellular side. You may be wondering whether you read
the last sentence correctly. If there are 20 times as many potassium ions inside the cell as
there are outside, why should the inside of the membrane have a negative charge? Should not
all those potassium ions in the intracellular fluid give the inside of the cell a positive charge
instead? No, because not quite enough potassium ions are able to enter the cell to balance
the negative charge of the protein anions.
Think of it this way: if the number of potassium ions that could accumulate on the
intracellular side of the membrane were unrestricted, the positively charged potassium
ions inside would exactly match the negative charges on the intracellular protein anions.
There would be no charge across the membrane at all. But the number of potassium ions
that accumulate inside the cell is limited, because when the intracellular K1 concentra-
tion becomes higher than the extracellular concentration, further potassium ion influx is
opposed by its concentration gradient.
Outside the Cell
The equilibrium of the potassium voltage and concentration gradients results in some potas-
sium ions remaining outside the cell. It is necessary to have only a few potassium ions outside
the cell to maintain a negative charge inside the cell. As a result, potassium ions contribute
to the charge across the membrane.
Sodium (Na1) and chloride (Cl2) ions also take part in producing the resting potential. If
positively charged sodium ions were free to move across the membrane, they would diffuse
into the cell and eliminate the transmembrane charge produced by the unequal distribution
of potassium ions inside and outside the cell. This diffusion does not happen, because a gate
on the sodium ion channels in the cell membrane is ordinarily closed (see Figure 4-11), block-
ing the entry of most sodium ions. Still, given enough time, sufficient sodium ions could
leak into the cell to neutralize its membrane potential. The cell membrane has a different
mechanism to prevent this neutralization.
When sodium ions do leak into the neuron, they are immediately escorted out again
by the action of a sodium–potassium pump, a protein molecule embedded in the cell
membrane. A membrane’s many thousands of pumps continually exchange three intra-
cellular sodium ions for two potassium ions, as shown in Figure 4-11. The potassium ions
are free to leave the cell through open potassium channels, but closed sodium channels
slow the reentry of the sodium ions. In this way, sodium ions are kept out to the extent
that about 10 times as many sodium ions reside on the outside of the axon membrane as
on its inside. The difference in sodium concentrations also contributes to the membrane’s
resting potential.
Now consider the chloride ions. Unlike sodium ions, chloride ions move in and out of
the cell through open channels in the membrane. The equilibrium point, at which the
chloride’s concentration gradient equals its voltage gradient, is approximately the same as
the membrane’s resting potential, and so chloride ions ordinarily contribute little to the
resting potential. At this equilibrium point, there are about 12 times as many chloride
ions outside the cell as inside it.
4-2 • Electrical Activity of a Membrane 119
The cell membrane’s semipermeability and the actions of its channels, Unequal distribution of different
gates, and pumps thus produce voltage across the cell membrane: its resting ions causes the inside of the axon
potential (Figure 4-12). to be relatively negatively charged.
+++++++++++++++++++++++++++
Graded Potentials – –– – – – – – – – – – – – – – – – – – – – – – – – –
The resting potential provides an energy store that can be used somewhat like – –– – – – – – – – – – – – – – – – – – – – – – – – –
the water in a dam: small amounts can be released by opening gates for irriga- +++++++++++++++++++++++++++
tion or to generate electricity. If the concentration of any of the ions across the
FIGUre 4-12 Resting Transmembrane
unstimulated cell membrane changes, the membrane voltage changes. These
Charge
graded potentials are small voltage fluctuations across the cell membrane.
Stimulating a membrane electrically through a microelectrode mimics the way the mem-
brane’s voltage changes to produce a graded potential in the living cell. If the voltage applied
to the inside of the membrane is negative, the membrane potential increases in negative
charge by a few millivolts. As illustrated in Figure 4-13A, it may change from a resting
potential of 270 mV to a slightly greater potential of 273 mV.
This change is a hyperpolarization because the charge (polarity) of the membrane
increases. Conversely, if positive voltage is applied inside the membrane, its potential
decreases by a few millivolts. As illustrated in Figure 4-13B, it may change from, say,
a resting potential of 270 mV to a slightly lower potential of 265 mV. This change is a
depolarization because the membrane charge decreases. Graded potentials usually last
only milliseconds.
Hyperpolarization and depolarization typically take place on the soma (cell body) mem-
brane and on neuronal dendrites. These areas contain gated channels that can open and
Neuron axon
Hyperpolarization is due to
an efflux of K+, making the
extracellular side of the
membrane more positive.
(A) Hyperpolarization
0 Extracellular fluid
Cl–
Voltage (mV)
–70
–73 K+
Intracellular fluid
Time (ms)
S An influx of Cl– also can
produce hyperpolarization.
(B) Depolarization
0 Extracellular fluid
Na+
Voltage (mV)
–65 graded potential Small voltage fluctuation
Depolarization across the cell membrane.
is due to an
influx of Na+ hyperpolarization Increase in electrical
–70 through Na+
Intracellular fluid charge across a membrane, usually due to
channels. the inward flow of chloride or sodium ions or
Time (ms)
S the outward flow of potassium ions.
FIGUre 4-13 Graded Potentials (A) Stimulation (S) that increases relative membrane depolarization Decrease in electrical charge
voltage produces a hyperpolarizing graded potential. (B) Stimulation that decreases relative across a membrane, usually due to the
membrane voltage produces a depolarizing graded potential. inward flow of sodium ions.
120 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
close, changing the membrane potential as illustrated in Figure 4-13. Three channels—for
potassium, chloride, and sodium ions—underlie graded potentials:
1. Potassium channels For the membrane to become hyperpolarized, its extracellular
side must become more positive, which can be accomplished with an efflux of potassium
ions. But if potassium channels are ordinarily open, how can the efflux of potassium ions
increase? Apparently, even though potassium channels are open, some resistance
to the outward flow of potassium ions remains. Reducing this resistance enables
hyperpolarization.
2. Chloride channels The membrane can also become hyperpolarized if an influx of chloride
ions occurs. Even though chloride ions can pass through the membrane, more ions remain
on the outside than on the inside, so a decreased resistance to Cl2 flow can result in brief
increases of Cl2 inside the cell.
3. Sodium channels Depolarization can be produced if normally closed sodium channel
gates open to allow an influx of sodium ions.
The Photo Library—Sidney/Science Source
Evidence that potassium channels have a role in hyperpolarization comes from the fact
that the chemical tetraethylammonium (TEA), which blocks potassium channels, also blocks
hyperpolarization. The involvement of sodium channels in depolarization is indicated by
the fact that the chemical tetrodotoxin (TTX), which blocks sodium channels, also blocks
depolarization. The puffer fish, considered a delicacy in some countries, especially Japan,
secretes this potentially deadly poison to fend off potential predators. Skill is required to
prepare this fish for dinner. It can be lethal to the guests of careless cooks because its toxin
Puffer Fish impedes the electrical activity of neurons.
Action Potential
Electrical stimulation of the cell membrane at resting potential produces local graded
potentials. An action potential is a brief but large reversal in an axon membrane’s polarity
(Figure 4-14A). It lasts about 1 ms. The voltage across the membrane suddenly reverses,
making the intracellular side positive relative to the extracellular side, then abruptly
reverses again to restore the resting potential. Because the action potential is brief, many
action potential Large, brief reversal in the action potentials can occur within a second, as illustrated in Figure 4-14B and C, where
polarity of an axon membrane. the time scales are compressed.
An action potential occurs when a large concentration of first Na1 and then K1 crosses the
threshold potential Voltage on a neural
membrane at which an action potential is membrane rapidly. The depolarizing phase of the action potential is due to Na1 influx, and the
triggered by the opening of sodium and hyperpolarizing phase, to K1 efflux. Sodium rushes in, then potassium rushes out. As shown
potassium voltage-sensitive channels; about in Figure 4-15, the combined flow of sodium and potassium ions underlies the action potential.
250 mV relative to extracellular surround. An action potential is triggered when the cell membrane is depolarized to about 250 mV.
Also called threshold limit. At this threshold potential, the membrane charge undergoes a remarkable further change
(A) Action potential (B) (C)
30
0
Voltage (mV)
Threshold
–50
–70
–100
0 1 0 1 2 3 10 20 30 40
Time (ms) Time (ms) Time (ms)
FIGUre 4-14 Measuring Action Potentials (A) Phases of a single action potential. The
time scales on the horizontal axes are compressed to chart (B) each action potential as a discrete
event and (c) the ability of a membrane to produce many action potentials in a short time.
4-2 • Electrical Activity of a Membrane 121
The combined influx of …results in an action potential that
Na+ and efflux of K+… consists of the summed voltage
changes due to Na+ and K+.
–50 mV Na+ K+ 20
Na+ + K+
Neuron axon
Voltage (mV)
0
–20
Na
–40 in Threshold
Na+ K+ –60 K out
–80
0 1 2 3 4
Time (ms)
FIGUre 4-15 Triggering an Action Potential
with no additional stimulation. The relative voltage of the membrane drops to zero and con-
tinues to depolarize until the charge on the inside of the membrane is as great as 130 mV—a
total voltage change of 100 mV. Then the membrane potential reverses again, becoming
slightly hyperpolarized—a reversal of a little more than 100 mV. After this second reversal,
the membrane slowly returns to its resting potential at 270 mV.
The action potential normally consists of the summed current changes caused first by
the inflow of sodium and then by the outflow of potassium on an axon. Experimental results
reveal that if an axon membrane is stimulated electrically while the solution surrounding
the axon contains the chemical TEA (to block potassium channels), the result is a smaller-
than-normal ion flow due entirely to an Na1 influx. Similarly, if an axon’s membrane is stimu-
lated electrically while the solution surrounding the axon contains TTX (to block sodium
channels), a slightly different ion flow due entirely to the efflux of K1 is recorded. Figure
4-16 illustrates these experimental results. The graphs in Figure 4-16 represent ion flow
rather than voltage change.
Role of Voltage-Sensitive Ion Channels
What cellular mechanisms underlie the movement of sodium and potassium ions to produce
an action potential? The answer is the behavior of a class of gated sodium and potassium
An action potential is produced by The opening of Na+ channels produces an Na+ influx.
changes in voltage-sensitive Na+ and
K+ channels, which can be blocked by
Extracellular fluid
TTX and TEA respectively.
Na+
TEA
Na+ influx
Ion flow
Neuron axon
K+
Intracellular fluid Na+
Na+
K+
TTX
Ion flow
K+ efflux
K+
0 1 2 3 4
Time (ms)
The opening of K+ channels produces a K+ efflux.
FIGUre 4-16 Blocking an Action Potential
122 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
−50 mV channels sensitive to the membrane’s voltage (Figure 4-17). These voltage-sensitive channels
K+ channel are closed when an axon’s membrane is at its resting potential: ions cannot pass through them.
When the membrane reaches threshold voltage, the configuration of the voltage-sensitive
channels alters: they open briefly, enabling ions to pass through, then close again to restrict
ion flow. The sequence of actions:
1. Both sodium and potassium voltage-sensitive channels are attuned to the threshold
voltage of about 250 mV. If the cell membrane changes to reach this voltage, both types
of channels open to allow ion flow across the membrane.
2. The voltage-sensitive sodium channels are more sensitive than the potassium channels
and so open first. As a result, the voltage change due to Na1 influx takes place slightly
Extracellular before the voltage change due to K1 efflux can begin.
fluid K+ 3. Sodium channels have two gates. Once the membrane depolarizes to about 130 mV, one
of the gates closes. Thus, Na1 influx begins quickly and ends quickly.
4. The potassium channels open more slowly than the sodium channels, and they remain
open longer. Thus, the efflux of K1 reverses the depolarization produced by Na1 influx
and even hyperpolarizes the membrane.
Intracellular K+
fluid
Action Potentials and Refractory Periods
FIGUre 4-17
Voltage-Sensitive There is an upper limit to how frequently action potentials occur, and sodium and potassium
Potassium Channel channels are responsible for it. Stimulation of the axon membrane during the depolarizing
phase of the action potential will not produce another action potential. Nor is the axon able
Exceptions do exist: some CNS neurons to produce another action potential when it is repolarizing. During these times, the mem-
discharge during the repolarizing phase. brane is described as being absolutely refractory.
If on the other hand the axon membrane is stimulated during hyperpolarization, another
action potential can be induced, but the second stimulation must be more intense than the
voltage-sensitive channel Gated protein first. During this phase, the membrane is relatively refractory.
channel that opens or closes only at specific Refractory periods result from the way gates of the voltage-sensitive sodium and potas-
membrane voltages. sium channels open and close. Sodium channels have two gates, and potassium channels
absolutely refractory The state of an axon have one gate. Figure 4-18 illustrates the position of these gates before, during, and after the
in the repolarizing period, during which a new
action potential cannot be elicited (with some
exceptions), because gate 2 of sodium channels,
which are not voltage sensitive, are closed.
relatively refractory The state of an axon in
the later phase of an action potential during
ctory
Absolu
which increased electrical current is required
a
ly refr
to produce another action potential; a phase
tely
during which potassium channels are still open. 0
ute
refracto
Absol
nerve impulse Propagation of an action
potential on the membrane of an axon.
ry
Threshold
Re y
lative tor
FIGUre 4-18
Phases of an Action ly refrac
Potential Initiated by changes in
Gate 1 Na+ K+ K+
voltage-sensitive sodium and potassium Extracellular fluid
(voltage-sensitive)
channels, an action potential begins with
a depolarization: gate 1 of the sodium
channel opens and then gate 2 closes.
Gate 2
The slower-opening potassium channel (not voltage-sensitive)
gate contributes to repolarization and Na+ K+ Na+ K+ K+ Intracellular fluid
hyperpolarization until the resting Resting Depolarize Repolarize Hyperpolarize Resting
membrane potential is restored.
4-2 • Electrical Activity of a Membrane 123
phases of the action potential. We describe changes first in the sodium channels and then
in the potassium channels.
During the resting potential, gate 1 of the sodium channel depicted in Figure 4-18 is
closed; only gate 2 is open. At the threshold level of stimulation, gate 1 also opens. Gate 2,
however, closes very quickly after gate 1 opens. This sequence produces a brief period during
which both sodium gates are open. When both gates are open and when gate 2 is closed, the
membrane is absolutely refractory.
The opening of the potassium channels repolarizes and eventually hyperpolarizes the
cell membrane. The potassium channels open and close more slowly than the sodium
channels do. The hyperpolarization produced by a continuing efflux of potassium ions
makes it more difficult to depolarize the membrane to the threshold that reopens the gates
underlying an action potential. While the membrane is hyperpolarizing, it is relatively
refractory.
The action of a lever-activated toilet is analogous to some of the changes in polarity
that take place during an action potential. Pushing the lever slightly produces a slight
water flow that stops when the lever is released. This activity is analogous to a graded FIGUre 4-19
Propagating an Action
potential. A harder lever press brings the toilet to threshold and initiates flushing, a Potential Voltage sufficient to open
Na1 and K1 channels spreads to adjacent
response that is out of all proportion to the lever press. This activity is analogous to the
sites of the axon membrane, inducing
action potential. voltage-sensitive gates to open. Here,
During the flush, the toilet is absolutely refractory: another flush cannot be voltage changes are shown on only one
induced at this time. During the refilling of the bowl, in contrast, the toilet is side of the membrane.
relatively refractory, meaning that flushing again is possible but harder. Only
after the cycle is over and the toilet is once again at rest can a full flush be Stimulator
produced again.
Nerve Impulse
Suppose you place two recording electrodes at a distance from one another on
an axon membrane, then electrically stimulate an area adjacent to one elec- 35
0
trode. That electrode would immediately record an action potential. A similar
recording would register on the second electrode in a flash. An action potential –70
has arisen near this second electrode also, even though it is some distance from Axon K+ Voltage spread
the original point of stimulation. ++ – + ++++++++++++
–– + – – – – – – –– – – – – –
Is this second action potential simply an echo of the first that passes down
Na+
the axon? No, it cannot be, because the action potential’s size and shape are
exactly the same at the two electrodes. The second is not just a faint, degraded
version of the first but is equal in magnitude. Somehow the full action potential
has moved along the axon. This propagation of an action potential along an 35
axon is called a nerve impulse. 0
Why does an action potential move? Remember that the total voltage change –70
during an action potential is 100 mV, far beyond the 20-mV change needed to K+ Voltage spread
bring the membrane from its resting state of 270 mV to the action potential + + + + + + + – +++ +++++
– – – – – – – + – –– – – – ––
threshold level of 250 mV. Consequently, the voltage change on the part of
Na+
the membrane where an action potential first occurs is large enough to bring
adjacent parts of the membrane to a threshold of 250 mV.
When the membrane at an adjacent part of the axon reaches 250 mV,
the voltage-sensitive channels at that location pop open to produce an action 35
0
potential there as well. This second occurrence in turn induces a change in the
membrane voltage still farther along the axon, and so on and on, down the axon’s –70
length. Figure 4-19 illustrates this process. The nerve impulse occurs because Voltage
K+ spread
each action potential propagates another action potential on an adjacent part of
++++++++++++++ – +
the axon membrane. The word propagate means to give birth, and that is exactly – – – – – – – – – – – – – – + –
what happens. Each successive action potential gives birth to another down the Na+
length of the axon.
124 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
Because they are propagated by gated ion channels acting on the membrane in their own
vicinity, action potentials on a nerve or tract are the same magnitude wherever they occur.
An action potential depends on energy expended where it occurs, and the same amount of
energy is expended at every site along the membrane as a nerve impulse is propagated.
As a result, action potentials do not dissipate: an action potential is either generated
completely or not generated at all. Action potentials are all-or-none events. As the nerve’s
impulse, or message, the action potential maintains a constant size and arrives unchanged
to every terminal on the nerve that receives it.
Think of the voltage-sensitive channels along the axon as a series of dominoes. When one
falls, it knocks over its neighbor, and so on down the line. There is no decrement in the size of the
fall. The last domino travels exactly the same distance and falls just as hard as the first one did.
Essentially, the domino effect happens when voltage-sensitive channels open. The open-
ing of one channel produces a voltage change that triggers its neighbor to open, just as one
domino knocks over the next. The channel-opening response does not grow any weaker as
it moves along the axon, and the last channel opens exactly like the first, just as the domino
action stays constant to the end of the line.
The domino effect
Refractory Periods and Nerve Action
Refractory periods are determined by the position of the gates that mediate ion flow in the
voltage-sensitive channels. This limits the frequency of action potentials to about 5 ms. The
action potential’s refractory phase thus has two practical uses for nerves that are conducting
information.
First, the maximum rate at which action potentials can occur is about 200 per second
(1 s or 1000 ms/5 ms limit 5 200 action potentials in 1 s). The sensitivity of voltage-sensitive
channels, which varies among kinds of neurons, likewise affects firing frequency.
Second, although an action potential can travel in either direction on an axon, refractory peri-
ods prevent it from reversing direction and returning to its point of origin. Refractory periods thus
produce a single, discrete impulse that travels away from the initial point of stimulation. When
an action potential begins near the cell body, it usually travels down the axon to the terminals.
To return to our domino analogy, once a domino falls, setting it back up takes time.
This is its refractory period. Because each domino falls as it knocks down its neighbor, the
sequence cannot reverse until the domino is set upright again: the dominos can fall in only
one direction. The same principle determines the action potential’s direction.
Saltatory Conduction and the
Myelin Sheath
Because the giant axons of squid are so large, they can transmit nerve impulses very quickly,
FIGUre 4-20 Myelination An axon is
much as a large-diameter pipe can rapidly deliver a lot of water. But large axons take up sub-
insulated by (A) oligodendroglia in the CNS
and (B) Schwann cells in the PNS. Each stantial space: a squid cannot accommodate many of them or its body would be too bulky. For
glial cell is separated by a gap, or node of us mammals, with our many axons producing repertoires of complex behaviors, giant axons
Ranvier. are out of the question. Our axons must be extremely slender because
our complex behaviors require a great many of them.
(A) (B)
Node
Our largest axons are only about 30 mm wide, so the speed with which
of Ranvier
Oligodendrocyte Nodes they convey information should not be especially fast. And yet, like most
of Ranvier
vertebrate species, we humans are hardly sluggish creatures. We process
information and generate responses with impressive speed. How do we
Wrapped
myelin
manage to do so if our axons are so thin? The vertebrate nervous system
has evolved a solution that has nothing to do with axon size.
Glial cells play a role in speeding nerve impulses in the vertebrate
nervous system. Schwann cells in the human peripheral nervous system
Wrapped Schwann and oligodendroglia in the central nervous system wrap around each
myelin Axon cell
Axons axon, forming the myelin sheath that insulates it (Figure 4-20). Action
4-2 • Electrical Activity of a Membrane 125
potentials cannot occur where myelin is wrapped around an axon. For one thing, the myelin
is an insulating barrier to ionic current flow. For another, axonal regions that lie under myelin
have few channels through which ions can flow, and ion channels are essential to generating To review glial cell types, appearance, and
an action potential. functions, see Table 3-1.
But axons are not totally encased in myelin. Unmyelinated gaps between successive
glial cells are richly endowed with voltage-sensitive channels. These tiny gaps in the myelin
sheath, the nodes of Ranvier, are sufficiently close to one another that an action potential
at one node can open voltage-sensitive gates at an adjacent node. In this way, a relatively slow
action potential jumps quickly from node to node, as shown in Figure 4-21. This flow of
energy is called saltatory conduction (from the Latin verb saltare, meaning to leap).
Myelin has two important consequences for propagating action potentials. First, propaga-
tion becomes energetically cheaper, since action potentials regenerate only at the nodes of
Ranvier, not along the axon’s entire length. Action potential conduction in unmyelinated
axons, by contrast, has a significant metabolic energy cost (Crotty et al., 2006). The second
consequence is that myelin improves the action potential’s conduction speed.
Jumping from node to node speeds the rate at which an action potential can travel along
an axon, because the current flowing within the axon beneath the myelin sheath travels
very fast. While the current moves speedily, the voltage drops quickly over distance. But the
nodes of Ranvier are spaced ideally to ensure sufficient voltage at the next node to regenerate
the action potential. On larger, myelinated mammalian axons, nerve impulses can travel at a
rate as high as 120 meters per second. On smaller, uninsulated axons they travel only about
30 meters per second.
Spectators at sporting events sometimes initiate a wave that travels around a stadium. Just
as one person rises, the next person begins to rise, producing the wave effect. This human
wave is like conduction along an unmyelinated axon. Now think of how much faster the wave
would complete its circuit around the field if only spectators in the corners rose to produce
it. This is analogous to a nerve impulse that travels by jumping from one node of Ranvier node of Ranvier The part of an axon that is
to the next. The quick reactions that humans and other mammals are capable of are due in not covered by myelin.
part to this saltatory conduction in their nervous system. saltatory conduction Fast propagation of
Neurons that send messages over long distances quickly, including sensory and motor an action potential at successive nodes of
neurons, are heavily myelinated. If myelin is damaged, a neuron may be unable to send any Ranvier; saltatory means leaping.
messages over its axons. In multiple sclerosis (MS), the myelin formed by oligodendroglia multiple sclerosis (Ms) Nervous system
is damaged, which disrupts the functioning of neurons whose axons it encases. Clinical disorder resulting from the loss of myelin
Focus 4-2, Multiple Sclerosis on page 126, describes the course of the disease. around axons in the CNS.
Current flow
Na+
35
0
K+
–70
Axon Node
Myelin of Ranvier
Current flow
Na+
35
0
K+
–70
FIGUre 4-21 Saltatory
Conduction Myelinated
stretches of axons are
Current flow
Na+ interrupted by nodes of Ranvier,
35 rich in voltage-sensitive
0 channels. In saltatory conduction,
K+ the action potential jumps rapidly
–70
from node to node.
126 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
CLINICAL F cus 4-2
Multiple Sclerosis
One day J. O., who had just finished university requirements to begin J. O. received corticosteroid treatment, which helped, but the condition
work as an accountant, noticed a slight cloudiness in her right eye. It did rebounded when she stopped treatment. Then it subsided and eventually
not go away when she wiped her eye. Rather, the area grew over the disappeared.
next few days. Her optometrist suggested that she see a neurologist, Since then, J. O. has had no major outbreaks of motor impairment,
who diagnosed optic neuritis, an indication that can be a flag for multiple but she reports enormous fatigue, takes long naps daily, and is ready
sclerosis (MS). for bed early in the evening. Her sister and a female cousin have expe-
MS is caused by a loss of myelin produced by oligodendroglia cells rienced similar symptoms, and recently a third sister began to display
in the CNS (see illustration). It disrupts the affected neurons’ ability similar symptoms in middle age. One of J. O.’s grandmothers was con-
to propagate action potentials via saltatory conduction. This loss of fined to a wheelchair, although the source of her problem was never
myelin occurs in patches, and scarring frequently results in the af- diagnosed.
fected areas. MS is difficult to diagnose. Symptoms usually
Eventually, a hard scar, or plaque, forms at the appear in adulthood, their onset is quite sudden
Normal
site of myelin loss. (MS is called a sclerosis from myelinated and their effects can be swift. Initial symptoms
the Greek word meaning hardness.) Associated nerve fiber may be loss of sensation in the face, limbs, or
with the loss of myelin is impairment of neuron body or loss of control over movements or loss
function, causing characteristic MS symptoms of of both sensation and control. Motor symptoms
Exposed fiber
sensory loss and difficulty in moving. Damaged myelin usually appear first in the hands or feet.
Nerve
Fatigue, pain, and depression are commonly affected Early symptoms often go into remission and
associated with MS. Bladder dysfunction, consti- by MS do not appear again for years. In some forms,
pation, and sexual dysfunction all complicate it. however, MS progresses rapidly over just a few
MS, about twice as common in women as in years until the person is bedridden.
men, greatly affects a person’s emotional, social, MS is common in the most northern and most
and vocational functioning. southern latitudes, so it may be related to a lack of vitamin D, which is
Multiple sclerosis is the most common of nearly 80 autoimmune produced by the action of sunlight on the skin. The disease may also
diseases, conditions in which the immune system makes antibodies to be related to genetic susceptibility, as is likely in J. O.’s case. Many MS
a person’s own body (Rezania et al., 2012). Although MS patients are patients take vitamin D3 and vitamin B12.
treated with anti-inflammatory agents, it has no cure as yet. It has been suggested that blood flow from the brain is reduced in
J. O.’s eye cleared over the next few months, and she had no further MS, allowing a buildup of toxic iron. Widening veins that drain blood
symptoms until after the birth of her first child 3 years later, when she from the brain is suggested as a treatment. Clinical trials have been
felt a tingling in her right hand. The tingling spread up her arm, until initiated on the basis of reports from media and in response to patient
gradually she lost movement in the arm for 5 months. Then J. O.’s arm groups rather than on established scientific evidence. It has been ar-
movement returned. But 5 years later, after her second child was born, gued that methodological flaws and lack of evidence disqualify both the
she felt a tingling in her left big toe that spread along the sole of her venous cause of MS and venous widening as an appropriate treatment
foot and then up her leg, eventually leading again to loss of movement. (Valdueza et al., 2013).
4-2 reVIeW
Electrical Activity of a Membrane
Before you continue, check your understanding.
1. The results from the unequal distribution of inside and
outside the cell membrane.
2. Because it is , the cell membrane prevents the efflux of large protein anions
and pumps sodium ions out of the cell to maintain a slightly charge in the
intracellular fluid relative to the extracellular fluid.
3. For a graded potential to arise, a membrane must be stimulated to the point that the
transmembrane charge increases slightly to cause a(n) or decreases
slightly to cause a(n) .
4-3 • How Neurons Integrate Information 127
4. The voltage change associated with a(n) is sufficiently large to stimulate
adjacent parts of the axon membrane to the threshold for propagating it along the length
of an axon as a(n) .
5. Briefly explain why nerve impulses travel faster on myelinated than on unmyelinated axons.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
4-3 How Neurons Integrate
Information
A neuron’s extensive dendritic tree is covered with spines, and through them it can establish
more than 50,000 connections from other neurons. Lying between its dendritic tree and
axon, a neuron’s cell body, too, can receive multiple connections. Nerve impulses traveling
from other neurons to each of these synaptic locations bombard the receiving neuron with Neurons that receive more than one kind of
excitatory and inhibitory inputs. input sum up the information they get.
In the 1960s, John C. Eccles (1965) and his students performed experiments that helped
to answer the question, how does the neuron integrate such an enormous array of in-
puts into a nerve impulse? Rather than recording from the giant axon of a squid, Eccles
recorded from the cell bodies of large motor neurons in the vertebrate spinal cord. In
doing so, he refined the electrical stimulating and recording techniques first developed
for studying squid axons (see Section 4-1). Eccles received the Nobel Prize in Physiology
or Medicine in 1963.
Motor neurons, for example, receive input from multiple sources. A spinal cord motor
neuron has an extensive dendritic tree with as many as 20 main branches that subdivide
numerous times and are covered with dendritic spines. Input from the skin, joints, muscles,
spinal cord, and brain make motor cells ideal for studying how a neuron responds to diverse
inputs. Each motor neuron sends its axon directly to a muscle. The motor neuron is the final
common pathway the nervous system takes to produce behavior.
Excitatory and Inhibitory Postsynaptic
Potentials
To study motor neuron activity, Eccles inserted a microelectrode into a vertebrate’s spinal Figure 2-29A diagrams the human spinal cord
cord until the tip was in or right beside a motor neuron’s cell body. He then placed stimulat- in cross section.
ing electrodes on sensory nerve fiber axons entering the spinal cord. By teasing apart the
incoming sensory fibers, he was able to stimulate one nerve fiber at a time.
Experiment 4-1 diagrams the experimental setup Eccles used. As shown at the
left in the Procedures section, stimulating some incoming sensory fibers produced autoimmune disease Illness resulting from
a depolarizing graded potential (reduced the charge) on the membrane of the motor an abnormal immune response by the body
neuron to which these fibers were connected. Eccles called these graded potentials against substances and tissues normally
excitatory postsynaptic potentials (EPSPs). As graphed at left in the Results section, EPSPs present in the body.
reduce the charge on the membrane toward the threshold level and increase the likelihood excitatory postsynaptic potential (EPsP)
that an action potential will result. Brief depolarization of a neuron membrane in
At the right in the Procedures section, when Eccles stimulated other incoming sen- response to stimulation, making the neuron
sory fibers, he produced a hyperpolarizing graded potential (increased the charge) more likely to produce an action potential.
on the receiving motor neuron membrane. Eccles called these graded potentials inhibitory postsynaptic potential (IPsP)
inhibitory postsynaptic potentials (IPSPs). As graphed at the right in the Results section, Brief hyperpolarization of a neuron membrane
IPSPs increase the charge on the membrane away from the threshold level and decrease the in response to stimulation, making the neuron
likelihood that an action potential will result. less likely to produce an action potential.
128 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
ExPERIMEnt 4-1
Question: How does stimulating a neuron influence its excitability?
Procedure
Using an oscilloscope, Eccles
recorded from the cell body of a
motor neuron while stimulating...
Oscilloscope
Stimulate Stimulate
...an excitatory sensory ...an inhibitory sensory
pathway or... pathway.
Excitatory Inhibitory
pathway pathway
Motor neuron
Results
EPSP IPSP
Voltage (mv)
Stimulating the excitatory Stimulating the inhibitory
pathway produced a pathway produced a
membrane depolarization, or membrane hyperpolarization,
excitatory postsynaptic or inhibitory postsynaptic
potential (EPSP). potential (IPSP).
Time (ms)
S S
Conclusion: EPSPs increase the likelihood that an action potential will result.
IPSPs decrease the likelihood that an action potential will result.
Both EPSPs and IPSPs last only a few milliseconds before they decay and the neuron’s
resting potential is restored. EPSPs are associated with the opening of sodium channels,
which allows an influx of sodium ions. IPSPs are associated with the opening of potassium
channels, which allows an efflux of potassium ions (or with the opening of chloride chan-
nels, which allows an influx of chloride ions).
Although the size of a graded potential is proportional to the intensity of the stimulation,
an action potential is not produced on the motor neuron’s cell body membrane even when an
EPSP is strongly excitatory. The reason is simple: the cell body membrane of most neurons
A brief video at www.youtube.com/ does not contain voltage-sensitive channels. The stimulation must reach the initial segment,
watch?v5-qdH3WGL99Q describes how the the area near or overlapping the axon hillock, where the action potential begins. The initial
initial segment initiates an action potential. segment is rich in voltage-sensitive channels (Bender & Trussel, 2012).
initial segment Area near or overlapping the Summation of Inputs
axon hillock where the action potential begins. A motor neuron’s myriad dendritic spines can each contribute to membrane voltage,
temporal summation Addition of one graded via either an EPSP or an IPSP. How do these incoming graded potentials interact at its
potential to another that occur close in time. membrane? What happens if two EPSPs occur in succession? Does it matter if the time
spatial summation Addition of one graded between them increases or decreases? What happens when an EPSP and an IPSP arrive
potential to another that occur close in space. together?
4-3 • How Neurons Integrate Information 129
(A) EPSPs (B) IPSPs
Wide temporal spacing Wide temporal spacing
0
0
Threshold
–50
–70
S1 S2 S1 S2
Close temporal spacing Close temporal spacing
0
0
Threshold
–50
–70
S1 S2 S1 S2
Simultaneous stimuli Simultaneous stimuli
0
0
Threshold
–50
–70
S1 S2 S1 S2
FIGUre 4-22 Temporal Summation (A) Two depolarizing pulses stimulation (S1 and S2)
separated in time produce two EPSPs similar in size. Pulses close together in time partly
sum. Simultaneous EPSPs sum as one large EPSP. (B) Two hyperpolarizing pulses (S1 and
S2) widely separated in time produce two IPSPs similar in size. Pulses coming fast partly
sum. Simultaneous IPSPs sum as one large IPSP.
Temporal Summation
If one excitatory pulse is followed some time later by a second excitatory pulse, one EPSP
is recorded and after a delay, a second identical EPSP is recorded, as shown at the top left
in Figure 4-22. These two widely spaced EPSPs are independent and do not interact. If the
delay between them is shortened so that the two occur in rapid succession, however, a single
large EPSP is produced, as shown in the left-center panel of Figure 4-22.
Here, the two excitatory pulses are summed—added together to produce a larger de-
polarization of the membrane than either would induce alone. This relation between
two EPSPs occurring close together or even at the same time (bottom left panel) is called
temporal summation. The right side of Figure 4-22 illustrates that equivalent results are ob-
tained with IPSPs. Therefore, temporal summation is a property of both EPSPs and IPSPs.
Spatial Summation
FIGUre 4-23 Spatial Summation The
How does spacing affect inputs to the cell body membrane? By using two recording elec-
process for EPSPs. The process for IPSPs
trodes (R1 and R 2) we can see the effects of spatial relations on the summation of inputs. is equivalent.
If two EPSPs are recorded at the same time but on widely
(A) (B)
separated parts of the membrane (Figure 4-23A), they do
not influence one another. If two EPSPs occurring close to- EPSPs produced at the same time, but EPSPs produced at the same time,
gether in time are also close together on the membrane, how- on separate parts of the membrane, and close together, sum to form a
do not influence each other. larger EPSP.
ever, they sum to form a larger EPSP (Figure 4-23B). This
spatial summation occurs when two separate inputs are very R1 R2 R1
close to one another both on the cell membrane and in time. S1
Similarly, two IPSPs produced at the same time sum if they S1 S2
occur at approximately the same place and time on the cell S2
body membrane but not if they are widely separated.
Role of Ions in Summation 0 0 0
Summation is a property of both EPSPs and IPSPs in any 1 1 1
combination. These interactions make sense when you S1 S2 S1 + S2
130 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
consider that ion influx and efflux are being summed. The influx of sodium ions accompa-
Summed EPSPs
and IPSPs on nying one EPSP is added to the influx of sodium ions accompanying a second EPSP if the
dendritic tree two occur close together in time and space. If the two influxes are remote in time or in space
EPSP and cell body… or in both, no summation is possible.
IPSP
The same is true regarding effluxes of potassium ions. When they occur close together
in time and space, they sum; when they are far apart in either or both ways, there is no
Cell body
summation. The patterns are identical for an EPSP and an IPSP. The influx of sodium ions
associated with the EPSP is added to the efflux of potassium ions associated with the IPSP,
and the difference between them is recorded as long as they are spatially and temporally
close together. If, on the other hand, they are widely separated in time or in space or in both,
Axon
hillock they do not interact and there is no summation.
A neuron with thousands of inputs responds no differently from one with only a few
…depolarize inputs. It democratically sums all inputs that are close together in time and space. The cell
membrane at body membrane, therefore, always indicates the summed influences of multiple temporal
Initial
initial segment to and spatial inputs. And so a neuron can be said to analyze its inputs before deciding what to
segment Axon threshold level,…
do. The ultimate decision is made at the initial segment, the region on the axon that initiates
…generating an the action potential.
action potential.
Action potential Voltage-Sensitive Channels and the
Terminal Action Potential
Nerve Unlike the cell body membrane, the axon is rich in voltage-sensitive channels, beginning at
impulse the initial segment (Figure 4-24). These channels, like those on the squid axon, open at a
particular membrane voltage. The actual threshold voltage varies with the type of neuron,
FIGUre 4-24
Triggering an Action but to keep things simple, we will stay with a threshold level of 250 mV.
Potential If the summated graded
To produce an action potential, the summed graded potentials—the IPSPs and EPSPs—on
potentials—the EPSPs and IPSPs—on the
dendritic tree and cell body of a neuron the cell body membrane must depolarize the membrane at the initial segment to 250 mV. If
charge the membrane to threshold level that threshold voltage is obtained only briefly, voltage-sensitive channels open, and just one or
at the initial segment, an action potential a few action potentials may occur. If the threshold level is maintained for a longer period, how-
is initiated, and it travels down the axon ever, action potentials will follow one another in rapid succession, just as quickly as the gates on
membrane.
the voltage-sensitive channels can reset. Each action potential is then repeatedly propagated
to produce a nerve impulse that travels from the initial segment down the length of the axon.
Many neurons have extensive dendritic trees, but dendrites and dendritic branches do not
back propagation Reverse movement of an
have many voltage-sensitive channels and ordinarily do not produce action potentials. And
action potential into the soma and dendritic
distant branches of dendrites may have less influence in producing action potentials initiated
field of a neuron; postulated to play a role in
at the initial segment than do the more proximal branches of the dendrites. Consequently,
plastic changes that underlie learning.
inputs close to the initial segment are usually much more influential than those occurring
optogenetics Transgenic technique that
some distance away. Those distant inputs usually have a modulating effect. As in all govern-
combines genetics and light to excite or inhibit
ments, some inputs have more say than others (Debanne, 2011).
targeted cells in living tissue.
The Versatile Neuron
Dendrites collect information as graded potentials (EPSPs and IPSPs), and the initial seg-
ment initiates discrete action potentials delivered to other target cells via the axon. Excep-
tions to this picture of how a neuron works do exist. For example, some cells in the developing
The hippocampus (from the Greek meaning hippocampus can produce additional action potentials, called giant depolarizing potentials,
seahorse because its shape is similar) when the cell would ordinarily be refractory. It is thought that giant depolarizing potentials
participates in aspects of memory and is aid in developing the brain’s neural circuitry (Mohajerani & Cherubini, 2006).
vulnerable to stress (see Section 6-5). Because the cell body membrane does not contain voltage-sensitive channels, a typi-
cal neuron does not initiate action potentials on its dendrites. In some neurons, however,
voltage-sensitive channels on dendrites do enable action potentials. The reverse movement
of an action potential from the initial segment into the dendritic field of a neuron is called
back propagation. Back propagation, which signals the dendritic field that the neuron is
4-3 • How Neurons Integrate Information 131
sending an action potential over its axon, may play a role in plastic changes in the neuron
that underlie learning. For example, back propagation may make the dendritic field refrac-
tory to incoming inputs, set the dendritic field to an electrically neutral baseline, or reinforce We explore the neuronal basis of learning in
signals coming in to certain dendrites (Legenstein and Maass, 2011). Sections 5-4 and 14-4.
The neurons of some nonmammalian species have no dendritic branches. And some ion
channels, rather than responding to voltage, respond to light by opening and allowing ions
to pass. The many differences among neurons suggest that the nervous system capitalizes
on structural and functional modifications to produce adaptive behavior in each species.
In research to determine the neuron’s specific functions, neuroscientists have incorporated Section 7-1 describes the promise of
into certain types of neurons ion channels that respond to light, as described in Research optogenetics for neuroscience research and
Focus 4-3, Optogenetics and Light-Sensitive Channels. for clinical applications.
RESEARCH F cus 4-3
Optogenetics and Light-Sensitive Ion Channels
Membrane channels that are responsive to light have been discovered The movements of worms, fruit flies, and mice with genetically intro-
in nonmammalian animal species. Using the transgenic technique of duced light-sensitive channels have been controlled when their nervous
optogenetics, researchers have successfully introduced light-sensitive system cells were illuminated with appropriate wavelengths of light. One
channels into worms, fruit flies, and mice. such species, Caenorhabditis elegans, is a roundworm about 1 millimeter
Optogenetics combines genetics and light to control targeted cells in long that lives in soil.
living tissue. Here we examine how introducing different light-sensitive C. elegans is popular in neuroscience experiments because it is trans-
channels into a species excites the organism’s movements with one parent and has a simple nervous system. It is also the first species to
wavelength and inhibits them with another wavelength. have all its neurons, synapses, and genome completely described. The
One class of light-activated ion channels in the green alga Chlamydo- illustration shows (A) the normal movements of C. elegans and the light-
monas reinhardtii is channelrhodopsin-2. The ChR2 channel absorbs sensitive membrane channel responses that (B) excite or (c) inhibit its
blue light and in doing so opens briefly to allow the passage of cations, movement.
including sodium and potassium. These light-sensitive channels allow Using optogenetic techniques, light-sensitive channels can be incor-
the passage of Na1 and K1 when a cell is illuminated with blue light. porated into specific neural circuits so that light stimulation controls only
The resulting depolarization excites the cell to generate action potentials. a subset of neurons. The promise is that investigating specific neuron
Halorhodopsin (NpHR) is a light-driven ion pump, specific for chlo- populations can provide insight into brain disease, including conditions
ride ions and found in phylogenetically ancient bacteria (archaea) known such as addiction (Cao et al., 2011).
as halobacteria. When illuminated with green-yellow light, the halorho- Also encouraging are the results of a study suggesting that impaired
dopsin pumps chloride anions into the cell, hyperpolarizing it and so vision due to the loss of the light-sensitive retina of the eye could be
inhibiting its activity. restored with light-sensitive channels (Fenno et al., 2011).
(A) C. elegans (B) Excitation (C) Inhibition
Sinclair Stammers/Science Source
Light-Sensitive Channels
(A) Normal movements of Extracellular fluid Extracellular fluid
C. elegans. (B) When light-sensitive
Blue light Green-yellow light
channelrhodopsin-2 ion channels are
Na+
introduced into its neurons, C. elegans Cl–
ChR2 NpHR
becomes active and coils when
exposed to blue light. Information
from Zhang et al., 2007. (c) With light-
sensitive halorhodopsin ion pumps
introduced into its muscles, C. elegans
elongates and becomes immobile K+
when exposed to green-yellow light.
Intracellular fluid Intracellular fluid
Information from Liewald et al., 2008.
132 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
4-3 reVIeW
How Neurons Integrate Information
Before you continue, check your understanding.
1. Graded potentials that decrease the charge on the cell membrane, moving it toward
the threshold level, are called because they increase the likelihood that
an action potential will occur. Graded potentials that increase the charge on the cell
membrane, moving it away from the threshold level, are called because
they decrease the likelihood that an action potential will result.
2. EPSPs and IPSPs that occur close together in both and
are summed. This is how a neuron the information it receives from other
neurons.
3. The membrane of the does not contain voltage-sensitive ion channels,
but if summed inputs excite the to a threshold level, action potentials are
triggered and then propagated as they travel along the cell’s as a nerve
impulse.
4. Explain what happens during back propagation.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
4-4 Into the Nervous System
and Back Out
stretch-sensitive channel Ion channel on The nervous system allows us to respond to afferent sensory stimuli by detecting them and
a tactile sensory neuron that activates in sending messages about them to the brain. The brain interprets the information, trigger-
response to stretching of the membrane, ing efferent responses that contract muscles and produce behavior. Until now, we have
initiating a nerve impulse. been dealing only with the middle of this process—how neurons convey information to
end plate On a muscle, the receptor–ion one another, integrate the information, and generate action potentials. Now we explore the
complex that is activated by the release of beginning and end of the journey.
the neurotransmitter acetylcholine from the To fill in the missing pieces, we explain how a sensory stimulus initiates a nerve impulse
terminal of a motor neuron. and how a nerve impulse produces a muscular contraction. Once again, ion channels are
transmitter-sensitive channel Receptor vitally important, but in muscles, the channels are different from those described so far.
complex that has both a receptor site for
a chemical and a pore through which ions
can flow. How Sensory Stimuli Produce Action
Potentials
We receive information about the world through bodily sensations (touch and balance),
auditory sensations (hearing), visual sensations (sight), and chemical sensations (taste and
olfaction). Each sensory modality has one or more separate functions. In addition to touch,
for example, the body senses include pressure, joint sense, pain, temperature, and itch.
Receptors for audition and balance are modified touch receptors. The visual system has
receptors for light and for colors. And taste and olfactory senses respond to a plethora of
For detail on how sensory receptors
chemical compounds.
transduce external energy into action
To process all these varied sensory inputs requires a remarkable array of sensory receptors.
potentials:
Hearing, Section 10-1 But in all our sensory systems, the neurons related to these diverse receptors have one thing
Sensation and perception, Section 9-1 in common: conduction of information begins at ion channels. They initiate the chain of
Smell and taste, Section 12-2 events that produces a nerve impulse.
Touch, pain, and balance, Section 11-4 An example is touch. Each hair on the human body allows us to detect even a very slight
Vision, Section 9-2 displacement. You can demonstrate this sensitivity to yourself by selecting a single hair on
4-4 • Into the Nervous System and Back Out 133
your arm and bending it. If you are patient and precise Feather FIGUre 4-25 Tactile Stimulation
in your experimentation, you will discover that some A hair’s touch receptor activated by
hairs are sensitive to displacement in one direction a feather results in a nerve impulse
only, whereas others respond to displacement in any heading to the brain.
direction. What enables this finely tuned sensitivity?
The base of each hair is wrapped in a dendrite of
Displacement …causes stretch- This Na+ influx causes
a touch neuron. When you bend a hair or otherwise sensitive channels voltage-sensitive Na+
of hair…
mechanically displace it, the encircling dendrite is on dendrite to and K+ channels to
stretched (Figure 4-25). The displacement opens open, allowing an open, producing a
influx of Na+. nerve impulse.
stretch-sensitive channels in the dendrite’s mem-
brane. When open, these channels allow an influx of Extracellular
sodium ions sufficient to depolarize the dendrite to fluid Current Nerve
Na+ flow Na+ impulse
threshold. At threshold, the voltage-sensitive sodium Hair
and potassium channels initiate a nerve impulse that
conveys touch information to your brain.
Other kinds of sensory receptors have similar mech-
Dendrite
anisms for transducing (transforming) the energy of a of sensory K+
sensory stimulus into nervous system activity. When neuron Stretch-sensitive Voltage-sensitive
displaced, the hair receptors that provide information wrapped channel channels
around
about hearing and balance likewise activate stretch- hair Intracellular fluid
sensitive channels. In the visual system, photons (light
particles) strike opsin proteins in receptors within specialized cells in the eye. The resulting
chemical change activates ion channels in relay neuron membranes. An odorous molecule in
the air that lands on an olfactory receptor and fits itself into a specially shaped compartment
opens chemical-sensitive ion channels. When tissue is damaged, injured cells release chemi-
cals that activate channels on a pain nerve. The point here is that ion channels originate
conduction of information in all our sensory systems.
FIGUre 4-26 Muscle Contraction
(A) When a motor neuron’s axon
How Nerve Impulses Produce Movement collaterals contact a muscle fiber end plate,
(B) acetylcholine attaches to receptor sites
What happens at the end of the neural journey? After sensory information has traveled to the
on the end plate’s transmitter-sensitive
brain and been interpreted, how does the brain generate output—a behavioral response that channels, opening them. These large
includes muscle contractions? Behavior, after all, is movement, and for movement to take membrane channels allow simultaneous
place, muscles must contract. Motor neurons in the spinal cord are responsible for activating influx of Na1 and efflux of K1, generating
muscles. Without them movement becomes impossible and muscles atrophy, as described in current sufficient to activate voltage-sensitive
Clinical Focus 4-4, ALS: Lou Gehrig’s Disease. channels, triggering action potentials, and
causing the muscle to contract.
Motor neurons send nerve impulses to synapses on muscle cells. These synapses are
instrumental in making the muscle contract. Each motor neuron axon makes one or a few (A)
Motor nerve
synapses with its target muscle, synapses similar to those neurons make with one another
Axon
Figure 4-26A). The axon terminal contacts a specialized area of the muscle membrane called
End plate
an end plate. Onto the muscle’s end plate the axon terminal releases the chemical transmit-
Axon terminal
ter acetylcholine.
Acetylcholine does not enter the muscle but rather attaches to transmitter-sensitive
Muscle fiber
channels on the end plate (Figure 4-26B). When these channels open in response, they allow
a flow of Na1 and K1 across the muscle membrane sufficient to depolarize the muscle to (B)
the threshold for its action potential. Yes, to contract, muscles generate action potentials. Acetylcholine
Na+ Current flow
At this threshold, adjacent voltage-sensitive channels open. They in turn produce an action Receptor Na+
site
potential on the muscle fiber, as they do in a neuron.
The transmitter-sensitive channels on muscle end plates are somewhat different
from the channels on axons and dendrites. A single end plate channel is larger than two
sodium and two potassium channels on a neuron, combined. So when its transmitter- K+
sensitive channels open, they allow both Na1 influx and K1 efflux through the same Transmitter-sensitive Voltage-sensitive
channel channel
pore. Generating a sufficient depolarization on the end plate to activate neighboring
134 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
CLINICAL F cus 4-4
ALS: Lou Gehrig’s Disease
In 1869, French physician Jean-Martin Charcot first described ALS, systems, cognitive functions, bowel or bladder control, or even sexual
amyotrophic lateral sclerosis. In North America, ALS is also known as function. Even as his motor neurons continue to die, Stephen Hawking’s
Lou Gehrig’s disease. Gehrig, a baseball legend who played for the New mind-blowing advancements continue to enrich our understanding of
York Yankees from 1923 until 1939, set a host of individual records. He the universe.
was an outstanding hitter, and his incredible durability earned him the At present, no cure for ALS exists, although some newly developed
nickname the Iron Horse. drugs appear to slow its progression and offer some hope for future
Gerhig played on many World Series championship teams, but ALS treatments. In 2014 the ALS Ice Bucket Challenge appeared on YouTube
sapped his strength, forcing him to retire from baseball at age 36. to promote awareness of ALS and encourage donations to research. The
Amyotrophic means muscle weakness; lateral sclerosis means hardening Challenge went viral.
of the lateral spinal cord. Gehrig’s condition deteriorated rapidly. He died
2 years later. ALS strikes most commonly at age 50 to 75, although its
onset can be as early as the teenage years.
While death often occurs within 5 years of diagnosis, internationally
renowned theoretical physicist and cosmologist Stephen Hawking is a no-
table exception. Diagnosed at age 21, Hawking has a rare early-onset and
slowly progressing form of ALS. As a doctoral student at Oxford, he grew
increasingly clumsy, and his speech was slightly slurred. In his late twen-
ties he began to use crutches. In his thirties his speech deteriorated until
and only his family and close friends understood him. Now in his seventies,
and confined to a wheelchair, Hawking, pictured at right, communicates
by using a single cheek muscle attached to a speech-generating device.
Roughly 10 percent of people with ALS have a family history of the
disorder. About 5000 new cases are reported in the United States each
Rex Features via AP Images
year. ALS is due primarily to the death of spinal motor neurons but can
affect brain neurons as well in some cases.
ALS typically begins with general weakness, at first in the throat
or upper chest and in the arms and legs. Gradually, walking becomes
difficult and falling common. ALS does not usually affect any sensory
voltage-sensitive channels on the muscle membrane requires the release of an appropriate
amount of acetylcholine.
Sections 5-2 and 5-3 describe the varieties of Should the acetylcholine receptors on muscle end plates be blocked, acetylcholine
chemical transmitters and how they function. released from the motor neuron cannot properly exert its depolarizing effect. This prevents
muscular contraction in conditions such as the autoimmune disease myasthenia gravis. In
FIGUre 4-27 Myasthenia Gravis affected individuals the thymus, an immune system gland that normally produces antibodies
Asked to look up (1), this patient’s eyelids to foreign material like viruses, makes antibodies to the acetylcholine receptors on muscles,
quickly become fatigued and droop (2, 3).
causing weakness and fatigue (Figure 4-27).
After a few minutes of rest her eyelids
open normally (4). Unlike MS, another autoimmune disease, myasthenia gravis is usually well con-
trolled by treatments including drugs that suppress the immune system or inhibit
1 2 acetylcholine breakdown, extending the time it can act, and by removal of the thymus
Courtesy of Y. Harati, M.D./Baylor College of Medicine,
gland (thymectomy).
The actions of membrane channels can explain a wide range of neural events.
Some channels generate the transmembrane charge. Others mediate graded poten-
tials. Still others trigger the action potential. Sensory stimuli activate channels on
neurons to initiate a nerve impulse, and the nerve impulse eventually activates chan-
3 4 nels on motor neurons to produce muscle contractions.
These various channels and their different functions evolved over a long time in
Houston, Texas
the same way that new species of animals and their behaviors evolve. We have not
described all the different ion channels that neural membranes possess, but you will
learn about some additional ones in subsequent chapters.
Summary 135
4-4 reVIeW
Into the Nervous System and Back Out
Before you continue, check your understanding.
1. Different sensory stimuli initiate nerve impulses for each in a similar way.
2. A(n) membrane contains a mechanism for transducing sensory energy
into changes in ion channels. In turn, the channels allow ion flow to alter the membrane
voltage to the point that channels open, initiating a nerve impulse.
3. Sensory stimuli activate ion channels to initiate a nerve impulse that activates channels
on neurons, which in turn contract .
4. In myasthenia gravis, a(n) disease, the thymus gland produces antibodies to
receptors on muscles, causing weakness and fatigue.
5. Why have so many kinds of ion channels evolved on cell membranes?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
Summary
4-1 Searching for Electrical Activity An action potential is a brief but large change in axon membrane
in the Nervous System polarity triggered when the transmembrane voltage drops to
Electrical stimulation studies dating as far back as the eighteenth a threshold level of about 250 mV. During an action potential,
century show that stimulating a nerve with electrical current induces transmembrane voltage suddenly reverses—the intracellular side
a muscle contraction. In more recent recording studies, the brain’s becomes positive relative to the extracellular side—and abruptly
electrical current, measured using an oscilloscope, shows that reverses again. Gradually, the resting potential is restored. These
electrical activity in the nervous system is continuous. membrane changes result from voltage-sensitive channels—sodium
In the twentieth century, researchers used giant axons of the and potassium channels sensitive to the membrane’s voltage.
squid to measure the electrical activity of a single neuron. Using When an action potential is triggered at the initial segment, it can
microelectrodes that they could place on or in the cell, they recorded propagate along the axon as a nerve impulse. Nerve impulses travel
small, rapid electrical changes with an oscilloscope. Today, digital more rapidly on myelinated axons because of saltatory conduction:
oscilloscopes and computers record these measurements. the action potentials leap between the nodes separating the glial cells
A neuron’s electrical activity is generated by ions flowing across that form the axon’s myelin sheath.
the cell membrane. Ions flow both down a concentration gradient
(from an area of relatively high concentration to an area of lower 4-3 How Neurons Integrate Information
concentration) and down a voltage gradient (from an area of relatively Inputs to neurons from other cells can produce both excitatory
high voltage to an area of lower voltage). The opening, closing, and postsynaptic potentials and inhibitory postsynaptic potentials. The
pumping of ion channels in neural cell membranes also affect ion membrane sums their voltages both temporally and spatially to
distribution. integrate the incoming information. If the summed EPSPs and IPSPs
move the membrane voltage at the initial segment to threshold, the
4-2 Electrical Activity of a Membrane axon generates an action potential.
Unequal ion distribution on a cell membrane’s two sides generates The neuron is a versatile kind of cell. Some species’ ion channels
the neuron’s resting potential. At rest, the intracellular membrane respond to light rather than to voltage changes, an attribute that genetic
registers about 270 mV relative to the extracellular side. Negatively engineers are exploiting. Most of our neurons do not initiate action
charged protein anions are too large to leave the neuron, and the potentials on dendrites, because the cell body membrane does not
cell membrane actively pumps out positively charged sodium ions. contain voltage-sensitive channels. But some voltage-sensitive channels
Unequal distributions of potassium cations and chloride anions on dendrites do enable action potentials. Back propagation, the reverse
contribute to the resting potential as well. movement of an action potential from the initial segment into the dendritic
Graded potentials, short-lived small increases or decreases in field of a neuron, may play a role in plastic changes that underlie learning.
transmembrane voltage, result when the neuron is stimulated. Voltage
changes affect the membrane’s ion channels and in turn change the 4-4 Into the Nervous System and Back Out
cross-membrane ion distribution. An increase in transmembrane Sensory receptor cells convert sensory energy to graded potentials.
voltage causes hyperpolarization; a decrease causes depolarization. These changes, in turn, alter transmembrane voltage to trigger an
136 Chapter 4 • HOW DO NEURONS USE ELECTRICAL SIGNALS TO TRANSMIT INFORMATION?
action potential and propagate a nerve impulse that transmits sensory cell membrane to the threshold for its action potential. In turn, this
information to relevant parts of the nervous system. depolarization activates voltage-sensitive channels, producing an
Ion channels come into play to activate muscles as well, because action potential on the muscle fiber, hence the muscle contractions
the chemical transmitter acetylcholine, released at the axon terminal that enable movement. In myasthenia gravis, antibodies to the
of a motor neuron, activates channels on the end plate of a muscle acetylcholine receptor prevent muscle depolarization, which is the
cell membrane. The subsequent ion flow depolarizes the muscle basis of weakness and fatigue.
Key termS
absolutely refractory, p. 122 electrographic seizures, p. 109 multiple sclerosis (MS), p. 125 stretch-sensitive channel,
action potential, p. 120 end plate, p. 132 nerve impulse, p. 122 p. 132
autoimmune disease, p. 127 excitatory postsynaptic node of Ranvier, p. 125 temporal summation, p. 128
back propagation, p. 130 potential (EPSP), p. 127 optogenetics, p. 130 threshold potential, p. 120
concentration gradient, p. 114 graded potential, p. 119 oscilloscope, p. 113 transmitter-sensitive channel,
hyperpolarization, p. 119 p. 132
depolarization, p. 119 relatively refractory, p. 122
inhibitory postsynaptic potential voltage gradient, p. 114
diffusion, p. 114 resting potential, p. 116
(IPSP), p. 127 voltage-sensitive channel,
electrical stimulation, p. 109 saltatory conduction, p. 125
initial segment, p. 128 p. 122
electroencephalogram (EEG), spatial summation, p. 128
microelectrode, p. 113 voltmeter, p. 111
p. 111
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
5 How Do Neurons RESEARCH FOCUS 5-1 The BaSiS of Neural CommuNiCaTioN
iN a hearTBeaT
Communicate
5-1 A CHEmiCAl mESSAgE
EXPERimENT 5-1 QueSTioN: how doeS a NeuroN
paSS oN a meSSage?
and Adapt? CliNiCAl FOCUS 5-2 parKiNSoN diSeaSe
STruCTure of SyNapSeS
NeuroTraNSmiSSioN iN four STepS
VarieTieS of SyNapSeS
exCiTaTory aNd iNhiBiTory meSSageS
eVoluTioN of Complex NeuroTraNSmiSSioN SySTemS
5-2 VARiETiES OF NEUROTRANSmiTTERS ANd RECEPTORS
four CriTeria for ideNTifyiNg NeuroTraNSmiTTerS
four ClaSSeS of NeuroTraNSmiTTerS
CliNiCAl FOCUS 5-3 awaKeNiNg wiTh l-dopa
VarieTieS of reCepTorS
5-3 NEUROTRANSmiTTER SySTEmS ANd BEHAViOR
NeuroTraNSmiSSioN iN The SomaTiC NerVouS SySTem
dual aCTiVaTiNg SySTemS of The auToNomiC NerVouS SySTem
eNTeriC NerVouS SySTem auToNomy
four aCTiVaTiNg SySTemS iN The CeNTral NerVouS SySTem
CliNiCAl FOCUS 5-4 The CaSe of The frozeN addiCT
5-4 AdAPTiVE ROlE OF SyNAPSES iN lEARNiNg ANd mEmORy
haBiTuaTioN reSpoNSe
EXPERimENT 5-2 QueSTioN: whaT happeNS To The gill reSpoNSe
afTer repeaTed STimulaTioN?
SeNSiTizaTioN reSpoNSe
EXPERimENT 5-3 QueSTioN: whaT happeNS To The gill reSpoNSe
iN SeNSiTizaTioN?
learNiNg aS a ChaNge iN SyNapSe NumBer
RESEARCH FOCUS 5-5 deNdriTiC SpiNeS: Small BuT mighTy
Katherine Streeter
137
138 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
RESEARCH F cus 5-1
The Basis of Neural Communication in a Heartbeat
Discoveries about how neurons communicate stem from experiments into the fluid bath to influence the second heart. His experiment therefore
designed to study what controls an animal’s heart rate. As with any ani- demonstrated that the vagus nerve contains a chemical that tells the
mal, your heartbeat quickens if you are excited or exercising; if you are heart to slow its rate.
resting, it slows. Heart rate changes to match energy expenditure—that Loewi subsequently identified the messenger chemical. Later, he
is, to meet the body’s nutrient and oxygen needs. also identified a chemical that tells the heart to speed up. The heart
Heartbeat undergoes a most dramatic change when you dive beneath adjusts its rate in response to at least two different messages: an excit-
water: it slows almost to stopping. This drastic slowing, called diving atory message that says speed up and an inhibitory message that says
bradycardia, conserves the body’s oxygen when you are not breathing. slow down.
Bradycardia (brady-, meaning slow, and -cardia, meaning heart) is a use-
ful survival strategy. This energy-conserving response under water is
common to many animals. But what controls your heartbeat?
Otto Loewi, a great storyteller, recounted that his classic experiment,
which earned him a Nobel Prize in 1936, came to him in a dream. As
shown in the Procedure section of Experiment 5-1. Loewi first maintained
a frog’s heart in a salt bath, then electrically stimulated the vagus nerve—
the cranial nerve that leads from the brain to the heart. At the same
time, he channeled some of the fluid bath from the vessel containing the
Helgiskulason/Getty Images
stimulated heart through a tube to another vessel in which a second heart
was immersed but not electrically stimulated.
Loewi recorded both heart rates. His findings are represented in the
Results section of Experiment 5-1. The electrical stimulation decreased
the rate of the first heart, but more important, the second heartbeat also
slowed. This result indicated that the fluid transferred from the first to Puffins fish by diving underwater, propelling themselves by flapping their
the second container carried instructions to slow down. short, stubby wings as if flying. During these dives, their heart displays the
Where did the message come from originally? Loewi reasoned that a diving bradycardia response, just as our heart does. Here, a puffin emerges
chemical released from the stimulated vagus nerve must have diffused from a dive, fish in beak.
In this chapter, first we explain how neurons communicate with one another using excita
tory and inhibitory signals. Next we describe how chemicals carried by one neuron signal
receptors on receiving neurons to produce a response. We conclude the chapter by exploring
the neural bases of learning—that is, how neural synapses adapt physically as a result of an
organism’s experience.
5-1 A Chemical Message
Acetylcholine (ACh) Loewi’s successful heartbeat experiment, diagrammed in Experiment 5-1, marked the
beginning of research into how chemicals carry information from one neuron to another
in the nervous system. Loewi was the first to isolate a chemical messenger. We now know
that chemical as acetylcholine (ACh), the same transmitter that activates skeletal muscles,
as described in Section 44. Yet here, ACh acts to inhibit heartbeat, to slow it down. It turns
out that ACh activates skeletal muscles in the somatic nervous system and may either excite
or inhibit various internal organs in the autonomic system. And, yes, acetylcholine is the
chemical messenger that slows the heart in diving bradycardia.
Epinephrine (EP) Norepinephrine (NE) In further experiments modeled on his procedure in Experiment 51, Loewi stimulated
another nerve to the heart, the accelerator nerve, and heart rate increased. The fluid that
Three-dimensional space-filling models
bathed the accelerated heart also speeded the beat of a second heart that was not electri
contrast the molecular structure of
ACh, which inhibits heartbeat, to EP cally stimulated. Loewi identified the chemical that carries the message to speed up heart
and NE, which excite the heart in frogs rate in frogs as epinephrine (EP; epi, above; nephron, kidney), also known as adrenaline.
and humans, respectively. Adrenaline (Latin) and epinephrine (Greek) are the same substance, produced by the adrenal
5-1 • A Chemical Message 139
ExPErimENt 5-1 acetylcholine (Ach) First neurotransmitter
Question: How does a neuron pass on a message? discovered in the PNS and CNS; activates
skeletal muscles in the SNS; may either excite
Procedure or inhibit internal organs in the ANS.
Stimulating Recording
epinephrine (EP, or adrenaline) Chemical
device device
messenger that acts as a neurotransmitter
1 Vagus nerve 2 Fluid is transferred in the CNS and as a hormone to mobilize the
of frog heart 1 from first to second
body for fight or flight during times of stress.
is stimulated. container.
norepinephrine (NE, or noradrenaline)
Neurotransmitter that accelerates heart rate
in mammals; found in the brain and in the
sympathetic division of the ANS.
Vagus
neurotransmitter Chemical with an
nerve
excitatory or inhibitory effect when released
Fluid transfer by a neuron onto a target.
Results
Frog heart 1 Frog heart 2
Rate of
heartbeats
Stimulation
3 Recording from frog heart 4 …as does the recording
1 shows decreased rate of from frog heart 2 after the
beating after stimulation,… fluid transfer.
Conclusion: The message is a chemical released by the nerve.
glands located atop the kidneys. Adrenaline is the name more people know, in part because
a drug company used it as a trade name, but epinephrine is common parlance in the science
community.
Further experimentation eventually demonstrated that in mammals, the chemical that
accelerates heart rate is norepinephrine (NE; also noradrenaline), a chemical closely related
to EP. The results of Loewi’s complementary experiments showed that acetylcholine from
the vagus nerve inhibits heartbeat, and epinephrine from the accelerator nerve excites it. The vagus nerve influences the heart
Chemical messengers released by a neuron onto a target to cause an excitatory or inhibi and other internal body processes;
tory effect are neurotransmitters. Outside the central nervous system, many of the same see Figure 2-29.
chemicals, epinephrine among them, circulate in the bloodstream as hormones. Under con
trol of the hypothalamus, the pituitary gland releases hormones into the bloodstream to
excite or inhibit targets such as the organs and glands in the autonomic and enteric nervous
systems. In part because hormones travel throughout the body to distant targets, their action
is slower than that of CNS neurotransmitters prodded by the lightningquick nerve impulse.
But the real difference between neurotransmitters and hormones is the distances they travel Section 6-5 explains how hormones influence
before they encounter their receptors. the brain and behavior.
Loewi’s discoveries led to the search for more neurotransmitters and their functions.
The actual number of transmitters is an open question, with 100 posited as the maxi
mum. The confirmed number is 60. Whether a chemical is accepted as a neurotransmitter
depends on the extent to which it meets certain criteria. As this chapter unfolds, you will
learn those criteria along with the names and functions of many neurotransmitters. You
will also learn how groups of neurons form neurotransmitter systems throughout the brain
140 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
CliniCAl F cus 5-2
Parkinson Disease
Case VI: The gentleman . . . is seventy-two years of age. . . . About eleven 3. Confirming the role of dopamine in a neural pathway connecting the
or twelve, or perhaps more, years ago, he first perceived weakness in the substantia nigra to the basal ganglia, Urban Ungerstedt found in 1971
left hand and arm, and soon after found the trembling to commence. In that injecting a neurotoxin called 6-hydroxydopamine into rats selec-
about three years afterwards the right arm became affected in a similar tively destroyed these dopamine-containing neurons and produced
manner: and soon afterwards the convulsive motions affected the whole
symptoms of Parkinson disease.
body and began to interrupt speech. In about three years from that time
the legs became affected. (James Parkinson, 1817/1989) Researchers have now linked the loss of dopamine-containing sub-
In the 1817 essay from which this case study is taken, British physician stantia nigra neurons to an array of causes, including genetic predisposi-
James Parkinson reported similar symptoms in six patients, some of whom tion, the flu, pollution, insecticides, herbicides, and toxic drugs. Dopamine
he had observed only in the streets near his clinic. Shaking was usually the itself in other brain areas has been linked not only to motor behavior but
first symptom, and it typically began in a hand. Over a span of years, the also to some forms of learning and to neural structures that mediate
shaking spread to include the arm and then other parts of the body. reward and addiction. This remarkable series of discoveries, initiated by
As the disease progressed, patients had a propensity to James Parkinson, has yielded tremendous insight into brain function.
lean forward and walk on the balls of their feet. They also
tended to run forward to prevent themselves from falling.
In the later stages, patients had difficulty eating and swal-
lowing. They drooled, and their bowel movements slowed.
Eventually, the patients lost all muscular control and were
unable to sleep because of the disruptive tremors.
More than 50 years after James Parkinson’s
descriptions, French neurologist Jean-Martin Charcot
Photo by Mike Coppola/Getty Images for the Michael J. Fox
named the condition Parkinson’s disease, known today
as Parkinson disease. Three findings have helped
researchers understand its neural basis:
1. In 1919, Constantin Tréatikoff (1974) studied the brains
Foundation for Parkinson’s Research
of nine Parkinson patients on autopsy and found that
Universal Pictures/Photofest
the substantia nigra, a small midbrain nucleus, had
degenerated. In the brain of one patient who had par-
kinsonian symptoms only on one side of the body, the
substantia nigra had degenerated on the side opposite
that of the symptoms.
2. Chemical examination of the brains of Parkinson Actor Michael J. Fox gained wide fame in the 1980s for his starring role in the Back to
patients showed that disease symptoms appear when the Future film series, which included his rendition of Chuck Berry’s pop classic, “Johnny
the level of dopamine, then a proposed neurotransmit- B. Goode” (left). In 1991, at age 30, Fox was diagnosed with young-onset Parkinson disease.
ter, was reduced to less than 10 percent of normal in the When he performed the song 20 years later to benefit the Michael J. Fox Foundation for
basal ganglia (Ehringer & Hornykiewicz, 1960/1974). Parkinson’s Research, he labored but still had the moves (right).
to modulate, or temper, aspects of behavior. The three Clinical Focus boxes in this chapter
tell the fascinating story of how one such neurotransmitter system has yielded deep insight
into brain function. When depleted in a particular brain area, this neurotransmitter is
associated with a specific neurological disorder. The story begins with Clinical Focus 52,
Parkinson Disease.
Structure of Synapses
Loewi’s discovery about the chemical messengers that regulate heart rate was the first of
two seminal findings that form the foundation for current understanding of how neurons
communicate. The second had to wait nearly 30 years, for the invention of the electron
microscope. Shown at the right in Figure 5-1, it enables scientists to see the structure
of a synapse.
5-1 • A Chemical Message 141
Light microscope Electron microscope FIGUre 5-1 Microscopic Advance
Whereas an observer can use a light
microscope (left) to see the general
Electron gun features of a cell, an electron microscope
(right) allows the observer to examine the
cell’s organelles in detail.
Specimen
Specimen
Light
Image
Joseph f. gennaro Jr./Science Source,
Biophoto associates/Science
Colorization by: mary martin
Source
The electron microscope uses some principles of a light microscope, shown at the left in
Figure 51, and an oscilloscope. The light microscope illuminates the tissue and magni Figure 4-5 describes how a digital
fies the image. The electron microscope projects a beam of electrons through a very thin oscilloscope measures voltage in biological
slice of tissue. The tissue’s varying structures scatter the electron beam onto a reflective tissue.
surface, where they leave an image, or shadow, of the tissue. Electron waves are smaller
than light waves and scatter much less when the beam strikes tissue, allowing for much
higher resolution.
To see how much finer an electron microscope’s resolution is relative to that of a light
microscope, compare the images at the bottom of Figure 51. An electron microscope’s
resolution can be much higher than a light microscope because electron waves are smaller
than light waves, so much less scatter attends the beam striking the tissue. When tissue is
stained with a substance that reflects electrons, vanishingly fine structural details emerge.
Chemical Synapses
The first good electron micrographs, made in the 1950s, revealed synaptic structure for the
first time. In the center of the micrograph in Figure 5-2A, the upper part of the synapse is
the axon terminal, or end foot; the lower part is the receiving dendrite. The round granular
substances in the terminal are the synaptic vesicles, containing neurotransmitter. Parkinson disease Motor system disorder
Dark patches on the axon terminal membrane are proteins that serve largely as ion chan correlated with dopamine loss in the substantia
nels to signal the release of the transmitters or as pumps to recapture the transmitter after its nigra; characterized by tremors, muscular
release. The dark patches on the dendrite consist mainly of receptor molecules also made up rigidity, and reduction in voluntary movement.
of proteins that receive chemical messages. The terminal and the dendrite are separated by a dopamine (DA) Amine neurotransmitter
small space, the synaptic cleft. The synaptic cleft is central to synapse function, because neu involved in coordinating movement, attention,
rotransmitter chemicals must bridge this gap to carry a message from one neuron to the next. learning, and in reinforcing behaviors.
You can also see in the micrograph that the synapse is sandwiched by many surrounding synaptic vesicle Membranous compartment
structures, including glial cells, other axons and dendritic processes, and other synapses. The that encloses a quantum of neurotransmitter.
surrounding glia contribute to chemical neurotransmission in several ways—by supplying the synaptic cleft Gap separating the neuronal
building blocks for neurotransmitter synthesis, by confining the movement of neurotrans presynaptic membrane from the postsynaptic
mitters to the synapse, and by mopping up excess neurotransmitter molecules, for example. membrane.
142 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
(A) (B)
Axon
Joseph f. gennaro Jr./Science Source, Colorization by: mary martin
Presynaptic
Presynaptic Microtubule: Transport
neuron
terminal structure that carries
Presynaptic substances to the axon
membrane terminal.
Dendrite of
Synaptic postsynaptic
vesicles neuron Mitochondrion:
Organelle that provides
Synaptic
the cell with energy.
cleft
Postsynaptic
Synaptic vesicle:
membrane
Round granule
Dendritic Presynaptic membrane: that contains
spine Glial cell neurotransmitter.
Encloses molecules
that transmit chemical
FIGUre 5-2 Chemical Synapse messages. Storage granule:
(A) Surrounding the central synapse in this Large compart-
electron micrograph are glial cells, axons, ment that holds
dendrites, other synapses, and a synaptic Synaptic cleft: Small Presynaptic synaptic vesicles.
space separating terminal
cleft. (B) Within a chemical synapse,
storage granules hold vesicles containing presynaptic terminal Neurotransmitter
and postsynaptic
neurotransmitter that travel to the
dendritic spine. Channel
presynaptic membrane in preparation for Dendritic
release. Neurotransmitter is expelled into spine
Postsynaptic receptor:
the synaptic cleft by exocytosis, crosses Postsynaptic membrane: Site to which a
the cleft, and binds to receptor proteins Contains receptor neurotransmitter
on the postsynaptic membrane. molecules that receive molecule binds.
chemical messages.
Figure 52B details the process of neurotransmission at a chemical synapse, the junction
where messenger molecules are released from one neuron to interact with the next neuron.
Here the presynaptic membrane forms the axon terminal, the postsynaptic membrane forms
the dendritic spine, and the space between the two is the synaptic cleft. Within the axon
Cell 1 Cell 2 terminal are specialized structures, including mitochondria, the organelles that supply the
membrane membrane
cell’s energy needs; storage granules, large compartments that hold several synaptic vesicles;
and microtubules, which transport substances, including neurotransmitter, to the terminal.
Electrical Synapses
Chemical synapses are the rule in mammalian nervous systems, but they are not the only
kind of synapse. Some neurons influence each other electrically through a gap junction,
or electrical synapse, where the cell membranes of two neurons come into direct contact
(Figure 5-3). Ion channels in one cell membrane connect to ion channels in the other mem
brane, forming a pore that allows ions to pass from one neuron to the other in both directions.
This fusion eliminates the brief delay in information flow—about 5 milliseconds per
Gap
junction synapse—of chemical transmission (compare Figure 53 with Figure 52B). For example, the
crayfish’s gap junctions activate its tail flick, a response that provides quick escape from a
Gap predator. Gap junctions are found in the mammalian brain, where in some regions they allow
junction groups of interneurons to synchronize their firing rhythmically. Gap junctions also allow
channel
glial cells and neurons to exchange substances (Dere & Zlomuzica, 2012).
Why, if chemical synapses transmit messages more slowly, do mammals rely on them
more than on gap junctions? The answer is that chemical synapses flexibly control whether
Intracellular Extracellular
fluid fluid a message is passed from one neuron to the next; they can amplify or diminish a signal sent
from one neuron to the next; and they can change with experience to alter their signals and
FIGUre 5-3 Gap Junction so mediate learning.
5-1 • A Chemical Message 143
Neurotransmission in Four Steps 1 Synthesis: Some neurotransmitters
The fourstep process of transmitting information across a chemical synapse are transported from the cell nucleus
to the terminal button. Others,…
is illustrated in Figure 5-4. In brief, the neurotransmitter must be
Precursor chemicals
1. synthesized somewhere inside the neuron and stored at the axon
Neurotransmitter
terminal.
2. transported to the presynaptic membrane and released into the cleft in … made from building
blocks imported into
response to an action potential.
the terminal, are
3. able to bind to and activate receptors on the postsynaptic membrane. packaged into vesicles
there.
4. inactivated, so it will not continue to work indefinitely.
2 Release: In response
Step 1: Neurotransmitter Synthesis to an action potential,
the transmitter is
and Storage released across the
Neurotransmitters are derived in two general ways, and these origins define membrane by exocytosis.
4 Inactivation: The
two broad classes of neurotransmitters. Some are synthesized in the cell body
3 Receptor action: transmitter is either
according to instructions in the neuron’s DNA, packaged in membranes on The transmitter crosses taken back into the
the Golgi bodies, and transported on microtubules to the axon terminal. Cell the synaptic cleft and terminal or inactivated
derived neurotransmitters may also be manufactured within the presynaptic binds to a receptor. in the synaptic cleft.
terminal from mRNA transported to the terminal.
FIGUre 5-4 Synaptic Transmission
Other neurotransmitters are synthesized in the axon terminal from building blocks
derived from food. Transporters, protein molecules that pump substances across the cell
membrane, absorb the required precursor chemicals from the blood supply. (Sometimes For a refresher on protein export, review
transporter proteins absorb the neurotransmitter readymade.) Mitochondria in the axon Figure 3-17.
terminal provide the energy needed both to synthesize precursor chemicals into the neuro
transmitter and to wrap them in membranous vesicles.
Regardless of their origin, neurotransmitters in the axon terminal can usually be found
in three locations, depending on their type. Some vesicles are warehoused in granules, some
are attached to microfilaments (a type of microtubule; see Figure 52B) in the terminal, and
still others are attached to the presynaptic membrane. These sites are the steps by which
a transmitter is transported from a granule to the membrane, ready to be released into the
synaptic cleft. chemical synapse Junction at which
messenger molecules are released when
Step 2: Neurotransmitter Release stimulated by an action potential.
Synaptic vesicles loaded with neurotransmitters must dock near release sites on the pre
presynaptic membrane Axon terminal
synaptic membrane. Then the vesicles are primed to prepare them to fuse rapidly in response
membrane on the transmitter, or output, side
to calcium (Ca21) influx. When an action potential reaches the presynaptic membrane, vol
of a synapse.
tage changes on the membrane set the release process in motion. Calcium cations play a
postsynaptic membrane Membrane on the
critical role. The presynaptic membrane is rich in voltagesensitive calcium channels, and
transmitter, or input, side of a synapse.
the surrounding extracellular fluid is rich in Ca21. As illustrated in Figure 5-5, the action
potential’s arrival opens these calcium channels, allowing an influx of calcium ions into the storage granule Membranous compartment
axon terminal. that holds several vesicles containing a
neurotransmitter.
Primed vesicles fuse with the presynaptic membrane quickly in response to the calcium
influx and empty their contents into the synaptic cleft by exocytosis. The vesicles from stor gap junction (electrical synapse) Area of
age granules and on filaments then move up to replace the vesicles that just emptied their contact between adjacent cells in which ion
contents. channels form a pore that allows ions to pass
directly from one cell to the next.
Step 3: Receptor-Site Activation transporter Protein molecule that pumps
After its release from vesicles on the presynaptic membrane, the neurotransmitter dif substances across a membrane.
fuses across the synaptic cleft and binds to specialized protein molecules embedded in transmitter-activated receptor Protein
the postsynaptic membrane. These transmitter-activated receptors have binding sites that has a binding site for a specific
for the transmitter, which we elaborate on in Section 53. Depending on the properties of neurotransmitter and is embedded in the
receptors on the postsynaptic membrane, the postsynaptic cell may be affected in one of membrane of a cell.
144 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
three ways. The receptor and its associated ion channel or
1 When an action
intracellular messenger system may
potential reaches
the voltage-sensitive Action 1. depolarize the postsynaptic membrane and so have an
terminal, it opens potential excitatory action on the postsynaptic neuron.
calcium channels.
+ 2. hyperpolarize the postsynaptic membrane and so have an
Ca2
inhibitory action on the postsynaptic neuron.
2 Incoming
3. initiate other chemical reactions that modulate either
calcium ions 3 This complex binds
bind to Complex to vesicles, releasing effect, inhibitory or excitatory, or that influence other
proteins, some from filaments functions of the receiving neuron.
forming a and inducing others to
complex. Binding In addition to interacting with the postsynaptic mem
bind to the presynaptic
proteins membrane and tobrane’s receptors, a neurotransmitter may interact with
Calcium empty their contents
ions receptors on the presynaptic membrane: it may influence
by exocytosis.
the cell that just released it. That is, a neurotransmitter may
activate presynaptic receptors called autoreceptors (self
Postsynaptic
receptor sites
receptors) to receive messages from their own axon terminals.
How much neurotransmitter is needed to send a message? Bernard Katz was
awarded a Nobel Prize in 1970 for providing an answer. Recording electrical activity
FIGUre 5-5 Neurotransmitter Release from the postsynaptic membranes of muscles, he detected small, spontaneous depo
larizations now called miniature postsynaptic potentials. The potentials varied in size, but
each size appeared to be a multiple of the smallest potential.
Katz concluded that the smallest postsynaptic potential is produced by the release of the
contents of just one synaptic vesicle. This amount of neurotransmitter is called a quantum.
To produce a postsynaptic potential large enough to initiate a postsynaptic action potential
requires the simultaneous release of many quanta from the presynaptic cell.
The results of subsequent experiments show that the number of quanta released from
the presynaptic membrane in response to a single action potential depends on two factors:
(1) the amount of Ca21 that enters the axon terminal in response to the action potential and
(2) the number of vesicles docked at the membrane, waiting to be released. Both factors are
relevant to synaptic activity during learning, which we consider in Section 54.
autoreceptor Self-receptor in a neuronal Step 4: Neurotransmitter Deactivation
membrane; that is, it responds to the same Chemical transmission would not be an effective messenger system if a neurotransmitter
transmitter released by the neuron.
lingered within the synaptic cleft, continuing to occupy and stimulate receptors. If this hap
quantum (pl. quanta) Amount of pened, the postsynaptic cell could not respond to other messages sent by the presynaptic
neurotransmitter, equivalent to the content of neuron. Thus, after a neurotransmitter has done its work, it is quickly removed from receptor
a single synaptic vesicle, that produces a just- sites and from the synaptic cleft. Deactivation is accomplished in at least four ways:
observable change in postsynaptic electric
potential. 1. Diffusion. Some of the neurotransmitter simply diffuses away from the synaptic cleft and
is no longer available to bind to receptors.
reuptake Deactivation of a neurotransmitter
when membrane transporter proteins bring 2. Degradation. Enzymes in the synaptic cleft break down the transmitter.
the transmitter back into the presynaptic axon 3. Reuptake. Membrane transporters specific to that transmitter may bring it back into the
terminal for reuse. presynaptic axon terminal for reuse. The byproducts of degradation by enzymes also may
be taken back into the terminal to be used again in the cell.
Table 3-1 describes astrocytes and other 4. Astrocyte uptake. Some neurotransmitters are taken up by neighboring astrocytes.
types of glial cells and their functions. Potentially, the astrocytes can also store transmitters for reexport to the axon terminal.
Highlighting the flexibility of synaptic function, an axon terminal has chemical mecha
nisms that enable it to respond to the frequency of its own use. If the terminal is very active,
the amount of neurotransmitter made and stored there increases. If the terminal is not often
used, however, enzymes within the terminal buttons may break down excess transmitter.
The byproducts are then reused or excreted from the neuron. Axon terminals may even send
messages to the neuron’s cell body requesting increased supplies of the neurotransmitter or
the molecules with which to make it.
5-1 • A Chemical Message 145
Varieties of Synapses
So far we have considered a generic chemical synapse, with features possessed by most syn
apses. Synapses vary widely in the nervous system. Each type is specialized in location, struc
ture, function, and target. Figure 5-6 illustrates this diversity on a single hypothetical neuron.
You have already encountered two kinds of synapses. One is the axomuscular synapse, in Figure 4-26 shows both microscopic and
which an axon synapses with a muscle end plate, releasing acetylcholine. The other synapse schematic views of an axomuscular synapse
familiar to you is the axodendritic synapse, detailed in Figure 52B, in which the axon termi
nal of a neuron synapses with a dendrite or dendritic spine of another neuron.
Figure 56 diagrams axon terminals at the axodendritic synapse as well as the axosomatic
synapse, at a cell body; the axoaxonic synapse, on another axon; and the axosynaptic synapse,
on another presynaptic terminal—that is, at the synapse between some other axon and its
target. Axoextracellular synapses have no specific targets but instead secrete their transmit
ter chemicals into the extracellular fluid. In the axosecretory synapse, a terminal synapses
with a tiny blood vessel, a capillary, and secretes its transmitter directly into the blood.
Finally, synapses are not limited to axon terminals. Dendrites also may send messages to
other dendrites through dendrodendritic synapses.
This wide variety of connections makes the synapse a versatile chemical delivery system.
Synapses can deliver transmitters to highly specific sites or diffuse locales. Through connec
tions to the dendrites, cell body, or axon of a neuron, transmitters can control the neuron’s
actions in different ways.
Through axosynaptic connections, they can also exert exquisite control over another
neuron’s input to a cell. By excreting transmitters into extracellular fluid or into the blood,
axoextracellular and axosecretory synapses can modulate the function of large areas of tissue
or even the entire body. Many transmitters secreted by neurons act as hormones circulating More about hormones in Section 6-5.
in your blood, with widespread influences on your body.
Gap junctions, shown in Figure 53, further increase the signaling diversity between neu
rons. Such interneuronal communication may occur via dendrodendritic and axoaxonic gap
Dendrodendritic: Dendrites
send messages to other
dendrites.
Dendrites
Axodendritic: Axon terminal
of one neuron synapses on
dendritic spine of another.
Axoextracellular: Terminal
with no specific target.
Secretes transmitter into
extracellular fluid.
Axosomatic: Axon terminal
Cell
body ends on cell body.
Axosynaptic: Axon terminal
Axon ends on another terminal.
Axoaxonic: Axon terminal
ends on another axon.
Capillary
Axosecretory: Axon terminal
ends on tiny blood vessel
and secretes transmitter
directly into blood.
FIGUre 5-6 The Versatile Synapse
146 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
junctions. Gap junctions also allow neighboring neurons to synchronize their signals through
somatosomatic (cell body to cell body) connections, and they allow glial cells, especially astro
cytes, to pass nutrient chemicals to neurons and to receive waste products from them.
Excitatory and Inhibitory Messages
A neurotransmitter can influence a neuron’s functioning through a remarkable variety of mech
anisms. In its direct actions in influencing a neuron’s electrical activity, however, a neurotrans
mitter acting through its receptors has only one of two effects. It influences transmembrane ion
flow either to increase or to decrease the likelihood that the cell with which it comes in contact
will produce an action potential. Thus, despite the wide variety of synapses, they all convey mes
Each neuron receives thousands of excitatory sages of only these two types, excitatory or inhibitory. To be precise, neurotransmitters them
and inhibitory signals every second. The selves do not determine excitation or inhibition. The receptor makes the call.
nervous system works by juxtaposing these Excitatory and inhibitory synapses differ in their appearance and are generally located on
signals. different parts of the neuron. As shown in Figure 5-7, excitatory synapses are typically on the
shafts or spines of dendrites, whereas inhibitory synapses are typically on the cell body. Excit
atory synapses have round synaptic vesicles; the vesicles in inhibitory synapses are flattened.
The material on the presynaptic and postsynaptic membranes is denser in an excitatory synapse
than it is in an inhibitory synapse, and the excitatory synaptic cleft is wider. Finally, the active
zone on an excitatory synapse is larger than that on an inhibitory synapse.
The differing locations of excitatory and inhibitory synapses divide a neuron into two zones:
an excitatory dendritic tree and an inhibitory cell body. Think of excitatory and inhibitory mes
Behaviors are lost when a disorder prevents sages as interacting from these two different perspectives. Viewed from an inhibitory perspec
excitatory instructions and released when a tive, you can picture excitation coming in over the dendrites and spreading past the axon hillock
disorder prevents inhibitory instructions. to trigger an action potential at the initial segment. If the message is to be stopped, it is best
stopped by inhibiting the cell body close to the initial segment. In this model of excitatory–inhibi
tory interaction, inhibition blocks excitation by a “cut ’em off at the pass” strategy.
Large active Another way to conceptualize excitatory–inhibitory interaction is to picture
Dendritic
spine zone excitation overcoming inhibition. In fact, excitatory synaptic inputs that are far
Wide cleft
ther away from the soma are larger, to counteract the loss of signal that occurs
Dendritic shaft Excitatory over distance (Magee & Cook, 2000). If the cell body is typically in an inhibited
synapse state, the only way to generate an action potential is to reduce cell body inhibition.
In this “open the gates” strategy, the excitatory message is like a racehorse ready to
run down the track, but first the inhibitory starting gate must be removed.
Cell body
Dense material Round Evolution of Complex
Inhibitory
synapse
on membranes vesicles
Neurotransmission Systems
Small active Considering all the biochemical steps required for getting a message across a
zones synapse and the variety of synapses, you might well wonder why—and how—
Narrow cleft
Axon hillock
such a complex communication system ever evolved. How did chemical trans
mitters originate?
To make the origin of chemical secretions for neuronal communication
easier to imagine, think about the feeding behaviors of simple singlecelled
creatures. The earliest unicellular creatures secreted juices onto bacteria to
immobilize and prepare them for ingestion. These digestive juices were prob
ably expelled from the cell body by exocytosis: a vacuole or vesicle attaches
Sparse material Flat itself to the cell membrane then opens into the extracellular fluid to discharge
on membranes vesicles its contents. The prey thus immobilized is captured through the reverse pro
cess of endocytosis.
FIGUre 5-7 Excitatory and
The exocytosis mechanism for digestion in a singlecelled organism parallels its use to
Inhibitory Zones Excitatory synapses
typically occupy spines and dendritic release a neurotransmitter for communication in more complex creatures. Quite possibly,
shafts on a neuron. Inhibitory synapses are evolution long ago adapted these primordial digestive processes into processes of neural com
typically found on the cell body. munication in more complex organisms.
5-2 • Varieties of Neurotransmitters and Receptors 147
5-1 reVIeW
A Chemical Message
Before you continue, check your understanding.
1. In mammals, the principal form of communication between neurons occurs via ,
even though this structure is slower and more complex than the fused .
2. The principal benefit of chemical synapses over electrical synapses is that they can
change with to alter their signals and so mediate .
3. The nervous system has evolved a variety of synapses:
between axon terminals and dendrites,
between axon terminals and cell bodies,
between axon terminals and muscles,
between axon terminals and other axons,
between axon terminals and other synapses.
A(n) synapse releases chemical transmitters into extracellular fluid, a(n)
synapse releases transmitter into the bloodstream as hormones, and still
another, the synapse, connects dendrites to other dendrites.
4. Excitatory synapses are usually located on a(n) , whereas inhibitory
synapses are usually located on a(n) .
5. Describe the four steps in chemical neurotransmission.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
5-2 Varieties of Neurotransmitters
and Receptors
Subsequent to Otto Loewi’s 1921 discovery that excitatory and inhibitory chemicals control heart
rate, many researchers thought that the brain must work under much the same type of dual
control. They reasoned that norepinephrine and acetylcholine were the transmitters through
which excitatory and inhibitory brain cells worked. They did not imagine what we know today: the
human brain employs a dazzling variety of neurotransmitters and receptors. The neurotransmit
ters operate in even more versatile ways: some may be excitatory at one location and inhibitory at
another, for example, and two or more may team up in a single synapse so that one
makes the other more potent. Moreover, each neurotransmitter may interact with 1 Chemical must
several varieties of receptors, each with a somewhat different function. be synthesized or
present in neuron.
In this section, you will learn how neurotransmitters are identified and how
they fit within four broad categories on the basis of their chemical structure.
The functional aspects of neurotransmitters interrelate and are intricate, with 2 When released,
chemical must
no simple onetoone relation between a single neurotransmitter and a single
produce a response
behavior. Furthermore, receptor variety is achieved by the unique combination in target cell.
of protein molecules that come together to form a functional receptor.
Chemical
Four Criteria for Identifying
Neurotransmitters
3 Same receptor action
Among the many thousands of chemicals in the nervous system, which are neu must be obtained when 4 There must be a mechanism
rotransmitters? Figure 5-8 presents four identifying criteria: chemical is experimentally for removal after the
placed on the receptor. chemical’s work is done.
1. The chemical must be synthesized in the neuron or otherwise be present in it.
2. When the neuron is active, the chemical must be released and produce a FIGUre 5-8 Criteria for Identifying
response in some target. Neurotransmitters
148 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
3. The same response must be obtained when the chemical is experimentally placed on
small-molecule transmitter Quick-acting
the target.
neurotransmitter synthesized in the axon
terminal from products derived from the diet. 4. A mechanism must exist for removing the chemical from its site of action after its work
histamine (H) Neurotransmitter that is done.
controls arousal and waking; can cause These identifying criteria are fairly easy to apply for examining the somatic nervous sys
the constriction of smooth muscles; when tem, especially at an accessible nerve–muscle junction with only one main neurotransmitter,
activated in allergic reactions, constricts acetylcholine. But identifying chemical transmitters in the CNS is not so easy. In the brain
airway and contributes to asthma. and spinal cord, thousands of synapses are packed around every neuron, preventing easy
access to any single synapse and its activities. Consequently, multiple techniques, including
staining, stimulating, and collecting, are used to identify substances thought to be CNS
neurotransmitters. A suspect chemical that has not yet been shown to meet all the criteria
is called a putative (supposed) transmitter.
Researchers trying to identify new CNS neurotransmitters can use microelectrodes to
Figure 4-6 illustrates the use of a glass stimulate and record from single neurons. A glass microelectrode is small enough to be
microelectrode. placed on specific neuronal targets. It can be filled with a chemical of interest, and when a
current is passed through the electrode, the chemical can be ejected into or onto the neuron
to mimic neurotransmitter release onto the cell.
Many staining techniques can identify specific chemicals inside the cell. Methods have
also been developed for preserving nervous system tissue in a saline bath while experimenters
determine how the neurons in the tissue communicate. The use of such tissue slices simpli
fies the investigation by allowing the researcher to view a single neuron through a micro
scope while stimulating it or recording from it.
Acetylcholine was not only the first substance identified as a neurotransmitter but also
the first substance identified as a CNS neurotransmitter. A logical argument that predicted
its presence even before experimental proof was gathered greatly facilitated the process. All
motor neuron axons leaving the spinal cord use acetylcholine as a transmitter. Each axon has
an axon collateral within the spinal cord that synapses on a nearby CNS interneuron. The
interneuron, in turn, synapses on the motor neuron’s cell body. This circular set of connec
tions, called a Renshaw loop after the researcher who first described it, is shown in Figure 5-9.
Because the main axon to the muscle releases acetylcholine, investigators suspected that
its axon collateral also might release acetylcholine. For two terminals of the same axon to use
different transmitters seemed unlikely. Knowing what chemical to look for made it easier to
find and obtain the required evidence that ACh is in fact a neurotransmitter in both locations.
The loop made by the axon collateral and the interneuron in the spinal cord forms a
feedback circuit that enables the motor neuron to inhibit itself from overexcitation, should it
receive a great many excitatory inputs from other parts of the CNS. Follow the positive and
negative signs in Figure 59 to see how the Renshaw loop works. If the loop is blocked, as can
be done with the toxin strychnine, motor neurons become overactive, producing convulsions
that can choke off respiration and so cause death.
The term neurotransmitter is used more broadly now than it was when researchers began
to identify these chemicals. Today, the term applies to chemicals that
• carry a message from the presynaptic membrane of one neuron to another by
influencing postsynaptic membrane voltage.
• change the structure of a synapse.
• communicate by sending messages in the opposite direction. These retrograde (reverse
direction) messages influence the release or reuptake of transmitters on the presynaptic side.
Four Classes of Neurotransmitters
We can impose some order on the diversity of neurotransmitters by classifying them into
four groups based on their chemical composition: (1) smallmolecule transmitters, (2) peptide
transmitters, (3) lipid transmitters, and (4) gaseous transmitters.
5-2 • Varieties of Neurotransmitters and Receptors 149
FIGUre 5-9 Renshaw Loop Left: Some
spinal cord motor neurons project to the
rat’s forelimb muscles. Right: In a Renshaw
loop the main motor axon (green) projects
Inhibitory cell to a muscle, and its axon collateral remains
(Renshaw interneuron) in the spinal cord to synapse with a
Acetylcholine Renshaw interneuron (red). The Renshaw
interneuron contains the inhibitory
Glycine transmitter glycine, which acts to prevent
motor neuron overexcitation. Both the main
ian whishaw
Motor neuron motor axon and its collateral terminals
contain acetylcholine. When the motor
neuron is highly excited, it can modulate
Motor neurons in its activity level through the Renshaw loop
spinal cord of rat (plus and minus signs).
¶ Renshaw
loop
Axon
collateral
Muscle
Main axon
Acetylcholine
Small-Molecule Transmitters
The first neurotransmitters identified are the quickacting small-molecule transmitters, such
as acetylcholine. Typically, they are synthesized from dietary nutrients and packaged ready for
use in axon terminals. When a smallmolecule transmitter has been released from a terminal
button, it can quickly be replaced at the presynaptic membrane.
Because smallmolecule transmitters or their main components are derived from the food
we eat, diet can influence their abundance and activity in our bodies. This fact is important
in the design of drugs that act on the nervous system. Many neuroactive drugs are designed Taking drugs orally is easy and comparatively
to reach the brain by the same route that smallmolecule transmitters or their precursor safe, but not all drugs can traverse the
chemicals follow: the digestive tract. digestive tract. Section 6-1 explains.
Table 5-1 lists some of the bestknown and most extensively studied smallmolecule transmit
ters. In addition to acetylcholine, four amines (related by a chemical structure that contains an
NH group, or amine) and three amino acids are included in this list. A few other substances,
including histamine, also are classified as smallmolecule transmitters.
taBLe 5-1 Small-molecule Neurotransmitters
Among its many functions, which include control of arousal and of waking, the transmitter
histamine (H) can cause the constriction of smooth muscles. When activated in allergic reac Acetylcholine (ACh)
tions, histamine contributes to asthma, a constriction of the airways. You are probably familiar Histamine (H)
with antihistamine drugs used to treat allergies. Amines
aCet YLChOLINe SYNtheSIS Acetylcholine is present at the junction of neurons and Dopamine (DA)
muscles, including the heart, as well as in the CNS. Figure 5-10 illustrates how ACh mole Norepinephrine (NE, or noradrenaline, NA)
cules are synthesized from choline and acetate by two enzymes, then broken down. Choline Epinephrine (EP, or adrenaline)
is among the breakdown products of fats in foods such as egg yolk, avocado, salmon, and Serotonin (5-HT)
olive oil; acetate is a compound found in acidic foods, such as vinegar and lemon juice. Amino acids
As depicted in Figure 510, inside the cell, acetyl coenzyme A (acetyl CoA) carries acetate
Glutamate (Glu)
to the synthesis site, and a second enzyme, choline acetyltransferase (ChAT), transfers the
Gamma-aminobutyric acid (GABA)
acetate to choline to synthesize acetylcholine. After ACh has been released into the syn
aptic cleft and diffuses to receptor sites on the postsynaptic membrane, a third enzyme, Glycine (Gly)
150 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
1 Acetyl CoA carries 2 ChAT transfers 3 …to acetylcholinesterase (AChE), reverses the process, breaking down the transmit
acetate to the transmitter acetate to form ter by detaching acetate from choline. The breakdown products can then be
synthesis site. choline… ACh. taken back into the presynaptic terminal for reuse.
aMINe SYNtheSIS Some transmitters grouped together in Table 51 have
ChAT
Acetate common biochemical pathways to synthesis and so are related. You are familiar
with the amines dopamine (DA), norepinephrine (NE), and epinephrine (EP). To
review, DA loss figures in Parkinson disease, EP is the excitatory transmitter at the
Acetyl CoA
amphibian heart, and NE is the excitatory transmitter at the mammalian heart.
Figure 5-11 charts the biochemical sequence that synthesizes these amines
Products Choline ACh
in succession. The precursor chemical is tyrosine, an amino acid abundant
Intracellular fluid (presynaptic)
in food. (Hard cheese and bananas are good sources.) The enzyme tyrosine
Presynaptic membrane hydroxylase (enzyme 1 in Figure 511) changes tyrosine into ldopa, which other
enzymes convert into dopamine, then norepinephrine, and, finally, epinephrine.
Synaptic cleft
Interestingly, the supply of the enzyme tyrosine hydroxylase is limited. Con
AChE
Acetate
sequently, so is the rate at which dopamine, norepinephrine, and epinephrine
can be produced, regardless of how much tyrosine is present or ingested. This
AChE
rate-limiting factor can be bypassed by the oral administration of ldopa, which
ACh is why ldopa is a medication used in treating Parkinson disease, as described in
Clinical Focus 53, Awakening with lDopa, on page 152.
Synaptic cleft Choline SerOtONIN SYNtheSIS The amine transmitter serotonin (5HT, for
Postsynaptic membrane
5hydroxytryptamine) is synthesized from the amino acid ltryptophan. Tryp
tophan is abundant in pork, turkey, milk, and bananas, among other foods.
Intracellular fluid (postsynaptic) Serotonin plays a role in regulating mood and aggression, appetite and arousal,
respiration, and pain perception.
5 The breakdown products 4 In the synaptic cleft,
aMINO aCID SYNtheSIS Two amino acid transmitters, glutamate (Glu) and
can be taken back up into AChE detaches acetate
the cell and reused. from choline. gamma-aminobutyric acid (GABA), are closely related. GABA is formed by a sim
ple modification of the glutamate molecule, as shown in Figure 5-12. These two
FIGUre 5-10 Chemistry of Acetylcholine Two transmitters are the workhorses of the brain because so many synapses use them.
enzymes combine the dietary precursors of ACh within In the forebrain and cerebellum, glutamate is the main excitatory transmitter
the cell, and a third breaks them down in the synapse for and GABA is the main inhibitory transmitter. Thus, glutamate is a neurotransmit
reuptake.
ter in excitatory synapses, and GABA is a neurotransmitter in inhibitory synapses.
So a synapse’s appearance provides information about the neurotransmitter and its function
(review Figure 57). Interestingly, glutamate is widely distributed in CNS neurons, but it becomes
a neurotransmitter only if it is appropriately packaged in vesicles in the axon terminal. The
amino acid transmitter glycine (Gly) is a much more common inhibitory transmitter in the brain
stem and spinal cord, where it acts within the Renshaw loop, for example (review Figure 59).
FIGUre 5-11 Sequential Synthesis of
Three Amines A different enzyme is Enzyme 4
Enzyme 1 Enzyme 2 Enzyme 3
responsible for each successive molecular
modification in this biochemical sequence
Tyrosine L-Dopa Dopamine Norepinephrine Epinephrine
of amine neurotransmitters. The twins
featured in Focus 3-1 lack an enzyme that
enhances DA production.
Peptide Transmitters
More than 50 short amino acid chains of various lengths (fewer than 100) form the fami
lies of peptide transmitters, or neuropeptides, listed in Table 5-2. Synthesized through the
translation of mRNA from instructions contained in the neuron’s DNA, neuropeptides are
multifunctional chains of amino acids that act as neurotransmitters.
Figure 3-15 diagrams peptide bonding and In some neurons, peptide transmitters are made in the axon terminal, but most are assem
Figure 3-17, protein export. bled on the neuron’s ribosomes, packaged in a membrane by Golgi bodies, and transported
by the microtubules to the axon terminals. The entire process of neuropeptide synthesis and
transport is relatively slow compared with the nearly readymade smallmolecule neurotrans
mitters. Consequently, peptide transmitters act slowly and are not replaced quickly.
5-2 • Varieties of Neurotransmitters and Receptors 151
Neuropeptides, however, perform an enormous COOH COOH FIGUre 5-12 Amino Acid
range of functions in the nervous system, as might be Transmitters Top: Removal of a
CH2 CH2 carboxyl (COOH) group from the bottom of
expected from their large numbers. They act as hor
the glutamate molecule produces GABA.
mones that respond to stress, enable a mother to bond CH2 CH2
Bottom: Their different shapes, illustrated
with her infant, regulate eating and drinking and plea by three-dimensional space-filling models,
H2N CH H2N CH
sure and pain, and probably contribute to learning. thus allow these amino acid transmitters to
Opium and related synthetic chemicals such as COOH bind to different receptors.
morphine, long known both to produce euphoria and Glutamate GABA
to reduce pain, appear to mimic the actions of endog
enous brain opioid neuropeptides: enkephalins, dynor
phins, and endorphins. (The term enkephalin derives
from the phrase in the cephalon, meaning in the brain
or head, whereas the term endorphin is a shortened
form of endogenous morphine.)
A part of the amino acid chain in each of these nat
Met-enkephalin
urally occurring opioid peptides is structurally similar
Tyr Gly Gly Phe Met
to the others, as illustrated for two of them in Figure 5-13. Presumably, opium mimics this
part of the chain. The discovery of naturally occurring opiumlike neuropeptides suggested
that one or more of them might have analgesic properties and take part in pain perception. Leu-enkephalin
It turns out that betaendorphin, released in response to exercise and thought responsible Tyr Gly Gly Phe Leu
for runner’s high, has many times the analgesic potency of morphine.
Some CNS peptides take part in specific periodic behaviors, each month or each year FIGUre 5-13 Opioid Peptides Parts
perhaps. For instance, in female deer, neuropeptide transmitters act as hormones (luteini of the amino acid chains of some
neuropeptides that act on brain centers for
zing hormone) that prepare her for the fall mating season. Come winter, a different set
pleasure and pain are structurally similar
of biochemicals facilitates the developing deer fetus. When the mother gives birth in and also share similarities to drugs such
the spring, yet another set of highly specific neuropeptide hormones—such as oxytocin, as opium and morphine, which mimic their
which enables her to bond to her fawn, and prolactin, which enables her to nurse—takes functions (see Section 6-2).
control.
The same neuropeptides serve similar specific hormonal functions in humans. Others, Sections 12-4 and 12-5 explain hormonal
such as neuropeptide growth hormones, perform far more general functions in regulating influence over human emotional and
growth. Unlike smallmolecule transmitters that bind to ion channels, neuropeptides have motivated behavior.
no direct effects on postsynaptic membrane voltage. Instead, peptide transmitters activate
synaptic receptors that indirectly influence cell structure and function. Digestive processes
degrade neuropeptide amino acid chains, so they generally cannot be taken orally as drugs,
as smallmolecule transmitters can. rate-limiting factor Any chemical in limited
supply that restricts the pace at which
taBLe 5-2 peptide Neurotransmitters another chemical can be synthesized.
serotonin (5-Ht) Amine neurotransmitter;
Family examples
helps to regulate mood and aggression, appetite
Opioids Met-enkephalin, dynorphin, beta-endorphin and arousal, perception of pain, and respiration.
Neurohypophyseals Vasopressin, oxytocin
glutamate (Glu) Amino acid
Secretins Secretin, motilin, glucagon, growth hormone–releasing factor neurotransmitter; typically excites neurons.
Insulins Insulin, insulin growth factors gamma-aminobutyric acid (GABA) Amino
Gastrins Gastrin, cholecystokinin acid neurotransmitter; typically inhibits neurons.
Somatostatins Somatostatin neuropeptide Short (fewer than 100),
Tachykinins Neurokinin A, neurokinin B, substance P multifunctional amino acid chain; acts as a
neurotransmitter and can act as a hormone;
may contribute to learning.
Lipid Transmitters endocannabinoid Class of lipid
Predominant among the lipid neurotransmitters are the endocannabinoids (endogenous neurotransmitters, including anandamide
cannabinoids), a class of lipid neurotransmitters synthesized at the postsynaptic membrane and 2-AG, synthesized at the postsynaptic
to act on receptors at the presynaptic membrane. The endocannabinoids include anan membrane to act on receptors at the presynaptic
damide and 2AG (2arachidonoylglycerol), both derived from arachidonic acid, an unsatu membrane; affects appetite, pain, sleep, mood,
rated fatty acid. Poultry and eggs are especially good sources. Endocannabinoids participate memory, anxiety, and the stress response.
152 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
CliniCAl F cus 5-3
Awakening with l-Dopa
He was started on l-dopa in March 1969. The dose was slowly raised neurotransmitter. l-Dopa has since become a standard treatment for
to 4.0 mg a day over a period of three weeks without apparently Parkinson disease. Its effects have been improved by the administration
producing any effect. I first discovered that Mr. E. was responding to of drugs that prevent l-dopa from being converted to dopamine in the
l-dopa by accident, chancing to go past his room at an unaccustomed body before it passes through the blood–brain barrier and gets to dopa-
time and hearing regular footsteps inside the room. I went in and found
mine neurons in the brain.
Mr. E., who had been chair bound since 1966, walking up and down his
l-Dopa is not a cure. Parkinson disease still progresses during
room, swinging his arms with considerable vigor, and showing erectness
of posture and a brightness of expression completely new to him. When
treatment, and as more and more dopamine synapses are lost, the
I asked him about the effect, he said with some embarrassment: “Yes! treatment becomes less and less effective. Eventually, l-dopa begins
I felt the l-dopa beginning to work three days ago—it was like a wave to produce dyskinesias—involuntary, unwanted movements, such
of energy and strength sweeping through me. I found I could stand and as ballistic (throwinglike) or choreic (dancelike) movements. When
walk by myself, and that I could do everything I needed for myself—but I these side effects eventually become severe, the treatment must be
was afraid that you would see how well I was and discharge me from the discontinued.
hospital.” (Sacks, 1976)
In this case history, neurologist Oliver Sacks describes administering
l-dopa to a patient who had acquired parkinsonism as an aftereffect of
severe influenza in the 1920s. The relation between the influenza and
the parkinsonian symptoms suggests that the flu virus had entered the
brain and selectively attacked dopamine neurons in the substantia nigra.
By increasing the amount of DA in remaining synapses, l-dopa relieved
the patient’s symptoms.
Two separate groups of investigators independently gave l-dopa to
Parkinson patients beginning in 1961 (Birkmayer & Hornykiewicz, 1961;
Everett Collection
Barbeau et al., 1961). Both research teams knew that the chemical is
catalyzed into dopamine at DA synapses (see Figure 5-11). The l-dopa
turned out to reduce the patients’ muscular rigidity.
This work was the first demonstration that a neurological condi- The movie Awakenings recounts the l-dopa trials conducted by Oliver
tion can be relieved by a drug that aids in increasing the amount of a Sacks and described in his book of the same title.
in a diverse set of physiological and psychological processes that affect appetite, pain, sleep,
mood, memory, anxiety, and the stress response. Their scientific history is brief but illus
trates how science can progress, punctuated by short steps.
Fatty acid molecules that contribute to Because endocannabinoids are lipophilic (fatloving) molecules, they are not soluble in
forming the cell membrane likewise are water and are not stored in vesicles. Rather, investigators hypothesize that endocannabi
hydrophobic. See Figure 3-11. noids are synthesized on demand after a neuron has depolarized and calcium has entered.
Calcium activates the enzyme transacylase, the first step in producing anandamide. Once
anandamide or 2AG is synthesized, it diffuses across the synaptic cleft and interacts
with its receptor on the presynaptic membrane. Thus, both molecules act as retrograde
neurotransmitters, for a time reducing the amount of smallmolecule transmitter being
released. In this way, the postsynaptic neuron has some control over the amount of incom
ing neural signal.
The CB1 receptor is the target of all cannabinoids, whether generated by the body (endo
cannabinoids), from plants (phytocannabinoids), or synthetically. CB1 receptors are found at
both glutamate and GABA synapses, and so cannabinoids act as neuromodulators to inhibit
release of glutamate and GABA. Cannabinoids thus dampen both neuronal excitation and
inhibition.
Cannabis is among the psychotropic drugs Phytocannabinoids are obtained from the hemp plants Cannabis sativa and Cannabis
discussed in Section 6-2. indica. These plants have been used medically and recreationally for thousands of years, but
only recently was an extract from cannabis synthesized. Early in the last century, many con
stituents of cannabis, including cannabidiol and tetrahydrocannabinol (THC), were isolated
5-2 • Varieties of Neurotransmitters and Receptors 153
and their chemical structure determined. In 1964, Yehiel Gaoni and Raphael Mechoulam
nitric oxide (NO) Gaseous neurotransmitter;
reported the structure of the THC molecule, the main psychoactive constituent in cannabis.
acts, for example, to dilate blood vessels, aid
Next, investigators determined how THC is metabolized. (The process is quite slow, which
digestion, and activate cellular metabolism.
explains why THC can be detected in urine for weeks after cannabis use.)
carbon monoxide (cO) Gaseous
Research on the physiological and psychological effects of THC in animals and people,
neurotransmitter; activates cellular
which began after its isolation and purification, is ongoing. Twentyfour years after the struc
metabolism.
ture of the THC molecule was determined, the first cannabinoid receptor (CB1) was found.
Typically, receptors are activated by endogenous molecules, which motivated researchers to hydrogen sulfide (H2s) Gaseous
neurotransmitter; slows cellular metabolism.
look for endogenous cannabinoids. Four years later, in 1992, anandamide was isolated and
its structure determined, but it took another couple of decades to figure out that endocan ionotropic receptor Embedded membrane
nabinoids act as retrograde transmitters (Mechoulam et al., 2014). protein; acts as (1) a binding site for a
neurotransmitter and (2) a pore that regulates
Gaseous Transmitters ion flow to directly and rapidly change
membrane voltage.
The gases nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) further
expand the biochemical strategies that transmitter substances display. As watersoluble gases, metabotropic receptor Embedded
membrane protein with a binding site for
they are neither stored in synaptic vesicles nor released from them; instead, the cell syn
a neurotransmitter linked to a G protein;
thesizes them on demand. After synthesis, each gas diffuses away, easily crossing the cell
can affect other receptors or act with
membrane and immediately becoming active. Both NO and CO activate metabolic (energy
second messengers to affect other cellular
expending) processes in cells, including processes modulating the production of other neu processes, including opening a pore.
rotransmitters. H2S prevents oxygen from binding in the mitochondria and thus functions
to slow down metabolism.
All three gaseous transmitters serve as chemical messengers in many parts of the body.
NO and H2S control intestinal wall muscles and dilate blood vessels in active brain regions,
allowing these regions to receive more blood. Because NO and H2S also dilate blood vessels
in the sexual organs, both are active in producing penile erections. Drugs used to treat erec
tile dysfunction in men, such as Viagra and Cialis, act by enhancing the chemical pathways
influenced by NO. NO does not of itself produce sexual arousal.
Varieties of Receptors
Each of the two general classes of receptor proteins produces a different effect: one directly
changes the postsynaptic membrane’s electrical potential, and the other induces cellular change
indirectly. A dazzling array of receptor subtypes allows for subtle differences in receptor function.
Two Classes of Receptors
When a neurotransmitter is released from any of the wide varieties of synapses onto a wide
variety of targets, as illustrated in Figure 56, it crosses the synaptic cleft and binds to a recep
tor. What happens next depends on the receptor type.
Ionotropic receptors allow the ions, such as Na1, K1, and Ca21, to move across a mem Structurally, ionotropic receptors resemble
brane (the suffix tropic means moving toward). As Figure 5-14 illustrates, an ionotropic voltage-sensitive channels, which propagate
receptor has two parts: (1) a binding site for a neurotransmitter and (2) a pore, or channel. the action potential. See Figure 4-17.
When the neurotransmitter attaches to
the binding site, the receptor quickly
Transmitter binds The pore opens, allowing
changes shape, either opening the pore
to the binding site. the influx or efflux of ions.
and allowing ions to flow through it or
closing the pore and blocking the ion Extracellular Ion
flow. Thus, ionotropic receptors bring fluid Transmitter
about rapid changes in membrane volt Binding site
age and are usually excitatory: they trig
ger an action potential.
FIGUre 5-14 Ionotropic
In contrast, a metabotropic receptor Receptor When activated, embedded
has a binding site for a neurotransmit Intracellular Pore Pore transmitter proteins bring about direct,
ter but lacks its own pore through which fluid closed open rapid changes in membrane voltage.
154 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
ions can flow. Through a series of steps, activated metabotropic receptors indirectly pro
duce changes in nearby membranebound ion channels or in the cell’s metabolic activity.
Figure 5-15A shows the first of these two indirect effects. The metabotropic receptor con
sists of a single protein that spans the cell membrane, its binding site facing the synaptic cleft.
Each receptor is coupled to one of a family of guanyl nucleotide–binding proteins, G proteins
for short, shown on the inner side of the cell membrane in Figure 515A. When activated, a
G protein binds to other proteins.
A G protein consists of three subunits: alpha, beta, and gamma. (A subunit is a protein
that assembles with other proteins.) The alpha subunit detaches when a neurotransmitter
binds to the G protein’s associated metabotropic receptor. The detached alpha subunit can
then bind to other proteins within the cell’s membrane or its intracellular fluid. If the alpha
subunit binds to a nearby ion channel in the membrane, as shown at the bottom of Figure
515A, the channel structure changes, modifying the flow of ions through it. If the channel
is open, the alpha subunit may close it or, if closed, it may open. Changes in the channel and
the ion flow across the membrane influence the membrane’s electrical potential.
Metabotropic
FIGUre 5-15 The binding of a neurotransmitter to a metabotropic receptor can also trigger more
Receptors When activated by a complicated cellular reactions, summarized in Figure 515B. All these reactions begin when
neurotransmitter, embedded membrane
the detached alpha subunit binds to an enzyme. The enzyme in turn activates a second
receptor proteins trigger associated
G proteins, exerting indirect effects
(A) on nearby ion channels or (B) in the
cell’s metabolic activity.
(A) Metabotropic receptor coupled to an ion channel (B) Metabotropic receptor coupled to an enzyme
Transmitter Transmitter binds Transmitter
Binding site Ion to receptor in both
Binding site
reactions.
Receptor Receptor
β γ β γ
α α
G protein Closed ion
G protein Enzyme
channel
Receptor-bound Receptor-bound
transmitter transmitter
The binding of the
transmitter triggers
β γ β γ
α the activation of a α
G protein in both
reactions.
The subunit of the G
protein binds to a
Extracellular fluid channel, causing a
structural change in the
channel that allows ions
to pass through it.
The subunit binds to an
β γ α β γ α
enzyme, which activates
Alpha subunit Open ion a second messenger.
Alpha subunit
channel
Second messenger
The second messenger
can activate other cell Activates Forms new
Intracellular fluid
processes. DNA ion channel
5-2 • Varieties of Neurotransmitters and Receptors 155
messenger (the neurotransmitter being the first messenger) that carries instructions to other
G protein Guanyl nucleotide–binding protein
cellular structures. As illustrated at the bottom of Figure 515B, the second messenger can
coupled to a metabotropic receptor; when
• bind to a membranebound channel, causing the channel to change its structure and activated, binds to other proteins.
thus alter ion flow through the membrane.
subunit Protein molecule that assembles
• initiate a reaction that incorporates intracellular (within the cell) protein molecules into with other protein molecules.
the cell membrane, resulting, for example, in the formation of new ion channels. second messenger Chemical that initiates
• bind to sites on the cell’s DNA to initiate or cease the production of specific proteins. a biochemical process when activated by a
neurotransmitter (the first messenger).
Metabotropic receptors also allow for the possibility that a single neurotransmitter’s
binding to a receptor can activate an escalating sequence of events called an amplification
cascade. The cascade effect is that many downstream proteins (second messengers or chan
nels or both) are activated or deactivated. Ionotropic receptors do not have such a widespread
amplifying effect.
Recall that acetylcholine has an excitatory effect on skeletal muscles. Here it activates
an ionotropic receptor. Conversely, acetylcholine has an inhibitory effect on the heart rate.
Here it activates a metabotropic receptor. Further, each transmitter may bind with several
different kinds of ionotropic or metabotropic receptors. Elsewhere in the nervous system, for
example, ACh may activate a wide variety of either receptor type.
Receptor Subtypes
While there are two general classes of receptors, ionotropic and metabotropic, each
neurotransmitter may interact with a number of receptor subtypes specific to that neuro
transmitter. Serotonin (5HT), for instance, has one ionotropic receptor subtype (5HT3) and
12 subtypes of metabotropic receptors. Table 5-3 lists the variety of smallmolecule neuro
transmitter receptor subtypes.
How is this variety achieved? Alternative forms of each subunit can assemble in unique
combinations to make a functional receptor. For instance, the functional NMDA recep
tor, an ionotropic receptor for glutamate, is always composed of 4 subunits, but a total of Figure 14-18 diagrams how glutamate and
12 distinct subunits are available to come together in various combinations to form the the NMDA receptor function in associative
functional receptor. learning.
Why does the brain contain so many receptor subtypes for each neurotransmitter? The
answer seems to be that each subtype has slightly different properties, which confer dif
ferent activities. These activities can include the presence or absence of binding sites for
other molecules, how long a channel remains open or closed, and the ability to interact with
intracellular signaling molecules.
taBLe 5-3 Small-molecule Transmitter receptors*
Neurotransmitter Ionotropic receptors Metabotropic receptors
Acetylcholine (ACh) Nicotinic Muscarinic† M1, M2, M3, M4, M5
Dopamine (DA) — D 1, D2 , D 3 , D4 , D 5
GABA GABA A GABAB
Glutamate (Glu) NMDA, AMPA, kainate mGluR1, mGluR2, mGluR3, mGluR4,
mGluR5, mGluR6, mGluR7
Glycine (Gly) Glycine, NMDA —
Histamine (H) — H1, H 2 , H 3
Norepinephrine (NE) — a 1a, a 1b, a 1c, a 1d, a2a, a2b, a2c, a2d,
b1 , b 2 , b 3
Serotonin (5-HT) 5-HT3 5-HT1A , 5-HT1B, 5-HT1D, 5-HT1E,
5-HT1F, 5-HT2A , 5-HT2B, 5-HT2C,
5-HT4, 5-HT5, 5-HT6, 5-HT7
*Peptide neurotransmitters and the lipid neurotransmitters anandamide and 2-AG have specific metabotropic-class
receptors. Gaseous neurotransmitters do not have a specific receptor.
†
All metabotropic cholinergic receptors are muscarinic.
156 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
It should not be surprising that a brain such as ours, with its incredible complexity, is built
upon a vast array of units, including copious neurotransmitter types and even more copious
receptor types. All this, and more, allows the human brain to function successfully.
5-2 reVIeW
Varieties of Neurotransmitters and Receptors
Before you continue, check your understanding.
1. Neurotransmitters are identified using four experimental criteria: ,
, , and .
2. The four broad classes of chemically related neurotransmitters are ,
, , and .
3. Acetylcholine is composed of and . After release into the
synaptic cleft, ACh is broken down by , and the products can be recycled.
4. Endocannabinoids are neurotransmitters, made on demand and released
from the membrane.
5. Contrast the major characteristics of ionotropic and metabotropic receptors.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
5-3 Neurotransmitter Systems
and Behavior
When researchers began to study neurotransmission, they reasoned that any given neuron
would contain only one transmitter at all its axon terminals. Newer methods of analysis
revealed that this hypothesis isn’t strictly accurate. A single neuron may use one transmitter
at one synapse and a different transmitter at another synapse. Moreover, different transmit
ters may coexist in the same terminal or synapse. Neuropeptides have been found to coexist
in terminals with smallmolecule transmitters, and more than one smallmolecule transmit
ter may be found in a single synapse. In some cases, more than one transmitter may even be
packaged within a single vesicle.
All these findings allow for multiple combinations of neurotransmitters and receptors
for them. They caution as well against assuming a simple causeandeffect relation between
a neurotransmitter and a behavior. What are the functions of so many combinations? The
answer will likely vary, depending on the behavior that is controlled. Generally, neurotrans
mission is simplified by concentrating on the dominant transmitter within any given axon
terminal. The neuron and its dominant transmitter can then be associated with a function
or behavior.
We now consider some links between neurotransmitters and behavior. We begin by
exploring the three peripheral nervous system divisions: SNS, ANS, and ENS. Then we
investigate neurotransmission in the central nervous system.
Neurotransmission in the Somatic
cholinergic neuron Neuron that uses
Nervous System
acetylcholine as its main neurotransmitter; Motor neurons in the brain and spinal cord send their axons to the body’s skeletal muscles,
cholinergic applies to any neuron that uses including the muscles of the eyes and face, trunk, limbs, fingers, and toes. Without these SNS
ACh as its main transmitter. neurons, movement would not be possible. Motor neurons are also called cholinergic neurons
5-3 • Neurotransmitter Systems and Behavior 157
because acetylcholine is their main neurotransmitter. At a skeletal muscle, cholinergic neu
rons are excitatory, producing muscular contractions.
Just as a single main neurotransmitter serves the SNS, so does a single main receptor, a
Axon
transmitteractivated ionotropic channel called a nicotinic acetylcholine receptor (nAChr). terminal
When ACh binds to this receptor, its pore opens to permit ion flow, thus depolarizing the
muscle fiber. The nicotinic receptor pore is large enough to permit the simultaneous efflux
of K1 and influx of Na1. The molecular structure of nicotine, a chemical found in tobacco,
activates the nAChr in the same way that acetylcholine does, which is how this receptor Synaptic
got its name. The molecular structure of nicotine is sufficiently similar to that of ACh that cleft
nicotine acts as a mimic, fitting into acetylcholine receptor binding sites.
Acetylcholine is the primary neurotransmitter at skeletal muscles, but other neurotrans
mitters also occupy these cholinergic axon terminals and are released onto the muscle
along with ACh. One is a neuropeptide called calcitonin gene–related peptide (CGRP),
which acts through CGRP metabotropic receptors to increase the force with which a
Muscle Muscle
muscle contracts. membrane cell
Nicotinic ACh Receptor Research from
Dual Activating Systems of the Autonomic J. E. Heuser and T. Reese, 1977, in E. R. Kandel, ed, The
Nervous System Nervous System, vol. 1, Handbook of Physiology. Oxford
University Press, p. 266.
The complementary ANS divisions, sympathetic and parasympathetic, regulate the body’s
internal environment. The sympathetic division rouses the body for action, producing
the fightorflight response. Heart rate ramps up and digestive functions ramp down. The
parasympathetic division calms the body down, producing an essentially opposite rest
anddigest response. Digestive functions ramp up, heart rate ramps down, and the body is
ready to relax.
Figure 5-16 shows the neurochemical organization of the ANS. Both divisions are con
trolled by acetylcholine neurons that emanate from the CNS at two levels of the spinal cord.
The CNS neurons synapse with parasympathetic neurons that also contain acetylcholine
and with sympathetic neurons that contain norepinephrine. In other words, cholinergic
Sympathetic division KEY Parasympathetic division
fight or flight Acetylcholine rest and digest
Norepinephrine
FIGUre 5-16 Controlling Biological
Functions in the Autonomic
Nervous System The neurotransmitter
in all the neurons leaving the spinal cord
is acetylcholine. Left: In the sympathetic
division, ACh neurons activate autonomic
norepinephrine neurons in the sympathetic
ganglia. NE stimulates organs required for
fight or flight and suppresses activity in
organs used to rest and digest. Right: In
the parasympathetic division, ACh neurons
from the spinal cord activate ACh neurons
in the parasympathetic ganglia near their
target organs to suppress activity in organs
used for fight or flight and to stimulate
organs used to rest and digest. To review
the ANS divisions and connections in detail,
see Figure 2-30.
158 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
neurons in the CNS synapse with sympathetic NE neurons to prepare the body’s organs
for fight or flight. Cholinergic neurons in the CNS synapse with autonomic ACh neurons
in the parasympathetic division to prepare the body’s organs to rest and digest.
Which type of synapse is excitatory and which inhibitory depends on the particular body
organ’s receptors. During sympathetic arousal, norepinephrine turns up heart rate and turns
down digestive functions, because NE receptors on the heart are excitatory, whereas NE
receptors on the gut are inhibitory. Similarly, acetylcholine turns down heart rate and turns
up digestive functions because its receptors on these organs are reversed: on the heart,
inhibitory; on the gut, excitatory. Neurotransmitter activity, excitatory in one location and
inhibitory in another, mediates the sympathetic and parasympathetic divisions, forming a
complementary autonomic regulating system that maintains the body’s internal environ
ment under varying circumstances.
Enteric Nervous System Autonomy
The ENS can act without input from the CNS, which is why it has been called the second
brain. It uses all four classes of neurotransmitters, more than 30 transmitters in total. Most
are identical to those employed by the CNS. Chief among the smallmolecule neurotransmit
ters used by the enteric nervous system are serotonin and dopamine.
Sensory ENS neurons detect mechanical and chemical conditions in the system. Via
intestinal muscles, motor neurons in the ENS control the mixing of intestinal contents.
Secretion of digestive enzymes is also under ENS control.
Four Activating Systems in the Central
Nervous System
Just as there is an organization to the neurochemical systems of the PNS, there is an organi
zation of neurochemical systems in the CNS. These systems are remarkably similar across a
wide range of animal species, which allowed for their identification, first in the rat brain and
then in the human brain (Hamilton et al., 2010).
For each of the four activating systems that we describe here, a relatively small number
of neurons grouped together in one or a few brainstem nuclei send axons to widespread
CNS regions, suggesting that these nuclei and their terminals help to synchronize activity
throughout the brain and spinal cord. You can envision an activating system as analogous to
the power supply in a house. The fuse or breaker box is the source of the power, and from it
transmission lines go to each room.
Just as in the ANS, the precise action of the CNS transmitter depends on the brain region
that is innervated and on the types of receptors the transmitter acts on at that region. To con
tinue our analogy, precisely what the activating effect of the power is in each room depends
on the electrical devices in that room.
Each of four smallmolecule transmitters participates in its own neural activating
system—the cholinergic, dopaminergic, noradrenergic, and serotonergic systems. Figure 5-17
locates each system’s nuclei, with arrow shafts mapping the axon pathways and arrowheads
indicating axon terminal locales.
As summarized on the right in Figure 517, each CNS activating system is associated with
numerous behaviors. Associations among activating systems, behavior, and brain disorders
are far less certain. All these relations are subjects of ongoing research. Making definitive
activating system Neural pathways that correlations between activating systems and behavior or activating systems and a disorder is
coordinate brain activity through a single difficult, because the axons of these systems connect to almost every part of the brain and
neurotransmitter; its cell bodies lie in a spinal cord. They likely have both specific functions and modulatory roles. We detail some
brainstem nucleus; axons are distributed of the documented relations between the systems and behavior and disorders here and in
through a wide CNS region. many subsequent chapters.
5-3 • Neurotransmitter Systems and Behavior 159
FIGUre 5-17 Major Activating
Frontal Corpus callosum Cholinergic system (acetylcholine) Systems Each system’s cell bodies are
cortex • Active in maintaining attention and waking EEG pattern.
gathered into nuclei (shown as ovals) in the
• Thought to play a role in memory by maintaining
neuron excitability. brainstem. Their axons project diffusely
• Death of cholinergic neurons and decrease in ACh through the CNS and synapse on target
in the neocortex are thought to be related to structures. Each activating system is
Alzheimer disease. associated with one or more behaviors or
diseases.
Basal forebrain
nuclei
Midbrain nuclei
Substantia Dopaminergic system (dopamine)
nigra Nigrostriatal pathways (orange projections)
• Active in maintaining normal motor behavior.
• Loss of DA is related to muscle rigidity and
dyskinesia in Parkinson disease.
Caudate nucleus Mesolimbic pathways (purple projections)
• Dopamine release causes feelings of reward and
pleasure.
• Thought to be the neurotransmitter system most
affected by addictive drugs and behavioral addictions.
• Increases in DA activity may be related to
Nucleus
accumbens schizophrenia.
in basal ganglia • Decreases in DA activity may be related to deficits
of attention.
Ventral tegmentum Cerebellum
Noradrenergic system (norepinephrine)
• Active in maintaining emotional tone.
• Decreases in NE activity are thought to be related
to depression.
• Increases in NE are thought to be related to mania
(overexcited behavior).
Thalamus • Decreased NE activity is associated with
hyperactivity and attention-deficit/hyperactivity
disorder.
Locus coeruleus
Serotonergic system (serotonin)
• Active in maintaining waking EEG pattern.
• Changes in serotonin activity are related to
obsessive-compulsive disorder, tics, and
schizophrenia.
• Decreases in serotonin activity are related to
depression.
• Abnormalities in brainstem 5-HT neurons are linked
to disorders such as sleep apnea and SIDS.
Raphe nuclei
160 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
FIGUre 5-18 Cholinergic Activation Neocortex Basal ganglia
Cholinergic System
Drawing at left shows the cortical location
of the micrograph at right, stained to reveal Basal ganglia Figure 5-18 shows in cross sec
AChE. Cholinergic neurons in the rat’s basal tion a rat brain stained for the
forebrain project to the neocortex, and the enzyme acetylcholinesterase
ian whishaw
darkly stained bands in the cortex show (AChE), which breaks down ACh
areas rich in cholinergic synapses. The in synapses, as diagrammed ear
darker central parts of the section, also rich
lier in Figure 510. The darkly
in cholinergic neurons, are the basal ganglia. Acetylcholine
stained areas have high AChE
synapses
Basal forebrain concentrations, indicating the
cholinergic neurons
presence of cholinergic termi
nals. AChE permeates the cortex and is especially dense in the basal ganglia. Many of these
cholinergic synapses are connections from ACh nuclei in the brainstem, as illustrated in the
top panel of Figure 517.
The cholinergic system participates in typical waking behavior, attention, and memory.
The EEG detects electrical signals the brain For example, cholinergic neurons take part in producing one form of waking EEG activ
emits during various conscious states; see ity. People affected by the degenerative Alzheimer disease, which begins with minor
Sections 7-2 and 13-3. forgetfulness, progresses to major memory dysfunction, and later develops into generalized
dementia, show a profound loss of cholinergic neurons at autopsy. One treatment strategy
for Alzheimer disease is drugs that stimulate the cholinergic system to enhance alertness.
But the beneficial effects of these drugs are minor at best (Herrmann et al., 2011). Recall
that ACh is synthesized from nutrients in food; thus, the role of diet in maintaining ace
tylcholine levels also is being investigated.
Focus 14-3 details research on Alzheimer The brain abnormalities associated with Alzheimer disease are not limited to the cho
disease. Section 16-3 reviews dementias’ linergic neurons, however. Autopsies reveal extensive damage to the neocortex and other
causes and treatments. brain regions. As a result, what role, if any, the cholinergic neurons play in the progress of
the disorder is not yet clear. Perhaps their destruction causes degeneration in the cortex or
perhaps the causeandeffect relation is the other way around, with cortical degeneration
causing cholinergic cell death. Then too, the loss of cholinergic neurons may be just one
of many neural symptoms of Alzheimer disease.
Dopaminergic System
Figure 517 maps the dopaminergic activating system’s two dis
tinct pathways. The nigrostriatal dopaminergic system plays a
major role in coordinating movement. As described through
Copyright Katsuyoshi Tanaka, courtesy of the mark morris dance group
out this chapter in relation to parkinsonism, when dopamine
neurons in the substantia nigra are lost, the result is a condition
of extreme muscular rigidity. Opposing muscles contract at the
same time, making it difficult for an affected person to move.
Parkinson patients also exhibit rhythmic tremors, espe
cially of the limbs, which signals a release of formerly inhib
ited movement. Although the causes of Parkinson disease are
not fully known, it can actually be triggered by the ingestion
of certain toxic drugs, as described in Clinical Focus 54, The
Case of the Frozen Addict. Those drugs may act as selective
neurotoxins that specifically kill dopamine neurons in the
substantia nigra.
Dopamine in the mesolimbic dopaminergic system may
Rhythmic movement helps Parkinson patients restore the balance between be the neurotransmitter most affected in addiction—to
neural excitation and inhibition—between the loss and the release of
food, to drugs, and to other behaviors that involve a loss of
behavior. Some patients participate in a specially designed Dance for PD
(http://danceforparkinsons.org/) class for people with Parkinson’s (PwP). impulse control. A common feature of addictive behaviors
Participants at the Mark Morris Dance Center, pictured here, report that is that stimulating the mesolimbic dopaminergic system
moving to music helps them regain muscle control. enhances responses to environmental stimuli, thus making
5-3 • Neurotransmitter Systems and Behavior 161
CliniCAl F cus 5-4
The Case of the Frozen Addict
Patient 1: During the first 4 days of July 1982, a 42-year-old man used Patient 1 had no serious postoperative complications and was much
4½ grams of a “new synthetic heroin.” The substance was injected improved 24 months after the surgery. He could dress and feed him-
intravenously three or four times daily and caused a burning sensation self, visit the bathroom with help, and make trips outside his home. He
at the site of injection. The immediate effects were different from heroin, also responded much better to medication. The accompanying diagrams
producing an unusual “spacey” high as well as transient visual distortions
contrast DA levels in the brain of a Parkinson patient before (left) and
and hallucinations. Two days after the final injection, he awoke to find that
2 years, 4 months after implantation (right).
he was “frozen” and could move only in “slow motion.” He had to “think
through each movement” to carry it out. He was described as stiff, slow,
Transplantation of fetal neurons to treat Parkinson disease typi-
nearly mute, and catatonic during repeated emergency room visits from cally does not work. Unlike the case of the frozen addict, Parkinson
July 9 to July 11. (Ballard et al., 1985, p. 949) disease is associated with a continuing, active process that destroys
dopaminergic neurons, including transplanted neurons, in the substan-
Patient 1 was one of seven young adults hospitalized at about the
tia nigra. Because Parkinson disease can affect as many as 20 people
same time in California. All showed symptoms of severe Parkinson dis-
per 100,000, scientists continue to experiment with new approaches to
ease that appeared very suddenly after drug injection. These symptoms
transplantation and with genetic approaches for modifying remaining
are extremely unusual in this age group. All who were affected report-
dopamine neurons (Lane et al., 2010).
edly injected a synthetic heroin that was being sold on the streets in the
summer of 1982.
J. William Langston (2008) and his colleagues found that the synthetic
heroin contained a contaminant called MPTP (1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine) resulting from poor technique during its synthesis.
The results of experimental studies in rodents showed that MPTP was
not itself responsible for the patients’ symptoms but was metabolized
into MPP1 (1-methyl-4-phenylpyridinium), a neurotoxin.
The autopsy of one individual who was suspected of having died of MPTP
poisoning showed that the brain had selectively lost dopamine neurons in the
substantia nigra. The rest of the brain appeared healthy. Injecting MPTP into
monkeys, rats, and mice produced similar symptoms and a similar selective
loss of dopaminergic neurons in the substantia nigra. Thus, the combined
clinical and experimental evidence indicates that a toxin can selectively kill
dopamine neurons and that the die-off can induce Parkinson disease.
DA levels before fetal DA cell DA production at 2 years, 4 months
In 1988, Patient 1 received an experimental treatment at University Hos- implantation after implantation
pital in Lund, Sweden. Living dopamine neurons taken from human fetal
These diagrams represent PET scans that contrast DA levels in a Parkinson
brains at autopsy were implanted into the caudate nucleus and putamen patient’s brain before, and 28 months after, implantation. Research from
(Widner et al., 1992). Extensive work with rodents and nonhuman primates “Bilateral Fetal Mesencephalic Grafting in Two Patients with Parkinsonism Induced
in a number of laboratories had demonstrated that fetal neurons, before by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyradine (MPTP),” by H. Widner, J. Tetrud, S.
they develop dendrites and axons, can survive transplantation, mature, and Rehngrona, B. Snow, P. Brundin, B. Gustavii, A. Bjorklund, O. Lindvall, and J. W. Langston,
secrete neurotransmitters. 1992, New England Journal of Medicine, 327, p. 151.
those stimuli attractive and rewarding. Indeed, some Parkinson patients who take dopa Sections 6-3, 6-4, and 12-3 describe drug
mine receptor agonists as medications show a loss of impulse control that manifests effects on the mesolimbic DA system. Sections
in such behaviors as pathological gambling, hypersexuality, and compulsive shopping 6-2 and 7-4 discuss schizophrenia’s possible
(Moore et al., 2014). causes and Section 16-4, its neurobiology.
Excessive mesolimbic dopaminergic activity is proposed as well to play a role in
schizophrenia, a behavioral disorder characterized by delusions, hallucinations, disorga Alzheimer disease Degenerative brain
nized speech, blunted emotion, agitation or immobility, and a host of associated symptoms. disorder related to aging; first appears as
Schizophrenia is one of the most common and most debilitating psychiatric disorders, affect progressive memory loss and later develops
ing about 1 in 100 people. into generalized dementia.
schizophrenia Behavioral disorder
Noradrenergic System characterized by delusions, hallucinations,
Norepinephrine (noradrenaline) may participate in learning by stimulating neurons to disorganized speech, blunted emotion,
change their structure. Norepinephrine may also facilitate healthy brain development agitation or immobility, and a host of
and contribute to organizing movements. A neuron that uses norepinephrine as its associated symptoms.
162 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
transmitter is termed a noradrenergic neuron (derived from adrenaline, the Latin name
for epinephrine).
In the main, behaviors and disorders related to the noradrenergic system concern the emo
tions. Some symptoms of major depression—a mood disorder characterized by prolonged
feelings of worthlessness and guilt, the disruption of typical eating habits, sleep disturbances,
a general slowing of behavior, and frequent thoughts of suicide—may be related to decreased
activity of noradrenergic neurons. Conversely, some symptoms of mania (excessive excitability)
may be related to increased activity in these same neurons. Decreased NE activity has also
been associated both with hyperactivity and attentiondeficit/hyperactivity disorder (ADHD).
Serotonergic System
The serotonergic activating system maintains a waking EEG in the forebrain when we move
and thus participates in wakefulness, as does the cholinergic system. Like norepinephrine,
serotonin plays a role in learning, as described next in Section 54. Some symptoms of depres
sion may be related to decreased activity in serotonin neurons, and drugs commonly used to
treat depression act on 5HT neurons. Consequently, two forms of depression may exist, one
related to norepinephrine and another related to serotonin.
Likewise, some research results suggest that various symptoms of schizophrenia also may
be related to increases in serotonin activity, which implies that different forms of schizophre
nia may exist. Decreased serotonergic activity is related to symptoms observed in obsessive-
Consult the Index of Disorders inside the compulsive disorder (OCD), in which a person compulsively repeats acts (such as hand
book’s front cover for more information on washing) and has repetitive and often unpleasant thoughts (obsessions). Evidence also points
major depression, mania, ADHD, OCD, sleep to a link between abnormalities in serotonergic nuclei and conditions such as sleep apnea and
apnea, and SIDS. sudden infant death syndrome (SIDS).
5-3 reVIeW
Neurotransmitter Systems and Behavior
Before you continue, check your understanding.
1. Although neurons can synthesize more than one , they are usually
identified by the principal in their axon terminals.
2. In the peripheral nervous system, the neurotransmitter at somatic muscles is
; in the autonomic nervous system, neurons from the
spinal cord connect with neurons for parasympathetic activity and with
neurons for sympathetic activity.
3. The two principal small-molecule transmitters used by the enteric nervous system are
and .
4. The four main activating systems of the CNS are , ,
, and .
5. How would you respond to the comment that a behavior is caused solely by a chemical
imbalance in the brain?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
5-4 Adaptive Role of Synapses
in Learning and Memory
Among our most cherished abilities are learning and remembering. Neuroplasticity is a
requirement for learning and memory and a characteristic of the mammalian brain. In fact,
it is a trait of the nervous systems of all animals, even the simplest worms. Larger brains with
5-4 • Adaptive Role of Synapses in Learning and Memory 163
more connections are more plastic, however, and thus likely to show more adaptability in Experiment 2-1 demonstrates observational
neural organization. learning in the octopus and the ubiquity of
Greater adaptability happens because experience can alter the synapse. Not only are neuroplasticity.
synapses versatile in structure and function, they are plastic: they can change. The synapse,
therefore, is the site for the neural basis of learning, a relatively permanent change in behav
ior that results from experience.
Donald O. Hebb (1949) was not the first to suggest that learning is mediated by structural
changes in synapses. But the change that he envisioned in his book The Organization of
Behavior was novel 65 years ago. Hebb theorized, “When an axon of cell A is near enough to
excite a cell B and repeatedly or persistently takes part in firing it, some growth process or
metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells
firing B, is increased” (Hebb, 1949, p. 62). Simply put, cells that fire together wire together. A Hebb’s “cell-assembly” diagram appears at
synapse that physically adapts in this way is called a Hebb synapse today. the end of Section 15-1.
Eric Kandel was awarded a Nobel Prize in 2000 for his descriptions of the synaptic basis
of learning in a way that Hebb envisaged: learning in which the conjoint activity of nerve
cells serves to link them. Kandel’s subject, the marine slug Aplysia californica, is an ideal
Copyright © earley, Steve/animals
subject for learning experiments. Slightly larger than a softball and lacking a shell, Aplysia
animals—all rights reserved.
has roughly 20,000 neurons. Some are quite accessible to researchers, who can isolate and
study circuits having few synapses.
When threatened, Aplysia defensively withdraws its more vulnerable body parts—the gill
(through which it extracts oxygen from the water to breathe) and the siphon (a spout above
the gill that excretes seawater and waste). By stroking or shocking the slug’s appendages,
Kandel and his coworkers (Bailey et al., 2015) produced enduring changes in its defensive Aplysia californica
behaviors. They used these behavioral responses to study underlying changes in Aplysia’s
nervous system.
We illustrate the role of synapses in two kinds of learning that Kandel has studied: habit Section 14-4 investigates the neural bases of
uation and sensitization. For humans, both are called unconscious because they do not brain plasticity in conscious learning and in
depend on a person’s knowing precisely when and how they occur. memory.
Habituation Response
In habituation, the response to a stimulus weakens with repeated stimulus presentations.
If you are accustomed to living in the country, then move to a city, you might at first find
the sounds of traffic and people extremely loud and annoying. With time, however, you stop
noticing most of the noise most of the time. You have habituated to it. noradrenergic neuron From adrenaline,
Habituation develops with all our senses. When you first put on a shoe, you feel it on Latin for epinephrine; a neuron containing
your foot, but very soon it is as if the shoe were not there. You have not become insensitive norepinephrine.
to sensations, however. When people talk to you, you still hear them; when someone steps major depression Mood disorder characterized
on your foot, you still feel the pressure. Your brain simply has habituated to the customary by prolonged feelings of worthlessness and
background sensation of a shoe on your foot. guilt, the disruption of normal eating habits, sleep
Aplysia habituates to waves in the shallow tidal zone where it lives. These slugs are con disturbances, a general slowing of behavior, and
stantly buffeted by the flow of waves against their body, and they learn that waves are just frequent thoughts of suicide.
the background noise of daily life. They do not flinch and withdraw every time a wave passes mania Disordered mental state of extreme
over them. They habituate to this stimulus. excitement.
A sea slug that is habituated to waves remains sensitive to other touch sensations. Prodded obsessive-compulsive disorder (OcD)
with a novel object, it responds by withdrawing its siphon and gill. The animal’s reaction Behavior characterized by compulsively
to repeated presentations of the same novel stimulus forms the basis for Experiment 5-2, repeated acts (such as hand washing)
studying its habituation response. and repetitive, often unpleasant, thoughts
(obsessions).
Neural Basis of Habituation learning Relatively permanent change in
The Procedure section of Experiment 52 shows the setup for studying what happens to behavior that results from experience.
the withdrawal response of Aplysia’s gill after repeated stimulation. A gentle jet of water habituation Learned behavior in which
is sprayed on the siphon while gill movement is recorded. If the water jet is presented to the response to a stimulus weakens with
Aplysia’s siphon as many as 10 times, the gill withdrawal response is weaker some minutes repeated presentations.
164 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
ExPErimENt 5-2 later, when the animal is again tested. The decrement in the strength
of the withdrawal is habituation, which can last as long as 30 minutes.
Question: What happens to the gill response after repeated
stimulation? The Results section of Experiment 52 starts by showing a simple
representation of the pathway that mediates Aplysia’s gill withdrawal
Procedure response. For purposes of illustration, only one sensory neuron, one
1 Gill withdraws 2 Gill no longer motor neuron, and one synapse are shown; in actuality, about 300 neu
from water jet. withdraws from
water jet,
rons may take part in this response. The water jet stimulates the sen
Siphon
demonstrating sory neuron, which in turn stimulates the motor neuron responsible
habituation. for the gill withdrawal. But exactly where do the changes associated
After with habituation take place? In the sensory neuron? In the motor neu
repeated ron? In the synapse between the two?
stimulation Habituation does not result from an inability of either the sensory or the
Water jet motor neuron to produce action potentials. In response to direct electrical
stimulation, both the sensory neuron and the motor neuron retain the abil
Result ity to generate action potentials even after habituation. Electrical recordings
from the motor neuron show that as habituation develops, the excitatory
The sensory neuron stimulates the motor neuron
postsynaptic potentials (EPSPs) in the motor neuron become smaller.
to produce gill withdrawal before habituation.
The most likely way in which these EPSPs decrease in size is that
the motor neuron is receiving less neurotransmitter from the sen
sory neuron across the synapse. And if less neurotransmitter is being
Sensory neuron
Motor neuron received, then the changes accompanying habituation must be taking
Skin of place in the presynaptic axon terminal of the sensory neuron.
siphon
Gill
muscle Reduced Sensitivity of Calcium
Channels Underlies Habituation
+
1 With habituation, the influx
Ca2 Kandel and his coworkers measured neurotransmitter output from
of calcium ions in response to an
action potential decreases,… a sensory neuron and verified that less neurotransmitter is in fact
released from a habituated neuron than from a nonhabituated one.
Recall from Figure 55 that neurotransmitter release in response
to an action potential requires an influx of calcium ions across the
2 …resulting in less
neurotransmitter presynaptic membrane. As habituation takes place, that Ca21 influx
Presynaptic released at the decreases in response to the voltage changes associated with an action
membrane
presynaptic membrane... potential. Presumably, with repeated use, voltagesensitive calcium
channels become less responsive to voltage changes and more resis
tant to the passage of calcium ions.
Postsynaptic membrane The neural basis of habituation lies in the change in presynaptic
calcium channels. Its mechanism, which is summarized close up in
3 …and less the Results section of Experiment 52, is a reduced sensitivity of cal
2+
depolarization of the cium channels and a consequent decrease in neurotransmitter release.
Ca postsynaptic membrane. Thus, habituation can be linked to a specific molecular change, as
summarized in the experiment’s Conclusion.
Conclusion: The withdrawal response weakens with repeated
presentation of water jet (habituation) owing to decreased
Ca 21 influx and subsequently less neurotransmitter release
from the presynaptic axon terminal.
Sensitization Response
A sprinter crouched in her starting blocks is often hyperresponsive to
the starter’s gun: its firing triggers in her a rapid reaction. The stress
ful, competitive context of the race helps to sensitize the sprinter to
sensitization Learned behavior in which
this sound. Sensitization, an enhanced response to some stimulus, is the opposite of habitu
the response to a stimulus strengthens with
repeated presentations. ation. The organism becomes hyperresponsive to a stimulus rather than accustomed to it.
Sensitization occurs within a context. Sudden, novel stimulation heightens our general
posttraumatic stress disorder (PtsD)
awareness and often results in largerthantypical responses to all kinds of stimulation. If a
Syndrome characterized by physiological
loud noise startles you suddenly, you become much more responsive to other stimuli in your
arousal associated with recurrent memories
and dreams arising from a traumatic event surroundings, including some to which you previously were habituated. In posttraumatic
that occurred months or years earlier. stress disorder (PTSD), physiological arousal related to recurring memories and dreams
5-4 • Adaptive Role of Synapses in Learning and Memory 165
surrounding a traumatic event persist for months or years after the event. One characteristic Stress can foster and prolong PTSD effects.
of PTSD is a heightened response to stimuli, suggesting that the disorder is in part related See Sections 6-5 and 12-4. Section 16-4
to sensitization. covers treatment strategies.
The same thing happens to Aplysia. Sudden, novel stimuli can
heighten a slug’s responsiveness to familiar stimulation. When attacked
ExPErimENt 5-3
by a predator, for example, the slug displays heightened responses to Question: What happens to the gill response in sensitization?
many other stimuli in its environment. In the laboratory, a small electric
Procedure
shock to Aplysia’s tail mimics a predatory attack and effects sensitiza
tion, as illustrated in the Procedure section of Experiment 5-3. A single
electric shock to the slug’s tail enhances its gill withdrawal response for Gill withdrawal
a period that lasts for minutes to hours.
A single shock to the tail
Neural Basis of Sensitization enhances the gill withdrawal
response (sensitization).
The neural circuits participating in sensitization differ from those that
take part in a habituation response. The Results section of Experi
ment 53 shows the sensory and motor neurons that produce the gill
withdrawal response and adds an interneuron that is responsible for Water jet Shock
sensitization.
An interneuron that receives input from a sensory neuron in Aplysia’s Results
tail (and so carries information about the shock) makes an axoaxonic
synapse with a sensory neuron in the siphon. The interneuron’s axon An interneuron receives input from a shocked
terminal contains serotonin. Consequently, in response to a tail shock, sensory neuron in the tail and releases serotonin
onto the axon of a siphon sensory neuron.
the tail sensory neuron activates the interneuron, which in turn releases
5HT onto the axon of the siphon sensory neuron. Information from the
siphon still comes through the sensory neuron to activate the motor Interneuron
neuron leading to the gill muscle, but the interneuron’s action in releas
ing 5HT onto the sensory neuron’s presynaptic membrane amplifies
the gill withdrawal response. Sensory Motor
neuron neuron Gill
At the molecular level, shown close up in Experiment 53 Results,
Skin of muscle
the serotonin released from the interneuron binds to a metabotropic siphon
serotonin receptor on the siphon’s sensory neuron axon. This binding
activates second messengers in the sensory neuron. Specifically, the 1 Serotonin reduces K+ efflux through
serotonin receptor is coupled through its G protein to the enzyme potassium channels, prolonging an action
potential on the siphon sensory neuron.
adenyl cyclase. This enzyme increases the concentration of second Interneuron
messenger cyclic adenosine monophosphate (cAMP) in the presynaptic Motor
Serotonin
membrane of the siphon’s sensory neuron. K+ neuron
Through several chemical reactions, cAMP attaches a phosphate 2
molecule (PO4) to potassium channels, rendering them less responsive. 2 The prolonged
Second action potential
The closeup in Experiment 53 sums it up. In response to an action
Sensory messenger results in more
+
potential traveling down the axon of the siphon’s sensory neuron (such neuron Ca2 influx and
as one generated by a touch to the siphon), the potassium channels on increased
that neuron are slower to open. Consequently, K1 ions cannot repolar transmitter
release,...
ize the membrane as quickly as normal, so the action potential lasts
longer than it usually would. 3
3 …causing greater
Less-Responsive Potassium Channels depolarization of the
Underlie Sensitization postsynaptic
membrane after
The longerlasting action potential that occurs because potassium chan Ca2+ sensitization.
nels are slower to open prolongs Ca21 inflow. Ca21 influx is necessary
for neurotransmitter release. Thus, greater Ca21 influx results in more
Conclusion: Enhancement of the withdrawal response after
neurotransmitter being released from the sensory synapse onto the a shock is due to increased Ca 21 influx and subsequently
motor neuron. more neurotransmitter release from the presynaptic axon
This increased neurotransmitter release produces greater activa terminal.
tion of the motor neuron and thus a largerthannormal gill withdrawal
166 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
response. If the second messenger cAMP mobilizes more synaptic vesicles, making more
neurotransmitter ready for release into the sensory–motor synapse, gill withdrawal may also
be enhanced.
Sensitization, then, is the opposite of habituation at the molecular level as well as at the
behavioral level. In sensitization, more Ca21 influx results in more transmitter being released,
whereas in habituation, less Ca21 influx results in less neurotransmitter being released. The
structural basis of cellular memory in these two forms of learning is different, however. In
sensitization, the change takes place in potassium channels, whereas in habituation, the
change takes place in calcium channels.
Learning as a Change in Synapse Number
Neural changes associated with learning must last long enough to account for a relatively
permanent change in an organism’s behavior. The changes at synapses described in the pre
ceding sections develop quite quickly, but they do not last indefinitely, as memories often do.
How then, can synapses be responsible for the longterm changes associated with learning
and memory?
Repeated stimulation produces habituation and sensitization that can persist for months.
Brief training produces shortterm learning; longer training periods produce more enduring
learning. If you cram for an exam the night before you take it, you might forget the material
quickly, but if you study a little each day for a week, your learning may tend to endure. What
underlies this more persistent form of learning?
Researchers working with Eric Kandel (Bailey et al., 2015) found that the number and size
of sensory synapses change in welltrained, habituated, and sensitized Aplysia. Relative to a
control neuron, the number and size of synapses decrease in habituated animals and increase
in sensitized animals, as represented in Figure 5-19. Apparently, synaptic events associated
with habituation and sensitization can also trigger processes in the sensory cell that result in
the loss or formation of new synapses.
A mechanism through which these processes can take place begins with calcium ions
that mobilize second messengers to send instructions to nuclear DNA. The transcription
and translation of nuclear DNA in turn initiate structural changes at synapses, including
the formation of new synapses and new dendritic spines. Research Focus 55, Dendritic
Spines: Small but Mighty, summarizes experimental evidence about structural changes in
dendritic spines.
The second messenger cAMP plays an important role in carrying instructions regarding
these structural changes to nuclear DNA. The evidence for cAMP’s involvement comes from
studies of the fruit fly Drosophila. Two genetic mutations in the fruit fly can produce similar
learning deficiencies. Both render the second messenger cAMP inoperative, but in opposite
ways. One mutation, called dunce, lacks the enzymes necessary to degrade cAMP, so the
fruit fly has abnormally high cAMP levels. The other mutation, called rutabaga, reduces
levels of cAMP below the normal range for Drosophila neurons.
Significantly, fruit flies with either mutation are impaired in acquiring habituated and
sensitized responses because their levels of cAMP cannot be regulated. New synapses seem
Motor
FIGUre 5-19 Physical Basis of neuron
Memory Relative to a control neuronal
connection (left), the number of synapses
between Aplysia’s sensory neuron and Sensory
a motor neuron decline as a result of neuron
habituation (center) and increase as
a result of sensitization (right). Such
structural changes may underlie
enduring memories. Control Habituated Sensitized
5-4 • Adaptive Role of Synapses in Learning and Memory 167
RESEARCH F cus 5-5
Dendritic Spines: Small but Mighty
Dendritic spines, which protrude from the dendrite’s shaft, measure summarizes synaptic structures that can be measured and related to
about 1 to 3 micrometers (mm, one-millionth of a meter) long and learning and behavior and to structural changes that may subserve
less than 1 mm in diameter. Each neuron can have many thousands of learning.
spines. The number of dendritic spines in the human cerebral cortex is Dendritic spines provide the structural basis for our behavior, our
estimated at 1014. individual skills, and our memories (Bosch & Hayashi, 2012). Impair-
Dendritic spines originate in filopodia (from the Latin file, for thread, ments in forming spines characterize some kinds of mental disability, and
and the Greek podium, for foot) that bud out of neurons, especially at the loss of spines is associated with the dementia of Alzheimer disease.
dendrites. Microscopic observation of dendrites shows that filopodia
are constantly emerging and retracting over times on the order of
seconds.
This budding of filopodia is much more pronounced in developing
neurons and in the developing brain (see Figure 8-13). Because filo-
podia can grow into dendritic spines, their budding suggests that they
are searching for contacts from axon terminals to form synapses. Increased axonal
transport
When contact is made, some new synapses may have only a short Increase in terminal
life; others will endure. size or area
A permanent dendritic spine tends to have a large, mushroom-
shaped head, giving it a large contact area with a terminal button, and Increase in
a long stem, giving it an identity apart from that of its dendrite. The number of
heads of spines and the terminals of presynaptic connections form synaptic vesicles
functional compartments that can generate huge electrical potentials Increase in
and so influence the neuron’s electrical messages. density of
Dendritic spines mediate learning that lasts, including habitua- contact zones
Change in
tion and sensitization. To mediate learning, each spine must be able size of
to act independently, undergoing changes that its neighbors do not synaptic cleft Increase in
undergo. spine size or
Examination of dendritic spines in the nervous system shows that area
some are simple and others complex. The cellular mechanisms that Change in dendrite
allow synapses to appear on spines and to change shape include stem length and
microfilaments linked to the membrane receptors, protein transport width Increase in
from the cell body, and the incorporation of nutrients from the extra- protein transport
cellular space. for spine
construction
The variety suggests that all this activity changes the appear-
ance of both presynaptic and postsynaptic structures. The illustration Synaptic structures that may subserve learning.
to be required for learning to take place, and the second messenger cAMP seems to carry
Drosophila
instructions to form them. Figure 5-20 summarizes these research findings.
More lasting habituation and sensitization are mediated by relatively permanent changes
in neuronal structure—by fewer or more synaptic connections—and the effects can be
difficult to alter. As a result of sensitization, for example, symptoms of PTSD can persist
indefinitely. cAMP
No learning High levels dunce
Learning Normal levels No mutation
5-4 reVIeW
No learning Low levels rutabaga
Adaptive Role of Synapses in Learning and Memory
Before you continue, check your understanding. Genetic Disruption of
FIGUre 5-20
1. Experience alters the , the site of the neural basis of ,a Learning Either of two mutations in the
fruit fly Drosophila inactivates the second
relatively permanent change in behavior that results from experience.
messenger cAMP by moving its level either
2. Aplysia’s synaptic function mediates two basic forms of learning: and above or below the concentration range the
. cell can regulate, thus disrupting learning.
168 Chapter 5 • HOW DO NEURONS COMMUNICATE AND ADAPT?
3. Changes that accompany habituation take place within the of the
neuron, mediated by channels that grow
sensitive with use.
4. The sensitization response is amplified by that release serotonin onto the
presynaptic membrane of the sensory neuron, changing the sensitivity of presynaptic
channels and increasing the influx of .
5. One characteristic of , defined as physiological arousal related to recurring
memories and dreams surrounding a traumatic event that persist for months or years
after the event, is a heightened response to stimuli. This suggests that the disorder is in
part related to .
6. Describe the benefits and/or drawbacks of permanent habituation and sensitization.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
SUMMarY
5-1 A Chemical Message with other neurons as well as with muscles, blood vessels, and
In the 1920s, Otto Loewi suspected that nerves to the heart secrete a extracellular fluid.
chemical that regulates its beat rate. His subsequent experiments with Functionally, neurons can be both excitatory and inhibitory, and they
frogs showed that acetylcholine slows heart rate, whereas epinephrine can participate in local circuits or in general brain networks. Excitatory
increases it. This observation proved key to understanding the basis of synapses are usually on a dendritic tree, whereas inhibitory synapses
chemical neurotransmission. are usually on a cell body.
The systems for chemically synthesizing an excitatory or inhibitory Some neurotransmitters are associated with both ionotropic
neurotransmitter are in the presynaptic neuron’s axon terminal or its and metabotropic receptors. An ionotropic receptor quickly and
soma, whereas the systems for neurotransmitter storage are in its directly induces voltage changes on the postsynaptic cell membrane.
axon terminal. The receptor systems on which that neurotransmitter Slower-acting metabotropic receptors activate second messengers
acts typically are on the postsynaptic membrane. Such chemical to indirectly produce changes in the cell’s function and structure. A
neurotransmission is dominant in the human nervous system. plethora of receptors, formed from combinations of multiple types of
Nevertheless, neurons also make direct connections with each other proteins called subunits, exist for most transmitters.
through gap junctions, channel-forming proteins that allow direct
sharing of ions or nutrients. 5-3 Neurotransmitter Systems and Behavior
The four major stages in the life of a neurotransmitter are (1) synthesis Because neurotransmitters are multifunctional, scientists find it
and storage, (2) release from the axon terminal, (3) action on postsynaptic impossible to isolate relations between a single neurotransmitter and a
receptors, and (4) inactivation. After synthesis, the neurotransmitter is single behavior. Rather, activating systems of neurons that employ the
wrapped in a membrane to form synaptic vesicles in the axon terminal. same principal neurotransmitter influence various general aspects of
When an action potential is propagated on the presynaptic membrane, behavior. For instance, acetylcholine, the main neurotransmitter in the
voltage changes set in motion the vesicles’ attachment to the presynaptic SNS, controls movement of the skeletal muscles, whereas acetylcholine
membrane and neurotransmitter release by exocytosis. and norepinephrine, the main neurotransmitters in the ANS, control the
One synaptic vesicle releases a quantum of neurotransmitter into body’s internal organs. In the ENS, dopamine and serotonin serve as the
the synaptic cleft, producing a miniature potential on the postsynaptic main neurotransmitters regulating the gut’s functioning.
membrane. To generate an action potential on the postsynaptic cell The CNS contains not only widely dispersed glutamate and GABA
requires simultaneous release of many quanta of transmitter. After neurons—its main neurotransmitters—but also neural activating systems
a transmitter has done its work, it is inactivated by such processes that employ acetylcholine, norepinephrine, dopamine, or serotonin. All
as diffusion out of the synaptic cleft, breakdown by enzymes, and these systems ensure that wide areas of the brain act in concert, and
reuptake of the transmitter or its components into the axon terminal each is associated with various classes of behaviors and disorders.
(or sometimes uptake into glial cells).
5-4 Adaptive Role of Synapses
5-2Varieties of Neurotransmitters in Learning and Memory
and Receptors Changes in synapses underlie the neural basis of learning and memory.
Small-molecule transmitters, peptide transmitters, lipid transmitters, In habituation, a form of learning in which a response weakens as
and gaseous transmitters are broad classes for ordering the roughly a result of repeated stimulation, calcium channels become less
100 neurotransmitters that investigators propose might exist. responsive to an action potential. Consequently, less neurotransmitter
Neurons containing these transmitters make a variety of connections is released when an action potential is propagated.
Key Terms 169
In sensitization, a form of learning in which a response strengthens In Aplysia, the number of synapses connecting sensory neurons
as a result of stimulation, changes in potassium channels prolong the and motor neurons decreases in response to repeated sessions of
action potential’s duration, resulting in an increased influx of calcium habituation. Conversely, the number of synapses connecting sensory
ions and consequently, release of more neurotransmitter. With repeated and motor neurons increases in response to repeated sensitization
training, new synapses can develop, and both forms of learning can sessions. These changes in the numbers of synapses and dendritic
become relatively permanent. spines are related to long-term learning.
KeY terMS
acetylcholine (ACh), p. 139 gap junction (electrical synapse), nitric oxide (NO), p. 153 schizophrenia, p. 161
activating system, p. 158 p. 143 noradrenergic neuron, p. 163 second messenger, p. 155
Alzheimer disease, p. 161 glutamate (Glu), p. 151 norepinephrine (NE), p. 139 sensitization, p. 164
autoreceptor, p. 144 habituation, p. 163 obsessive-compulsive disorder serotonin (5-HT), p. 151
carbon monoxide (CO), p. 153 histamine (H), p. 148 (OCD), p. 163 small-molecule transmitter,
chemical synapse, p. 143 hydrogen sulfide (H2S), p. 153 Parkinson disease, p. 141 p. 148
cholinergic neuron, p. 156 ionotropic receptor, p. 153 postsynaptic membrane, p. 143 storage granule, p. 143
dopamine (DA), p. 141 learning, p. 163 posttraumatic stress disorder subunit, p. 155
major depression, p. 163 (PTSD), p. 164 synaptic cleft, p. 141
endocannabinoid, p. 151
mania, p. 163 presynaptic membrane, p. 143 synaptic vesicle, p. 141
epinephrine (EP), p. 139
metabotropic receptor, p. 153 quantum (pl. quanta), p. 144 transmitter-activated receptor,
G protein, p. 155
neuropeptide, p. 151 rate-limiting factor, p. 151 p. 143
gamma-aminobutyric acid
(GABA), p. 151 neurotransmitter, p. 139 reuptake, p. 144 transporter, p. 143
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
this page left intentionally blank
ch a p te r
6 How Do Drugs and CliniCal FoCus 6-1 Cognitive enhanCement
6-1 PrinCiPles oF PsyChoPharmaCology
Hormones Influence the Drug routeS into the nervouS SyStem
Drug aCtion at SynapSeS: agoniStS anD antagoniStS
Brain and Behavior? an aCetylCholine SynapSe: exampleS of Drug aCtion
toleranCe
exPeriment 6-1 QueStion: Will the ConSumption of alCohol
proDuCe toleranCe?
SenSitization
exPeriment 6-2 QueStion: DoeS the injeCtion of a Drug
alWayS proDuCe the Same behavior?
6-2 grouPing PsyChoaCtive Drugs
group i: antianxiety agentS anD SeDative-hypnotiCS
CliniCal FoCus 6-2 fetal alCohol SpeCtrum DiSorDer
group ii: antipSyChotiC agentS
group iii: antiDepreSSantS anD mooD StabilizerS
CliniCal FoCus 6-3 major DepreSSion
group iv: opioiD analgeSiCS
group v: pSyChotropiCS
6-3 FaCtors inFluenCing inDiviDual resPonses to Drugs
behavior on DrugS
Katherine Streeter
aDDiCtion anD DepenDenCe
Sex DifferenCeS in aDDiCtion
6-4 exPlaining anD treating Drug abuse
Wanting-anD-liKing theory
Why DoeSn’t everyone abuSe DrugS?
treating Drug abuSe
Can DrugS CauSe brain Damage?
CliniCal FoCus 6-4 Drug-inDuCeD pSyChoSiS
6-5 hormones
hierarChiCal Control of hormoneS
ClaSSeS anD funCtionS of hormoneS
homeoStatiC hormoneS
gonaDal hormoneS
anaboliC–anDrogeniC SteroiDS
gluCoCortiCoiDS anD StreSS
171
172 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
CliniCal F cus 6-1
Cognitive Enhancement
A new name for an old game? An article in the preeminent science pub- The complex neural effects of amphetamine stimulants center on
lication Nature floated the idea that certain “cognitive-enhancing” drugs learning at the synapse by means of habituation and sensitization. With
improve school and work performance in otherwise healthy individuals repeated use for nonmedicinal purposes, the drugs can also begin to
by improving brain function (Greely et al., 2008). The article was insti- produce side effects, including sleep disruption, loss of appetite, and
gated in part by reports that up to 20 percent—and in some schools headaches. Some people develop cardiovascular abnormalities and/or
up to 80 percent—of high school and university students were using become addicted to amphetamine.
the combination of Adderall (mainly dextroamphetamine) and methyl- Treating ADHD with prescription drugs is itself controversial, despite
phenidate (Ritalin) as a study aid to help meet deadlines and to cram for their widespread use for this purpose. According to Aagaard and Hansen
examinations. (2011), assessing the adverse effects of cognitive enhancement medica-
Both drugs are prescribed as a treatment for attention-deficit/ tion is hampered because many participants drop out of studies and the
hyperactivity disorder (ADHD), a developmental disorder characterized duration of the studies is short.
by core behaviors: impulsivity, hyperactivity, and/or inattention. Methyl- Despite the contention that stimulant drugs can improve school and
phenidate and dextroamphetamine are Schedule II drugs, signifying that work performance by improving brain function in otherwise healthy indi-
they carry the potential for abuse and require a prescription when used viduals, evidence for their effectiveness, other than a transient improve-
medically. Their main illicit source is through falsified prescriptions or ment in motivation, is weak.
purchase from someone who has a prescription. Both drugs share the
pharmacological properties of cocaine: stimulating dopamine release and
blocking its reuptake (see Section 6-2).
The use of cognitive enhancers is not new. In his classic paper on
cocaine, Viennese psychoanalyst Sigmund Freud stated in 1884, “The
main use of coca [cocaine] will undoubtedly remain that which the Indi-
ans [of Peru] have made of it for centuries . . . to increase the physical
capacity of the body.” Freud later withdrew his endorsement when he
robert Stolarik/the new york times
realized that cocaine is addictive.
In 1937, an article in the Journal of the American Medical Association
reported that a form of amphetamine, Benzedrine, improved performance
on mental efficiency tests. This information was quickly disseminated among
students, who began using the drug as a study aid for examinations. In the
1950s, dextroamphetamine, marketed as Dexedrine, was similarly prescribed
for narcolepsy, a sleep disorder, and used illicitly by students as a study aid.
psychopharmacology, the study of how drugs affect the nervous system and behavior,
is the subject of this chapter. We begin by looking at the major ways drugs are administered,
the routes they take to reach the central nervous system, and how they are eliminated from
the body. We then group psychoactive drugs based on their major behavioral effects and on
how they act on neurons. Next we consider why different people may respond differently
to the same dose of a drug and why people may become addicted to drugs. Many principles
related to drugs also apply to the action of hormones, the chapter’s final topic, which includes
a discussion of synthetic steroids that act as hormones.
Before we examine how drugs produce their effects on the brain for good or for ill,
we must raise a caution: the sheer number of neurotransmitters, receptors, and possible
sites of drug action is astounding. Most drugs act at many sites in the body and brain and
affect more than one neurotransmitter system, and most receptors on which drugs act
display many variations. Individual differences—sex, genetic makeup, age, height, and
weight—all influence how drugs affect people. Considering all the variables, psycho-
pharmacological research has made important advances in understanding drug action.
Yet it remains safe to say that neuroscientists do not know everything there is to know
about any drug.
6-1 • Principles of Psychopharmacology 173
6-1 rinciplesof
P attention-deficit/hyperactivity disorder
Psychopharmacology
(ADHD) Developmental disorder
characterized by core behavioral symptoms,
including impulsivity, hyperactivity, and/or
Drugs are chemical compounds administered to bring about some desired change in the
inattention.
body and brain. Drugs are usually used to diagnose, treat, or prevent illness; to relieve pain
and suffering; or to improve some adverse physiological condition. In this chapter, we focus psychopharmacology Study of how drugs
on psychoactive drugs—substances that alter mood, thought, or behavior; are used to man- affect the nervous system and behavior.
age neuropsychological illness; and may be abused. We also consider psychoactive drugs that psychoactive drug Substance that acts
can act as toxins, producing sickness, brain damage, or death. to alter mood, thought, or behavior; is used
to manage neuropsychological illness; or is
abused.
DrugRoutesintotheNervousSystem
To be effective, a psychoactive drug has to reach its target in the nervous system. The way
a drug enters and passes through the body to reach its target is called its route of adminis-
tration. Drugs can be administered orally, inhaled into the lungs, administered rectally in
a suppository, absorbed from patches applied to the skin or
mucous membranes, or injected into the bloodstream, into Injecting a drug directly Drugs injected into
a muscle, or even into the brain. Figure 6-1 illustrates some into the brain allows it to muscle encounter
of these routes of drug administration and summarizes the act quickly in low doses more barriers than do
because there are no drugs inhaled.
characteristics of drugs that allow them to pass through vari- barriers.
ous barriers to reach their targets. Drugs inhaled into the
Oral administration is easy and convenient but is nonethe- Taking drugs orally lungs encounter few
is the safest, barriers en route to
less a complex route. To reach the bloodstream, an ingested
easiest, and most the brain.
drug must first be absorbed through the lining of the stomach convenient way to
or small intestine. Drugs in liquid form are absorbed more administer them. Drugs injected into the
readily. Drugs taken in solid form are not absorbed unless the bloodstream encounter
Drugs that are weak the fewest barriers to
stomach’s gastric juices can dissolve them. Some drugs may acids pass from the the brain but must be
be destroyed or altered by enzymes in the gastrointestinal stomach into the hydrophilic.
tract’s microbiome. Whether a drug is an acid or a base influ- bloodstream.
Drugs contained in
ences its absorption.
Drugs that are adhesive patches are
Once absorbed by the stomach or intestine, the drug must weak bases pass absorbed through
enter the bloodstream. This leg of the journey requires that from the intestines the skin and into the
the drug have additional properties. Because blood has a to the bloodstream. bloodstream.
high water concentration, the drug must be water-soluble. It
Figure 6-1 RoutesofDrug
is then diluted by the approximately 6 liters of blood that circulates through an adult body.
Administration
When the drug leaves the bloodstream, the body’s roughly 35 liters of extracellular fluid
further dilute it.
Drugs administered as gases or aerosols penetrate the cell linings of the respiratory tract
easily and are absorbed across these membranes into the bloodstream nearly as quickly as
they are inhaled. Thus, they reach the bloodstream by circumventing the barriers in the
digestive system. When administered as a gas or in smoke, drugs of abuse, including nicotine,
cocaine, and marijuana, are similarly absorbed.
Our largest organ, the skin, has three cell layers designed to be a protective body coat.
Some small-molecule drugs (e.g., nicotine in a patch) penetrate the skin barrier almost as eas-
ily as they penetrate the lungs. Still fewer obstacles confront a drug destined for the brain if
that drug is injected directly into the bloodstream. The fewest obstacles are encountered if
a psychoactive drug is injected directly into the brain.
With each obstacle eliminated en route to the brain, a drug’s dosage can be reduced by
a factor of 10. For example, 1000 micrograms (mg; 1 mg is equal to one-millionth of a gram) 1000 mg = 1 mg (milligram)
of amphetamine, a psychomotor stimulant and major component of the drugs described
in Clinical Focus 6-1, Cognitive Enhancement, produces a noticeable behavioral change
when ingested orally. If inhaled into the lungs or injected into the blood, circumventing the
174 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
stomach, a dose of just 100 mg produces the same results. If amphetamine is injected into the
cerebrospinal fluid, bypassing both the stomach and the blood, 10 mg is enough to produce
an identical outcome, as is merely 1 mg if dilution in the cerebrospinal fluid also is skirted
and the drug is applied directly to target neurons.
This math is well known to sellers and users of illicit drugs. Drugs prepared for inhalation
or intravenous injection are much cheaper per dose, because the amount required is so much
smaller than that needed for an effective oral dose.
RevisitingtheBlood–BrainBarrier
The body presents barriers to the internal movement of drugs: cell membranes, capillary
walls, and the placenta. The passage of drugs across capillaries in the brain is made difficult
by the blood–brain barrier, the tight junctions between the cells of blood vessels in the brain
Figures 4-7 and 4-8 illustrate ion diffusion that block passage of most substances. The blood–brain barrier protects the brain’s ionic
and concentration and voltage gradients. balance and denies neurochemicals from the rest of the body passage into the brain, where
they can disrupt communication between neurons. It protects the brain from the effects of
many circulating hormones and from toxic and infectious substances. Injury or disease can
sometimes rupture the blood–brain barrier, letting pathogens through. For the most part,
however, the brain is well protected from harmful substances.
The brain has a rich capillary network. None of its neurons is farther than about
50 micrometers (mm; 1 mm is equal to one-millionth of a meter) from a capillary. As shown
at the left in Figure 6-2, like all capillaries, brain capillaries are composed of a single layer of
endothelial cells. In most parts of the body, endothelial cells in capillary walls are not fused,
so substances can pass through the clefts between the cells. In most parts of the brain, by
contrast, endothelial cell walls are fused to form tight junctions, so molecules of most sub-
stances cannot squeeze between them.
Figure 6-2 also shows that brain capillaries’ endothelial cells are surrounded by the end
feet of astrocytes attached to the capillary wall, covering about 80 percent of it. The glial
cells provide a route for the exchange of food and waste between capillaries and the brain’s
extracellular fluid and from there to other cells, shown at the right in Figure 6-2.
The cells of capillary walls in the three brain regions shown in Figure 6-3 lack a blood–
brain barrier. The pituitary is a source of many hormones secreted into the blood, and their
release is triggered in part by other hormones carried to the pituitary by the blood. The ab-
sence of a blood–brain barrier in the lower brainstem’s area postrema allows toxic substances
Section 13-2 details the pineal gland’s in the blood to trigger vomiting. The pineal gland also lacks a blood–brain barrier, enabling
pacemaking function. hormones to reach it and modulate the day–night cycles it controls.
Capillaries in the brain form tight Small, uncharged Certain other
junctions and are covered with astrocyte molecules are able molecules
feet. These properties prevent materials to pass through are carried across
from moving in and out easily. the endothelial the membrane by
membrane. active transport.
Amino
CO2 O2 acids Glucose Fats +
Transporter
Astrocyte
feet CO2 O2
Figure 6-2 Blood–BrainBarrier –
Capillaries in most of the body allow for Capillaries in the body have few
tight junctions. Materials can
substances to pass between capillary Capillary
move in and out quite easily. Astrocyte feet Tight junction
cell membranes, but those in the brain,
stimulated by the actions of astrocytes,
Large and electrically charged molecules
form the tight junctions of the blood–brain
Endothelial cells are unable to pass out of the capillary.
barrier.
6-1 • Principles of Psychopharmacology 175
To carry out its work, the brain needs, among other substances, oxygen and glucose for Pineal gland: Entry of chemicals
fuel and amino acids to build proteins. Fuel molecules reach brain cells from the blood, just that affect day–night cycles.
as carbon dioxide and other waste products are excreted from brain cells into the blood.
Molecules of these vital substances cross the blood–brain barrier in two ways:
1. Small molecules such as oxygen and carbon dioxide can pass through the endothelial
membrane.
2. Complex molecules of glucose, amino acids, and other food components are carried
across the membrane by active transport systems or ion pumps—transporter proteins
specialized to convey a particular substance.
Few psychoactive drug molecules are sufficiently small or have the correct chemical
structure to gain access to the CNS. An important property possessed by those few drugs
that have CNS effects, then, is an ability to cross the blood–brain barrier. Pituitary gland: Entry of
chemicals that influence
HowtheBodyEliminatesDrugs pituitary hormones.
After a drug is administered, the body soon begins to break it down (catabolize) and remove Area postrema: Entry of
it. Drugs are diluted throughout the body and are sequestered in many regions, including fat toxic substances that
cells. They are also catabolized throughout the body, including in the kidneys and liver, and induce vomiting.
in the intestine by bile. They are excreted in urine, feces, sweat, breast milk, and exhaled
Figure 6-3 Barrier-FreeBrainSites
air. Drugs developed for therapeutic purposes are usually designed not only to increase
The pituitary gland is a target for many
their chances of reaching their targets but also to enhance their survival time in the body. blood-borne hormones; the pineal gland,
The liver is especially active in catabolizing drugs. Owing to a family of enzymes involved for hormones that affect circadian
in drug catabolism, the cytochrome P450 enzyme family (some are also present in the gastro- rhythms. The area postrema initiates
intestinal tract microbiome), the liver is capable of breaking down many different drugs into vomiting of noxious substances.
forms more easily excreted from the body. Substances that cannot be catabolized or excreted
can build up in the body and become toxic. The metal mercury, for instance, is not easily Catabolic processes break down; metabolic
eliminated and can produce severe neurological effects. processes build up.
Drugs eliminated from the body and discharged into the environment are extensive and
problematic. They may be reingested, via food and water, by many animal species, including
Figure 6-4 PointsofInfluence
humans (Brown et al., 2015). Some may affect fertility, embryonic development, even the physi-
In principle, a drug can modify seven
ology and behavior of adult organisms. The solution is redesigning waste management systems major chemical processes, any of which
to remove by-products eliminated by humans as well as by other animals (Berninger et al., 2015). results in enhanced or reduced synaptic
transmission, depending on the drug’s
DrugActionatSynapses:Agonists action as an agonist or antagonist.
andAntagonists
Most drugs that produce psychoactive effects work by influencing chemical
reactions at synapses. So to understand how drugs work, we must explore the 1 Synthesis
ways they modify synaptic actions. Figure 6-4 summarizes seven major steps
in neurotransmission at a synapse—each a site of drug action:
Precursor
chemicals 7 Degradation
1. Synthesis of the neurotransmitter can take place in the cell body, the axon,
or the terminal. Neurotransmitter
2. Storage of the neurotransmitter is in granules or in vesicles or in both.
3. Release of the transmitter is from the terminal’s presynaptic membrane
into the synapse. 2 Storage 6 Reuptake
4. Receptor interaction takes place in the postsynaptic membrane, as the
transmitter acts on an embedded receptor. 3 Release
5. Inactivation of excess neurotransmitter occurs at the synapse.
5 Inactivation
6. Reuptake into the presynaptic terminal for reuse is one outcome.
4 Receptor interaction
7. Degradation of excess neurotransmitter by synaptic mechanisms and
removal of unneeded by-products from the synapse is the other outcome.
176 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
Ultimately, a drug that affects any of these synaptic functions either increases or dimin-
ishes neurotransmission. Drugs that increase neurotransmission are classified as agonists;
drugs that decrease neurotransmission are classified as antagonists. To illustrate, consider a
typical synapse: the acetylcholine synapse between motor neurons and muscles.
AnAcetylcholineSynapse:Examples
ofDrugAction
Figure 6-5 shows how some drugs and toxins act as agonists or antagonists at the ACh syn-
apse on skeletal muscles. ACh agonists excite muscles, increasing muscle tone, whereas ACh
antagonists inhibit muscles, decreasing muscle tone. Some of these substances may be new
to you, but you have probably heard of others. If you know their effects at the ACh synapse,
Figure 4-26 details the structure and action of you can understand the relationships between these substances’ neurochemical actions and
ACh at a neuromuscular synapse. their behavioral effects.
Figure 6-5 includes two toxins that influence ACh release from the axon terminal. Black
widow spider venom acts as an agonist by promoting ACh release to excess. A black widow
spider bite does not inject enough drug to paralyze a person, though a victim may feel some
muscle weakness.
Botulinum toxin, or botulin, is the poisonous agent in improperly processed canned
goods. An antagonist, it blocks ACh release, an effect that can last for weeks to months.
Severe poisoning can paralyze both movement and breathing and so cause death.
Botulin has medical uses. Injected into a muscle, it can selectively paralyze the muscle.
This action makes it useful for blocking excessive and enduring muscular twitches or con-
tractions, including the spasms that make movement difficult, for example in people with
Focus 11-2 describes the causes and range of cerebral palsy. Under the trade name Botox, botulin is also used cosmetically to paralyze
outcomes for cerebral palsy. facial muscles that cause wrinkling.
Figure 6-5 also shows two drugs that act on ACh receptors. Nicotine’s molecular structure
As illustrated in Section 5-3, a single main is similar enough to that of ACh to allow nicotine to fit into ACh receptors’ binding sites,
receptor serves the sympathetic nervous where it acts as an agonist. Curare acts as an ACh antagonist by occupying cholinergic recep-
system: the nicotinic ACh receptor (nAChR). tors and so preventing ACh from binding to them. Once introduced into the body, curare
acts quickly and is cleared from the body in a few minutes. Large doses, however, arrest
movement and breathing for a period sufficient to result in death.
Agonist
Choline-rich diet increases
acetylcholine (ACh).
Agonist
Black widow spider venom
promotes release. Acetylcholine
terminal
Antagonist
Acetylcholine
Botulin toxin blocks release.
Figure 6-5 AcetylcholineAgonists
Agonist
andAntagonists Drugs and nutrients
can affect ACh transmission by altering Nicotine stimulates receptors.
Antagonist Agonist
its synthesis or release or by binding to
Curare blocks receptors. Physostigmine and organo-
the postsynaptic receptor and affecting its
phosphates block inactivation.
breakdown or inactivation.
6-1 • Principles of Psychopharmacology 177
Early European explorers of South America discovered that the indigenous peoples liv-
ing along the Amazon River in South America killed small animals using arrowheads coated
with curare prepared from the seeds of a plant. The hunters did not poison themselves
when eating the animals, because ingested curare cannot pass from the gut into the body.
Many curarelike drugs have been synthesized. Some are used to briefly paralyze large
animals for examination or tagging for identification. You have probably seen this use of
these drugs in wildlife videos. Skeletal muscles are more sensitive to curarelike drugs than
are respiratory muscles; an appropriate dose paralyzes an animal’s movement temporarily
but allows it to breathe.
The final drug action shown in Figure 6-5 is that of physostigmine, an agonist that
inhibits acetylcholinesterase (AChE), the enzyme that breaks down ACh, thus increasing Figure 5-10 illustrates ACh synthesis and how
the amount available in the synapse. Physostigmine, obtained from an African bean, is used AChE breaks it down.
as a poison by hunters.
Large doses of physostigmine can be toxic because they produce excessive excitation of
the neuromuscular synapse, disrupting movement and breathing. In small doses, however,
physostigmine is used to treat myasthenia gravis, a condition of muscular weakness in which In myasthenia gravis, muscle receptors lose
muscle receptors are less than normally responsive to ACh. Physostigmine’s action is short their sensitivity to motor neuron messages,
lived, lasting only a few minutes or at most a half hour. as illustrated in Section 4-4.
Organophosphate compounds bind irreversibly to AChE and consequently allow a toxic
buildup of ACh in the synaptic space. Many insecticides and chemical weapons are organo-
phosphates. Insects use glutamate as a neurotransmitter at the nerve–muscle junction, but
elsewhere in their nervous system, they have nicotinic receptors. Thus, organophosphates The Basics, Section 1-3, charts nervous
poison insects by acting centrally, but they poison chordates by acting peripherally as well. system evolution in the animal kingdom.
The Chemical Weapons Convention of 1993 banned one potent organophosphate agent, the
lethal nerve gas Sarin. That international ban did not restrain the governments of Iraq, in
1999, and Syria, in 2013, from using Sarin against their own citizens.
Does a drug or toxin that affects neuromuscular synapses also affect ACh synapses in
the brain? That depends on whether the substance can cross the blood–brain barrier. Phys-
ostigmine and nicotine readily pass the barrier; curare cannot. Nicotine is the psychoactive
ingredient in cigarette smoke, and its actions on the brain account for its addictive proper-
ties (see Section 6-4). Physostigminelike drugs reportedly have some beneficial effects for
memory disorders.
Tolerance
Tolerance is a decreased response to a drug with repeated exposure. Harris Isbell and
coworkers (1955) conducted an experiment that, while questionable by today’s ethical In tolerance, as in habituation, learning takes
standards, did suggest how tolerance comes about. The researchers gave volunteers in a place when the response to a stimulus
prison enough alcohol daily in a 13-week period to keep them in a constant state of intoxi- weakens with repeated presentations
cation. Yet they found that the participants did not remain drunk for 3 months straight. (see Experiment 5-2).
When the experiment began, the participants showed rapidly rising blood alcohol levels
and behavioral signs of intoxication, as shown in the Results section of Experiment 6-1, on
page 178. Between the twelfth and twentieth days of alcohol consumption, however, blood
alcohol and the signs of intoxication fell, even though the participants maintained their
alcohol intake. Thereafter, blood alcohol levels and signs of intoxication fluctuated; one did
not always correspond to the other. A relatively high blood alcohol level was sometimes as-
sociated with a low outward appearance of intoxication. Why? agonist Substance that enhances synapse
The three results were the products of three kinds of tolerance, each much more likely to function.
develop with repeated drug use: antagonist Substance that blocks synapse
1. In metabolic tolerance, the number of enzymes needed to break down alcohol in the liver, function.
blood, and brain increases. As a result, any alcohol consumed is metabolized more quickly, tolerance Decrease in response to a drug
so blood alcohol levels fall. with the passage of time.
178 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
2. In cellular tolerance, brain cell activities adjust to
ExpErimEnt 6-1
minimize the effects of alcohol in the blood. Cellular
Question: Will the consumption of alcohol produce tolerance?
tolerance can help explain why the behavioral signs of
intoxication may be so low despite a relatively high blood
Procedure
alcohol level.
Participants were given alcohol
3. Learned tolerance explains a drop in outward signs of
every day for 13 weeks—enough
to keep them intoxicated. intoxication. As people learn to cope with the demands of
living under the influence of alcohol, they may no longer
appear intoxicated.
Results Does it surprise you that learning plays a role in alcohol
tolerance? It has been confirmed in many studies, includ-
Alcohol intake
400 When the experiment began, ing a description of the effect first reported by John Wenger
(ml/day)
all the participants increased and his coworkers (1981). They trained rats to prevent electric
their intake of alcohol. foot shocks as they walked on a narrow conveyor belt sliding
200
over an electrified grid. One group of rats received alcohol
after training in walking the belt; another group received al-
0 5 10 15 20 cohol before training. A third group received training only,
Days
and a fourth group received alcohol only.
After several days’ exposure to their respective condi-
Average blood alcohol
After 15–20 days of alcohol
tions, all groups received alcohol before a walking test.
consumption, blood-alcohol
level (mg/ml)
2.0 The rats that had received alcohol before training per-
levels fell…
formed well, whereas those that had received training and
1.0 alcohol separately performed just as poorly as those that
had never had alcohol or those that had not been trained.
0 5 10 15 20 Despite alcohol intoxication, then, animals can acquire
Days the motor skills needed to balance on a narrow belt. With
motor experience, they can learn to compensate for being
3 …and the signs of intoxicated.
Average degree
of intoxication
intoxication fell, too.
2
Sensitization
1 Drug tolerance is much more likely to develop with repeated
use than with periodic use, but tolerance does not always
0 5 10 15 20 follow repeated exposure to a drug. Tolerance resembles
Days habituation in that the response to the drug weakens with
Conclusion: Because of tolerance, as the study progressed, much more repeated presentations. The drug user may have the oppo-
alcohol was required to obtain the same level of intoxication that was site reaction, sensitization—increased responsiveness to suc-
produced at the beginning.
cessive equal doses. Whereas tolerance generally develops
Information from H. Isbell, H. F. Fraser, A. Winkler, R. E. Belleville, and A. J. Eisenman (1955). An
experimental study of the etiology of “rum fits” and delirium tremens. Quarterly Journal of Studies
with repeated drug use, sensitization is much more likely to
on Alcohol, 16, pp. 1–21. develop with periodic use.
To demonstrate drug sensitization, Terry Robinson
and Jill Becker (1986) isolated rats in observation boxes and recorded their reactions to
an injection of amphetamine, which stimulates dopamine receptors. Every 3 or 4 days,
the investigators injected the rats and found their motor activities—sniffing, rearing, and
walking—more vigorous with each administration of the same drug dose, as graphed in
Results 1 of Experiment 6-2.
The increased motor activity on successive tests was not due to the animals becoming
comfortable with the test situation. Control animals that received no drug failed to display
Experiment 5-3 describes sensitization at the a similar escalation. Administering the drug to rats in their home cages did not affect activ-
level of neurons and synapses. Section 14-4 ity in subsequent tests, either. Moreover, the sensitization to amphetamine was enduring.
relates sensitization to neuroplasticity and Even when two injections were separated by months, the animals still showed an escalation
learned addictions. of motor behavior. Even a single exposure to amphetamine produced sensitization.
6-1 • Principles of Psychopharmacology 179
ExpErimEnt 6-2
Question: Does the injection of a drug always produce the same behavior?
Procedure 1 Procedure 2
In the Robinson and Becker study, In the Whishaw study, animals were
animals were given periodic injections of given different numbers of swims after
the same dose of amphetamine. Then being injected with Flupentixol. Then
the researchers measured the number of the researchers measured their speed to
times each rat reared in its cage. escape to a platform in a swimming pool.
Agonist Antagonist
Amphetamine Flupentixol
Release
enhanced
Reuptake Receptor
transporter
Dopamine blocked
blocked
Flupentixol
Results 1 Results 2
24 60
Number of incidents
Time to platform(s)
of rearing
12 3
1 3 5 9 1 4 8 12
Number of injections Number of trials
Conclusion 1: Sensitization Conclusion 2: Sensitization depends on
indicated by increased rearing, the occurrence of a behavior: the number
develops with periodic repeated of swims increases the time that it takes
injections. the rat to reach the platform.
Left: Information from T. E. Robinson and J. B. Becker (1986). Enduring changes in brain and behavior produced by
chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis. Brain
Research Reviews, 397, pp. 157–198. Right: Information from I. Q. Whishaw, G. Mittleman, and J. L. Evenden (1989).
Training-dependent decay in performance produced by the narcoleptic cist(Z)-flupentixol on spatial navigation by rats in
a swimming pool. Pharmacology, Biochemistry, and Behavior, 32, pp. 211–220.
180 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
Sensitization is not always characterized by an increase in an elicited behavior but
may also manifest as a progressive decrease in behavior. Ian Whishaw and his colleagues
(1989) administered flupentixol, a drug that blocks dopamine receptors, to rats that had
been well trained in a swimming task. As illustrated in Results 2 of Experiment 6-2, the
rats displayed such a marked trial-dependent slowing in swimming speed when escaping
from the water that they completely stopped swimming over successive trials. The trial-
dependent decrease in swimming was similar whether the trials were massed on the same
day or spaced over days or weeks.
The neural basis of sensitization lies in part in changes at the synapse. Studies on the do-
pamine synapse after sensitization to amphetamine show more dopamine released from the
presynaptic terminal in sensitized animals. Sensitization can also be associated with changes
in receptor numbers on the postsynaptic membrane, in the rate of transmitter metabolism in
the synaptic space, in transmitter reuptake by the presynaptic membrane, and in the number
and size of synapses.
Another basis of sensitization is learned. Animals show a change in learned responses to
environmental cues as sensitization progresses. Consequently, sensitization is difficult to
achieve in an animal tested in its home cage. In the Whishaw group’s experiment, adminis-
tering flupentixol to rats left in their home environment did not influence their performance
in subsequent swim tests.
Sabina Fraioli and her coworkers (1999) gave amphetamine to two groups of rats and
recorded the behavioral responses to successive injections. One group of rats lived in the
test apparatus, so for that group, home was the test box. The other group was taken out
of their home cage and placed in the test box for each day’s experimentation. The home
group showed no sensitization to amphetamine, whereas the out group displayed robust
sensitization.
At least part of the explanation of the home–out effect is that the animals are accustomed
to engaging in a certain behavioral repertoire in their home environment, so it is difficult
to get them to change their response to home cues even when influenced by a drug. When
subjects are away from home, they receive novel out cues, which favor conditioning of new
responses.
Sensitization is relevant to understanding some psychopharmacological effects of drugs:
1. Many drug therapies, including those for the psychiatric disorder schizophrenia, must
Focus 8-5 relates the possible origin of be taken for several weeks before they produce beneficial effects. Possibly sensitization
schizophrenia and its progress. underlies the development of these beneficial effects.
2. Sensitization is related to drug dependence. Before a person becomes dependent on or
addicted to a drug, he or she must be sensitized by numerous experiences with the drug
away from the home environment.
3. Life experiences, especially stressful ones, can produce effects resembling sensitization
that prime the nervous system for addiction (Roberts et al., 2015).
6-1 review
PrinciplesofPsychopharmacology
Before you continue, check your understanding.
1. , substances that produce changes in behavior by acting on the nervous
system, are one subject of , the study of how drugs affect the nervous
system and behavior.
2. Perhaps the most important obstacle on a psychoactive drug’s journey between its
entry into the body and its action at a target is the , which generally
allows only substances needed for nourishment to pass from the capillaries into the
.
6-2 • Grouping Psychoactive Drugs 181
3. Most drugs that have psychoactive effects influence chemical reactions at neuronal
. Drugs that influence communication between neurons do so by acting
either as (increasing the effectiveness of neurotransmission) or as
(decreasing the effectiveness of neurotransmission).
4. Behavior may change with the repeated use of a psychoactive drug. These changes
include and , in which the effect of the drug decreases or
increases, respectively, with repeated use.
5. The body eliminates drugs through , , ,
, and .
6. Describe briefly how tolerance and sensitization might affect someone who uses
cognitive enhancers occasionally (a) at home or (b) at work.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
6-2 GroupingPsychoactiveDrugs
Did you know that most psychoactive drugs and their effects were discov-
ered by accident? Scientists and pharmaceutical companies have experi-
mented ever since, to explain drug action, to synthesize alternative forms taBLe 6-1 grouping psychoactive Drugs
for therapeutic treatments, and to modify drugs to reduce side effects. group i: antianxiety agents and sedative-hypnotics
But the process is complex. Drugs with similar chemical structure can
Benzodiazepines: diazepam (Valium), alprazolam (Xanax), clonazepam
have different effects, and drugs with different structure can have similar (Klonopin)
effects. And a single drug usually acts on many neurochemical systems Barbiturates (anesthetic agents); alcohol
and has many effects.
Other anesthetics: gamma-hydroxybutyrate (GHB), ketamine
A full appreciation of any drug’s action requires a multifaceted de- (Special K), phencyclidine (PCP, angel dust)
scription, such as can be found in compendiums of drug action. Unam-
group ii: antipsychotic agents
biguously grouping psychoactive drugs is virtually impossible, because
First generation: phenothiazines: chlorpromazine (Thorazine);
most drugs influence many behaviors. Behavioral descriptions undergo butyrophenones: haloperidol (Haldol)
constant review, as illustrated by continuing revisions of the Diagnostic
Second generation: clozapine (Clozaril), aripiprazole (Abilify, Aripiprex)
and Statistical Manual of Mental Disorders (DSM-5). Published by the
group iii: antidepressants and mood stabilizers
American Psychiatric Association and now in its fifth edition, the DSM
offers a classification system for diagnosing neurological and behavioral Antidepressants
MAO inhibitors
disorders. Tricyclic antidepressants: imipramine (Tofranil)
Table 6-1 groups psychoactive drugs based on their most pronounced SSRIs (atypical antidepressants): fluoxetine (Prozac); sertraline
behavioral or psychoactive effects (Advokat et al., 2014). Each of the five (Zoloft); paroxetine (Paxil, Seroxat)
groups may contain a few to thousands of chemicals in its subcategories. Mood stabilizers
Lithium, sodium valproate, carbamazepine (Tegretol)
In the following sections we highlight drug actions, both on neurochemi-
cal systems in the brain and on synaptic function. group iv: Opioid analgesics
Most psychoactive drugs have three names: chemical, generic, and Opium derivatives: morphine, codeine, heroin
branded. The chemical name describes a drug’s structure; the generic Endogenous opioid neuropeptides: enkephalins, dynorphins, endorphins
name is nonproprietary and is spelled lowercase; and the proprietary, or group v: psychotropics
brand, name, given by the pharmaceutical company that sells it, is capi- Behavioral stimulants: amphetamine, cocaine
talized. Some psychoactive drugs also sport street names or are known
Psychedelic and hallucinogenic stimulants (listed by neurotransmitter)
as club drugs. Acetylcholine psychedelics: atropine, nicotine
Anandamide psychedelics: tetrahydrocannabinol (THC)
Glutamate psychedelics: phencyclidine (PCP, angel dust), ketamine
GroupI:AntianxietyAgentsand (Special K)
Sedative-Hypnotics Norepinephrine psychedelics: mescaline
Serotonin psychedelics: Lysergic acid diethylamide (LSD), psilocybin,
At low doses, antianxiety drugs and sedative-hypnotics reduce anxiety; at MDMA (Ecstasy)
medium doses, they sedate; at high doses, they anesthetize or induce coma. General stimulants: caffeine
182 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
Death At very high doses, they can kill (Figure 6-6). Even so, antianxiety drugs are safer at high doses
Coma than sedative-hypnotics are. Indeed, the prescribing of sedative-hypnotics for all purposes is
decreasing.
General anesthesia
Many psychoactive drugs have sedative-hypnotic and antianxiety actions. They include
Sleep
Effect of drug
phencyclidine (PCP, angel dust) and two drugs—gamma-hydroxybutyric acid (GHB) and ket-
Sedation
amine (Special K)—that gained notoriety as date rape drugs. Both are soluble in alcohol, act
Disinhibition
quickly, and, like other sedative-hypnotics, impair memory of recent events. Because they
Relief from anxiety
can be dissolved in a drink, partygoers and clubbers should never accept drinks from anyone,
Normal drink from punch bowls, or leave drinks unattended.
Increasing dose
Figure 6-6 BehavioralContinuum DrugActionintheBrain
ofSedation Increasing doses of The best-known antianxiety agents, or minor tranquilizers, are the benzodiazepines. One,
sedative-hypnotic and antianxiety drugs
diazepam, is marketed as the widely prescribed brand-name drug Valium. Others are alpra-
affect behavior: low doses reduce anxiety
and very high doses result in death. zolam (Xanax) and clonazepam (Klonopin). Benzodiazepines are often used by people who
are having trouble coping with a major life stress, such as a traumatic accident or a death in
the family. They aid sleep and also are used as presurgical relaxation agents.
Sedative-hypnotics include alcohol and barbiturates. Both induce sleep, anesthesia, and
coma at doses only slightly higher than those that sedate. Alcohol is well known to most
people and widely consumed. While sometimes prescribed as a sleeping medication, today
barbiturates are mainly used to induce anesthesia before surgery.
A characteristic feature of sedative-hypnotics is that the user who takes repeated doses
develops a tolerance for them. A larger dose is then required to maintain the drug’s initial
effect. Cross-tolerance results when the tolerance for one drug is carried over to a different
member of the drug group.
DrugActionattheSynapse
Cross-tolerance suggests that antianxiety and sedative-hypnotic drugs act on the nervous
system in similar ways. One target common to both alcohol and barbiturate drugs is a recep-
GABA is an amino acid. Figure 5-12 shows its tor for gamma-aminobutyric acid (GABA), the inhibitory neurotransmitter that is widely
chemical structure. distributed in the CNS. The GABA A receptor, illustrated in Figure 6-7, contains a chloride
ion channel.
Excitation of the GABA A receptor produces an influx of Cl– through its pore. An influx
of Cl– increases the concentration of negative charges inside the cell membrane, hyper-
polarizing it and making it less likely to propagate an action potential. GABA therefore has
its inhibitory effect by decreasing a neuron’s firing rate. Widespread reduction of neuronal
firing underlies the behavioral effects of drugs that affect the GABA A synapse.
The GABA A receptor illustrated in Figure 6-7 has different binding sites for GABA,
barbiturates, and benzodiazepines. Activation of each site promotes an influx of Cl–, but
in different ways. Because the effects of actions at these three sites summate, sedative-
antianxiety agent Drug that reduces hypnotics, including alcohol and antianxiety drugs, should not be consumed together.
anxiety, including minor tranquilizers such Combined doses of drugs reportedly contribute to as many deaths as occur annually from
as benzodiazepines and sedative-hypnotic automobile accidents in the United States. Such was the case in 2012, when singer Whit-
agents. ney Houston drowned.
barbiturate Drug that produces sedation and The GABA A receptor also has binding sites that block the ion pore when active, reduc-
sleep. ing the flow of Cl– and increasing the target neuron’s excitability. Picrotoxin, a compound
cross-tolerance Reduction of response that blocks the pore, produces epileptic discharges in postsynaptic neurons. Administering
to a novel drug because of tolerance to a GABA A agonists can block picrotoxin’s action. Sedative-hypnotic and antianxiety drugs are
chemically related drug. thus useful in treating epileptic discharges.
fetal alcohol spectrum disorder (FAsD) Drugs that act on GABA receptors may affect brain development, because GABA is
Range of physical and intellectual impairments one of the substances that regulate brain development. Clinical Focus 6-2, Fetal Alco-
observed in some children born to alcoholic hol Spectrum Disorder, explores alcohol’s potentially devastating effects on developing
parents. fetuses.
6-2 • Grouping Psychoactive Drugs 183
Alcohol or Figure 6-7 DrugEffectsatthe
barbiturate
GABA Benzodiazepine
GABA AReceptor Sedative-
hypnotics act at the barbiturate site
Barbiturate GABA Benzodiazepine
site (left), and antianxiety agents act at the
site
benzodiazepine site (center). Taken
together (right), these two types of drugs
can be lethal.
Chloride
channel Cl– Cl– Cl–
Sedative-hypnotic drugs Antianxiety drugs Because their different
(alcohol or barbiturates) (benzodiazepines) actions summate, these
increase GABA binding, influence the frequency of drugs should not be
thereby maximizing the pore opening. taken together.
time the pore is open.
CliniCal F cus 6-2
Fetal Alcohol Spectrum Disorder
The term fetal alcohol syndrome (FAS) was coined in 1973 to describe A major question raised by FASD is how much alcohol is too much to
a pattern of physical malformation and intellectual disability observed in drink during pregnancy. To be completely safe, it is best not to drink at all
some children born to alcoholic mothers. It is now called fetal alcohol in the months preceding as well as during pregnancy. This conclusion is
spectrum disorder (FASD) to acknowledge the range of its effects. Chil- supported by findings that as little as a single drink of alcohol per day dur-
dren with FASD may have abnormal facial features, such as unusually ing pregnancy can lead to a decrease in children’s intelligence test scores.
wide spacing between the eyes. Their brains display a range of abnor-
malities, from small size with abnormal gyri to abnormal clusters of cells
and misaligned cells in the cortex.
Related to these brain abnormalities are certain behavioral symptoms Discriminating features Associated features
that children with FASD tend to have in common. They display varying Low nasal
Short palpebral bridge
degrees of learning disabilities and low intelligence test scores as well fissures Minor ear
as hyperactivity and other social problems. Individuals with FASD are 19 anomalies
Short nose
times as likely to be incarcerated as those without it (Popova et al., 2011). Epicanthal
Flat midface
The offspring of approximately 6 percent of alcoholic mothers have folds
pronounced FASD. In major cities, its incidence is about 1 in 700 births Indistinct
Small jaw
philtrum
and is especially high among Native Americans on reservations in Canada,
some other minority groups, and single mothers (Mead & Sarkar, 2014). Thin upper
lip
A major problem is that women who are most at risk for bearing
FASD babies are poor and not well educated, their alcohol consumption
problems predate pregnancy, and they have little access to prenatal care.
It is often difficult to inform these women about the dangers that alcohol
Courtesy of Sterling K. Clarren, m.D., professor
poses to a fetus and to encourage them to abstain from drinking before
of pediatrics, university of british Columbia
and while they are pregnant.
Alcohol-induced abnormalities can vary from hardly noticeable physi-
cal and psychological effects to full-blown FASD. The severity of effects
is related to when, how much, and how frequently alcohol is consumed
faculty of medicine.
over the course of pregnancy. The effects are worse if alcohol is con-
sumed in the first trimester, a time when many women do not yet realize
that they are pregnant.
Severe FASD is also more likely to coincide with binge drinking, which
produces high blood alcohol levels. Other factors related to a severe out-
come are poor nutritional health of the mother and the mother’s use of (Top) Characteristic facial features that indicate FASD. Effects are not merely
other drugs, including nicotine. In addition, alcohol use by mothers and physical; many children endure severe intellectual disabilities. (Bottom) The
fathers before conception can change the methylation status of some genes convolutions characteristic of the brain of a healthy child at age 6 weeks (left)
that contribute to disabilities found on the spectrum (Lee et al., 2015). are grossly underdeveloped in the brain of a child with FASD (right).
184 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
GroupII:AntipsychoticAgents
The term psychosis is applied to behavioral disorders such as schizophrenia, which is charac-
dopamine hypothesis of schizophrenia
terized by hallucinations (false sensory perceptions) and delusions (false beliefs), among a host
Idea that excess dopamine activity causes
of symptoms. The use of antipsychotic drugs has improved the functioning of schizophrenia
symptoms of schizophrenia.
patients. Since 1955, when psychoactive drugs were introduced into widespread therapeutic
major depression Mood disorder characterized
use, resident patient populations in state and municipal mental hospitals in the United States
by prolonged feelings of worthlessness and
guilt, disruption of normal eating habits, sleep have decreased dramatically.
disturbances, a general slowing of behavior, and The success of antipsychotic agents is an important therapeutic achievement, because
frequent thoughts of suicide. the incidence of schizophrenia is high—about 1 in every 100 people. Although antipsychotic
monoamine oxidase (mAO) inhibitor agents make mental disorders manageable, they do not constitute cures. In fact, according
Antidepressant drug that blocks the enzyme to the National Institute on Disability and Rehabilitation Research, although the number
monoamine oxidase from degrading such of people in mental institutions remains relatively low, as many as 75% of the homeless
neurotransmitters as DA, NE, and 5-HT. and 50% of incarcerated people have mental health issues. According to Human Rights
tricyclic antidepressant First-generation Watch, in 2015, 10 times as many mentally ill people were incarcerated as resided in mental
antidepressant; its chemical structure, institutions.
characterized by three rings, blocks 5-HT Antipsychotic agents have been widely used since the mid-1950s, beginning with the
reuptake transporter proteins. development of what are now called first-generation antipsychotics (FGAs). They include
second-generation antidepressant Drug the drug classes phenothiazines (e.g., chlorpromazine, Thorazine) and butyrophenones (e.g.,
that acts similarly to tricyclics (first-generation
haloperidol, Haldol). FGAs act mainly by blocking the dopamine D2 receptor. Beginning in
antidepressants) but more selectively on
the 1980s, newer drugs such as clozapine (Clozaril) and several other compounds emerged
5-HT reuptake transporter proteins; also
as the second-generation antipsychotics (SGAs). SGAs weakly block dopamine D2 receptors
called atypical antidepressant.
but also block serotonin 5-HT2 receptors. Antipsychotic drugs now in development will likely
selective serotonin reuptake inhibitor (ssri)
Tricyclic antidepressant drug that blocks 5-HT form a third generation.
reuptake into the presynaptic terminal. Antipsychotic agents’ therapeutic actions are not understood fully, and these drugs can
produce many unwanted side effects. Joint experimentation by patients and physicians with
different drugs and doses is common (Pouget et al., 2014). The dopamine hy-
pothesis of schizophrenia holds that some forms of the disease may be related
to excessive dopamine activity—especially in the frontal lobes. Other support
for the dopamine hypothesis comes from the schizophrenialike symptoms of
chronic users of amphetamine, a stimulant.
As Figure 6-8 shows, amphetamine is a dopamine agonist. It fosters do-
Agonist pamine release from the presynaptic membrane of D2 synapses and blocks
Amphetamine and cocaine dopamine reuptake from the synaptic cleft. The logic is that if amphetamine
block the reuptake of causes schizophrenialike symptoms by increasing dopamine activity, perhaps
dopamine.
Dopamine naturally occurring schizophrenia is related to excessive dopamine action too.
terminal Both FGAs and SGAs block the D2 receptor, which immediately reduces motor
activity and alleviates the excessive agitation of some schizophrenia patients.
Agonist Because schizophrenia involves more than just D2 receptors, changes in dopa-
Dopamine Amphetamine mine synapses do not completely explain the disorder or the effects of antipsy-
promotes the chotic agents.
release of
dopamine.
Chlorpromazine D receptor
2
GroupIII:Antidepressantsand
Antagonist MoodStabilizers
Chlorpromazine occupies the dopamine site on
Major depression—a mood disorder characterized by prolonged feelings of
the D2 receptor, preventing receptor activation.
worthlessness and guilt, disruption of normal eating habits, sleep disturbances,
Figure 6-8 DrugEffectsatD2 a general slowing of behavior, and frequent thoughts of suicide—is rather common. At any
Receptors The antipsychotic agent given time, about 6 percent of the U.S. adult population has major depression, and in the
chlorpromazine can lessen schizophrenia
course of a lifetime, 30 percent may have at least one episode that lasts for months or longer.
symptoms, and amphetamine or cocaine
abuse can produce them. This suggests Depression is diagnosed in twice as many women as men.
that schizophrenia is related to excessive Inadequate nutrition, stress from difficult life conditions, acute changes in neuronal
activity at the D2 receptor. function, and damage to brain neurons are among the factors implicated in depression.
6-2 • Grouping Psychoactive Drugs 185
These factors may be related: nutritional deficiencies may increase vulnerability to
stress; stress may change neuronal function; and if unrelieved, altered neuronal function
may lead to neuron damage. Section 6-5 offers more information on stress.
Among the nutrient deficiencies that may be related to depression (Smith et al., 2010) are
folic acid and other B vitamins and omega-3 fatty acids, a rich source of vitamin D obtained
from fish. Our skin synthesizes vitamin D on exposure to sunlight, but our body cannot
store it. Vitamin D deficiency is reportedly widespread in people living in northern climates
because they don’t eat enough fish and they lack exposure to sunlight in winter. Although
vitamin D deficiency is associated with depressive symptoms, little is known about the rela-
tions among long-term deficiencies in nutrients, depression and associated brain changes,
and the effectiveness of dietary supplements (Kerr et al., 2015). Section 12-4 explores the neuroanatomy of
Not surprisingly, alongside improved nutrition, a number of pharmacological approaches emotional disorders such as depression and
to depression are available. They include normalizing stress hormones, modifying neuronal Section 16-4 its neurobiology and treatments
responses, and stimulating neuronal repair. for it.
AntidepressantMedications
Three types of drugs have antidepressant effects: the monoamine oxidase (MAO) inhibi-
tors; the tricyclic antidepressants, so called because of their three-ring chemical structure;
and the second-generation antidepressants, sometimes called atypical antidepressants (see
Table 6-1). Second-generation antidepressants lack a three-ring structure but do share some
similarities to the tricyclics in their actions.
Antidepressants are thought to act by improving chemical neurotransmission at sero-
tonin, noradrenaline (norepinephrine), histamine, and acetylcholine synapses, and perhaps
at dopamine synapses as well. Figure 6-9 shows the actions of MAO inhibitors and second-
generation antidepressants at a 5-HT synapse, on which most research is focused. MAO
inhibitors and the tricyclic and second-generation antidepressants all act as agonists but have
different mechanisms for increasing serotonin availability.
MAO inhibitors provide for more serotonin release with each action potential by inhib- Reuptake is part of transmitter deactivation,
iting monoamine oxidase, an enzyme that breaks down serotonin in the axon terminal. In the last of the four steps of neurotransmission
contrast, the tricyclics and second-generation antidepressants block the reuptake trans- (see Figure 5-4).
porter that takes serotonin back into the axon terminal. The second-generation antidepres-
Figure 6-9 DrugEffectsat5-HT
sants are thought to be especially selective in blocking serotonin reuptake; consequently,
Receptors Different antidepressant
some are also called selective serotonin reuptake inhibitors (SSRIs). Because the trans- drugs act on the serotonin synapse in
porter is blocked, serotonin remains in the synaptic cleft, prolonging its action on post- different ways to increase its availability.
synaptic receptors.
Although these drugs begin to affect synapses very quickly, their
antidepressant actions take weeks to develop. One explanation is that
antidepressants, especially SSRIs, stimulate second messengers in neu- Agonist
rons to activate the repair of neurons damaged by stress. Of interest in this
MAO inhibitor
respect, one SSRI, fluoxetine (Prozac), increases the production of new inhibits the MAO inhibitor
neurons in the hippocampus, a limbic structure in the temporal lobes. As breakdown of
detailed in Section 6-5, the hippocampus is vulnerable to stress-induced serotonin…
damage, and its restoration by fluoxetine is proposed to underlie one of the …so that more Serotonin
drug’s antidepressant effects (Hill et al., 2015). serotonin is available terminal
for release.
Most people recover from depression within a year of its onset. If left
untreated, however, depression’s incidence of suicide is high, as described Agonist
in Clinical Focus 6-3, Major Depression, on page 186. Of all psychologi- Selective serotonin Serotonin
cal disorders, major depression is one of the most treatable, and cog- reuptake inhibitors
block transporter
nitive and intrapersonal therapies are as effective as drug therapies
protein for serotonin
(Comer, 2011). reuptake: serotonin
Even so, about 20 percent of patients with depression fail to respond stays in synaptic cleft
to antidepressant drugs. Accordingly, depression likely can have many longer.
other causes, including dysfunction in other transmitter systems and even
186 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
CliniCal F cus 6-3
Major Depression
P. H. was a 53-year-old high school teacher who, although popular with Prompted by complaints from family members that antidepressant
his students, was deriving less and less satisfaction from his work. His drug treatments have caused suicide, especially in children, the U.S.
marriage was foundering because he was growing apathetic and no Food and Drug Administration has advised physicians to monitor the
longer wanted to socialize or go on vacations. He was having difficulty side effects of SSRIs, including fluoxetine (Prozac), sertraline (Zoloft),
getting up in the morning and arriving at school on time. and paroxetine (Paxil, Seroxat). Findings from several studies show no
P. H. eventually consulted a physician, complaining of severe chest difference in the suicide rate between children and adolescents who
pains, which he feared signaled an impending heart attack. He informed receive SSRIs and a placebo, and the incidence of suicide after prescrip-
his doctor that a heart attack would be a welcome relief because it would tions were curtailed subsequent to the FDA warning actually increased
end his problems. The physician concluded that P. H. had depression and (Isacsson and Rich, 2014).
referred him to a psychiatrist.
Since the 1950s, depression has been treated with antidepressant
drugs, a variety of cognitive-behavioral therapies (CBTs), and electro-
convulsive therapy (ECT), in which electrical current is passed briefly
through one hemisphere of the brain. Of the drug treatments available,
tricyclic antidepressants and SSRIs are favored.
The risk of suicide and self-injurious behaviors is high in major
depression, especially among depressive adolescents who are resistant
to treatment with SSRIs (Asarnow et al., 2011). Even for patients who
do respond positively to SSRI treatment, the benefits may not occur for
weeks.
David braun/masterfi le
The glutamate antagonist ketamine, when given in smaller than anes-
thetic doses, can produce rapid beneficial effects that last for weeks,
even in patients who are resistant to SSRI medication (Reinstatler and
Youssef, 2015). Ketamine is thus proposed to be useful as an acute treat-
ment for patients with major depression who are at risk for suicide and Depressed? Virtually everyone who exercises will tell you that it can
even for patients with bipolar depression who are at risk for suicide. work wonders to brighten your mood.
brain damage, including frontal lobe damage. Some people have difficulty tolerating the
side effects of antidepressants—increased anxiety, sexual dysfunction, sedation, dry mouth,
blurred vision, and memory impairment among them.
MoodStabilizers
Bipolar disorder, once referred to as manic-depressive psychosis, is characterized by periods
of depression alternating with normal periods and periods of intense excitation, or mania.
According to the National Institute of Mental Health, bipolar disorder may affect as much
as 2.6% of the adult population of the United States.
The difficulty in treating bipolar disorder with drugs relates to the difficulty in under-
standing how a disease produces symptoms that appear to be opposites: mania and depres-
sion. Consequently, bipolar disorder often is treated with numerous drugs, each directed
toward a different symptom. Mood stabilizers, which include the salt lithium, mute the
intensity of one pole of the disorder, thus making the other less likely to occur. Lithium does
not directly affect mood and so may act by stimulating mechanisms of neuronal repair, such
as the production of neuron growth factors.
A variety of drugs for epilepsy (carbamazepine, valproate) have positive effects; perhaps
they mute the excitability of neurons during the mania phase. And antipsychotic drugs that
block D2 receptors effectively control the hallucinations and delusions associated with mania.
It is important to remember, though, that all these treatments have side effects: enhancing
beneficial effects while minimizing side effects is a major focus of new drug development
(Grande and Vieta, 2015).
6-2 • Grouping Psychoactive Drugs 187
GroupIV:OpioidAnalgesics
An opioid is any compound that binds to a group of morphine-sensitive brain receptors. The
term narcotic analgesic was first used to describe these drugs because opioid analgesics
have sleep-inducing (narcotic) and pain-relieving (analgesic) properties. There are two natural
sources of opioids.
One source is opium, an extract of the seeds of the opium poppy, Papaver somniferum,
shown at left in Figure 6-10. Opium has been used for thousands of years to produce eu-
phoria, analgesia, sleep, and relief from diarrhea and coughing. In 1805, German chemist
Friedrich Sertürner synthesized two chemicals from opium: codeine and morphine. Codeine
is often an ingredient in prescription cough medicine and pain relievers. The liver converts it
to morphine. Morphine, shown at center in Figure 6-10 and named for Morpheus, the Greek
god of dreams, is a powerful pain reliever. Despite decades of research, no other drug has
been found that exceeds morphine’s effectiveness as an analgesic.
The second natural source of opioids is the brain. In the 1970s, several groups of scientists
injected radioactive opioids into the brain of experimental animals and identified receptors
there to which opioids bind. At roughly the same time, other groups of investigators identi- Peptides, including the endorphins illustrated
fied several brain peptides as the neurotransmitters that naturally affect these receptors. in Figure 5-13, are molecular amino acid
The peptides in the body that have opioidlike effects are collectively called endorphins chains connected by peptide bonds. Table 5-2
(endogenous morphines). lists the families of peptide neurotransmitters.
Research has identified four classes of opioid peptides: endorphins, enkephalins, dynorphins,
and endomorphins. The three receptors on which each endorphin is relatively specific are,
respectively, mu, kappa, and delta. All endorphins and their receptors occur in many CNS
regions as well as in other areas of the body, including the enteric nervous system. Morphine
most closely mimics the endomorphins and binds most selectively to the mu receptors.
In addition to the natural opioids, synthetic opioids such as heroin affect mu receptors. bipolar disorder Mood disorder
Heroin, shown at right in Figure 6-10, is synthesized from morphine. It is more fat-soluble characterized by periods of depression
than morphine and penetrates the blood–brain barrier more quickly, allowing it to produce alternating with normal periods and periods
of intense excitation, or mania.
very rapid but shorter-acting pain relief. Heroin is a legal drug in some countries but is illegal
in others, including the United States. Notwithstanding, in some parts of the country, heroin mood stabilizer Drug for treating bipolar
use is on the rise. disorder; mutes the intensity of one pole of
Among the synthetic opioids prescribed for clinical use in pain management are hydro- the disorder, thus making the other pole less
likely to recur.
morphone, levorphanol, oxymorphone, methadone, meperidine, oxycodone, and fentanyl.
All opioids are potently addictive, and abuse of prescription opioids is growing more com- opioid analgesic Drug such as morphine,
mon. Opioids are also illegally modified, manufactured, and distributed. People who use with sleep-inducing (narcotic) and pain-
opioids for relief of chronic pain and take them when they are not in pain can become ad- relieving (analgesic) properties; originally
called narcotic analgesic.
dicted; some obtain multiple prescriptions and sell them illicitly.
Many drugs, including nalorphine (Lethidrone, Nalline) and naloxone (Narcan, Nalone), endorphin Opioid peptide that acts as a
act as antagonists at opioid receptors. These drugs are competitive inhibitors: they compete neurotransmitter and may be associated
with opioids for neuronal receptors. Because they can enter the brain quickly, they rapidly with feelings of pain or pleasure; mimicked
by opioid drugs such as morphine, heroin,
block the actions of morphine and so are essential aids in treating morphine overdoses.
opium, and codeine.
competitive inhibitor Drug, such as
nalorphine and naloxone, that acts quickly
to block opioid action by competing with the
opioid for binding sites; used to treat opioid
addiction.
bonnie Kamin/photoedit
Figure 6-10 PotentPoppy Opium
eye ubiquitous/Corbis
is obtained from the seeds of the opium
Science Source
poppy (left). Morphine (center) is extracted
from opium, and heroin (right) is in turn
synthesized from morphine.
188 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
Many people addicted to opioids carry a competitive inhibitor as a treatment for overdosing.
Because they can also be long-acting, competitive inhibitors can be used to treat opioid
addiction after the addicted person has recovered from withdrawal symptoms.
Feeling and treating pain are topics in Section Researchers have extensively studied whether opioid peptides produced in the brain can
11-4. Focus 12-1 reports that emotional pain be used as drugs to relieve pain without morphine’s addictive effects. The answer so far is
activates the same neural areas as physical mixed, and one of the objectives of pain research, producing an analgesic that does not pro-
pain. duce addiction, may be difficult to realize.
Opioid drugs, such as heroin, are addictive and are abused worldwide. The hypodermic
needle was developed in 1853 and used in the American Civil War for the intravenous injec-
tion of morphine for pain treatment. This practice is said to have produced 400,000 cases of
the “Soldier’s Disease,” morphine addiction. Morphine has many routes of administration,
but intravenous injection is preferred because it produces a euphoria described as a rush.
Morphine does not readily cross the blood–brain barrier, but heroin does and is even more
likely to produce a rush.
If opioids are used repeatedly, they produce tolerance such that within a few weeks the
effective dose may increase tenfold. Thereafter, many desired effects with respect to both
pain and addiction no longer occur. An addicted person cannot simply stop using the drug:
a severe sickness called withdrawal results if drug use is abruptly stopped.
Because morphine results in both tolerance and sensitization, the morphine user is always
flirting with the possibility of overdosing. The unreliability of appropriate information on the
purity of street forms of morphine contributes to the risk. A lack of sterile needles for injec-
tions also leaves the morphine user at risk for many other diseases, including AIDS (acquired
immunodeficiency syndrome) and hepatitis.
Opioid ingestion produces wide-ranging physiological changes in addition to pain
relief, including relaxation and sleep, euphoria, and constipation. Other effects include
respiratory depression, decreased blood pressure, pupil constriction, hypothermia, drying
of secretions (e.g., dry mouth), reduced sex drive, and flushed, warm skin. Withdrawal is
characterized by symptoms that are physiologically and behaviorally opposite those pro-
duced by the drug. A major part of the addiction syndrome, then, is the drive to prevent
withdrawal symptoms.
GroupV:Psychotropics
Psychotropic drugs are stimulants that mainly affect mental activity, motor activity, arousal,
perception, and mood. Behavioral stimulants affect motor activity and mood. Psychedelic
and hallucinogenic stimulants affect perception and produce hallucinations. General stimu-
lants mainly affect mood.
BehavioralStimulants
Behavioral stimulants increase motor behavior as well as elevating mood and alertness.
Rapid administration of behavioral stimulants is most likely to be associated with addiction.
As shown in Figure 6-1, the quicker a drug reaches its target—in this case, the brain—the
quicker it takes effect. Further, with each obstacle eliminated en route to the brain, drug dos-
age can be reduced by a factor of 10, making it cheaper per dose. Two behavioral stimulants
are amphetamine and cocaine.
Section 5-1 describes experiments Otto Amphetamine is a synthetic compound. It was discovered in attempts to synthesize
Loewi performed to identify epinephrine, or the CNS neurotransmitter epinephrine, which also acts as a hormone to mobilize the
adrenaline. Section 7-7 details symptoms and body for fight or flight in times of stress (see Figure 6-20). Both amphetamine and cocaine
outcomes of ADHD and the search for an are dopamine agonists that act first by blocking the dopamine reuptake transporter.
animal model of the disease. Interfering with the reuptake mechanism leaves more dopamine available in the synaptic
cleft. Amphetamine also stimulates dopamine release from presynaptic membranes. Both
mechanisms increase the amount of dopamine available in synapses to stimulate dopa-
mine receptors. As noted in Focus 6-1, amphetamine-based drugs are widely prescribed
to treat ADHD.
6-2 • Grouping Psychoactive Drugs 189
Figure 6-11 Behavioral
Stimulant Cocaine (left)
tek image/Science photo library/Science Source
is obtained from the leaves of
the coca plant (center). Crack
cocaine (right) is chemically
gregory g. Dimijian/Science Source
altered to form rocks that
timothy ross/the image Works
vaporize when heated at low
temperatures.
One form of amphetamine was first used as an asthma treatment: Benzedrine was sold
in inhalers as a nonprescription drug through the 1940s. Soon people discovered that they
could open the container and ingest its contents to obtain an energizing effect. Amphet-
amine was widely used in World War II—and is still used today to help troops and pilots
stay alert, increase confidence and aggression, and boost morale—and also was used then
to improve wartime workers’ productivity. Today, amphetamine is also used as a weight loss
aid. Many over-the-counter compounds marketed as stimulants or weight loss aids have
amphetaminelike pharmacological actions.
An illegal amphetamine derivative, methamphetamine (also known as meth, speed,
crank, smoke, or crystal ice) continues in widespread use. Lifetime prevalence of metham-
phetamine use in the U.S. population, once estimated to be as high as 8 percent (Durell
et al., 2008), is related to its ease of manufacture in illicit laboratories and to its potency,
thus making it a relatively inexpensive, yet potentially devastating, drug.
Cocaine is a powder extracted from the Peruvian coca shrub, both shown in Figure 6-11.
the granger Collection
The indigenous people of Peru have chewed coca leaves through the generations to increase
their stamina in the harsh environment and high elevations where they live. Refined cocaine
powder can either be sniffed (snorted) or injected. Cocaine users who do not like to inject
cocaine intravenously or cannot afford it in powdered form sniff or smoke rocks, or crack, a
potent, highly concentrated form shown at right in Figure 6-11. Crack is chemically altered Figure 6-12 WarningLabel Cocaine
so that it vaporizes at low temperatures, and the vapors are inhaled. was once an ingredient in such invigorating
Sigmund Freud (1974) popularized cocaine in the late 1800s as an antidepressant. It was beverages as Coca-Cola.
once widely used in soft drinks and wine mixtures promoted as invigorating tonics. It is the
origin of the trade name of Coca-Cola, which once contained cocaine (Figure 6-12). Its ad-
dictive properties soon became apparent, however.
Freud also recommended that cocaine be used as a local anesthetic. Cocaine did prove
amphetamine Drug that releases the
valuable for this purpose, and many derivatives, such as xylocaine (often called Novocain),
neurotransmitter dopamine into its synapse
are used today. These local anesthetic agents reduce a cell’s permeability to sodium ions and
and like cocaine, blocks dopamine reuptake.
so reduce nerve conduction.
psychedelic drug Drug that can alter
PsychedelicandHallucinogenicStimulants sensation and perception; examples are
Psychedelic drugs alter sensory perception and cognitive processes and can produce hal- lysergic acid diethylamide (LSD), mescaline,
and psilocybin.
lucinations. We categorize the major groups of psychedelics by their actions on specific
neurotransmitters, here and in Table 6-1 on page 181.
aCet ylCholine psyChedeliCs These drugs either block (atropine) or facilitate (nico-
tine) transmission at ACh synapses.
anandamide psyChedeliCs Results from numerous lines of research suggest that the Anandamide (from Sanskrit, meaning joy
endogenous neurotransmitter anandamide enhances forgetting. Anandamide prevents the or bliss) acts on a receptor that naturally
brain’s memory systems from being overwhelmed by all the information to which we are inhibits adenyl cyclase, part of a second
exposed each day. Tetrahydrocannabinol (THC) is one of 84 cannabinoids and the main psy- messenger system active in sensitization
choactive constituent in marijuana, obtained from the hemp plant Cannabis sativa, shown (see Section 5-4).
190 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
in Figure 6-13. THC alters mood primarily by interacting with the anandamide CB1 recep-
tor found on neurons, and it also binds with the anandamide CB2 receptors found on glial
cells and in other body tissues. THC has low toxicity but may have a detrimental effect on
memory as well as a positive effect on mental overload.
Evidence points to the usefulness of THC, or other cannabinoids, as a therapeutic agent
for a number of disorders. It relieves nausea and emesis (vomiting) in patients undergoing
cancer chemotherapy who are not helped by other treatments and stimulates the appetite in
phil Schermeister/Stone/getty images
AIDS patients with anorexia–cachexia (wasting) syndrome. THC has been found helpful for
treating chronic pain through mechanisms that appear to be different from those of the opi-
oids. It has also proved useful for treating glaucoma (increased pressure in the eye), for spastic
disorders such as multiple sclerosis, for disorders associated with spinal cord injury, and for
epilepsy. THC may also have some neuroprotective properties (see Section 6-4). Many people
self-prescribe THC for a wide range of ailments, including PTSD (Roitman et al., 2014).
Synthetic and derived forms of THC have been developed in part to circumvent legal
Figure 6-13 Cannabis sativa The restrictions on its use. Nevertheless, legal restrictions against THC use hamper investiga-
hemp plant, an annual herb, grows over tions into its useful medicinal effects.
a wide range of altitudes, climates, and
soils. Hemp has myriad uses, including in Glutamate psyChedeliCs PCP (angel dust) and ketamine (Special K) can produce
manufacturing rope, cloth, and paper. hallucinations and out-of-body experiences. Both drugs, formerly used as anesthetics (see
Table 6-1, Group I), exert part of their action by blocking glutamate NMDA receptors
involved in learning. Other NMDA receptor antagonists include dextromethorphan and
nitrous oxide (NO).
Glutamate is the main excitatory Although PCP’s primary psychoactive effects last for a few hours, its total elimination rate
neurotransmitter in the forebrain and from the body can extend its action for 8 days or longer. That psychotropic drugs, includ-
cerebellum. Section 14-4 describes how ing PCP and ketamine, can produce schizophrenialike symptoms, including hallucinations
Glu and NMDA receptors affect long-term and out-of -body experiences, suggests the involvement of excitatory glutamate synapses in
learning. schizophrenia.
norepinephrine psyChedeliCs Mescaline, obtained from the peyote cactus, is legal
in the United States for use by Native Americans for religious practices. Mescaline produces
pronounced psychic alterations, including a sense of spatial boundlessness and visual hal-
lucinations. The effects of a single dose last up to 10 hours.
serotonin psyChedeliCs The synthetic drug lysergic acid diethylamide (LSD) and
naturally occurring psilocybin (obtained from various mushrooms) stimulate some 5-HT
receptors and block the activity of other serotonergic neurons through 5-HT autoreceptors.
Serotonin psychedelics may stimulate other transmitter systems, including norepi-
nephrine receptors. MDMA (Ecstasy), one of several synthetic amphetamine derivatives,
induces a sense of well-being and disembodiment as well as visual distortions. Repeated
MDMA use is associated with sleep, mood, and anxiety disorders and may also be asso-
ciated with memory and attention deficits. Drug models of schizophrenia include LSD,
which produces hallucinations and is a serotonin agonist that acts at the 5-HT2 receptor.
Again, that hallucinations are a symptom of schizophrenia suggests that excess 5-HT action
can be involved.
GeneralStimulants
General stimulants cause an overall increase in cells’ metabolic activity. Caffeine, a widely
used stimulant, inhibits an enzyme that ordinarily breaks down the second messenger cyclic
adenosine monophosphate (cAMP). The resulting increase in cAMP leads to increased glu-
cose production, making more energy available and allowing higher rates of cellular activity.
A cup of coffee contains about 100 mg of caffeine; many common soft drinks contain
Caffeine boosts cAMP concentrations, action almost as much; and some energy drinks pack as much as 500 mg. You may be using more
potentials last longer than usual, and we get caffeine than you realize. Excessive levels can lead to the jitters. Regular caffeine users who
the coffee jitters. quit may have headaches, irritability, and other withdrawal symptoms.
6-3 • Factors Influencing Individual Responses to Drugs 191
6-2 review
GroupingPsychoactiveDrugs
Before you continue, check your understanding.
1. Because of their diverse actions, it is useful to group drugs in terms of their most
pronounced or effects.
2. Antianxiety and sedative-hypnotic drugs affect the receptor, which through
influx hyperpolarizes neurons.
3. Among the antidepressant drug types, increase the amount of 5-HT available
in the presynaptic terminal, while block 5-HT reuptake at the synapse.
4. Opioids mimic the action of by binding to the same receptors.
5. Amphetamine stimulates and cocaine blocks at the
synapse.
6. On which neurotransmitters do drugs that produce psychotropic effects act?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
6-3 F actorsInfluencingIndividual
ResponsestoDrugs
Many behaviors trigger predictable results. You strike the same piano key repeatedly and
hear the same note each time. You flick a light switch today, and the bulb glows exactly as
it did yesterday. This cause-and-effect consistency does not extend to the effects of psycho-
active drugs. Individuals respond to drugs in remarkably different ways at different times.
BehavioronDrugs
Ellen is a healthy, attractive, intelligent 19-year-old university freshman who knows the risks
of unprotected sexual intercourse. She learned about HIV and other sexually transmitted
diseases (STDs) in her high school health class. A seminar about the dangers of unprotected
sexual intercourse was part of her college orientation: seniors provided the freshmen in her
residence free condoms and safe sex literature. Ellen and her former boyfriend were always
careful to use latex condoms during intercourse.
At a homecoming party in her residence hall, Ellen has a great time, drinking and dancing
with her friends and meeting new people. She is particularly taken with Brad, a sophomore
at her college, and the two of them decide to go back to her room to order a pizza. One thing
leads to another, and Ellen and Brad have sexual intercourse without using a condom. The
next morning, Ellen wakes up, dismayed and surprised at her behavior and concerned that
she may be pregnant or may have contracted an STD. She is terrified that she may have
AIDS (MacDonald et al., 2000).
What happened to Ellen? What is it about drugs, especially alcohol, that make people
sometimes do things they would not ordinarily do? Alcohol links to many harmful behav-
iors that are costly both to individuals and to society. These harmful behaviors include not
only unprotected sexual activity but also driving while intoxicated, date rape, spousal or
child abuse and other aggressive behaviors, and crime. Among the explanations for alcohol’s disinhibition theory Explanation holding
effects are disinhibition, learning, and behavioral myopia. that alcohol has a selective depressant
effect on the brain’s frontal cortex, which
DisinhibitionandImpulseControl controls judgment, while sparing subcortical
An early and still widely held explanation of alcohol’s effects is disinhibition theory. It structures responsible for more instinctual
holds that alcohol has a selective depressant effect on the cortical brain region that controls behaviors, such as desire.
192 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
judgment while sparing subcortical structures, those responsible for more instinctual behav-
iors, such as desire. Stated differently, alcohol depresses learned inhibitions based on reason-
ing and judgment while releasing the “beast” within.
A variation of disinhibition theory argues that the frontal lobes check impulsive behavior.
According to this idea, impulse control is impaired after drinking alcohol because of a higher
relative sensitivity of the frontal lobes to alcohol. A person may then engage in risky behavior
(Hardee et al., 2014).
Proponents of these theories often excuse alcohol-related behavior, saying for example,
“She was too drunk to know better” or “The boys had a few too many and got carried away.”
Do disinhibition and impulse control explain Ellen’s behavior? Not entirely. Ellen had used
alcohol in the past and managed to practice safe sex despite its effects. Neither theory
explains why her behavior was different on this occasion. If alcohol is a disinhibitor, why is
it not always so?
Learning
Craig MacAndrew and Robert Edgerton (1969) questioned disinhibition theory along just
these lines in their book Drunken Comportment. They cite many instances in which behav-
ior under the influence of alcohol changes from one context to another. People who engage
in polite social activity at home when consuming alcohol may become unruly and aggressive
when drinking in a bar.
Even behavior at the bar may be inconsistent. Take Joe, for example. While drinking
one night at a bar, he acts obnoxious and gets into a fight. On another occasion, he is
charming and witty, even preventing a fight between two friends; on a third occasion, he
becomes depressed and worries about his problems. MacAndrew and Edgerton also cite
examples of cultures in which people are disinhibited when sober only to become inhib-
ited after consuming alcohol and cultures in which people are inhibited when sober and
become more inhibited when drinking. What explains all these differences in alcohol’s
effects?
MacAndrew and Edgerton suggested that behavior under the effects of alcohol is learned.
Learned behavior is specific to culture, group, and setting and can in part explain Ellen’s
decision to sleep with Brad. Where alcohol is used to facilitate social interactions, behavior
while intoxicated is a time-out from more conservative rules re-
garding dating.
BehavioralMyopia
But Ellen’s lapse in judgment regarding safe sex is more difficult
to explain by learning theory. Ellen had never practiced unsafe
sex before and had never made it a part of her time-out social
activities. So why did she engage in it with Brad?
A different explanation for alcohol-related lapses in judg-
ment, behavioral myopia (nearsightedness), is the tendency for
people under the influence of (in this case) alcohol to respond to
oliver furrer/brand x/Corbis
a restricted set of immediate and prominent cues while ignoring
more remote cues and possible consequences. Immediate and
prominent cues are very strong and obvious and close at hand
(Griffin et al., 2010).
In an altercation, the person with behavioral myopia will be
quicker than usual to throw a punch, because the fight cue is so
People who enjoy high-risk adventure may strong and immediate. At a raucous party, the myopic drinker will be more eager than usual
be genetically predisposed to experiment
to join in, because the immediate cue of boisterous fun dominates his or her view. Once
with drugs, but people with no interest in
risk taking are just as likely to use drugs. Ellen and Brad arrived at Ellen’s room, the sexual cues at the moment were far more imme-
Section 6-4 discusses genetic influences diate than concerns about long-term safety. As a result, Ellen responded to those immediate
on drug taking. cues and behaved atypically.
6-3 • Factors Influencing Individual Responses to Drugs 193
Behavioral myopia can explain many lapses in judgment that lead to risky behavior—
behavioral myopia “Nearsighted” behavior
aggression, date rape, and reckless driving while intoxicated. Individuals who have been
displayed under the influence of alcohol:
drinking may also have poor insight into their level of intoxication: they may assume that
local and immediate cues become prominent;
they are less impaired than they actually are (Sevincer and Oettingen, 2014). remote cues and consequences are ignored.
substance abuse is a pattern of drug use in
AddictionandDependence which people rely on a drug chronically and
B. G. started smoking when she was 13 years old. She has quit many times without excessively, allowing it to occupy a central
success. After successfully abstaining from cigarettes by using a nicotine patch for more place in their life.
than 6 months, B. G. began smoking again. Because the university where she works has a addiction Desire for a drug; manifested by
no smoking policy, she has to leave campus and stand across the street to smoke. Her voice frequent use, leading to physical dependence
has developed a rasping sound, and she has an almost chronic “cold.” She says that she used in addition to abuse; often associated with
to enjoy smoking but does not any more. Concern about quitting dominates her thoughts. tolerance and unpleasant, sometimes
B. G. has a drug problem. She is one of the 25 percent or so of North Americans who dangerous, withdrawal symptoms on
smoke. Like B. G., most smokers realize that it is a health hazard, have experienced unpleas- cessation. Per the DSM-5, called substance
ant side effects from it, and have attempted to quit but cannot. B. G. is exceptional only in use disorder.
her white-collar occupation. Today, most smokers are found in blue-collar occupations rather withdrawal symptom Physical and
than among professional workers. And the use of electronic cigarettes (e-cigarettes) by young psychological behavior displayed by an addict
people is on the rise (Czoli et al., 2015). The health hazards posed by nicotine delivery via when drug use ends.
e-cigarettes are unknown. psychomotor activation Increased
Substance abuse is a pattern of drug use in which people rely on a drug chronically and behavioral and cognitive activity: at certain
excessively, allowing it to occupy a central place in their life. In a more advanced state of levels of consumption, the drug user feels
substance dependence, popularly known as addiction, people are physically dependent on a energetic and in control.
drug in addition to abusing it. They have developed tolerance for the drug and so require
increased doses to obtain the desired effect.
Drug addicts may also experience unpleasant, sometimes dangerous physical withdrawal
symptoms if they suddenly stop taking the abused drug. Symptoms can include muscle aches
and cramps, anxiety attacks, sweating, nausea, and even, for some drugs, convulsions and
death. Symptoms of alcohol or morphine withdrawal can begin within hours of the last dose
and tend to intensify over several days before they subside.
Although B. G. abuses nicotine, she is not physically dependent on it. She smokes ap- To view the brain areas nicotine affects most,
proximately the same number of cigarettes each day (she has not developed tolerance to see Figure 12-30.
nicotine), and she does not get sick if she is deprived of cigarettes (does not have severe with-
drawal symptoms but does display irritability, anxiety, increased appetite, and insomnia).
B. G. illustrates that the power of psychological dependence can be as influential as the
power of physical dependence.
Many abused or addictive drugs—including sedative-hypnotics, antianxiety agents, opi-
oids, and stimulants—have a common property: they produce psychomotor activation in
some part of their dose range. That is, at certain levels of consumption, these drugs make
the user feel energetic and in control. This common effect has led to the hypothesis that all
abused drugs may act on the same target in the brain: dopamine in the mesolimbic pathways
of the dopaminergic activating system. Drugs of abuse increase mesolimbic dopamine activ-
ity, either directly or indirectly, and drugs that blunt abuse and addiction decrease mesolim-
bic dopamine activity.
SexDifferencesinAddiction
Vast differences in individual responses to drugs are due to differences in age, body size, me-
tabolism, and sensitivity to a particular substance. Larger people, for instance, are generally
less sensitive to a drug than smaller people are: their greater volume of body fluids dilutes
drugs more. Old people may be twice as sensitive to drugs as young people are. The elderly
often have less effective barriers to drug absorption as well as less effective processes for
metabolizing and eliminating drugs from their body. Individuals also respond to drugs in
different ways at different times.
194 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
Females are about twice as sensitive to drugs as are males, on average, owing in part to their
smaller size but also to hormonal differences. The long-held general assumption that human
males are more likely to abuse drugs than are human females led investigators to neglect re-
searching drug use and abuse in human females. But the results of recent research support quite
the opposite view: females are less likely to become addicted to some drugs than are males, but
females are catching up and for some drugs are surpassing males in the incidence of addiction.
Although the general pattern of drug use is similar in males and females, the sex differences
are striking (Becker and Hu, 2008). Females are more likely than males to abuse nicotine, alco-
hol, cocaine, amphetamine, opioids, cannabinoids, caffeine, and PCP. Females begin to regu-
larly self-administer licit and illicit drugs of abuse at lower doses than do males; females’ use
escalates more rapidly to addiction; and females are at greater risk for relapse after abstinence.
6-3 review
FactorsInfluencingIndividualResponsestoDrugs
Before you continue, check your understanding.
1. Of the three explanations for alcohol’s effects on behavior, and
are less explicative than .
2. is a condition in which people rely on drugs chronically and to excess,
whereas is a condition in which people are physically dependent on a drug
as well.
3. The evidence that many abused or addictive drugs produce , which makes
the user feel energetic and in control, suggests that activation in the plays
a role in drug abuse and addiction.
4. Common wisdom is incorrect in suggesting that are less likely to abuse
drugs than are.
5. Why can alcohol-related behavior vary widely in a single individual from time to time?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
6-4 ExplainingandTreating
DrugAbuse
Why do people become addicted to drugs? Early explanations centered on pleasure and
dependence: habitual drug users initially feel pleasure but then endure psychological and
physiological withdrawal symptoms as the drug wears off. They feel anxious, insecure, or just
plain sick without the drug, so they take it again to alleviate those symptoms. In this way,
they get hooked on the drug.
Although this dependency hypothesis may account for part of drug-taking behavior, it has
shortcomings as a general explanation. For example, an addict may abstain from a drug for
months, long after any withdrawal symptoms have abated, yet still be drawn back to using
it. In addition, some psychoactive drugs, such as the tricyclic antidepressants, produce with-
drawal symptoms when discontinued, but these drugs are not abused.
wanting-and-liking theory Explanation
holding that when a drug is associated with
Wanting-and-LikingTheory
certain cues, the cues themselves elicit desire To account for all the facts about drug abuse and addiction, Terry Robinson and Kent
for the drug; also called incentive sensitization Berridge (2008) proposed the incentive sensitization theory, also called the wanting-
theory. and-liking theory because wanting and liking are produced by different brain systems.
6-4 • Explaining and Treating Drug Abuse 195
Their wanting is craving, whereas liking is the
Wanting
pleasure the drug produces. With repeated use,
tolerance for liking develops, and the expression of
liking (pleasure) decreases as a consequence (Figure
Effect
6-14). In contrast, the system that mediates wanting
peter Dokus/Stone
sensitizes, and craving increases.
The first step on the proposed road to drug depen- Initial Liking
use
dence is the initial experience, when the drug affects
a neural system associated with pleasure. At this stage,
Use
the user may like the substance—including liking to take it within a given social context.
With repeated use, liking the drug may decline from its initial level. At this stage, the user Figure 6-14 Wanting-and-Liking
may also begin to show tolerance to the drug’s effects and so may begin to increase the dos- Theory With repeated drug use, wanting
age to increase liking. a drug and liking the drug progress in
opposite directions. Wanting (craving) is
With each use, the drug taker increasingly associates the cues related to drug use—be
associated with drug cues.
it a hypodermic needle, the room in which the drug is taken, or the people with whom the
drug is taken—with the drug-taking experience. The user makes this association because
the drug enhances classically conditioned cues associated with drug taking. Eventually, In classical (Pavlovian) conditioning, learning
these cues come to possess incentive salience: they induce wanting, or craving, the drug- to associate a formerly neutral stimulus (the
taking experience. sound of a bell) with a stimulus (food) elicits
The neural basis of addiction is proposed to involve multiple brain systems. The decision an involuntary response (salivation).
to take a drug is made in the prefrontal cortex, an area that participates in most daily deci-
sions. When a drug is taken, it activates opioid systems in the brainstem that are generally
related to pleasurable experiences. And wanting drugs may spring from activity in the meso-
limbic pathways of the dopaminergic activating system.
In these mesolimbic pathways, diagrammed in Figure 6-15, the axons of dopamine neu-
rons in the midbrain project to structures in the basal ganglia, to the frontal cortex, and
to the limbic system. When drug takers encounter cues associated with drug taking, the
mesolimbic system becomes active, releasing dopamine. Dopamine release is the neural
correlate of wanting.
Another brain system may be responsible for conditioning drug-related cues to drug tak-
ing. Barry Everitt (2014) proposes that the repeated pairing of drug-related cues to drug When a rat is placed in an environment
taking forms neural associations, or learning, in the dorsal striatum, a region in the basal where it anticipates a favored food or sex,
ganglia consisting of the caudate nucleus and putamen. As the user repeatedly takes the investigators record dopamine increases in
drug, voluntary control gives way to unconscious processes—a habit. The result: drug users the striatum (see Section 7-5).
lose control of decisions related to drug taking, and the wanting—the voluntary control over
drug taking—gives way to the craving of addiction. Figure 6-15 MesolimbicDopamine
Multiple findings align with the wanting-and-liking explanation of drug addiction. Ample Pathways Axons of neurons in the
evidence confirms that abused drugs and the context in which they are taken initially has midbrain ventral tegmentum project to
the basal ganglia, prefrontal cortex, and
a pleasurable effect and that habitual users continue using their drug of choice, even when
hippocampus.
taking it no longer produces any pleasure. Heroin addicts sometimes report that they are
miserable: their lives are in ruins, and the drug is not even pleasurable anymore. But they Prefrontal
still want it. What’s more, desire for the drug often is greatest just when the addicted person cortex
is maximally high, not during withdrawal. Finally, cues associated with drug taking—the
social situation, the sight of the drug, and drug paraphernalia—strongly influence decisions
to take, or continue taking, a drug.
Notwithstanding support for a dopamine basis for addiction, recent research suggests more
than one type of addiction. Some rats become readily conditioned to cues associated with
Basal ganglia
reinforcement, for example a bar that delivers a reward when pressed. Other animals ignore
the bar’s incentive salience but are attracted to the location where they receive reinforcement.
Animals that display the former behavior are termed sign trackers and the other group, goal
Hippocampus Ventral
trackers. Sign trackers exposed to addictive drugs appear to attribute incentive salience to (part of limbic tegmental
drug-associated cues. Their drug wanting is dependent upon the brain’s dopamine systems. system) area of midbrain
196 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
Goal trackers may also become addicted, possibly via different neural systems. Such findings
imply at least two types of addiction (Yager et al., 2015).
We can extend wanting-and-liking theory to many life situations. Cues related to
sexual activity, food, and even sports can induce wanting, sometimes in the absence of
liking. We frequently eat when prompted by the cue of other people eating, even though
we may not be hungry and derive little pleasure from eating at that time. The similari-
ties between exaggerating normal behaviors and drug addiction suggest that they depend
on the same learning and brain mechanisms. For this reason, any addiction is extremely
difficult to treat.
WhyDoesn’tEveryoneAbuseDrugs?
Observing that some people are more prone than others to drug abuse and dependence,
scientists have investigated and found three lines of evidence suggesting a genetic con-
tribution to differences in drug use. First, if one identical twin (same genotype) abuses
alcohol, the other twin is more likely to abuse it than if the twins are fraternal (have only
some genes in common). Second, people adopted shortly after birth are more likely to
abuse alcohol if their biological parents were alcoholic, even though they have had almost
no contact with those parents. Third, although most animals do not care for alcohol,
selective breeding of mice, rats, and monkeys can produce strains that consume large
quantities of it.
Each line of evidence presents problems, however. Perhaps identical twins show greater
concordance rates (incidence of similar behavioral traits) for alcohol abuse because their
environments are more similar than those of fraternal twins. And perhaps the link between
alcoholism in adoptees and their biological parents has to do with nervous system changes
due to prenatal exposure to the drug. Finally, the fact that animals can be selectively bred
for alcohol consumption does not mean that all human alcoholics have a similar genetic
makeup. The evidence for a genetic basis of alcohol abuse will become compelling only when
a gene or set of genes related to alcoholism is found.
Epigenetics offers another explanation of susceptibility to addiction (Hillemacher et al.,
2015). Addictive drugs may reduce the transcriptional ability of genes related to voluntary
Less-than-perfect concordance rates control and increase the transcriptional ability of other genes related to behaviors susceptible
between identical twins for diseases ranging to addiction. Epigenetic changes in an individual’s gene expression may be relatively perma-
from schizophrenia to asthma point to nent and can be passed along, perhaps through the next few generations. For these reasons,
epigenetic inheritance of behaviors by the epigenetics can account both for the enduring behaviors that support addiction and for the
next generation (see Section 3-3). tendency of drug addiction to be inherited.
TreatingDrugAbuse
Figure 6-16 charts the relative incidence of drug use in the United States—people aged
12 and older who reported using at least one psychoactive drug during the year preceding
in a national survey conducted by the U.S. Department of Health and Human Services
in 2013. The two most-used drugs, alcohol and tobacco, are legal. The drugs that carry
the harshest penalties, cocaine and heroin, are used by far fewer people. But criminal-
izing drugs clearly is not a solution to drug use or abuse, as illustrated by the widespread
use of marijuana, the third most used drug on the chart. In response to its widespread
use, several states have legalized marijuana to some degree, but it remains illegal under
federal law.
Treating drug abuse is difficult in part because legal proscriptions are irrational. In the
United States, the Harrison Narcotics Act of 1914 made heroin and a variety of other drugs
illegal and made the treatment of addicted people by physicians in their private offices il-
legal. The Drug Addiction Treatment Act of 2000 partly reversed this prohibition, allowing
the treatment of patients but with a number of restrictions. In addition, legal consequences
attending drug use vary greatly with the drug and the jurisdiction.
6-4 • Explaining and Treating Drug Abuse 197
From a health standpoint, tobacco has much higher proven health risks than does mari- Hallucinogen 1.2% Heroin 0.3%
juana. Moderate use of alcohol is likely benign. Moderate use of opioids is likely impossible. Cocaine 1.5%
Social coercion is useful in reducing tobacco use: witness the marked decline in smoking as
a result of prohibitions against smoking in public places. Medical intervention is necessary
to provide methadone and other drug treatment of opioid abusers.
The numerous approaches to treating drug abuse vary, depending on the drug. Many
online sites support self-help groups and professional groups that address the treatment of Marijuana 20%
various drug addictions. Importantly, because addiction is influenced by unconscious condi-
tioning to drug-related cues and by a variety of brain changes, relapse remains an enduring Alcohol 52%
risk for people who have apparently kicked their habit. Tobacco 25%
Neuroscience research will continue to lead to a better understanding of the neural basis
of drug use and to better treatment. The best approach to any drug treatment likely recog-
nizes that addiction is a lifelong problem for most people. Thus, drug addiction must be
treated in the same way as chronic behavioral addictions and medical problems—analogous
to recognizing that controlling weight with appropriate diet and exercise is a lifelong struggle
for many people. Figure 6-16 DrugUseintheUnited
States,2013 Results from an annual
CanDrugsCauseBrainDamage? national survey of Americans aged 12
and older who reported using at least
Many natural substances can act as neurotoxins; Table 6-2 lists some of them. Ongoing one psychoactive drug during the past
investigations of the neurotoxicity of these substances and other drugs in animal mod- year. Percentages for alcohol, tobacco,
els show that many cause brain damage. Whether drugs of abuse cause brain damage in and marijuana are rounded to the nearest
whole number. Data from the 2013 National
humans—especially whether they can do so at the doses that humans take—is more diffi-
Survey on Drug Use and Health: Summary of National
cult to determine. It is difficult to sort out other life experiences from drug taking. It is also Findings, U.S. Department of Health and Human
difficult to obtain the brains of drug users for examination at autopsy. Nevertheless, there is Services, Substance Abuse and Mental Health Services
evidence that the developing brain can be particularly sensitive to drug effects, especially in Administration, Center for Behavioral Health Statistics and
adolescence, a time when drug experimentation is common (Teixeira-Gomes, 2015). Quality. Available for download at www.hhs.gov.
In the late 1960s, many reports linked monosodium glutamate, MSG, a salty-tasting,
flavor-enhancing food additive, to headaches in some people. In investigating this effect,
scientists placed large doses of MSG on cultured neurons, which died. Subsequently, they
injected MSG into the brains of experimental animals, where it also killed neurons. Figure 6-17 Neurotoxicity Domoic acid
This line of research led to the discovery that many glutamatelike substances, including damage in this rat’s hippocampus and to a
domoic acid and kainic acid, both toxins in seaweed, and ibotenic acid, which is found in lesser extent in many other brain regions,
indicated by the darkest coloring. Domoic
some poisonous mushrooms, similarly kill neurons (Figure 6-17). Some drugs, such as PCP
acid, a Glu antagonist, is the causative
and ketamine, also act as glutamate agonists, leaving open the possibility that at high doses agent in amnesic shellfish poisoning,
they too can cause neuronal death. which can result in permanent short-term
memory loss, brain damage, and in severe
taBLe 6-2 Some neurotoxins, their Sources, and their actions cases, death.
Substance Origin action
Domoic acid produces hippocampal
Tetrodotoxin Puffer fish Blocks membrane permeability to Na+ damage, as shown by a dark silver
Magnesium Natural element Blocks Ca2+ channels stain that highlights degeneration.
Reserpine Tree Destroys storage granules
Colchicine Crocus plant Blocks microtubules
Caffeine Coffee bean Blocks adenosine receptors, blocks Ca2+ channels
Spider venom Black widow spider Stimulates ACh release
micrograph from neuroScience associates
Hippocampus
Botulin Spoiled food Blocks ACh release
Curare Berry Blocks ACh receptors
Rabies virus Infected animal Blocks ACh receptors
Ibotenic acid Mushroom Similar to domoic acid, mimics glutamate
Strychnine Plant Blocks glycine
Apamin Bees and wasps Blocks Ca2+ channels
198 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
Glutamatelike drugs are toxic because they act on glutamate receptors. Glutamate recep-
tor activation results in an influx of Ca2+ into the cell, which through second messengers
activates a suicide gene leading to apoptosis (cell death). This discovery shows that a drug
might be toxic not only because of its general effect on cell function but also as an agent that
activates normal cell processes related to apoptosis.
We must add that there is no evidence that moderate consumption of MSG is harmful.
What about the many recreational drugs that affect the nervous system? Are any neu-
Monosodium glutamate Glutamate
(MSG) rotoxic? Sorting out the effects of the drug itself from the effects of other factors related to
taking the drug is a major problem. Chronic alcohol use, for instance, can be associated with
damage to the thalamus and limbic system, producing severe memory disorders. Alcohol,
however, does not directly cause this damage. Alcoholics typically obtain low amounts of
thiamine (vitamin B1) in their diet, and alcohol interferes with the intestine’s absorption of
thiamine. Thiamine plays a vital role in maintaining cell membrane structure.
Similarly, among the many reports of people who have a severe psychiatric disorder
subsequent to abusing certain recreational drugs, in most cases determining whether the
drug initiated the condition or aggravated an existing problem is difficult. Exactly deter-
Focus 5-4 reports the chilling case of heroin mining whether the drug itself or some contaminant in it caused a harmful outcome also
addicts who developed Parkinson disease is difficult. With the increasing sensitivity of brain imaging studies, however, evidence
after using synthetic heroin, owing to a is increasing that many drugs used recreationally can cause brain damage and cognitive
contaminant (MPTP) in the drug. impairments.
The strongest evidence comes from the study of the synthetic amphetaminelike drug
MDMA, also called Ecstasy, and in pure powdered form, Molly (Büttner, 2011). Although
MDMA is structurally related to amphetamine, it produces hallucinogenic effects and is
called a hallucinogenic amphetamine. Findings from animal studies show that doses of
MDMA approximating those taken by human users result in the degeneration of very fine
serotonergic nerve terminals. In monkeys, significant terminal loss may be permanent, as
shown in Figure 6-18.
Memory impairments and damage in MDMA users revealed by brain imaging may be
a result of similar neuronal damage (Cowan et al., 2008). MDMA may also contain a con-
taminant, paramethoxymethamphetamine (PMMA). This notoriously toxic amphetamine
is often called Dr. Death because the difference between a dose that causes behavioral ef-
fects and a dose that causes death is minuscule (Vevelstad et al., 2012). Contamination by
unknown compounds can occur in any drug purchased on the street.
The psychoactive properties of cocaine are similar to those of amphetamine, and so co-
caine also is suspect with respect to brain damage. Cocaine use is related to the blockage of
cerebral blood flow and other changes in blood circulation. Brain imaging studies suggest
that cocaine use can be toxic to neurons, because several brain regions are reduced in size
in cocaine users (Liu et al., 2011).
Chronic marijuana use has been associated with psychotic attacks. Clinical Focus 6-4,
Focus 7-3 explores the hypothesis that Drug-Induced Psychosis, describes one. The marijuana plant contains at least 400 chemicals,
genetic vulnerability predisposes some 60 or more of which are structurally related to its active ingredient, tetrahydrocannabinol.
adolescents to develop a psychosis when Determining whether a psychotic attack is related to THC or to some other chemical in
exposed to cannabis. marijuana is almost impossible.
Whether or not THC can cause psychosis, there is no evidence that the disease is a
result of brain damage. Indeed, beyond the therapeutic applications of TCH cited in
Section 6-2, recent studies suggest that THC may have neuroprotective properties. It
can aid brain healing after traumatic brain injury and slow the progression of diseases
associated with brain degeneration, including Alzheimer disease and Huntington disease
(Nguyen et al., 2014).
6-4 • Explaining and Treating Drug Abuse 199
CliniCal F cus 6-4
Drug-Induced Psychosis
At age 29, R. B. S. smoked marijuana chronically. For years, he had been cloth, and a host of other products. And marijuana has a number of ben-
selectively breeding a potent strain of marijuana in anticipation of the day eficial medical effects. In the Pacific Northwest, marijuana is the largest
when it would be legalized. R. B. S. made his living as a pilot, flying small agricultural crop and makes a larger contribution to the economy than
freight aircraft into coastal communities in the Pacific Northwest. does forestry. In some states marijuana can legally be purchased for
One evening, R. B. S. had a sudden revelation: he was no longer in personal use, and in many states its medical use is legal. Under federal
control of his life. Convinced that a small computer had been implanted law, however, it remains illegal everywhere in the United States.
in his brain when he was 7 years old and was manipulating his behavior, R. B. S.’s heavy marijuana use certainly raises the suspicion that the
he confided in a close friend, who urged him to consult a doctor. R. B. S. drug had some influence on his delusional condition (Wilkinson et al.,
insisted that he had undergone the surgery when he participated in an 2014). Cannabis use has been reported to moderately increase the risk
experiment at a local university. He also claimed that all the other children of psychotic symptoms in young people and has a much stronger effect
who participated in the experiment had been murdered. in those with a predisposition for psychosis, especially if potent strains
The doctor told R. B. S. that the computer implantation was unlikely are used (Di Forti et al., 2015). Although there is evidence that heavy
but called the psychology department at the university and got confir- marijuana use may be associated with alterations in brain development,
mation that children had in fact taken part in an experiment conducted it is unclear whether brain abnormalities are a result of marijuana use
years before. The records of the study had long since been destroyed. or a causal factor in its use (Lubman et al., 2015).
R. B. S. believed that this information completely vindicated his story. His
delusional behavior persisted and eventually cost him his pilot’s license.
R. B. S. seemed to compartmentalize the delusion. When asked why
he could no longer fly, he intently recounted the story of the implant and
the murders, asserting that its truth had cost him the medical certifica-
tion needed for a license. Then he happily and appropriately discussed
other topics.
R. B. S. had a mild focal psychosis: he was losing contact with reality. In
some cases, this break is so severe and the capacity to respond to the envi-
jim Wilson/the new york times/redux
ronment so impaired and distorted that the person can no longer function.
People in a state of psychosis may hallucinate, may have delusions, or may
withdraw into a private world isolated from people and events around them.
A variety of drugs can produce psychosis, including LSD, amphet-
amine, cocaine, and, as shown by this case, marijuana. At low doses
THC, the active ingredient in marijuana, has mild sedative-hypnotic
effects similar to those of alcohol. At the high doses that R. B. S. used,
THC can produce euphoria and hallucinations. Employees fill prescriptions at a medical marijuana clinic in San
Marijuana comes from the leaves of the hemp plant, Cannabis sativa. Francisco. At this writing California is one of more than 20 states that
Humans have used hemp for thousands of years to make rope, paper, have decriminalized the use of medical marijuana.
6-4 review
ExplainingandTreatingDrugAbuse
Before you continue, check your understanding.
1. The wanting-and-liking theory of addiction suggests that with repeated use,
of the drug decreases as a result of , while
increases as a result of .
2. At the neural level, the decision to take a drug is made in the brain’s .
Once taken, the drug activates opioid systems related to pleasurable experiences
in the . Drug cravings may originate in the , and the
repeated pairing of drug-related cues and drug taking forms neural associations in the
that loosen voluntary control over drug taking.
200 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
3. As an alternative to explanations of susceptibility to addiction based on genetic
, can account both for the enduring behaviors that support
addiction and for the tendency of drug addiction to be inherited.
4. It is hard to determine whether recreational drugs cause brain damage in humans
because it is difficult to distinguish the effects of from the effects of
.
5. Briefly describe the basis for a reasonable approach to treating drug addiction.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
6-5 Hormones
In 1849, European scientist A. A. Berthold removed a rooster’s testes and found that it no
Berthold’s experiment demonstrated that
hormones—chemicals released by endocrine longer crowed, nor did it engage in sexual or aggressive behavior. Berthold then reimplanted
glands into the bloodstream—circulate to one testis in the rooster’s body cavity. The rooster began crowing and displaying normal
a body target and affect it. The endocrine sexual and aggressive behavior again. The reimplanted testis did not establish any nerve con-
glands operate under CNS and ANS influence nections, so Berthold concluded that it must release a chemical into the rooster’s circulatory
(see Figure 2-30). system that influenced the animal’s behavior.
That chemical, we now know, is testosterone, the sex hormone secreted by the testes and
responsible for the distinguishing characteristics of the male. The effect Berthold produced
by reimplanting the rooster’s testis mimics the effect of administering testosterone to a cas-
trated rooster, or capon. The hormone is sufficient to make the capon behave like a rooster.
We now know that many hormones affect the sexual characteristics and reproductive
behavior of animals, including us humans. Hormonal effects are not limited to sexual
behavior but also influence eating and drinking, growth, stress responses, and other bodily
functions. Hormones are secreted by glands in the body and by the brain. Interacting brain
and body hormones form feedback loops that regulate their activity. Hormonal influences
Intact rooster change across the life-span, influencing development and body and brain function (Nugent
et al., 2012). In many respects, hormone systems are like neurotransmitter-activating systems
except that hormones use the bloodstream as a conveyance. Indeed, many hormones act as
neurotransmitters, and many neurotransmitters act as hormones.
HierarchicalControlofHormones
Many hormones operate in a feedback system that includes the brain and the body.
Figure 6-18 shows how the hypothalamus produces neurohormones that stimulate the
Capon (rooster with pituitary gland to secrete releasing hormones into the circulatory system. The pituitary hor-
gonads removed)
mones in turn influence the remaining endocrine glands to release appropriate hormones
into the bloodstream to act on various targets in the body and send feedback to the brain
about the need for more or less hormone release.
Hormones not only affect body organs but also target virtually all aspects of brain func-
tion. Almost every neuron in the brain contains receptors on which various hormones
can act. In addition to influencing sex organs and physical appearance, hormones affect
neurotransmitter function, especially in neurons that influence sexual development and
behavior (Barth et al., 2015). Hormones can influence gene expression by binding to
special receptors on or in the cell, then being transported to the nucleus to influence
gene transcription. Transcription in turn influences the synthesis of proteins needed for
a variety of cellular processes. Thus, hormones influence brain and body structure and
behavior.
6-5 • Hormones 201
1 In response to sensory stimuli and cognitive activity, the hypothalamus testosterone Sex hormone secreted by
produces neurohormones that enter the anterior pituitary through veins
and the posterior pituitary through axons.
the testes that produces the distinguishing
characteristics of the male.
Hypothalamus steroid hormone Fat-soluble chemical
messenger synthesized from cholesterol.
Sensory
stimuli peptide hormone Chemical messenger
synthesized by cellular DNA that acts to affect
the target cell’s physiology.
homeostatic hormone One of a group of
hormones that maintain internal metabolic
balance and regulate physiological systems in
Pituitary gland
an organism.
3 Endocrine glands
Target organs
release their own
and tissues
hormones that
Endocrine stimulate target
2 On instructions from
hormones organs, including
these releasing hormones,
the pituitary sends hormones the brain.
into the bloodstream to Target endocrine
target endocrine glands. gland
Figure 6-18 HormonalHierarchy
Although many questions remain about how hormones produce or contribute to complex
behavior, the diversity of their functions clarifies why the body uses hormones as messen-
gers: their targets are so widespread that the best possible way of reaching all of them is to Consult the entry Hormonal Disorders inside
travel in the bloodstream, which goes everywhere in the body. the book’s front cover for more information.
ClassesandFunctionsofHormones
Hormones can be used as drugs to treat or prevent disease. People take synthetic hormones
as replacement therapy if the glands that produce the hormones are removed or malfunction.
People also take hormones, especially sex hormones, to counteract the effects of aging, to
increase physical strength and endurance, and to gain an advantage in sports. In the human
body, as many as 100 hormones are classified chemically as either steroids or peptides.
Steroid hormones, such as testosterone and cortisol, are synthesized from cholesterol and
are lipid (fat) soluble. Steroids diffuse away from their site of synthesis in glands, including
the gonads, adrenal cortex, and thyroid. They bind to steroid receptors on the cell membrane
or in the cell and frequently act on cellular DNA to influence gene transcription.
Peptide hormones, such as insulin, growth hormone, and the endorphins, are made by
cellular DNA in the same way other proteins are made. They influence their target cell’s
activity by binding to metabotropic receptors on the cell membrane, generating a second To refresh your understanding of
messenger that affects the cell’s physiology or gene transcription. metabotropic receptors, review Figure 5-15.
Steroid and peptide hormones fall into one of three main functional groups with respect
to behavior, and they may function in more than one group:
1. Homeostatic hormones maintain a state of internal metabolic balance and regulate
physiological systems. Mineralocorticoids (e.g., aldosterone) control both the concentration
of water in blood and cells and the levels of sodium, potassium, and calcium in the body,
and they promote digestive functions.
202 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
2. Gonadal (sex) hormones control reproductive functions. They instruct the body to develop
as male (testosterone) or female (estrogen); influence sexual behavior and conception; and
in women, control the menstrual cycle (estrogen and progesterone), birthing of babies,
and release of breast milk (prolactin, oxytocin). These hormones, especially oxytocin,
influence mother–infant bonding, and in some species, including sheep, are essential for
bonding to occur.
3. Glucocorticoids (e.g., cortisol and corticosterone), a group of steroid hormones secreted in
times of stress, are important in protein and carbohydrate metabolism and in controlling
blood sugar levels and cellular absorption of sugar. Hormones activated in psychologically
challenging events or emergencies prepare the body to cope by fighting or fleeing.
HomeostaticHormones
Homeostasis comes from the Greek words Homeostatic hormones are essential to life. The body’s internal environment must remain
stasis (standing) and homeo (in the same within relatively constant parameters for us to function. An appropriate balance of sugars,
place). proteins, carbohydrates, salts, and water is necessary in the blood, in the extracellular com-
partments of muscles, in the brain and other body structures, and in all cells. The internal
environment must be maintained regardless of a person’s age, activities, or conscious state.
As children or adults, at rest or in strenuous work, when we have overeaten or when we are
hungry, to survive we need a relatively constant internal environment.
A typical homeostatic function is controlling blood sugar level. After a meal, digestive
processes result in increased glucose in the blood. One group of cells in the pancreas
releases insulin, a homeostatic hormone that instructs the enzyme glycogen synthase
in liver and muscle cells to start storing glucose in the form of glycogen. The resulting
decrease in glucose decreases the stimulation of pancreatic cells so that they stop produc-
ing insulin, and glycogen storage stops. When the body needs glucose for energy, another
Normal glucose concentration in the hormone in the liver, glucagon, acts as a countersignal to insulin. Glucagon stimulates
bloodstream varies between 80 and 130 mg another enzyme, glycogen phosphorylase, to initiate glucose release from its glycogen
per 100 milliliters (about 3.3 oz) of blood. storage site.
Diabetes mellitus is caused by a failure of the pancreatic cells to secrete enough insulin,
or any at all. As a result, blood sugar levels can fall (hypoglycemia) or rise (hyperglycemia).
In hyperglycemia, blood glucose levels rise because insulin does not instruct body cells to
take up glucose. Consequently, cell function, including neuronal function, can fail through
glucose starvation, even in the presence of high glucose levels in the blood. Chronic high
blood glucose levels cause damage to the eyes, kidneys, nerves, heart, and blood vessels.
In hypoglycemia, inappropriate diet can lead to low blood sugar severe enough to cause
fainting. Eric Steen and his coworkers (2005) propose that insulin resistance in brain cells
may be related to Alzheimer disease. They raise the possibility that Alzheimer disease may
be a third type of diabetes.
Hunger and eating are influenced by a number of homeostatic hormones, including
leptin and ghrelin. Leptin (from the Greek for thin), secreted by adipose (animal fat) tissue,
inhibits hunger and so is called the satiety hormone. Ghrelin (from the Indio-European
gher, meaning to grow), secreted by the gastrointestinal tract, regulates growth hormones
and energy use. Ghrelin also induces hunger. It is secreted when the stomach is empty;
secretion stops when the stomach is full. Leptin and ghrelin act on receptors on the same
neurons of the arcuate nucleus of the hypothalamus and so contribute to energy homeo-
stasis by managing eating.
GonadalHormones
We are prepared for our adult reproductive roles by the gonadal hormones that give us our
sexual appearance, mold our identity on the continuum of male to female, and allow us to
6-5 • Hormones 203
engage in sex-related behaviors. Sex hormones begin to act on us even before we are born
and continue their actions throughout our lives.
The male Y chromosome contains a gene called the sex-determining region Y, or SRY,
gene. If cells in the undifferentiated gonads of the early embryo contain an SRY gene, they
develop into a testis, and if they do not, they develop into an ovary. In the male, the testes Section 8-4 explains how gonadal hormones
produce testosterone, which masculinizes the body and the brain. participate in brain development.
The organizational hypothesis proposes that hormone action in the course of develop-
ment alters tissue differentiation. Thus, testosterone masculinizes the brain early in life,
having been taken up in brain cells, where it is converted into estrogen by the enzyme aro-
matase. Estrogen then acts on estrogen receptors to initiate a chain of events that includes
activating certain genes in the cell nucleus. These genes contribute to the masculinization
of brain cells and their interactions with other brain cells.
That estrogen, a hormone usually associated with the female, masculinizes the male
brain may seem surprising. Estrogen does not have the same effect on the female brain,
because females have a blood enzyme that binds to estrogen and prevents its entry into the
brain. Hormones play a somewhat lesser role in producing the female body and brain, but
they control the mental and physical aspects of menstrual cycles, regulate many facets of
pregnancy and birth, and stimulate milk production for breastfeeding. In males, gonadal
hormones demethylate, and so release, genes in the preoptic area of the hypothalamus to
become active. The expression of these genes influences male sexual characteristics and
behavior. Thus, active methylation of male sex–related genes maintains the female pheno-
type (Nugent et al., 2015).
Gonadal hormones contribute to surprising differences in the brain and in cognitive Section 12-5 describes gonadal hormones’
behavior and play a role in male–female differences in drug dependence and addiction (see effects on sexual behavior. Section 15-5
Section 6-3). The male brain is slightly larger than the female brain after corrections are recounts sex differences in thinking patterns.
made for body size, and the right hemisphere is somewhat larger than the left in males.
The female brain has a higher rate both of cerebral blood flow and of glucose utilization.
Differences in size appear in different brain regions, including nuclei in the hypothalamus
related to sexual function, parts of the corpus callosum that are larger in females, and a
somewhat larger language region in the female brain.
Three lines of evidence, summarized by Elizabeth Hampson and Doreen Kimura (2005),
support the conclusion that sex-related cognitive differences result from these anatomical
brain differences and that these cognitive differences also depend in part on the continuing
circulation of the sex hormones. The evidence:
1. Spatial and verbal tests given to females and males in many different settings and cultures
show that males tend to excel in spatial tasks and females in verbal tasks.
2. Results of similar tests given to female participants in the course of the menstrual cycle
show fluctuations in these test scores with phases of the cycle. During the phase in which
the female sex hormones estradiol (metabolized from estrogen) and progesterone are at
their lowest levels, women perform comparatively better on spatial tasks; during the phase
in which levels of these hormones are high, women do comparatively better on verbal gonadal (sex) hormone One of a group of
tasks. hormones, such as testosterone, that control
reproductive functions and bestow sexual
3. Tests comparing premenopausal and postmenopausal women, women in various stages
appearance and identity as male or female.
of pregnancy, and females and males with varying levels of circulating sex hormones all
glucocorticoid One of a group of steroid
provide some evidence that hormones affect cognitive function.
hormones, such as cortisol, secreted in
Sex hormone–related differences in cognitive function are not huge. Performance scores times of stress; important in protein and
between males and females overlap broadly. Yet statistically, the differences are reliable. carbohydrate metabolism.
Similar influences of sex hormones on behavior are found in other species. Berthold’s rooster organizational hypothesis Proposal
experiment described earlier shows the behavioral effects of testosterone. Findings from that hormonal action during development
many studies demonstrate that motor skills in female humans and other animals improve at alters tissue differentiation; for example,
estrus, a time when progesterone levels are high. testosterone masculinizes the brain.
204 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
Anabolic–AndrogenicSteroids
A class of synthetic hormones related to testosterone has both muscle-building (anabolic)
and masculinizing (androgenic) effects. Commonly known simply as anabolic steroids, they
were synthesized originally to build body mass and enhance endurance. Russian weight
lifters were the first to use them, in 1952, to enhance performance and win international
competitions.
Synthetic steroid use rapidly spread to other countries and sports, eventually leading to a
ban from track and field and then from many other sports, enforced by drug testing. Testing
policy has led to a cat-and-mouse game in which new anabolic steroids and new ways of tak-
ing them and masking them are devised to evade detection.
Today, the use of anabolic steroids is about equal among athletes and nonathletes. More
than 1 million people in the United States have used anabolic steroids not only to enhance
athletic performance but also to enhance physique and appearance. Anabolic steroid use in
high schools may be as high as 7 percent for males and 3 percent for females.
The use of anabolic steroids carries health risks. Their administration results in the body
reducing its manufacture of testosterone, which in turn reduces male fertility and sper-
matogenesis. Muscle bulk is increased and so is aggression. Cardiovascular effects include
increased risk of heart attack and stroke. Liver and kidney function may be compromised,
and the risk of tumors may increase. Male-pattern baldness may be enhanced. Females may
have an enlarged clitoris, acne, increased body hair, and a deepened voice.
Anabolic steroids have approved clinical uses. Testosterone replacement is a treatment
for hypogonadal males. It is also useful for treating muscle loss subsequent to trauma and for
the recovery of muscle mass in malnourished people. In females, anabolic steroids are used
to treat endometriosis and fibrocystic disease of the breast.
GlucocorticoidsandStress
Stress is a term borrowed from engineering to describe a process in which an agent exerts
a force on an object. Applied to humans and other animals, a stressor is a stimulus that
challenges the body’s homeostasis and triggers arousal. Stress responses, behavioral as well
as physiological, include both arousal and attempts to reduce stress. A stress response can
outlast a stress-inducing incident and may even occur in the absence of an obvious stressor.
Living with constant stress can be debilitating.
ActivatingaStressResponse
Surprisingly, the body’s response is the same whether the stressor is exciting, sad, or fright-
ening. Robert Sapolsky (2004) uses the vivid image of a hungry lion chasing down a zebra
to illustrate the stress response. The chase elicits divergent behavior in the two animals,
but their physiological responses are identical. The stress response begins when the body is
subjected to a stressor and especially when the brain perceives a stressor and responds with
arousal, directed from the brain by the hypothalamus. The response consists of two separate
sequences, one fast and the other slow.
the Fast response Shown at left in Figure 6-19, the sympathetic division of the ANS
is activated to prepare the body and its organs for fight or flight. The parasympathetic divi-
sion for rest and digest is turned off. The sympathetic division stimulates the medulla on the
interior of the adrenal gland to release epinephrine. The epinephrine surge (often called the
adrenaline surge after epinephrine’s original name) prepares the body for a sudden burst of
anabolic steroid Class of synthetic activity. Among its many functions, epinephrine stimulates cell metabolism, readying the
hormones related to testosterone that body’s cells for action.
have both muscle-building (anabolic) and
masculinizing (androgenic) effects; also called the sloW response As shown at right in Figure 6-19, the slow response is controlled
anabolic–androgenic steroid. by the steroid cortisol, a glucocorticoid released from the outer layer (cortex) of the
6-5 • Hormones 205
Fast-acting pathway Slow-acting pathway
1 In the fight-or-flight 1 In the brain, the
response, the Hypothalamus hypothalamus
hypothalamus sends a releases CRH into
neural message the pituitary gland.
through the spinal CRH
CHR
cord.
2 The pituitary
ACTH gland releases
2 The sympathetic
division of the ACTH, which acts
Pituitary on the cortex of
autonomic nervous gland
system is activated to Spinal the adrenal gland.
cord
stimulate the medulla
of the adrenal gland.
To brain To brain 3 The adrenal
Adrenal Adrenal cortex releases
3 The adrenal medulla medulla To body To body cortex
cells cells cortisol into the
releases epinephrine Co circulatory system.
into the circulatory To endocrine To endocrine rt
nephri s ol
Epi glands glands
i
n
system.
e
Adrenal
glands 4 Cortisol
4 Epinephrine activates the
activates the body‘s body's cells,
Kidneys
cells, endocrine glands, endocrine glands,
and the brain. and the brain.
Figure 6-19 ActivatingaStressResponse Two pathways to the adrenal gland
control the body’s stress response. The fast-acting pathway primes the body immediately
for fight or flight. The slow-acting pathway both mobilizes the body’s resources to confront
a stressor and repairs stress-related damage. CRH, corticotropin-releasing hormone; ACTH,
adrenocorticotropic hormone.
adrenal gland. Activating the cortisol pathway takes anywhere from minutes to hours.
Cortisol has wide-ranging functions, which include turning off all bodily systems not im-
mediately required to deal with a stressor. For example, cortisol turns off insulin so that
the liver starts releasing glucose, thus temporarily increasing the body’s energy supply. It
also shuts down reproductive functions and inhibits the production of growth hormone.
In this way, it concentrates the body’s energy on dealing with the stress.
EndingaStressResponse
Normally, stress responses are brief. The body mobilizes its resources, deals with the chal-
lenge physiologically and behaviorally, and shuts down the stress response. Just as the brain is
responsible for turning on the stress reaction, it is also responsible for turning it off. Consider
what can happen if the stress response is not shut down:
• The body continues to mobilize energy at the cost of energy storage.
• Proteins are used up, resulting in muscle wasting and fatigue.
• Growth hormone is inhibited, so the body cannot grow.
• The gastrointestinal system remains shut down, reducing the intake and processing of
nutrients to replace used resources.
• Reproductive functions are inhibited.
• The immune system is suppressed, contributing to the possibility of infection or
disease.
Sapolsky (2005) argues that the hippocampus plays an important role in turning off
the stress response. The hippocampus contains a high density of cortisol receptors, and
206 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
it has axons that project to the hypothalamus. Consequently, the hippocampus is well
struction o
De ampal ne f suited to detecting cortisol in the blood and instructing the hypothalamus to reduce blood
c uro
p po
cortisol levels.
ns
hi
There may, however, be a more insidious relation between the hippocampus and blood
More Fewer cortisol levels. Sapolsky observed wild-born vervet monkeys that had become agricultural
Prolonged cortisol hippocampal
stress secretion neurons pests in Kenya and had therefore been trapped and caged. He found that some monkeys
sickened and died of a syndrome that appeared to be related to stress. Those that died
seemed to have been subordinate animals housed with particularly aggressive dominant
De o
n hu t
re
a os
c
ff c sed ability t io
monkeys. Autopsies showed high rates of gastric ulcers, enlarged adrenal glands, and pro-
ortis t
o l s e c re nounced hippocampal degeneration. The hippocampal damage may have been due to pro-
longed high cortisol levels produced by the unremitting stress of being caged with the
Figure 6-20 ViciousCircle Unrelieved aggressive monkeys.
stress promotes excessive release of Cortisol levels are usually regulated by the hippocampus, but if these levels remain
cortisol, which damages hippocampal elevated because a stress-inducing situation continues, cortisol eventually damages the hip-
neurons. The damaged neurons cannot
pocampus, reducing its size. The damaged hippocampus is then unable to do its work of
detect cortisol and therefore cannot signal
the adrenal gland to stop producing it. The reducing the level of cortisol. Thus, a vicious circle is set up in which the hippocampus
resulting feedback loop enhances cortisol undergoes progressive degeneration and cortisol levels are not controlled (Figure 6-20).
secretion, further damaging hippocampal Interestingly, other research with rats suggests that following similar stress, the size of the
neurons. amygdala is increased (Bourgin et al., 2015).
Because stress response circuits in rats and monkeys are similar to those in humans, it
is possible that excessive stress in humans can lead to similar brain changes. Because the
hippocampus is thought to play a role in memory, stress-induced hippocampal damage is
postulated to result in impaired memory. Because the amygdala is thought to play a role in
PTSD, introduced in Section 5-4 in relation to emotion, stress-induced changes are postulated to result in increased emotional responses.
sensitization, is among the anxiety disorders This pattern of behavioral changes resembles posttraumatic stress disorder. People with
detailed in Section 12-4. Focus 16-1 and PTSD feel as if they are reliving the trauma, and the accompanying physiological arousal
Section 16-4 consider treatments. enhances their belief that danger is imminent.
Research has not yet determined whether the cumulative effects of stress damage the
human hippocampus. For example, research on women who were sexually abused in child-
hood and were diagnosed with PTSD yields some reports of changes in memory or in hip-
pocampal volume, as measured with brain imaging techniques. Other studies report no
differences in abused and nonabused subjects (Landré et al., 2010). The fact that such appar-
ently similar studies can obtain different results can be explained in several ways.
First, the amount of damage to the hippocampus that must occur to produce a stress
syndrome is not certain. Second, brain imaging techniques may not be sensitive to subtle
changes in hippocampal cell function or to moderate cell loss. Third, wide individual and
environmental differences influence how people respond to stress. Fourth, neonatal stress
can influence hippocampal neurogenesis (Lajud and Torner, 2015). The long-term conse-
quence is a smaller hippocampus and increased susceptibility to stress.
Finally, humans are long-lived and gather many life experiences that complicate simple
extrapolations from a single stressful event. Nevertheless, Patrick McGowan and his cowork-
ers (2009) report that the density of glucocorticoid receptors in the hippocampus of people
who committed suicide after sexual abuse in childhood was lower than that of both controls
and suicide victims who had not been abused.
The decrease in receptors and in glucocorticoid mRNA suggests that childhood abuse
induces epigenetic changes in the expression of glucocorticoid genes. The decrease in
glucocorticoid receptors presumably renders the hippocampus less able to depress stress
responses. The importance of the McGowan study is its suggestion of a mechanism through
which stress can influence hippocampal function without necessarily being associated with a
decrease in hippocampal volume. This study further underscores the point that stress likely
produces many changes in many brain regions. It is unlikely that all have been described or
are understood (Clauss et al., 2015).
Summary 207
6-5 review
Hormones
Before you continue, check your understanding.
1. The hypothalamus produces that stimulate the to secrete
into the circulatory system. Hormone levels circulating in the bloodstream
send feedback to the .
2. Hormones are classified chemically as or .
3. Broadly speaking, hormones regulate metabolic balance;
hormones regulate reproduction; and regulate stress.
4. One class of synthetic hormones is , which increase and
have effects.
5. The stress response has a fast-acting pathway mediated by the release of
and a slow-acting pathway mediated by the release of .
6. Describe the proposed relationship among stress, cortisol, and the hippocampus.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
summary
6-1 PrinciplesofPsychopharmacology FactorsInfluencingIndividual
6-3
Psychoactive drugs—substances that alter mood, thought, or behavior— ResponsestoDrugs
produce their effects by acting on neuronal receptors or on chemical A drug does not have a uniform action on every person. Physical
processes in the nervous system, especially on neurotransmission at differences—in body weight, sex, age, or genetic background—
synapses. Drugs act either as agonists to stimulate neuronal activity influence a given drug’s effects on a given person, as do behaviors,
or as antagonists to depress it. Psychopharmacology is the study of such as learning, and cultural and environmental contexts.
drug effects on the brain and behavior. The influence of drugs on behavior varies widely with the situation
Drugs are administered by mouth, by inhalation, by absorption through and as a person learns drug-related behaviors. Behavioral myopia,
the skin, rectally by suppository, and by injection. To reach a nervous for example, can influence a person to focus primarily on prominent
system target, a psychoactive drug must pass through numerous environmental cues. These cues may encourage the person to act in
barriers posed by digestion and dilution, the blood–brain barrier, and uncharacteristic ways.
cell membranes. Drugs are diluted by body fluids as they pass through Females are more sensitive to drugs than males are and may
successive barriers, are metabolized in the body, and are excreted become addicted more quickly than males to lower doses of drugs.
through sweat glands and in feces, urine, breath, and breast milk. The incidence of female abuse of many kinds of drugs equals or
A common misperception about psychoactive drugs is that they exceeds male abuse of those drugs.
act specifically and consistently, but learning also affects individual
responses to drugs. The body and brain may rapidly become tolerant 6-4 ExplainingandTreatingDrugAbuse
of (habituated to) many drugs, so the dose must increase to produce The neural mechanisms implicated in addiction are the same neural
a constant effect. Alternatively, people may become sensitized to a systems responsible for wanting and liking more generally. So anyone
drug: the same dose produces increasingly strong effects. These is likely to be a potential drug abuser. Addiction develops in a number
forms of unconscious learning also contribute to a person’s behavior of stages as a result of repeated drug taking.
under a drug’s influence. Initially, drug taking produces pleasure (liking), but with repeated
use the behavior becomes conditioned to associated objects, events,
6-2 GroupingPsychoactiveDrugs and places. Eventually, the conditioned cues motivate the drug user
Psychoactive drugs can be organized according to their major to seek them out (wanting), which leads to more drug taking. These
behavioral effects into five groups: antianxiety agents and sedative- subjective experiences become associated with prominent cues, and
hypnotics, antipsychotic agents, antidepressants and mood stabilizers, drug seeking promotes craving for the drug. As addiction proceeds,
opioid analgesics, and psychotropics. Each group, summarized in the subjective experience of liking decreases while wanting increases.
Table 6-1 on page 181, contains natural or synthetic drugs or both, and Treatment varies with the drug. Whatever the treatment approach,
they may produce their actions in different ways. success likely depends on permanent lifestyle changes. Considering
208 Chapter 6 • HOW DO DRUGS AND HORMONES INFLUENCE THE BRAIN AND BEHAVIOR?
how many people use tobacco, drink alcohol, use recreational drugs, activity in the brain that stimulates the pituitary gland through the
or abuse prescription drugs, to find someone who has not used a drug hypothalamus. The pituitary stimulates or inhibits the endocrine
when it was available is probably rare. But because of either genetic glands, which send feedback to the brain via other hormones.
or epigenetic influences, some people do seem particularly vulnerable Homeostatic hormones regulate the balance of sugars, proteins,
to drug abuse and addiction. carbohydrates, salts, and other substances in the body. Gonadal
Excessive alcohol use can be associated with damage to the hormones regulate the physical features and behaviors associated
thalamus and hypothalamus, but the damage is caused by poor nutrition with sex characteristics and behaviors, reproduction, and parenting.
rather than the direct actions of alcohol. Cocaine can produce brain Glucocorticoids are steroid hormones that regulate the body’s ability
damage by reducing blood flow or by bleeding into neural tissue. to cope with stress—with arousing and challenging situations.
MDMA (Ecstasy) use can result in the loss of fine axon collaterals of The hippocampus plays an important role in ending the stress
serotonergic neurons and associated impairments in cognitive function. response. Failure to turn stress responses off after a stressor
Psychedelic drugs, such as marijuana and LSD, can be associated has passed can contribute to susceptibility to PTSD and other
with psychotic behavior. Whether this behavior is due to the drugs’ psychological and physical diseases. Stress may activate epigenetic
direct effects or to the aggravation of preexisting conditions is not clear. changes that modify the expression of genes regulating hormonal
responses to stress and may produce brain changes persisting long
6-5 Hormones after the stress-provoking incident has passed.
Steroid and peptide hormones produced by endocrine glands circulate Synthetic anabolic steroids, used by athletes and others alike,
in the bloodstream to affect a wide variety of targets. Interacting to mimic the effects of testosterone and so increase muscle bulk,
regulate hormone levels is a hierarchy of sensory stimuli and cognitive stamina, and aggression but can have deleterious side effects.
Key terms
addiction, p. 193 competitive inhibitor, p. 187 major depression, p. 184 second-generation
agonist, p. 177 cross-tolerance, p. 182 monoamine oxidase (MAO) antidepressant, p. 184
amphetamine, p. 189 disinhibition theory, p. 191 inhibitor, p. 184 selective serotonin reuptake
mood stabilizer, p. 187 inhibitor (SSRI), p. 184
anabolic steroid, p. 204 dopamine hypothesis of
schizophrenia, p. 184 opioid analgesic, p. 187 steroid hormone, p. 201
antagonist, p. 177
endorphin, p. 187 organizational hypothesis, p. 203 substance abuse, p. 193
antianxiety agent, p. 182
fetal alcohol spectrum disorder peptide hormone, p. 201 testosterone, p. 201
attention-deficit/hyperactivity
disorder (ADHD), p. 173 (FASD), p. 182 psychedelic drug, p. 189 tolerance, p. 177
barbiturate, p. 182 glucocorticoid, p. 203 psychoactive drug, p. 173 tricyclic antidepressant, p. 184
behavioral myopia , p. 193 gonadal (sex) hormone, p. 203 psychomotor activation, p. 193 wanting-and-liking theory, p. 194
bipolar disorder, p. 187 homeostatic hormone, p. 201 psychopharmacology, p. 173 withdrawal symptom, p. 193
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
7 How Do We Study the 7-1
ReseaRch Focus 7-1 Tuning in To Language
MeasuRing and Manipulating BRain and BehavioR
Brain’s Structures Linking neuroanaTomy and Behavior
expeRiMent 7-1 QuesTion: do hippocampaL
and Functions?
neurons conTriBuTe To memory formaTion?
meThods of BehavioraL neuroscience
manipuLaTing Brain–Behavior inTeracTions
7-2 MeasuRing the BRain’s electRical activity
recording acTion poTenTiaLs from singLe ceLLs
eeg: recording graded poTenTiaLs from Thousands of ceLLs
mapping Brain funcTion wiTh evenT-reLaTed poTenTiaLs
clinical Focus 7-2 miLd head injury and depression
magneToencephaLography
7-3 anatoMical iMaging techniques: ct and MRi
7-4 Functional BRain iMaging
funcTionaL magneTic resonance imaging
opTicaL Tomography
posiTron emission Tomography
7-5 cheMical and genetic MeasuRes oF BRain and BehavioR
measuring Brain chemisTry
measuring genes in Brain and Behavior
clinical Focus 7-3 cannaBis use, psychosis, and geneTics
epigeneTics: measuring gene expression
7-6 coMpaRing neuRoscience ReseaRch Methods
7-7 using aniMals in BRain–BehavioR ReseaRch
BenefiTs of animaL modeLs of disease
animaL weLfare and scienTific experimenTaTion
ReseaRch Focus 7-4 aTTenTion-deficiT/hyperacTiviTy disorder
katherine streeter
209
210 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
ReseaRch F cus 7-1
Tuning In to Language
The continuing search to understand the organization and operation
neonate neural response to speech?” by L. May, K. Byers-Heinlein, J. Gervain, and
of the human brain is driven largely by emerging technologies. Over
J.F. Werker, 2011. Frontiers in Psychology, 2, 1–9. Photo by Krista Byers-Heinlein
“Language and the newborn brain: does prenatal language experience shape the
the past decade, neuroscience researchers have developed dramatic
new noninvasive ways to image the brain’s activity in people who are
awake. One technique, functional near-infrared spectroscopy (fNIRS),
gathers light transmitted through cortical tissue to image oxygen con-
sumption in the brain. NIRS, a form of optical tomography, is detailed in
Section 7-4.
fNIRS allows investigators to measure oxygen consumption as a sur-
rogate marker of neuronal activity in relatively select cortical regions,
even in newborn infants. In one study (May et al., 2011), newborns
(0–3 days old) wore a mesh cap containing the NIRS apparatus, made
up of optical fibers, as they listened to a familiar or unfamiliar language.
When newborns listened to a familiar language, their brain showed
a general increase in oxygenated hemoglobin; when they heard an
unfamiliar language, oxygenated hemoglobin decreased overall. But
when the babies heard the same sentences played backward, there was
no difference in brain response to either language. Newborn with probes placed on the head.
The opposing responses to familiar and
unfamiliar languages mean that prena-
“Language and the newborn brain: does prenatal language experi-
K. Byers-Heinlein, J. Gervain, and J.F. Werker, 2011. Frontiers in
ence shape the neonate neural response to speech?” by L. May,
tal language experience shapes how the
newborn brain responds to familiar and
unfamiliar tongues. This finding leads to
many questions. Among them: How does
Psychology, 2, 1–9. Image by Judit Gervain.
prenatal exposure to language influence
later language learning? Do children who
are exposed to multiple languages prena-
tally show better language acquisition than
those exposed to just one? How much pre-
natal language exposure is necessary, and
do premature infants show the same results
as full-term babies?
Whatever the answers, this study shows Probe configurations overlaid on schematics of an infant’s left and right hemispheres. Red
that the prenatal brain is tuned in to the lan- dots indicate light-emitting fibers; blue dots indicate light detectors. The light detectors in the
guage environment into which it will be born. outer strips in both hemispheres sit over regions specialized for language in adults.
the simple, noninvasive nature of fNIRS likely will yield new insights not only
into brain development but also into adult brain function. Over the coming decades, our
understanding of the brain–behavior relationship will continue to be driven in large part by
new and better technologies and by cleverly exploiting existing ones.
To understand how far neuroscience research methods have progressed, imagine that
it is the year 1800. You are a neurologist interested in studying how the brain works. The
challenge is how to begin. The two most obvious choices are to dissect the brains of dead
people and other animals or to study people who have sustained a brain injury. Indeed, this
was how the relationship between brain and behavior was studied well into the twentieth
century.
Techniques for studying the brain’s physiological processes emerged in the years be-
Section 4-1 reviews how the EEG enabled tween World War I and World War II. One breakthrough was the electroencephalograph
investigators to explain electrical activity in (EEG), developed for humans by Hans Berger in the 1930s. Advances in understanding ge-
the nervous system. netics and the analysis of behavior in the early 1950s set the stage for phenomenal advances
7-1 • Measuring and Manipulating Brain and Behavior 211
in neuroscience knowledge. Scientists recognize that new technologies allow for novel
functional near-infrared spectroscopy
insights, lead to more questions, and can dramatically advance their discipline. A large num-
(fNIRs) Noninvasive technique that gathers
ber of Nobel Prizes have been awarded for the development and implementation of new
light transmitted through cortical tissue to
technologies.
image oxygen consumption; form of optical
Today, brain–behavior analyses combine the efforts of anatomists and geneticists, psy- tomography.
chologists and physiologists, chemists and physicists, endocrinologists and neurologists, phar-
neuropsychology Study of the relations
macologists and psychiatrists, engineers and biologists. For the aspiring brain researcher in
between brain function and behavior,
the twenty-first century, the range of available research methods is breathtaking.
especially in humans.
We begin this chapter by reviewing how investigators measure behavior in both human
and nonhuman subjects and how neuroscientists can manipulate behavior by perturbing the
brain. We then consider electrical techniques, including the EEG, for recording brain activ-
ity; noninvasive procedures, such as fNIRS, that image the brain; and chemical and genetic
methods for measuring brain and behavior. After comparing these methods at the chapter’s
end, we review some issues surrounding the use of nonhuman animals in research.
7-1 MeasuringandManipulating
BrainandBehavior
During a lecture at a meeting of the Anthropological Society of Paris in 1861, Ernest
Auburtin, a French physician, argued that language functions are located in the brain’s
frontal lobes. Five days later a fellow French physician, Paul Broca, observed a brain-injured
patient who had lost his speech and was able to say only “tan” and utter a swear word. The
patient soon died. Broca and Auburtin examined the man’s brain and found the focus of his
injury in the left frontal lobe.
By 1863 Broca had collected eight similar cases and concluded that speech is located Section 10-4 explores the anatomy of
in the third frontal convolution of the left frontal lobe—a region now called Broca’s area. language and music and describes Broca’s
Broca’s findings attracted others to study brain–behavior relationships in patients. The field contributions.
that developed is what we now call neuropsychology, the study of the relations between
brain function and behavior with a particular emphasis on humans. Today, measuring brain
and behavior increasingly includes noninvasive imaging, complex neuroanatomical measure-
ment, and sophisticated behavioral analyses.
LinkingNeuroanatomyandBehavior
At the beginning of the twentieth century, neuroanatomy’s primary tools were histological:
brains were sectioned postmortem and the tissue (histo- in Greek) stained with various dyes. As
shown in Figure 7-1, staining sections of brain tissue can identify cell bodies in the brain viewed
with a light microscope (A), and selectively staining individual neurons reveals their complete
structure (B). An electron microscope (C) makes it possible to view synapses in detail.
By 1905, light microscopic techniques allowed researchers such as Korbinian Brodmann Compare Brodmann’s map of the cortex,
to divide the cerebral cortex into many distinct zones based on the characteristics of neurons based on staining, shown in Figure 2-23.
in those zones. Investigators presumed that cortical zones had specific functions. By the
dawn of the twenty-first century, dozens of techniques had developed for labeling neurons
and their connections, as well as glial cells. Contemporary techniques allow researchers to
identify molecular, neurochemical, and morphological (structural) differences among neu-
ronal types and ultimately to relate these characteristics to behavior. One fast-developing
technique, shown in Figure 7-1D, uses a multiphoton microscope that makes it possible to
image living brain tissue in three dimensions.
Connections between anatomy and behavior can be seen in studies of animals trained on
various types of learning tasks, such as spatial mazes. Such learning can be correlated with
a variety of neuronanatomical changes, such as modifications in the synaptic organization
of cells in specific cortical regions—the visual cortex in animals trained in visually guided
212 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
FIGUre 7-1 StainingCerebral (A) Light microscope, (B) Light microscope,
Neurons V iewed through a light low magnification high magnification
microscope, (A) Nissl-stained section of
parietal cortex shows all cell bodies but
no cell processes (axons and dendrites).
(B) At higher magnification, an individual A
Golgi-stained pyramidal cell from the
parietal cortex is visible. The cell body
(dark triangular shape at center) and
spiny dendrites (A and B) are visible in A
detail at right. (c) The view through an
electron microscope shows neuronal B
synapses in detail. (D) Multiple images
from a multiphoton microscope, merged
to generate a three-dimensional image of
living tissue.
Bryan kolb
Bryan kolb
B
(C) Electron microscope (D) Multiphoton microscope
n. kasthuri and jw Lichtman, harvard university
douglas Bray, university of Lethbridge
mazes is one example—or in the number of newly generated cells that survive in the hippo-
campus. The hippocampus is necessary, in mammals, for remembering the context in which
we encounter information.
Although changes in synaptic organization or cell survival have not yet been proved to
be the basis of the new learning, experimental evidence reveals that preventing the growth
of new hippocampal neurons leads to memory deficits. To test the idea that hippocampal
Corticosterone, a steroid hormone secreted neurons contribute to memory formation, researchers tested healthy rats and ADX rats—rats
in times of stress, is important in protein and with adrenal glands removed, which eliminates the hormone corticosterone. Without corti-
carbohydrate metabolism (see Section 6-5). costerone, neurons in the hippocampus die.
Procedure 1 in Experiment 7-1 contrasts the appearance of a healthy rat hippocampus
(left) and neuronal degeneration in an ADX rat after surgery (right). The behavior of healthy
and ADX rats was studied in the object–context mismatch task diagrammed in Procedure 2.
During the training phase, the rats were placed in two distinct contexts, A and B, for
10 minutes on each of 2 days. Each context contained a different type of object. On the test
day, the rats were placed in either context A or context B but with two different objects, one
from that context and a second from the other context.
As noted in the Results section of the experiment, when healthy rats encounter objects in
the correct context, they spend little time investigating because the objects are familiar. If,
however, they encounter an object in the wrong context, they are curious and spend about
three-quarters of their time investigating, essentially treating the mismatched object as new.
But the ADX rats with hippocampal cell loss treated the mismatched and in-context objects
the same, spending about half of their investigation time with each object.
7-1 • Measuring and Manipulating Brain and Behavior 213
ExpERImENt 7-1
Question: Do hippocampal neurons contribute to memory formation?
Procedure 1
Rat hippocampus before (left) and after (right) surgical removal of the adrenal glands.
Arrows point to neuronal degeneration resulting from a lack of corticosterone.
Healthy rat hippocampus ADX-induced hippocampal degeneration
granule cells after adrenalectomy in rats.
spanswick s.c., sutherland r.j. (2010).
object-context specifi c memory defi cits
associated with loss of hippocampal
Learning and Memory, 17:241–245.
Hippocampus
Procedure 2
The behavior of healthy and ADX rats was studied in an object–context mismatch task in
which two distinct contexts each contained a different type of object.
Training phase Testing phase
During the training phase, each rat was
placed in contexts A and B, each for 10 Contexts A and B with
minutes on each of 2 days. Each mismatched objects
context contained one type of object.
During the testing
phase, each rat was
placed either in
context A or in
context B, but with
two different
OR
objects, one from
that context and a
second from the
Context A Context B
other context.
Results
Healthy rats investigate the mismatch object more than the object that is in context, but
the ADX rats performed at chance. The rats in another ADX group were given treatments
known to increase neuron generation in the hippocampus (enriched housing and exercise
in running wheels). The rats with hippocampal regeneration were not impaired at the
mismatch task.
The confocal photo at right shows a rat hippocampus. A specific stain was used to identify
courtesy Bryan kolb
new neurons, which appear yellow.
Conclusion: Hippocampal neurons are necessary for the contextual learning.
Information from S. Spanswick & R. J. Sutherland (2010). Object/context-specific memory deficits associated with loss of
hippocampal granule cells after adrenalectomy in rats. Learning and Memory, 17, 241–245. Information from S. Spanswick,
H. Lethman, & R. J. Sutherland (2011). A novel animal model of hippocampal cognitive deficits, slow neurodegeneration, and
neuroregeneration. Journal of Biomedicine and Biotechnology. Article ID 527201.
214 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
Another group of ADX rats given treatment known to increase neuron generation in the
behavioral neuroscience Study of the
hippocampus—enriched housing and exercise in running wheels—was unimpaired at the
biological bases of behavior in humans and
context mismatch task. Experiment 7-1 concludes that cellular changes in the hippocampus
other animals.
and behavioral changes are closely linked: hippocampal neurons are necessary for contextual
learning.
MethodsofBehavioralNeuroscience
The brain’s ultimate function is to produce behavior (movement). It follows that brain dys-
function should alter behavior in some way. The study of brain–behavior relationships in
both humans and laboratory animals is behavioral neuroscience, the study of the biological
bases of behavior.
A major challenge to behavioral neuroscientists is developing methods for studying both typi-
cal and atypical behavior. Measuring behavior in humans and laboratory animals differs in large
part because humans speak: investigators can ask them about their symptoms. It is also possible
to use both paper-and-pencil and computer-based tests to identify specific symptoms in people.
Measuring behavior in laboratory animals is more complex. Researchers must learn to
speak “ratese” with rat subjects or “monkeyese” with monkeys. In short, researchers must
develop ways to enable the animals to reveal their symptoms. The development of the fields
of animal learning and ethology, the objective study of animal behavior, especially under
Table 7-2 on page 239 summarizes selected natural conditions, provided the basis for modern behavioral neuroscience (see Whishaw &
brain measurement techniques, their goals, Kolb, 2005). To illustrate the logic of behavioral neuroscience, we describe some measure-
and examples. ment tools used with humans and some used with rats.
NeuropsychologicalTestingofHumans
The brain has exquisite control of an amazing array of functions ranging from movement
control and sensory perception to memory, emotion, and language. As a consequence, any
analysis of behavior must be tailored to the particular function(s) under investigation. Con-
sider the analysis of memory.
People with damage to the temporal lobes often complain of memory disturbance. But
memory is not a single function; rather, multiple as well as independent memory systems
exist. We have memory for events, colors, names, places, and motor skills, among other cat-
egories, and each must be measured separately. It would be rare indeed for someone to be
Sections 14-1 through 14-3 analyze the varied impaired in all forms of memory. Neuropsychological tests of three distinct forms of memory
categories of memory. are illustrated in Figure 7-2.
(A) Corsi block-tapping test (B) Mirror-drawing task (C) Test of recent memory
The examiner taps out a Participants’ task is to trace Participants’ task is to
sequence of blocks. between the two outlines identify which picture
of the star while looking they saw most recently.
only at their hand in a
2 mirror.
1
4 3
5
7 6
?
9
8
Examiner’s view
Crossing a line
The block numbers are visible on the constitutes an error.
examiner’s side of the board but not
on the participant’s side.
FIGUre 7-2 NeuropsychologicalTestsofMemory
7-1 • Measuring and Manipulating Brain and Behavior 215
The Corsi block-tapping test shown in Figure 7-2A requires participants to observe an
experimenter tap a sequence of blocks—blocks 4, 6, 1, 8, 3, for instance. The task is to repeat
the sequence correctly. The subject does not see numbers on the blocks but rather must
remember the location of the tapped blocks.
The Corsi test provides a measure of short-term recall of spatial position, an ability we can
call block span. The test can be made more difficult by determining the maximum block span
of an individual (say, 6 blocks) and then adding one (span + 1). By definition, the participant
will fail on the first presentation, but given the span + 1 repeatedly, will eventually learn it.
Span + 1 identifies a different form of memory from block span. Different types of neu-
rological dysfunction interfere differentially with tasks that superficially appear quite similar.
Block span measures the short-term recall of information, whereas the span + 1 task reflects
the learning and longer-term memory storage of information.
The mirror-drawing task (Figure 7-2B) requires a person to trace a pathway, such as a star,
by looking in a mirror. This motor task initially proves difficult because our movements ap-
pear backward in the mirror. With practice, participants learn how to accomplish the task In this book, we refer to healthy human
accurately, and they show considerable recall of the skill when retested days later. Curiously, volunteers in research studies as participants
patients and subjects with certain types of memory problems have no recollection of learning and to people or animals that have a brain or
the task on the previous day but nevertheless perform it flawlessly. behavioral impairment as patients or subjects.
In the recency memory task (Figure 7-2C), participants are shown a long series of cards,
each bearing two stimulus items that are words or pictures. On some trials a question mark
appears between the items. The subjects’ task is to indicate whether they have seen the items
before and if so, which item they saw most recently. People may be able to recall that they
have seen items before but be unable to recall which was most recent. Conversely, they may
not be able to identify the items as being familiar, but when forced to choose the most recent
one, they can identify it correctly.
The latter, counterintuitive result reflects the need for behavioral researchers to develop Focus 15-4 compares effects of injuries to
ingenious ways of identifying memory abilities. It is not enough simply to ask people to recall particular brain regions on performance of
information verbally, although this too measures a form of memory. particular neuropsychological tasks.
BehavioralAnalysisofRats
Over the past century, psychologists interested in the neural basis of memory have devised
a vast array of mazes and other tests and tasks to investigate different forms of memory in
laboratory animals. Figure 7-3 illustrates three tests based on a task devised by Richard
Morris in 1980. Researchers place rats in a large swimming pool where an escape platform
lies just below the water surface, invisible to the rats.
In one version of the task, place learning, the rat must find the platform from any starting
location in the pool (Figure 7-3A). The only cues available are outside the pool, so the rat
must learn the relation between several cues in the room and the platform’s location. In a
second version of the task, matching-to-place learning, the rat has already learned that a plat-
form always lies somewhere in the pool but is moved to a different location every day. The
rat is released and searches for the platform (Figure 7-3B). Once the rat finds the platform,
the animal is removed from the pool and after a brief delay (such as 10 seconds) is released
again. The rat’s task is to swim directly to the platform.
The challenge for the rat in the matching-to-place test is to develop a strategy for finding
the platform consistently: it is always in the same location on each trial each day, but each
new day brings a new location. In the landmark version of the task, the platform’s location
is identified by a cue on the pool wall (Figure 7-3C). The platform moves on every trial, but
the relation to the cue is constant. In this task the brain is learning that the distant cues
outside the pool are irrelevant; only the local cue is relevant. Rats with different neurologi-
cal perturbations are selectively impaired in the three versions of the swimming pool task.
Another type of behavioral analysis in rats is related to movement. A major problem facing
people with stroke is a deficit in controlling hand and limb movements. The prevalence of
stroke has prompted considerable interest in devising ways to analyze such motor behaviors
216 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
SwimmingPool
FIGUre 7-3
Room
Tasks General arrangement of cues
the swimming pool used in three
visuospatial learning tasks for rats.
Red lines in parts A, B, and C mark the
rat’s swimming path on each trial (T).
(A) Information from R. G. M. Morris (1981). Spatial
localization does not require the presence of local
cues. Learning and Motivation, 12, 239–260.
(B) Information from I. Q. Whishaw (1989).
Dissociating performance and learning deficits
in spatial navigation tasks in rats subjected to
cholinergic muscarinic blockade. Brain Research
Bulletin, 23, 347–358. (c) Information from Kolb, B.,
and Walkey, J. (1987). Behavioural and anatomical
studies of the posterior parietal cortex of the rat.
Behavioural Brain Research, 23, 127–145.
Submerged
platform
(A) Place-learning task (B) Matching-to-place task (C) Landmark-learning task
Pool
T2 Hidden T3
platform
T1
T1
T5 T1
T3
T2
Cue
T4 T2 (on wall
of pool)
A rat placed in the pool at various The rat is again put into the pool at The rat must ignore the room cues and
starting locations must learn to find a random locations, but the hidden learn that only the cue on the wall of
hidden platform. The rat can do this platform is in a new location on each the pool signals the location of the
only by considering the configuration test day. The animal must learn that platform. The platform and cue are
of visual cues in the room—windows, the location where it finds the moved on each trial, so the animal is
wall decorations, potted plants, and platform on the first trial each day is penalized for using room cues to try to
the like. its location for all trials on that day. solve the problem.
for the purpose of testing new therapies for facilitating recovery. Ian Whishaw (Whishaw &
Kolb, 2005) has devised both novel tasks and novel scoring methods to measure the fine
details of skilled reaching movements in rats.
Experiments in Chapter 14 demonstrate In one test, rats are trained to reach through a slot to obtain a piece of sweet food. The
fear conditioning in rats, plasticity in the movements, which are remarkably similar to the movements people make in a similar task,
monkey’s motor cortex, and neuronal can be broken down into segments. Investigators can score the segments separately, as they
effects of amphetamine sensitization in rats. are differentially affected by different types of neurological perturbation.
The photo series in Figure 7-4 details how a rat orients its body to the slot (A), puts its
hand through the slot (B), rotates the hand horizontally to grasp the food (C), then rotates
the hand vertically and withdraws it to obtain the food (D). Contrary to reports common
in neurology textbooks, primates are not the only animals to make fine digit movements,
but because the rat’s hand is small and moves so quickly, digit dexterity can be seen in ro-
dents only with use of high-speed videography.
7-1 • Measuring and Manipulating Brain and Behavior 217
(A) (B) (C) (D)
Bryan kolb
SkilledReachingin
FIGUre 7-4
Rats Movement series displayed by rats
ManipulatingBrain–BehaviorInteractions trained to reach through a narrow vertical
slot to obtain sweet food: (A) aim the hand,
One strategy for studying brain–behavior relationships is to manipulate some aspect of brain
(B) reach over the food, (c) grasp the food,
function and see how behavior changes. Investigators do so to develop hypotheses about how (D) withdraw and move food to the mouth.
the brain affects behavior, then to test those hypotheses.
Neuroscientists hypothesize about the functions of brain regions by studying how removing
or inhibiting them affects behavior. Broca studied patients with naturally occurring injuries and
made inferences about language organization. Similarly, Parkinson patients have motor distur- Focus features 5-2, 5-3, and 5-4 detail many
bances and associated cell death in the substantia nigra (Figure 7-5). It is a small step experimen- aspects of Parkinson disease.
tally to injure specific brain regions in laboratory animals, then study their behavior. Such studies
tell investigators not only about the injured region’s function but also what the remaining brain
can do in the absence of the injured region. Neuroscientists also study brain region functions
to form hypotheses, for example, on how exciting a region affects behavior. Certain drugs and
stimulation techniques that increase brain region activity result in behavioral change.
A second reason to manipulate the brain is to develop animal models of neurological and Table 7-1 on page 238 summarizes selected
psychiatric disorders. The general presumption in neurology and psychiatry is that it ought brain manipulation techniques, their goals,
to be possible to restore at least some healthy functioning by pharmacological, behavioral, and examples.
or other interventions. A major hurdle for developing such treatments is that, like most new
medical treatments, they must be tested in nonhuman subjects first. (In Section 7-7, we take
up scientific and ethical issues surrounding the use of animals in research.)
For brain disorders, researchers must develop models of diseases before they can be treated.
Consider dementia, a progressive memory impairment that appears to be related to neuronal
death in specific brain regions. The goal for treatment is to reverse or prevent cell death, but
developing effective treatments requires an animal model that mimics dementia.
Brains can be manipulated in various ways, the precise manner depending on the specific
PathologyinParkinson
FIGUre 7-5
research question being asked. Researchers can manipulate the whole animal by exposing it Disease A variety of motor disturbances
to differing diets, social interactions, exercise, sensory stimulation, and a host of other experi- appear when enough dopamine-producing
ences. For brain manipulation, the principal direct techniques are to inactivate the brain via cells in the substantia nigra die. Information
lesion or with drugs or to activate it with electrical stimulation, drugs, or light. from healthguide.howstuffworks.com/substantia-nigra-
and-parkinsons-disease-picture.htm
Dorsal view of substantia nigra,
a nucleus in the midbrain
involved in initiating movement.
A healthy substantia nigra, rich In a weakened substantia nigra,
in the cell bodies of dopamine dopamine neurons have
neurons, shown in cross section. degenerated, contributing to
symptoms of Parkinson disease.
218 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
BrainLesions
The first—and the simplest—technique used was to ablate (remove or destroy) tissue. Begin-
ning in the 1920s, Karl Lashley, a pioneer of neuroscience research, used ablation, and for
the next 30 years he tried to find the site of memory in the brain. He trained monkeys and
rats on various mazes and motor tasks, then removed bits of cerebral cortex with the goal of
producing amnesia for specific memories.
To his chagrin, Lashley failed in his quest. He observed instead that memory loss was
related to the amount of tissue he removed. The only conclusion Lashley could reach was that
memory is distributed throughout the brain and not located in any single place. Subsequent
research strongly indicates that specific brain functions and associated memories are indeed
Scoville’s patient, H. M., profiled in Section 14-2, localized to specific brain regions. Ironically, just as Lashley was retiring, William Scoville
became the most-studied case in and Brenda Milner (1957) described a patient from whose brain Scoville had removed both
neuroscience. hippocampi as a treatment for epilepsy. The surgery rendered this patient amnesic. During
his ablation research, Lashley had never removed the hippocampi because he had no rea-
son to believe the structures had any role in memory. And because the hippocampus is not
accessible on the brain’s surface, other techniques had to be developed before subcortical
lesions could be used.
The solution to accessing subcortical regions is to use a stereotaxic apparatus, a device
that permits a researcher or a neurosurgeon to target a specific part of the brain for ablation,
as shown in Figure 7-6. The head is held in a fixed position, and because the location of brain
structures is fixed in relation to the junction of the skull bones, it is possible to visualize a
three-dimensional brain map.
Rostral–caudal (front to back) measurements, corresponding to the x-axis in Figure 7-6,
are made relative to the junction of the frontal and parietal bones (the bregma). Dorsal–
ventral (top to bottom) measurements, the y-axis, are made relative to the surface of the
Review the brain’s anatomical locations and brain. Medial–lateral measurements, the z-axis, are made relative to the midline junction
orientations in The Basics, in Section 2-1. of the cranial bones. Atlases of the brains of humans and laboratory animals have been
The brain atlas in Figure 8-14 tracks cortical constructed from postmortem tissue so that the precise location of any structure can be
thickness over time. specified in three-dimensional space.
Consider the substantia nigra. To ablate this region to induce a rat to display symptoms of
Parkinson disease, the structure and its three-dimensional location in the brain atlas is located.
A small hole is then drilled in the skull, as shown in Figure 7-6, and an electrode lowered to the
stereotaxic apparatus Surgical instrument
substantia nigra. If a current is passed through the electrode, the tissue in the region of the
that permits the researcher to target a
electrode tip is killed, producing an electrolytic lesion.
specific part of the brain.
hypokinesia Slowness or absence of
movement. y-axis calibrating y
knob
z-axis calibrating
compensation Following brain damage,
Electrode knob
neuroplastic ability to modify behavior from carrier z
that used prior to the damage.
deep-brain stimulation (DBs) Neurosurgical
x
technique: electrodes implanted in the brain
Calibration
stimulate a targeted area with a low-voltage scale
electrical current to produce or facilitate behavior.
x-axis calibrating
knob
Stereotaxic
FIGUre 7-6
Ear bar
Apparatus This instrument allows
the precise positioning of electrodes for
lesioning or for stimulating brain regions. Nose bar
7-1 • Measuring and Manipulating Brain and Behavior 219
A problem with electrolytic lesions: not only are the neurons of the targeted tissue killed
but so are any nerve fibers passing through the region (in this case, substantia nigra). One
solution is to lower a narrow metal tube (a cannula) instead of an electrode, infuse a neuron-
killing chemical, and thus produce a neurotoxic lesion. (Figure 7-22 diagrams this procedure.)
A selective toxin can be injected that kills only neurons, sometimes only certain types of
neurons, and spares the fibers.
To make a rat parkinsonian, a toxin can be injected that is selectively taken up by dopami-
nergic neurons; this leads to a condition that mimics human Parkinson pathology. Animals
with such neurotoxic lesions have a variety of motor symptoms including hypokinesia (slow-
ness or absence of movement), short footsteps, and tremor. Drugs such as l-dopa, an agonist
that enhances dopamine production, and atropine, an antagonist that blocks acetylcholine
production, relieve these symptoms in Parkinson patients. Ian Whishaw and his colleagues
(Schallert et al., 1978) thus were able to selectively lesion the substantia nigra in rats to pro-
ian whishaw
duce a behavioral model of Parkinson disease.
The invasive techniques described so far result in permanent brain damage. With time,
the research subject will show compensation, the neuroplastic ability to modify behavior
Shuffling gait of a parkinsonian rat,
from that used prior to the damage. To avoid compensation following permanent lesions, captured in prints left by its ink-stained
researchers have also developed temporary and reversible lesion techniques such as regional hind feet.
cooling, which prevents synaptic transmission. A hollow metal coil is placed next to a neural
structure; then chilled fluid is passed through the coil, cooling the brain structure to about
18ºC (Lomber & Payne, 1996). When the chilled fluid is removed from the coil, the brain
structure quickly warms, and synaptic transmission is restored. Another technique involves
local administration of a GABA agonist, which increases local inhibition and in turn prevents
the brain structure from communicating with other structures. Degradation of the GABA
agonist reverses the local inhibition and restores function.
BrainStimulation
The brain operates on both electrical and chemical energy, so it is possible to selectively
turn brain regions on or off by using electrical or chemical stimulation. Wilder Penfield, in Read more about Penfield’s dramatic
the mid-twentieth century, was the first to use electrical stimulation directly on the human discoveries in Sections 10-4 and 11-2.
cerebral cortex during neurosurgery. Later researchers used stereotaxic instruments to place
an electrode or a cannula in specific brain locations. The objective: enhancing or blocking
neuronal activity and observing the behavioral effects.
Perhaps the most dramatic research example comes from stimulating specific regions of
the hypothalamus. Rats with electrodes placed in the lateral hypothalamus will eat whenever Figure 12-12 diagrams hypothalamus anatomy.
the stimulation is turned on. If the animals have the opportunity to press a bar that briefly Section 12-3 details its role in motivated and
turns on the current, they quickly learn to press the bar to obtain the current, a behavior emotional behavior.
known as electrical self-stimulation. It appears that the stimulation is affecting a neural cir-
cuit that involves both eating and pleasure.
Brain stimulation can also be used as a therapy. When the intact cortex adjacent to cortex
injured by a stroke is stimulated electrically, for example, it leads to improvement in motor
behaviors such as those illustrated in Figure 7-4. Cam Teskey and his colleagues (Brown
et al., 2011) successfully restored motor deficits in a rat model of Parkinson disease by electri-
cally stimulating a specific brain nucleus.
Deep-brain stimulation (DBS) is a neurosurgical technique. Electrodes implanted in
the brain stimulate a targeted area with a low-voltage electrical current to facilitate behav-
ior. DBS to subcortical structures—for example, the globus pallidus in the basal ganglia
of Parkinson patients—makes movements smoother. Medications can often be reduced
dramatically. DBS using several neural targets is an approved treatment for obsessive-
compulsive disorder. Experimental trials are underway to identify the brain regions optimal
for DBS to be used as a treatment for intractable psychiatric disorders such as major depres- View DBS in place in Figure 1-6.
sion (Schlaepfer et al., 2013), schizophrenia, and possibly for epilepsy; also for stimulating
recovery from TBI.
220 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
(A) (B)
composite mri and peT scan from dr. Tomáš paus, rotman
research institute, Baycrest centre for geriatric care
The TMS coil,
shown here in a
marcello massimini/university of milan.
composite MRI
and PET scan
photograph,
interferes with
brain function
TMS COIL in the adjacent
area.
L R
FIGUre 7-7TranscranialMagneticStimulation (A) In clinical therapy for
depression, TMS influences neural activity in a localized region. (B) Composite photo
shows how TMS works.
Electrical stimulation of the brain is invasive: holes must be drilled in the skull
and an electrode lowered into the brain. Researchers have taken advantage of the
relation between magnetism and electricity to develop a noninvasive technique,
transcranial magnetic stimulation (TMS). A small wire coil is placed adjacent to the skull,
as illustrated in Figure 7-7A. A high-voltage current pulsed through the coil produces a
rapid increase and subsequent decrease in the magnetic field around the coil. The magnetic
field easily passes through the skull and causes a population of neurons in the cerebral
cortex to depolarize and fire (Figure 7-7B).
If the motor cortex is stimulated, movement is evoked, or if a movement is in progress,
it is disrupted. Similarly, if the visual cortex is stimulated, the participant sees dots of light
(phosphenes). The effects of brief pulses of TMS do not outlive the stimulation, but repeti-
tive TMS (rTMS), or continuous stimulation for up to several minutes, produces more long-
Research Focus 16-2 describes use of rTMS lasting effects. TMS and rTMS can be used to study brain–behavior relationships in healthy
to treat depression and other behaviorral participants, and rTMS has been tested as a potential treatment for a variety of behavioral
disorders. disorders. A growing body of research also supports its antidepressant actions.
DrugManipulations
Brain activity can also be stimulated by administration of drugs that pass into the blood-
stream and eventually enter the brain or, through an indwelling cannula (illustrated in Figure
7-22), that allows direct application of them to specific brain structures. Drugs can influence
the activity of specific neurons in specific brain regions. For example, the drug haloperidol,
transcranial magnetic stimulation used to treat schizophrenia, reduces dopaminergic neuron function and makes healthy rats
(tms) Procedure in which a magnetic dopey and inactive (hypokinetic).
coil is placed over the skull to stimulate In contrast, drugs that increase dopaminergic activity, such as amphetamine, produce
the underlying brain; used either to induce hyperkinetic rats—rats that are hyperactive. The advantage of administering drugs is that
behavior or to disrupt ongoing behavior. their effects wear off in time as the drugs are metabolized. It thus is possible to study drug
synthetic biology Design and construction effects on learned behaviors, such as skilled reaching (see Figure 7-4), and then to reexamine
of biological devices, systems, and machines the behavior after the drug effect wears off.
not found in nature. Claudia Gonzalez and her colleagues (2006) administered nicotine to rats as they learned
optogenetics Transgenic technique that a skilled reaching task, then studied their later acquisition of a new skilled reaching task.
combines genetics and light to control The researchers found that the earlier nicotine-enhanced motor learning impaired the later
targeted cells in living tissue. motor learning. This finding surprised the investigators, but it now appears that repeated
chemogenetics Transgenic technique that exposure to psychomotor stimulants such as amphetamine, cocaine, and nicotine can produce
combines genetics and synthetic drugs to long-term effects on the brain’s later plasticity, its ability to change in response to experience,
activate targeted cells in living tissue. including learning specific tasks.
7-1 • Measuring and Manipulating Brain and Behavior 221
OptogeneticsandChemogenetics Excitation Inhibition
Extracellular fluid Extracellular fluid
Within the span of a decade, synthetic biology, the design and construction of bio-
logical devices, systems, and machines not found in nature, has transformed how neu- Blue light Green-yellow light
Na+
roscientists manipulate brain cells. Techniques include inserting a genetic sequence Cl–
ChR2 NpHR
into the genome of a living organism. The transgenic technique of optogenetics, for
example, combines genetics and light to control targeted cells in living tissue. A se-
quence that codes for a light-sensitive protein associated with an ion channel enables
investigators to use light to change the shape (conformation) of the channel.
Optogenetics is based on the discovery that light can activate certain proteins that K+
occur naturally and have been inserted into cells of model organisms. For example, Intracellular fluid Intracellular fluid
opsins, proteins derived from microorganisms, combine a light-sensitive domain with an
Action potential Action potential
ion channel. The first opsin used for the optogenetic technique was channelrhodopsin-2
(ChR2). When ChR2 is expressed in neurons and exposed to blue light, the ion channel
opens and immediately depolarizes the neuron, causing excitation. In contrast, stimu-
lation of halorhodopsin (NpHR) with a green-yellow light activates a chloride pump,
1 min 1 min
hyperpolarizing the neuron and causing inhibition. A fiber-optic light can be delivered
to selective brain regions such that all genetically modified neurons exposed to the light LightingUpNeurons Optogenetics allows
respond immediately (Haubensak et al., 2010). precise temporal control of cell firing and is rapidly
Optogenetics has tremendous potential as a research tool. Investigators can in- reversible. Specific wavelengths activate light-
sensitive proteins expressed in neurons. At bottom
sert light-sensitive proteins into specific neuron types, such as pyramidal cells, and
left, when blue light illuminates a cell in which ChR2
use light to selectively activate a single cell type. Researchers hail optogenetics has been incorporated, its firing rate increases
for its high spatial and temporal (time) resolution. Ion channels can be placed into dramatically. At right, when green-yellow light
specific cell lines and turned on and off on millisecond time scales. Optogenetics illuminates a cell in which NpHR is incorporated,
also finds application in behavioral studies. Within the limbic system, for example, its firing rate decreases dramatically. See more at
https://www.youtube.com/watch?v=I64X7vHSHOE.
the amygdala is a key structure in generating fear in animals. If it is targeted with
opsins then exposed to an inhibitory light, rats immediately show no fear and wander
about in a novel open space. As soon as the light is turned off, they scamper back to a safe
hiding place. Figure 2-25 diagrams the limbic structures.
In the transgenic technique, chemogenetics, the inserted synthetic genetic sequence
codes for a G protein–coupled receptor engineered to respond exclusively to a synthetic
small-molecule “designer drug.” Chemogenetics is best known by the acronym DREADD
(designer receptor exclusively activated by designer drugs). Its principle advantage is that the DREADD does not employ the sort of
drug will activate only the genetically modified receptors, and the receptors will be activated designer drug that may come to mind.
only by the designer drug, not by endogenous molecules (Wess et al., 2013). Thus, specificity Rather than synthetic versions of controlled
is high, but temporal resolution is much lower than with optogenetics because receptors are substances (e.g., heroin), these synthetic
activated by drugs rather than by light. drugs interact with a synthetic receptor.
7-1 reVIeW
MeasuringandManipulatingBrainandBehavior
Before you continue, check your understanding.
1. Behavioral neuroscience, the study of relations between and ,
employs memory tests such as in nonhuman animals such as rats.
2. Anatomical studies rely on techniques such as tissue postmortem or
visualizing living tissue using a .
3. Methods developed to manipulate the brain include , ,
, and .
4. Outline the various brain stimulation methods that either activate or inhibit neural activity.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
222 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
7-2 MeasuringtheBrain’s
ElectricalActivity
The brain is always electrically active, even when we sleep. Electrical measures of brain
activity are important for studying brain function, for medical diagnosis, and for monitor-
ing the effectiveness of therapies used to treat brain disorders. The four major techniques
for tracking the brain’s electrical activity are single-cell recording, electroencephalography
(EEG), event-related potentials (ERPs), and magnetoencephalography (MEG).
Figure 4-11 diagrams a cell membrane at In part, these techniques are used to record electrical activity from different parts of
rest, Figure 4-13 during graded potentials, neurons. The electrical behavior of cell bodies and dendrites, which give rise to graded
and Figure 4-15 generating the action potentials, tends to be much more varied and slower than that of axons, which conduct
potential. action potentials.
RecordingActionPotentials
fromSingleCells
By the early 1950s it was becoming possible to record the activity of individual cells by mea-
suring a single neuron’s action potentials with fine electrodes inserted into the brain. These
Figure 4-6 illustrates the structure and use of microelectrodes can be placed next to cells (extracellular recording) or inside cells (intracel-
microelectrodes. lular recording). Modern extracellular recording techniques make it possible to distinguish
the activity of as many as 40 neurons at once. Intracellular recording allows direct study and
recording of a single neuron’s electrical activity. The two disadvantages of inserting an elec-
trode into a cell are (1) it can kill the cell, and (2) it cannot be done in awake, freely moving
animals. Single-cell recording is therefore confined to neurons grown in a dish or, for short
See, for example, Seeing Shape and Seeing periods (hours), from neurons in living brain slices.
Color in Section 9-4 and Processing We now know that cells recorded extracellularly in the brain’s sensory regions are highly
Language in Section 10-4. specific to what excites them. Some cells in the visual system fire vigorously to specific
wavelengths of light (a color) or to specific orientations of bars of light (vertical, for example).
Other cells respond to more complex patterns, such as faces or hands. Similarly, cells in the
auditory system respond to specific sound frequencies (a low or high pitch) or to more com-
plex sound combinations, such as speech (the syllable ba, for example).
But certain cells have a far more complex nature that reveals much about brain–behavior
relationships. John O’Keefe and his colleagues (O’Keefe & Dostrovsky, 1971) showed that
neurons in the rat and mouse hippocampus vigorously fire when an animal is in a specific
Section 13-4 discusses how place cells help place in the environment. These place cells, illustrated in Figure 7-8, code the spatial
to store memories. location of the animal and contribute to a spatial map of the world in the brain. The Nobel
Prize in Physiology or Medicine 2014 was awarded to John O’Keefe, May-Britt Moser, and
(A) Place cell (B) Place-by-direction cell
ClassesofSpatially
FIGUre 7-8
RelatedCellsinthe
HippocampalFormation
(A and B) Place cells discharge when a
rat is at a spatial location, irrespective of
its orientation. (c) Head-direction cells
discharge to indicate where the rat’s head
points, irrespective of its location. (C) Head-direction cell (D) Grid cell
(D) Grid cells discharge at many locations,
forming a virtual grid that is invariant in
courtesy of john o’keefe.
the face of changes in the rat’s direction,
movement, or speed. At right in each part,
xy coordinates indicate the directional
selectivity of the cell recorded at left.
Courtesy of John O’Keefe.
7-2 • Measuring the Brain’s Electrical Activity 223
Edvard I. Moser “for their discoveries of cells that constitute a positioning system in the
place cells Neurons maximally responsive to
brain.”
specific locations in the world.
O’Keefe’s group (Cacucci et al., 2008) also demonstrated that, in mice with a genetically
engineered mutation that produces deficits in spatial memory, place cells lack specificity: electrocorticography (EcoG) Graded
the cells fire to a very broad region of their world. As a result, these mice have difficulty potentials recorded with electrodes placed
directly on the brain’s surface.
finding their way around, much as human patients with dementia tend to get lost. One
reason may be that a change, similar to the engineered mutation in mice, takes place in
human brain cells.
EEG:RecordingGradedPotentials
fromThousandsofCells
In the early 1930s, Hans Berger discovered that the brain’s electrical activ-
ity could be recorded simply by placing electrodes on the scalp. In Berger’s
southern illinois university/science source
words, recording these “brain waves” produces an “electrical record from
the head”—an electroencephalogram. The EEG measures the summed
michael rosenfeld/maximilian
graded potentials from many thousands of neurons. EEG waves, shown in
Figure 7-9, are recorded by computer. In electrocorticography, or ECoG,
stock Ltd./getty images
a method used during neurosurgery, electrodes are placed directly on the
cerebral cortex.
EEGs reveal some remarkable features of the brain’s electrical activity.
The EEG recordings in Figure 7-10 illustrate three:
1. EEG changes as behavior changes. 1 Electrodes attached to the 2 ...to record their
scalp correspond to specific electrical activity. This EEG
2. An EEG recorded from the cortex displays an array of patterns, some brain areas... indicates a relaxed person.
rhythmical.
3. The living brain’s electrical activity is never silent, even when a person is asleep or
FIGUre 7-9 RecordingEEGWaves A
simple, noninvasive method for recording
comatose. the brain’s electrical activity, EEG waves
When a person is aroused, excited, or even just alert, the EEG pattern has a low amplitude recorded via computer (see Figure 4-5)
and a fast frequency, as shown in Figure 7-10A. This pattern is typical of an EEG taken from can match wave activity to specific brain
regions.
anywhere on the skull of an alert subject, not only humans but other animals too. In contrast,
(B) Relaxed, eyes closed, alpha rhythms generated
(A) Awake or excited
(C) Drowsy—slowed frequency, increased-amplitude waves (D) Asleep—slower, higher-amplitude waves
(E) Deep sleep—even slower and higher-amplitude waves
(F) Coma—further slowing
1 2 3 4 5 6 7 1 2 3 4 5 6 7
Time (s) Time (s)
FIGUre 7-10 CharacteristicEEGRecordings Brain wave patterns reflect different
states of consciousness in humans. Data from W. Penfield & H. H. Jasper (1954). Epilepsy and the functional
anatomy of the human brain (p. 12). Boston: Little, Brown.
224 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
when a participant is calm and quietly relaxed, especially with eyes closed, the rhythmical
brain waves shown in Figure 7-10B often emerge. These alpha rhythms are extremely regu-
Amplitude is a recorded brain wave’s height. lar, with a frequency of approximately 11 cycles per second and amplitudes that wax and
Frequency is the number of brain waves wane as the pattern is recorded. In humans, alpha rhythms are generated in the region of
recorded per second. the visual cortex at the back of the brain. If a relaxed person is disturbed, performs mental
arithmetic, or opens his or her eyes, the alpha rhythms abruptly stop.
alpha rhythm Regular wave pattern in an EEG is a sensitive indicator of behaviors beyond simple arousal and relaxation. Parts C, D,
electroencephalogram; found in most people and E of Figure 7-10 illustrate EEG changes as a person moves from drowsiness to sleep and
when they are relaxed with eyes closed. finally into deep sleep. EEG rhythms become progressively slower and larger in amplitude.
event-related potential (ERp) Complex Still slower waves appear during anesthesia, after brain trauma, or when a person is in a coma
electroencephalographic waveform related in (shown in Figure 7-10F). Only in brain death does the EEG permanently become a flat line.
time to a specific sensory event. These distinctive brain wave patterns make EEG a reliable tool for monitoring sleep
Section 13-3 describes how EEG measures stages, estimating the depth of anesthesia, evaluating the severity of head injury, and search-
sleep and dreaming. Focus features 4-1 and ing for brain abnormalities. In epilepsy, for example, brief periods of impaired awareness or
10-3 detail epilepsy diagnoses and Section responsiveness and involuntary movements associated with spiking patterns in the EEG
16-3, treatments. characterize electrographic seizures.
The important point here is that EEG recording provides a useful tool both for research
and for diagnosing brain dysfunction. EEG can also be used in combination with the brain-
imaging techniques described in Sections 7-3 and 7-4 to provide more accurate identification
of the source of the large and highly synchronized EEG waves in epilepsy.
MappingBrainFunctionwith
1
Event-RelatedPotentials
Brief changes in an EEG signal in response to a discrete sensory stimulus produce complex
electroencephalographic waveforms called event-related potentials (ERPs). ERPs are largely
First response the graded potentials on dendrites that a sensory stimulus triggers. You might think that they
Number of tone presentations
should be easy to detect, but they are not.
ERPs are mixed in with so many other electrical signals in the brain that they are difficult
to spot just by visually inspecting an EEG record. One way to detect ERPs is to produce the
10
Average of stimulus repeatedly and average the recorded responses. Averaging tends to cancel out any
10 responses irregular and unrelated electrical activity, leaving in the EEG record only the potentials the
stimulus generated.
50 To clarify this procedure, imagine throwing a small stone into a lake of choppy water.
Average of Although the stone produces a splash, the splash is hard to see among all the ripples and
50 responses waves. Like the splash surrounded by choppy water, the ERP caused by a sensory stimulus
is hard to discern from all the other electrical activity around it.
N1
A solution is to throw a number of stones exactly the same size, always hitting the same
100 spot in the water, and producing the same splash over and over. If a computer then calculates
P1
P2 an average of the water’s activity, random wave movements will tend to average one another
Average of out, and you will see the splashes produced by the stones as clearly as a single stone thrown
100 responses
into a pool of calm water.
0 100 200 300 400
Figure 7-11 shows an ERP record (top) that results when a person hears a tone. The EEG
Time (ms)
Tone record is highly irregular when the tone is first presented. But after averaging over 100 stimu-
lus presentations, a distinctive wave pattern appears, as shown in the bottom panel of Figure
FIGUre 7-11 DetectingERPs In the
7-11. This ERP pattern consists of a number of negative (N) and positive (P) waves that occur
averaging process for an auditory ERP,
a tone is presented at time 0, and EEG within a few hundred milliseconds after the stimulus.
activity in response is recorded. After many The waves are numbered in time sequence. For instance, in Figure 7-11, N1 is a nega-
successive presentations of the tone, the tive wave occurring about 100 milliseconds after the stimulus, whereas P2 is a positive
EEG wave sequence develops a distinctive wave occurring about 200 milliseconds after the stimulus. (The waves may also be labeled
shape that becomes extremely clear after as N100 and P200.) Not all these waves are unique to this particular stimulus. Some are
100 responses are averaged (bottom
common to any auditory stimulus. Other waves, however, correspond to important differ-
panel). Positive and negative waves that
appear at different times after the stimulus ences in specific tone. ERPs to spoken words even contain distinctive peaks and patterns
presentation are used for analysis. that differentiate such similar-sounding words as cat and rat.
7-2 • Measuring the Brain’s Electrical Activity 225
clinical F cus 7-2
Mild Head Injury and Depression
When a pallet of boxed tools tipped and part of the load struck his head, his brain failed to find any injury that could explain his symptoms. In fact,
B. D., an industrial tool salesman, did not lose consciousness. He did B. D.’s serious emotional symptoms are common following mild head
sustain a serious cut to his scalp and damage to two spinal vertebrae. injury, even when no other neurological or radiological signs of brain
The attending physician at the hospital emergency room suspected mild injury present themselves.
concussion but ordered no further neurological workup at the time. One tool for investigating brain functioning in such cases is ERP. Reza
B. D.’s spinal symptoms gradually cleared, but irritability, anxiety, and colleagues (2007) compared healthy controls to groups of subjects
and depression persisted even 2 years later. B. D. was unable to work, with mild head injuries, with or without depression. The investigators
and his behavioral change placed a major strain on his family. His emo- found that all subjects with head injury displayed a delayed P3 wave, but
tional problems led him to withdraw from the world, only worsening his only those who were depressed as well also had a delayed N2 wave.
predicament. These findings demonstrate that ERP can identify cerebral processing
A neuropsychological exam administered to B. D. about 2 years after abnormalities in people with depression after mild head injury, even
the injury found his general cognitive ability to be well above average, when MRI scans are negative. Such evidence can be critical for people
with an IQ score of 115. But B. D. also had significant attentional and like B. D., who are seeking long-term disability support following what
short-term memory deficits. A subsequent magnetic resonance image of appears to be a mild head injury.
Among the many practical reasons for using ERPs to study the brain is the advantage Electrodes attached to the
that this EEG technique is noninvasive. Electrodes are placed on the scalp, not in the brain. scalp of a research subject
Therefore, ERPs can be used to study humans, including those most frequently used par- are connected to…
Electrodes in
ticipants: college students.
geodesic sensor net
Another advantage is cost. Compared to other techniques, such as brain imaging, EEG
and ERP are inexpensive and can be recorded from many brain areas simultaneously by past-
ing an array of electrodes (sometimes more than 200) to different parts of the scalp. Because
certain brain areas respond only to certain sensory stimuli (e.g., auditory areas respond to
sounds and visual areas to sights), relative responses at different locations can be used to map
brain function.
Figure 7-12 shows a multiple-recording method that uses 128 electrodes simultaneously
to detect ERPs at many cortical sites. Computed averaging techniques reduce the masses
of information obtained to simpler comparisons between electrode sites. For example, if the …a computer display of
electrical activity, showing
focus of interest is P3, a positive wave occurring about 300 milliseconds after the stimulus, a large positive (P3) wave
the computer can display a graph of the skull showing only the amplitude of P3. A computer at the posterior right side
can also convert the averages at different sites into a color code, graphically representing the of the head.
brain regions most responsive to the signal.
ERPs not only can detect which brain areas are processing particular stimuli but also
can be used to study the order in which different regions participate. This second use of
ERPs is important because we want to know the route that information takes as it travels
through the brain. In Figure 7-12, the participant is viewing a picture of a rat that appears
repeatedly in the same place on a computer screen. The P3 recorded from the posterior P3
right side of the head is larger than any other P3 occurring elsewhere, meaning that this
region is a hot spot for processing the visual stimulus. Presumably, this particular partici-
pant’s right posterior brain is central in decoding the picture of the rat 300 milliseconds
after it is presented. This electrical activity can be
converted into a color
Many other interesting research areas benefit from using ERPs, as described in Clinical representation showing the
Focus 7-2, Mild Head Injury and Depression. ERPs also can be used to study how children hot spot for the visual stimulus.
learn and process information differently as they mature. ERPs can examine how a person
with a brain injury compensates for the impairment by using undamaged brain regions.
ERPs can even help reveal which brain areas are most sensitive to aging and therefore con-
tribute most to declining behavioral functions among the elderly. This simple, inexpensive
research tool can address all these areas. Resting 300 ms after viewing
FIGUre 7-12 UsingERPstoImageBrainActivity
226 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
magnetoencephalogram (mEG) Magnetic Magnetoencephalography
potentials recorded from detectors placed Passing a magnetic field across a wire induces an electrical current in the wire. Conversely,
outside the skull. current flowing along a wire induces a magnetic field around the wire. The same is true in
computed tomography (ct) X-ray the brain. Neural activity, by generating an electrical field, also produces a magnetic field.
technique that produces a static three- Although the magnetic field produced by a single neuron is vanishingly small, the field
dimensional image of the brain in cross produced by many neurons is sufficiently strong to be recorded on the scalp. The record
section—a CT scan. of this phenomenon, a magnetoencephalogram (MEG), is the magnetic counterpart of the
magnetic resonance imaging (mRI) EEG or ERP.
Technique that produces a static three- Calculations based on MEG measurements not only describe neuronal groups’ electrical
dimensional brain image by passing a strong activity but also localize the cell groups generating the measured field in three dimensions.
magnetic field through the brain, followed by a Magnetic waves conducted through living tissue undergo less distortion than electrical sig-
radio wave, then measuring a radio frequency nals do, so an MEG can yield a higher resolution than an ERP. A major advantage of the
signal emitted from hydrogen atoms. MEG over the EEG and ERP, then, is MEG’s ability to more precisely identify the source of
the activity being recorded. For example, MEG has proved useful in locating the source of
epileptic discharges. MEG’s disadvantage is its high cost in comparison with the apparatus
used to produce EEGs and ERPs.
7-2 reVIeW
MeasuringtheBrain’sElectricalActivity
Before you continue, check your understanding.
1. The four major techniques for tracking the brain’s electrical activity are ,
, , and .
2. Single-cell recording measures from a single neuron.
3. EEG measures on the cell membrane.
4. Magnetoencephalography measures the and also provides a .
5. What is the advantage of EEG techniques over MEG?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
7-3 AnatomicalImagingTechniques:
CTandMRI
Until the early 1970s, the only way to actually image the living brain was by using X-rays
that produce static images of brain anatomy from one angle. The modern era of brain imag-
ing began in the early 1970s, when Allan Cormack and Godfrey Hounsfield independently
Tomo- comes from the Greek word for developed an X-ray approach now called computed tomography: the CT scan. Cormack
section, indicating that tomography yields a and Hounsfield both recognized that a narrow X-ray beam could be passed through the
picture through a single brain slice. same object at many angles, creating many images; the images could be combined with the
use of computing and mathematical techniques to produce a three-dimensional image of
the brain.
The CT method resembles the way in which our two eyes (and our brain) work in concert
to perceive depth and distance to locate an object in space. The CT scan, however, coor-
dinates many more than two images, roughly analogous to our walking to several vantage
points to obtain multiple views. X-ray absorption varies with tissue density. High-density
tissue, such as bone, absorbs a lot of radiation. Low-density material, such as ventricular fluid
or blood, absorbs little. Neural tissue absorption lies between these extremes. CT scanning
7-3 • Anatomical Imaging Techniques: CT and MRI 227
(A) (B) (C)
Lesion Anterior
Plane of section
Lesion in parts
A and B
Lesion
neil Borden/science source
Posterior
FIGUre 7-13 CTScanandBrainReconstruction (A) Dorsal view of a horizontal
CT scan of a subject with Broca’s aphasia. The dark region at the left anterior is the area
of the lesion. (B) A schematic representation of the horizontal section, with the area of the
lesion shown in blue. (c) A reconstruction of the brain, showing a lateral view of the left
hemisphere with the lesion shown in blue. Research from Damasio, H., & Damasio, A. R. (1989). Lesion
analysis in neuropsychology (p. 56). New York: Oxford University Press.
software translates these differences in absorption into a brain image in which dark colors
indicate low-density regions and light colors indicate high-density regions.
Figure 7-13A shows a typical CT scan. The dense skull forms a white border. The brain’s
gray matter density does not differ sufficiently from that of white matter for a CT scan to
distinguish between the two clearly, so the cortex and its underlying white matter show up as
a more or less homogeneous gray. Ventricles can be visualized, however, because the fluid in
them is far less dense: they, as well as some major fissures in the cortex, are rendered darker
in the CT scan. Each point on the image in Figure 7-13A represents about a 1-millimeter-
diameter circle of tissue, a resolution sufficient to distinguish two objects about 5 millimeters
apart and appropriate for localizing brain tumors and lesions.
The lesion revealed in Figure 7-13A is a damaged region where the presence of fewer
neurons and more fluid produces a contrast that appears as a dark area in the CT scan. This
subject presented with symptoms of Broca’s aphasia, the inability to speak fluently despite Section 10-4 delves into aphasias that result
having average comprehension and intact vocal mechanisms. The location of the lesion, from damaged speech areas.
in the left frontal cortex (adjacent to the butterfly-shaped lateral ventricles), confirms this
diagnosis. Figure 7-13B, a drawing of the same horizontal section, uses color to portray the
lesion. Figure 7-13C is a lateral view of the left hemisphere reconstructed from a series of
horizontal CT scans and showing the lesion’s extent.
An anatomical alternative to the CT scan, magnetic resonance imaging (MRI), is based
on the principle that hydrogen atoms behave like spinning bar magnets in the presence of a
magnetic field. The MRI procedure is illustrated in Figure 7-14. The dorsal view of the brain
portrays density differences among the hydrogen atoms in different neural regions as colors
on the horizontal slice through the head.
Normally, hydrogen atoms point randomly in different directions, but when placed in a
large, static magnetic field, they line up in parallel as they orient themselves with respect to
the static field’s lines of force. In an MRI scanner, radio pulses are applied to a brain whose
atoms have been aligned in this manner, and each radio pulse forms a second magnetic field.
The second field causes the spinning atoms to deviate from the parallel orientation caused
by the static magnetic field to a new orientation.
As each radio pulse ends and the hydrogen atoms realign with the static field, they emit a
tiny amount of energy, and a coil detects this realignment. Based on the signals from the coil,
a computer re-creates the position of the hydrogen nuclei, producing a magnetic resonance
image. MRI images may be based on the density of the hydrogen atoms in different brain
228 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
gregory g. dimijian/science source
© Bob schatz
Hollow
tube
FIGUre 7-14 MagneticResonanceImaging
The subject is placed in a long metal cylinder that has
two sets of magnetic coils arranged at right angles, as
shown in the drawing. An additional radiofrequency coil
(not shown) surrounds the head, perturbing the static
magnetic fields to produce an MRI image of a horizontal
section through the head, shown in dorsal view. The Magnetic
density differences in hydrogen atoms show up as coils
colors in the image.
medical Body scans/science source; colorization by
MagneticResonance
FIGUre 7-15
CSF-filled Image Electrical currents emitted by wobbling
ventricle atoms are recorded by MRI to represent different
types of tissue—cerebrospinal fluid, brain matter,
matthew Bologna
Brain
tissue and bone, for example—as lighter or darker
diffusion tensor imaging (DtI) Magnetic depending on the density of hydrogen atoms in
Skull
resonance imaging method that can image the tissue.
fiber pathways in the brain by detecting the
directional movements of water molecules.
magnetic resonance spectroscopy (mRs)
Magnetic resonance imaging method that regions. Areas with high water (H2O) content (cell body–rich areas), for example, stand out
uses the hydrogen proton signal to determine from areas with lower water content (axon-rich areas). Figure 7-15 shows such a magnetic
the concentration of brain metabolites. resonance image.
Diffusion tensor imaging (DTI) is an MRI method that detects the directional move-
ments of water molecules to image nerve fiber pathways in the brain. Water can move rela-
tively freely along the axon but less freely across cell membranes. The direction of this water
movement is detected by a coil and interpreted by a computer. DTIs can delineate abnormali-
Clinical Focus 4-2 describes how myelin loss ties in neural pathways. They are also used to identify changes in fiber myelination, such as
in MS disrupts neuronal function. the damage that leads to myelin loss in multiple sclerosis.
Each scan in the series of DTIs shown in Figure 7-16 represents a dorsal view at increas-
ing depths through the brain. Although the images appear to show real fibers, DTIs are vir-
tual and based on computer reconstructions of water movement along axons, which should
correspond to actual fibers. Nonetheless, DTI easily detects abnormalities, such as those
Focus 16-3 explores the relationship between that occur in multiple sclerosis, stroke, or concussion, in the imaged fiber pathways and in
concussion and degenerative brain disease. their myelin sheaths.
7-4 • Functional Brain Imaging 229
Zephyr/science source
DiffusionTensor
FIGUre 7-16
Imaging MRI can measure the diffusion
of water molecules in white matter,
allowing the visualization of nerve fiber
tracts. The front of the brain is at the top in
these scans of sections through a healthy
brain. The axons are colored according to
orientation: fibers running left–right are
red, front–back are blue, and up–down
are green. Section 15-3 outlines how DTI
is helping researchers develop a brain
connectome to map functional connections
in the living brain.
Magnetic resonance spectroscopy (MRS) is an MRI method that uses the hydrogen
proton signal to determine the concentration of brain metabolites such as N-acetylaspartate
(NAA) in brain tissue. This measurement is especially useful for detecting persisting abnor-
malities in brain metabolism in disorders such as concussion.
7-3 reVIeW
AnatomicalImagingTechniques:CTandMRI
Before you continue, check your understanding.
1. The principal anatomical brain imaging methods are and .
2. Diffusion tensor imaging identifies , whereas magnetic resonance
spectroscopy determines .
3. In addition to imaging the density of different brain regions, CT and MRI can be used to
assess .
4. Explain briefly how the development of the CT scan ushered in the brain-imaging
techniques used today in neuroscience research.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
7-4 FunctionalBrainImaging
Advances in MRI and computing technologies led from anatomical to functional brain-imaging
techniques, which allow investigators to measure the amount of blood, oxygen, and glucose the
brain uses as subjects or participants solve cognitive problems. When a brain region is active,
the amount of blood, oxygen, and glucose flowing to the region increases. It therefore is pos-
sible to infer changes in brain activity by measuring either blood flow or levels of the blood’s
constituents, such as oxygen, glucose, and iron. Three techniques developed from this logic
are functional MRI, optical tomography, and positron emission tomography.
230 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
FIGUre 7-17 ImagingChangesinBrainActivity Functional MRI sequence of a
horizontal section at mid-occipital lobe (bottom of each image) in a normal human brain
during visual stimulation. A baseline acquired in darkness (far left) was subtracted from
the subsequent images. The participant wore tightly fitting goggles containing light-emitting
diodes that were turned on and off as a rapid sequence of scans was obtained over 270
seconds. Note the prominent activity in the visual cortex when the light is on and the rapid
cessation of activity when the light is off, all measured in the graph of signal intensity below
the images. ”Dynamic Magnetic Resonance Imaging of Human Brain Activity During Primary Sensory Stimulation,”
by K. K. Kwong et al., 1992, Proceedings of the National Academy of Sciences (USA), 89, 5678.
Baseline
Off Off On On Off Off On On
6050
Light off Light off
fMRI signal intensity
5900
5750
Light on Light on
5600
0 65 135 200 270
Time (s)
FunctionalMagneticResonanceImaging
As neurons become active, they use more oxygen, resulting in a temporary dip in the blood
functional magnetic resonance imaging oxygen level. At the same time, active neurons signal blood vessels to dilate to increase blood
(fmRI) Magnetic resonance imaging in which flow and bring more oxygen to the area. Peter Fox and colleagues (1986) discovered that
changes in elements such as iron or oxygen when human brain activity increases, the extra oxygen produced by increased blood flow
are measured during the performance of a actually exceeds the tissue’s needs. As a result, the amount of oxygen in an activated brain
specific behavior; used to measure cerebral area increases.
blood flow during behavior or resting. Oxygen is carried on the hemoglobin molecule in red blood cells. Changes in the ratio
resting-state fmRI (rs-fmRI) Magnetic of oxygen-rich hemoglobin to oxygen-poor hemoglobin alters the blood’s magnetic prop-
resonance imaging method that measures erties, because oxygen-rich hemoglobin is less magnetic than oxygen-poor hemoglobin.
changes in elements such as iron or oxygen In 1990, Segi Ogawa and his colleagues showed that MRI could accurately match these
when the individual is resting (not engaged in changes in magnetic properties to specific brain locations (Ogawa et al., 1990). This process,
a specific task).
functional magnetic resonance imaging (fMRI), signals which areas are displaying changes
in activity.
Figure 7-17 shows changes in the fMRI signal in the visual cortex of a person who is
being stimulated with light. When the light is turned on, the visual cortex (bottom of the
brain images) becomes more active than during baseline (no light). In other words, functional
changes in the brain are inferred from increases and decreases in the MRI signal produced
by changes in oxygen levels.
When superimposed on MRI-produced anatomical brain images, fMRI changes in activ-
Figure 2-7 diagrams the extent of the major ity can be attributed to particular structures. The dense blood vessel supply to the cerebral
cerebral arteries. cortex allows for a spatial resolution of fMRI on the order of 1 millimeter, affording good
spatial resolution of the brain activity’s source. On the other hand, because changes in blood
flow take as long as a third of a second, the temporal resolution of fMRI is not as precise as
that obtained with EEG recordings and ERPs.
fMRI also has the disadvantage that subjects must lie motionless in a long, noisy tube,
an experience that can prove claustrophobic. The confined space and lack of mobility also
7-4 • Functional Brain Imaging 231
restrict the types of behavioral experiments that can be performed. Nonetheless, fMRI is a
major tool in cognitive neuroscience.
The living brain is always active, and researchers have succeeded in inferring brain func-
tion and connectivity by studying fMRI signals when participants are resting, that is, not
engaged in any specific task. This signal, resting-state fMRI (rs-fMRI), is collected when
participants are asked to look at a fixation cross and to keep their eyes open.
The scanner collects brain activity, typically for at least 4-minute blocks. Researchers
are attempting to shorten the period by increasing the strength of the static magnetic
field and developing more sensitive coils. Statistical analysis of the data entails correlat-
ing activity in different brain regions over time. Although rs-fMRI is still in its growth
phase, investigators already have identified many consistent networks of brain activity and
abnormalities in disease states such as dementia and schizophrenia (Van den Heuvel &
Hulshoff Pol, 2010).
OpticalTomography
Research Focus 7-1, Tuning into Language, describes a brain-imaging study that used func-
tional near-infrared spectroscopy (fNIRS) to investigate newborn infants’ responses to lan-
guage. fNIRS is a form of optical tomography, a functional imaging technique that operates
on the principle that an object can be reconstructed by gathering light transmitted through
it. One requirement is that the object at least partially transmit light. Thus, optical tomog-
raphy can image soft body tissue, such as that in the breast or the brain.
In fNIRS, reflected infrared light is used to determine blood flow because oxygen-rich
hemoglobin and oxygen-poor hemoglobin differ in their absorption spectra. By measuring
the blood’s light absorption it is possible to measure the brain’s average oxygen consumption.
So fNIRS and fMRI measure essentially the same thing but with different tools. In fNIRS, FIGUre 7-18 HowNIRSWorks (A) Light
an array of optical transmitter and receiver pairs are fitted across the scalp, as illustrated in injectors (red) and detectors (blue) are
Figure 7-18A. distributed in an array across the head.
The obvious advantage of fNIRS is that it is relatively easy to hook subjects up repeatedly (B) Light injected through the scalp and
and record from them for short periods, from infancy to senescence. The disadvantage is skull penetrates the brain to a depth of
about 2 centimeters. A small fraction of the
that the light does not penetrate far into the brain, so researchers are restricted to measuring
light is reflected and captured by a detector
cortical activity (Figure 7-18B). The spatial resolution is also not as good as with other non- on the scalp surface. Light is reflected
invasive methods, although NIRS equipment now uses over 100 light detectors on the scalp, from as deep as 2 centimeters but also
from the tissue above it, as illustrated by
the banana shape of the curves. Information
from L. Spinney (2005). Optical topography and the color
of blood, The Scientist, 19, 25–27.
(A)
(B)
Light injector Light detector
hitachi, Ltd. research & development group. photo by atsushi maki
Scalp
Skull
Dura mater
Arachnoid layer and cerebral
2 cm
spinal fluid
Cerebral cortex
(gray matter)
White matter
232 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
which allows acceptable spatial resolution in the image. NIRS has been used to differentiate
positron emission tomography (pEt)
cancerous from noncancerous brain tissue. This advance should lead to safe, extensive surgi-
Imaging technique that detects changes in
cal removal of brain cancers and improved outcomes (Kut et al., 2015).
blood flow by measuring changes in the
uptake of compounds such as oxygen or
glucose; used to analyze the metabolic activity
of neurons. PositronEmissionTomography
Researchers use positron emission tomography (PET) to study the metabolic activity of
brain cells engaged in processing brain functions such as language. PET imaging detects
changes in the brain’s blood flow by measuring changes in the uptake of compounds such
Tagged to a glucose molecule, fluorine-18 (18F) as oxygen and glucose (Posner & Raichle, 1997). A PET camera, like the one shown in
acts as a marker for metabolism and is used Figure 7-19, is a doughnut-shaped array of radiation detectors that encircles a person’s head.
far more in PET than is 15O. The methods are A small amount of water, labeled with radioactive molecules, is injected into the blood-
essentially the same. stream. The person injected with these molecules is in no danger because those used, includ-
ing the radioactive isotope oxygen-15 (15O), are very unstable. They break down in just a few
minutes and are quickly eliminated from the body. (Most of the oxygen in air we breathe is
the stable 16O molecule.)
Radioactive 15O molecules release tiny, positively charged subatomic particles known as
positrons (electrons with a positive charge). Positrons are emitted from an unstable atom
because it is deficient in neutrons. The positrons are attracted to the negatively charged
electrons in the brain, and the collision of the two particles leads to annihilation of both,
which produces energy.
This energy, in the form of two photons (a unit of light energy), leaves the head at the
speed of light and is detected by the PET camera. The photons leave the head in exactly
opposite directions from the site of positron–electron annihilation, so annihilation photon
detectors can detect their source, as illustrated in Figure 7-19. A computer identifies the
coincident photons and locates the annihilation source to generate the PET image.
The PET system enables blood flow measurement in the brain because the unstable
radioactive molecules accumulate there in direct proportion to the rate of local blood flow.
Local blood flow in turn is related to neural activity because potassium ions released from
stimulated neurons dilate adjacent blood vessels. The more the blood flow, the higher the
radiation counts recorded by the PET camera.
Sophisticated computer imaging can map blood flow in the brain when a person is at
FIGUre 7-19 PETScannerand rest with closed eyes (Figure 7-20). The resting-state map shows, in a series of frames, where
Image Subject lying in a PET scanner, blood flow is highest. Even though the distribution of blood is not uniform, it is still difficult
whose design is illustrated in the drawing.
In the scan, the bright red and yellow areas
are regions of high blood flow.
A small amount of radioactively labeled Annihilation photon Annihilation
detectors photons
water is injected into a subject. Active areas
of the brain use more blood and thus have
more radioactive labels.
science source
hank morgan/science source
Positrons from the radioactivity are
released; they collide with electrons in the
brain, and photons (a form of energy) are
produced, exit the head, and are detected.
7-4 • Functional Brain Imaging 233
Dorsal
1 2 3 4 5 6 7 8 9
m. e. raichle, mallinckrodt institute of radiology, washington university school of medicine
10 11 12 13 14 15 16 17 18
19 20 21 22 23 24 25 26 27
Anterior
FIGUre 7-20 RestingState PET images
28 29 30 31 Left Right of blood flow obtained while a single
Ventral subject rested quietly with eyes closed.
Posterior Each scan represents a horizontal brain
section, from the dorsal surface (1) to
0 Maximum the ventral surface (31). Development of
rs-fMRI suggests that resting-state PET
analysis may emerge.
to conclude much from such a map because the entire brain
m. e. raichle, mallinckrodt institute of radiology, washington university school of medicine
is receiving oxygen and glucose.
But PET researchers who are studying the link between
blood flow and mental activity use a subtraction procedure.
They subtract the blood flow pattern when the brain is in a
carefully selected control state from the pattern of blood flow
imaged when the subject is engaged in the task under study,
as illustrated in the top row of Figure 7-21. This subtraction
process images the change in blood flow between the two
states. The change can be averaged across subjects (middle
row) to yield a representative average image difference that
reveals which brain areas are selectively active during the task
(bottom). PET does not measure local neural activity directly;
rather, it infers activity on the assumption that blood flow
increases where neuron activity increases.
A significant limitation of PET is that radiochemicals,
including so-called radiopharmaceuticals used in diagnos-
ing human patients, must be prepared in a cyclotron quite
close to the scanner because their half-lives are so short that FIGUre 7-21 TheProcedureof
transportation time is a severely limiting factor. Generating these materials is very ex- Subtraction In the upper row of
pensive. But in spite of the expense, PET has important advantages over other imaging scans, the control condition, resting
while looking at a static fixation point
methods:
(control), is subtracted from the
experimental condition, looking at a
• PET can detect the decay of literally hundreds of radiochemicals, which allows the flickering checkerboard (stimulation). The
mapping of a wide range of brain changes and conditions, including changes in pH, subtraction produces a different scan for
glucose, oxygen, amino acids, neurotransmitters, and proteins. each of five experimental subjects, shown
in the middle row, but all show increased
• PET can detect relative amounts of a given neurotransmitter, the density of blood flow in the occipital region. The
neurotransmitter receptors, and metabolic activities associated with learning, brain difference scans are averaged to produce
poisoning, and degenerative processes that might be related to aging. the representative image at the bottom.
234 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
• PET is widely used to study cognitive function with great success. For example, PET
confirms that various brain regions perform differing functions.
• There are now hybrid scanners for diagnostic imaging and they come in different
combinations in which the imaging modalities combines PET with CT, PET with MRI
and also PET with MRI and EEG. The advantage of these hybrid scanners is that they
can acquire high-quality anatomical images and then overlay the functional/metabolic
image information, allowing for precise localization that was not available before, and
all within a single examination.
7-4 reVIeW
FunctionalBrainImaging
Before you continue, check your understanding.
1. The principal methods of functional brain imaging are , , and
.
2. PET uses to measure brain processes and to identify
changes in the brain.
3. fMRI and optical imaging measure changes in .
4. Why are resting-state measurements useful to researchers?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
7-5 ChemicalandGeneticMeasures
ofBrainandBehavior
Our focus so far has been on how neuroscientists study the individual and collective activity
of neurons and how neuronal activity relates to behavior. Neurons are regulated by genes,
Section 3-2 investigates how neurons DNA segments that encode the synthesis of particular proteins within cells. Genes control
function. Section 3-3 relates genes to cell the cell’s production of chemicals, so it is possible to relate behavior to genes and to chemi-
function, genetic engineering, and epigenetic cals inside and outside the cell. Chemical and genetic approaches require sophisticated tech-
mechanisms. nologies that have seen major advances in the past decade.
MeasuringBrainChemistry
microdialysis Technique used to determine The brain contains a wide mixture of chemicals ranging from neurotransmitters and
the chemical constituents of extracellular fluid hormones to glucose and gases, among many others. Abnormalities in amounts of these
in freely moving animals. chemicals can cause serious disruptions in behavior. Prime examples are Parkinson disease,
striatum Caudate nucleus and putamen of characterized by low dopamine levels in the substantia nigra, and depression, correlated
the basal ganglia. with low serotonin and/or noradrenaline production. The simplest way to measure brain
cerebral voltammetry Technique used chemistry in such diseases is to extract tissue postmortem from affected humans or labora-
to identify the concentration of specific tory animals and undertake traditional biochemical techniques, such as high-performance
chemicals in the brain as animals behave liquid chromatography (HPLC), to measure specific chemical levels.
freely. Fluctuations in brain chemistry are associated not only with behavioral dysfunction but
also with ongoing healthy behavior. For example, research over at least the past 30 years
shows that dopamine levels fluctuate in the nucleus accumbens (a structure in the subcor-
Section 12-6 explores neural effects of tical basal ganglia) in association with stimuli related to rewarding behaviors such as food
rewarding events. and sex. Changes in brain chemistry can be measured in freely moving animals using two
methods, cerebral microdialysis and cerebral voltammetry.
7-5 • Chemical and Genetic Measures of Brain and Behavior 235
Microdialysis, which can determine the chemical constituents of extracellular fluid, is
widely used in the laboratory. The technique has found clinical application over the past
decade. A catheter with a semipermeable membrane at its tip is placed in the brain, as illus-
trated in Figure 7-22. A fluid flows through the cannula and passes along the cell membrane.
Simple diffusion drives extracellular molecules across the membrane along their concentra- Section 4-1 explains diffusion and
tion gradient. concentration gradients in detail.
Fluid containing the molecules from the brain exits through tubing to be collected for
analysis. The fluid is removed at a constant rate so that changes in brain chemistry can
be correlated with behavior. For example, if a rat is placed in an environment in which
it anticipates sex or a favored food, microdialysis will record an increase in dopamine
within the basal ganglia regions of the caudate nucleus and putamen, known as the This result mirrors wanting-and-liking theory
striatum. described in Section 6-4.
Microdialysis is used in some medical centers to monitor chemistry in the injured brain.
The effects of TBI or stroke can be worsened by secondary events such as a drastic increase
in the neurotransmitter glutamate. Such biochemical changes can lead to irreversible cell Section 6-4 investigates why glutamate and
damage or death. Physicians are beginning to use microdialysis to monitor such changes, similar chemicals can act as neurotoxins.
which can then be treated.
Cerebral voltammetry works on a different principle. A small carbon fiber electrode and
a metal electrode are implanted in the brain, and a weak current is passed through the metal
electrode. The current causes electrons to be added to or removed from the surrounding
chemicals. Changes in extracellular levels of specific neurotransmitters can be measured as
they occur.
Because different currents lead to changes in different compounds, it is possible to iden-
tify levels of different transmitters, such as serotonin or dopamine, and related chemicals.
Voltammetry has the advantage of not requiring the chemical analysis of fluid removed from
the brain, as microdialysis does, but it has the disadvantage of being destructive. That is, the
chemical measurements require the degradation of one chemical into another. Thus this FIGUre 7-22 Microdialysis
technique is not well suited to clinical uses. Information from M. M. Tisdall & M. Smith (2006).
Cerebral microdialysis: Research technique or clinical tool.
British Journal of Anaesthesia, 97, 18–25.
MeasuringGenesinBrain Fluids injected and
andBehavior Skull
collected through here
Most human behaviors cannot be explained by genetic inheri- Cannula
tance alone, but variations in gene sequences do contribute sig-
nificantly to brain organization. About 1 in 250 live births are
identical twins, people who share an identical genome. Identi-
cal twins often have remarkably similar behavioral traits. Twin
studies show strong concordance rates that support genetic
contributions to drug addiction and other psychiatric disorders.
But twin studies also show that environmental factors and life
Fluid with brain chemicals Fluid runs into
experience must be involved: concordance for most behavioral collected for analysis the brain
disorders, such as schizophrenia and depression, is far less than
100 percent. Life experiences are acting epigenetically to alter Semipermeable
gene expression. cannula membrane
Genetic factors can also be studied by comparing people who
Microdialysis
were adopted early in life and usually would not have a close catheter
Molecules in extracellular
genetic relationship to their adoptive parents. Here, a high con- fluid equilibrate across
cordance rate for behavioral traits would imply a strong environ- cannula membrane
mental influence on behavior. Ideally, an investigator would be
able to study both the adoptive and biological parents to tease out
the relative heritability of behavioral traits.
236 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
clinical F cus 7-3
Cannabis Use, Psychosis, and Genetics
Cannabis is the most widely used illicit drug in the world. Because it is These results show that genetic variations can predispose people to
nearly impossible to overdose, cannabis is usually considered safe, but it show adverse effects of environmental experiences and that the experi-
is not completely free of side effects. A relationship has been established ences may have age-related effects. Presumably these effects relate to
between cannabis use and the emergence of psychosis, especially with the significant development the brain undergoes during adolescence.
use in adolescence: earlier use is associated with both an earlier onset
and worse long-term prognosis of disease.
Given that most adolescents who use cannabis do not develop psy- 20
Symptoms of psychosis diagnosed
chosis, however, some genetic vulnerability likely predisposes certain
individuals to develop a psychotic condition when exposed to it. Cannabis
15
at age 26, percent
use thus may act more as a trigger for the onset of schizophrenia than
as the primary cause of the disease.
A working hypothesis contends that one culprit may be the COMT 10
gene, because COMT has been associated with schizophrenia. The
COMT gene product is an enzyme involved in metabolizing dopamine in 5
the synapse, and abnormalities in dopaminergic activity are associated
with psychosis. The hypothesis predicts that adolescents who develop
0
psychosis after cannabis use have an abnormality in the COMT gene. Met/Met Met/Val Val/Val Met/Met Val/Met Val/Val
Avshalom Caspi and colleagues (2005) analyzed the COMT gene in COMT genotype, adolescent- COMT genotype, adult-
nearly a thousand 26-year-old adults who had participated in a long-term onset schizophrenia onset schizophrenia
health study in New Zealand. As shown in the nearby figure, although Adolescent-onset cannabis use
no genotype was more likely to use cannabis in adolescence, carriers of No adolescent cannabis use
the Val allele were far more likely to develop psychotic symptoms if they Information from A. Caspi, T. E. Moffitt, M. Cannon, J. McClay, R. Murray, et al. (2005).
did use cannabis in adolescence (graph on the left) but not if they used Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a
it in adulthood (graph on the right). The Met/Met genotype showed no functional polymorphism in the catechol-O-methyltransferase gene: Longitudinal evidence
adverse effect of cannabis use in adolescence. of a gene X environment interaction. Biological Psychiatry, 57, 1117–1122.
With the development of relatively inexpensive methods of identifying specific genes in
people, it is now possible to relate the alleles (different forms) of specific genes to behaviors.
Section 8-2 explains how neurotrophic A gene related to the production of a compound called brain-derived neurotrophic factor
factors, nourishing chemical compounds, (BDNF) is representative. BDNF plays an important role in stimulating neural plasticity, and
support growth and differentiation in low levels of BDNF have been revealed in mood disorders such as depression. The two alleles
developing neurons. of this gene are BDNF Val 66Met and BDNF Val 66Val.
Joshua Bueller and his colleagues (2006) showed that the Met allele is associated with an
11 percent reduction in hippocampal volume in healthy participants. Other studies have
Sections 2-6 and 5-3 introduce factors that associated the Met allele with poor memory for specific events (episodic memory) and a high
contribute to dementias. Focus 14-3 describes incidence of dementia later in life. However, the Val allele is by no means the better variant:
research and Section 16-3, treatments. although Val carriers have better episodic memory, they also have a higher incidence of neu-
roticism and anxiety disorders, as illustrated in Clinical Focus 7-3, Cannabis Use, Psychosis,
and Genetics. The two alleles produce different phenotypes because they influence brain
Focus 6-4 relates a case in which chronic structure and functions differently. Other genes that were not measured also differed among
cannabis use may have led to psychosis. Bueller’s participants and may have contributed to the observed difference.
Epigenetics:MeasuringGeneExpression
An individual’s genotype exists in an environmental context fundamental to gene expres-
sion, the way genes become active or not. While epigenetic factors do not change the DNA
sequence, the genes that are expressed can change dramatically in response to environment
See A Case of Inheriting Experience in and experience. Epigenetic changes can persist throughout a lifetime and even across mul-
Section 3-3. tiple generations.
7-5 • Chemical and Genetic Measures of Brain and Behavior 237
Changes in gene expression can result from widely ranging experiences, including
chronic stress, traumatic events, drugs, culture, and disease. A study by Mario Fraga and
his colleagues (2005) stands as a powerful example of gene–experience interactions. The
investigators examined epigenetic patterns in 40 pairs of identical twins by measuring two
molecular markers related to gene expression.
Although twins’ patterns of gene expression were virtually identical when measured in
childhood, 50-year-old twins exhibited differences so remarkable as to make them as different
epigenetically as young non-twin siblings! The specific cause or causes of such differences
are unknown but thought to be related to lifestyle factors, such as smoking and exercise
habits, diet, stressors, drug use, and education, and to social experiences, such as marriage
and child rearing, among others. The epigenetic drift in the twins supports the findings of
less than 100 percent concordance for diseases in identical twins.
The role of epigenetic differences can also be seen across populations. Moshe Szyf,
Michael Meaney, and their colleagues (e.g., 2008) have shown, for example, that the amount
of maternal attention mother rats give to their newborn pups alters the expression of certain
genes in the adult hippocampus. These genes are related to the infants’ stress response when
they are adults. (Maternal attention is measured as the amount and type of mother–infant
contact; a difference of up to 6 hours per day can exist between attentive and inattentive
mothers.)
A subsequent study by the same group (McGowan et al., 2009) examined epigenetic dif-
ferences in hippocampal tissue obtained from two groups of humans: (1) suicides with histo-
ries of childhood abuse and (2) either suicides with no childhood abuse or controls who died
of other causes. The epigenetic changes found in the abused suicide victims parallel those
found in the rats with inattentive mothers, again suggesting that early experiences can alter
hippocampal organization and function via changes in gene expression.
Experience-dependent changes in gene expression are probably found not only in the hip-
pocampus but throughout the brain as well. For example, Richelle Mychasiuk and colleagues
(2011) found that stressing pregnant rat dams led to wide changes in gene expression in
their offspring, in both the frontal cortex and the hippocampus. However, the investigators
found virtually no overlap in the altered genes in the two brain regions: the same experience
changed different brain regions differently.
Epigenetic studies promise to revolutionize our understanding of gene–brain interactions
in healthy brain development and brain function. They will also help researchers develop
new treatments for neurological disorders. For example, specific epigenetic changes appear Consult the Index entry epigenetics to locate
to be related to the ability to make a functional recovery after stroke. coverage throughout the book.
7-5 reVIeW
ChemicalandGeneticMeasuresofBrainandBehavior
Before you continue, check your understanding.
1. Concentrations of different chemicals in the brain can be measured in postmortem tissue
using a(n) assay or in vivo using or .
2. Gene–environment interactions can be investigated in human populations by comparing
of behavioral traits in identical twins and adopted children.
3. The study of genes and behavior focuses on individual differences in ,
whereas the study of epigenetics and behavior examines differences in .
4. Describe briefly how epigenetic studies have led to the recognition that life experience
and the environment can alter brain function.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
238 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
7-6 ComparingNeuroscience
ResearchMethods
We have considered a wide range of research methods for manipulating and measuring
brain–behavior interactions. Tables 7-1 and 7-2 summarize these methods, including goals
and examples of each method. How do researchers choose among them all? Their main con-
sideration is their research question. Ultimately, that question is behavioral, but many steps
lie along the route to understanding behavior.
Some researchers focus on morphology (structure) in postmortem tissue. This approach
allows detailed analysis of both macro and micro structure, depending on the method cho-
sen. Identifying brain pathology, as in Parkinson disease, can lead to insights about the
causes and nature of a disorder.
Other investigators focus more on the ways neurons generate electrical activity in rela-
tion to behavior or on functional changes in brain activity during specific types of cognitive
processing. Both approaches are legitimate: the goal is gaining an understanding of brain–
behavior relationships.
But investigators must consider practical issues, too. Temporal resolution (how quickly
the measurement or image is obtained); spatial resolution (how accurate localization is in
the brain); and the degree of invasiveness all are pertinent. It is impractical to consider MRI-
based methods for studies of very young children, for example, because although the images
are highly accurate, the participants must remain absolutely still for long periods.
Similarly, studies of brain-injured patients must take into account factors such as the
subject’s ability to maintain attention for long periods—during neuropsychological testing or
imaging studies, for example. And practical problems such as motor or language impairment
may limit the types of methods that researchers can use.
Of course, cost is an ever-present practical consideration. Studying brain and behavior
linkages by perturbing the brain are generally less costly than some imaging methods, many
of which require expensive machinery. EEG, ERP, and fNIRS are noninvasive and relatively
inexpensive to set up (less than $100,000). MRI-based methods, MEG, and PET are very
table 7-1 manipulating Brain and Behavior
Method Goal examples
Whole-animal manipulations (Section 7-1) Determine how an environmental condition Diet, exercise, social interactions, sensory
affects brain and behavior stimulation, drug usage
Brain lesions, permanent (Section 7-1) Remove or destroy neural tissue to observe Knife cuts or aspirations
behavioral changes Electrolytic lesions
Neurotoxic lesions
Brain lesions, temporary and reversible Short-term silencing of neural tissue to observe Regional cooling to arrest synaptic transmission
(Section 7-1) behavioral changes Delivery of an agonist for GABA through a
cannula to increase local inhibition
Genetic lesions (Section 3-3) Remove genetic material Knockout technology
Genetic stimulation (Section 3-3) Add genetic material Knock-in technology
Drug manipulations (Section 7-1) Determine receptor system’s role in the CNS Use drugs to activate (agonists) or inactivate
(antagonists) a receptor system
Electrical and magnetic stimulation Excite tissue activity DBS
(Section 7-1) TMS
Optogenetics (Section 7-1) Use light to activate specific ion channels and Insertion of specific light-sensitive proteins
relate to behavior
Chemogenetics (Section 7-1) Use specific synthetic drugs to activate designer Insertion of specific G protein–coupled receptors
receptors
7-7 • Using Animals in Brain–Behavior Research 239
table 7-2 measuring Brain and Behavior
Method Goal examples
Behavioral analysis (Section 7-1) Observe behavior; generate tests to allow people and lab animals to Naturalistic observation; tests, mazes
demonstrate behavioral capacities
Tissue analysis (Section 7-1) Identify cell types and connections; identify disease states Stains
Record electrical and magnetic activity Measure action potentials from individual neurons; measure graded Single cell recording; EEG, ERP; MEG
(Section 7-2) potentials to assess coordinated activity of thousands of neurons;
measure magnetic fields
Anatomical brain imaging (Section 7-3) Noninvasive examination of brain structures Miniature microscopes; X-ray; CT; MRI; DTI
Functional brain imaging (Section 7-4) Measure brain activity as specific behaviors are performed fMRI; fNIRS; MRS; PET
In vivo chemistry (Section 7-5) Relate fluctuations in transmitter release to behavior HPLC; microdialysis, voltammetry
Genetics (Section 7-5) Determine presence of a gene and its products DNA, RNA, protein analysis
Epigenetics (Section 7-5) Discover effect of experience on gene expression, brain, and behavior Gene expression analysis
expensive (more than $2 million) and therefore typically found only in large research centers
or hospitals. Similarly, epigenetic studies can be very expensive if investigators consider the
entire genome in a large number of biological samples.
7-6 reVIeW
ComparingNeuroscienceResearchMethods
Before you continue, check your understanding.
1. Neuroscience measurements and imaging vary along the dimensions of ,
, and .
2. Relative to the expense of fMRI and PET imaging, noninvasively perturbing the
brain using methods such as or administering neuropsychological
testing is .
3. The main consideration for choosing a research method is the question being asked. What
is the fundamental goal of neuroscience research?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
7-7 UsingAnimalsin
Brain–BehaviorResearch
A complete understanding of brain–behavior relationships is limited in part by the voluntary
ethical constraints investigators place upon experimentation on humans and nonhuman
species. Most individual countries decide independently which experimental practices are
acceptable for humans, for other vertebrates, and for invertebrate species. In general, the
experimental methods acceptable for use on our species are fewer than those employed on
our most closely related primate relatives. Thus, like most new treatments in medicine, a
wide variety of nonhuman species have been used to develop and test treatments for human
neurological or psychiatric disorders before they are tested on humans.
Although the human and the nonhuman brain have obvious differences with respect to
language, the general brain organization across mammalian species is remarkably similar,
240 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
and the functioning of basic neural circuits in nonhuman mammals appears to generalize
to humans. Thus, neuroscientists use widely varying animal species to model human brain
diseases as well as to infer typical human brain functioning.
Two important issues surface in use of animal models to develop treatments for brain and
behavioral disorders. The first is whether animals actually display neurological diseases in
ways similar to humans. The second surrounds the ethics of using animals in research. We
consider each separately.
BenefitsofAnimalModelsofDisease
Some disorders—stroke, for example—seem relatively easy to model in laboratory animals
because it is possible to interrupt blood supply to a brain area and induce injury and con-
sequent behavioral change. However, it is far more difficult to determine whether human
behavioral disorders can actually be induced in laboratory animals. Consider attention-
deficit/hyperactivity disorder (ADHD), a developmental disorder characterized by core
behavioral symptoms: impulsivity, hyperactivity, and/or inattention. The most common
issue for children with ADHD is problems at school. Lab animals such as rats and mice do
not go to school, so how does one model ADHD in rodents?
ADHD has proved difficult to treat in children, and interest in developing an animal
model is high. One way to proceed is to take advantage of the normal variance in the perfor-
mance of rats on a variety of tests of working memory and cognitive functioning—tests that
Focus 6-1 reports on illicit use of prescription require attentional processes. The idea is that we can think of ADHD in people or in rats as
ADHD medications to boost performance at one extreme on a spectrum of behaviors that are part of a normal distribution in the general
school and at work. Section 15-4 explores the population. Many studies show that treating rats with the dopaminergic agonist methylphe-
nature of attention and disorders that result in nidate (Ritalin), a common treatment for children diagnosed with ADHD, actually improves
deficits of attention. the performance of rats that do poorly on tests requiring attentional processes.
One rat strain, the Kyoto SHR rat, has proved an especially good model for ADHD
and is widely used in the lab. The strain presents known abnormalities in prefrontal dopa-
minergic innervation that correlate with behavioral abnormalities such as hyperactivity.
Dopaminergic abnormalities are believed to be one underlying symptom of ADHD in
children, as explained in Research Focus 7-4, Attention-Deficit/Hyperactivity Disorder.
Methylphenidate can reverse behavioral abnormalities, both in children with ADHD and
in the SHR rats.
AnimalWelfareandScientific
Experimentation
Using nonhuman animals in scientific research has a long history, but only in the past half-
century have ethical issues surrounding animal research gained considerable attention and
laws been instituted. Just as the scientific community has established ethical standards for
We present experiments that predate research on humans, it has also developed regulations governing experimentation on ani-
current ethical standards. Bartholow’s brain mals. The governments of most developed nations regulate the use of animals in research;
stimulation (Section 4-1), the inmate volunteers most states and provinces have additional legislation. Universities and other organizations
in Experiment 6-1, and Magendie’s studies engaged in research have their own rules governing animal use, as do professional societies
with puppies (Focus 2-4) are examples. of scientists and the journals in which they publish.
Here are four principles, used as guidelines in Canada, for reviewing experimental and
teaching protocols that will use animals:
1. The use of animals in research, teaching, and testing is acceptable only if it promises
to contribute to the understanding of environmental principles or issues, fundamental
biological principles, or development of knowledge that can reasonably be expected to
benefit humans, animals, or the environment.
2. Optimal standards for animal health and care result in enhanced credibility and
reproducibility of experimental results.
7-7 • Using Animals in Brain–Behavior Research 241
ReseaRch F cus 7-4
Attention-Deficit/Hyperactivity Disorder
Together, attention-deficit/hyperactivity disorder (ADHD) and attention- dextroamphetamine) act to increase brain levels of noradrenaline and
deficit disorder (ADD) are probably the most common disorders of brain dopamine and are widely used for treating ADHD. About 70 percent of
and behavior in children, with an incidence of 4 percent to 10 percent of children show improvement of attention and hyperactivity symptoms
school-aged children. Although it often goes unrecognized, an estimated with treatment, but there is little evidence that drugs directly improve
50 percent of children with ADHD still show symptoms in adulthood, academic achievement. This is important because about 40 percent of
where its behaviors are associated with family breakups, substance children with ADHD fail to get a high-school diploma, even though many
abuse, and driving accidents. receive special education for their condition.
The neurobiological basis of ADHD and ADD is generally believed Stephen Faraone and coworkers (Lecendreux et al., 2015) have chal-
to be a dysfunction in the noradrenergic or dopaminergic activating lenged a common view, that ADHD is a cultural phenomenon reflecting
system, especially in the frontal basal ganglia circuitry. Psychomo- parents’ and teachers’ tolerance of children’s behavior. These investiga-
tor stimulants such as methylphenidate (Ritalin) and Adderall (mainly tors conclude that the prevalence of ADHD worldwide is remarkably
similar when the same rating criteria are used. Little is known
about incidence in developing countries, however. It is entirely pos-
sible that the incidence may actually be higher in developing coun-
tries, given that the learning environment for children is likely to be
less structured than it is in developed nations.
The cause of ADHD is unknown but probably involves dopamine
receptors in the forebrain. The most likely areas are the frontal lobe
and subcortical basal ganglia. Evidence of reduced brain volumes
in these regions in ADHD patients is growing, as is evidence of
an increase in the dopamine transporter protein. The dopamine
transporter increase would mean that dopamine reuptake into the
presynaptic neuron occurs faster than it does in the brain of people
without ADHD. The result is a relative decrease in dopamine. Ritalin
robin nelson/photo edit
works by blocking dopamine reuptake.
ADHD is believed to be highly heritable, a conclusion supported
by twin studies showing a concordance of about 75 percent in iden-
tical twins. Molecular genetic studies have identified at least seven
In this mainstreamed first-grade classroom, a special education student with candidate genes, and several of them are related to the dopamine
ADHD uses the turtle technique to cope with frustration and stress. synapse, in particular to the D4 receptor gene.
3. Acceptance of animal use in science critically depends on maintaining public confidence in
the mechanisms and processes used to ensure necessary, humane, and justified animal use.
4. Animals are used only if the researcher’s best efforts to find an alternative have failed.
Researchers who use animals employ the most humane methods on the smallest number
of appropriate animals required to obtain valid information.
Legislation concerning the care and use of laboratory animals in the United States is
set forth in the Animal Welfare Act, which includes laws passed by Congress in 1966, 1970,
1976, and 1985. Legislation in other countries is similar and in some European countries
much stricter. The U.S. act covers mammals, including rats, mice, cats, dogs, primates, and
birds, but it excludes farm animals that are not used in research. The U.S. Department of
Agriculture (USDA) administers the Act through inspectors in the Animal Care section of
the Animal and Plant Health Inspection Service.
In addition, the Office of Human Research Protections of the National Institutes of
Health (NIH) administers the Health Research Extension Act (passed in 1986). The act covers
all animal uses conducted or supported by the U.S. Public Health Service and applies to any
live vertebrate animal used in research, training, or testing. The Act requires that each institu-
tion provide acceptable assurance that it meets all minimum regulations and conforms with
The Guide for the Care and Use of Laboratory Animals (National Research Council, 2011)
242 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
before conducting any activity that includes animals. The typical method for demonstrat-
ing conformance with the Guide is to seek voluntary accreditation from the Association for
Assessment and Accreditation of Laboratory Animal Care International.
All accredited U.S. and Canadian universities that receive government grant support are
required to provide adequate treatment for all vertebrate animals. Reviews and specific pro-
tocols for vertebrates, including fish, amphibians, reptiles, birds, and mammals, to be used
in research, teaching, or testing are administered through the same process. Anyone using
animals in a U.S. or Canadian university submits a protocol to the university’s institutional
animal care and use committee, composed of researchers, veterinarians, people who have
some knowledge of science, and laypeople from the university and the community.
Companies that use animals for research are not required to follow this process. In effect,
however, if they do not, they will be unable to publish the results of their research, because
journals require that research conform to national guidelines on animal care. In addition,
discoveries made using animals are not recognized by government agencies that approve
drugs for clinical trials with humans if they do not follow the prescribed process. Companies
therefore use Good Laboratory Practice (GLP) standards, which are as rigorous as those
used by government agencies.
Regulations specify that researchers consider alternatives to procedures that may cause
more than momentary or slight pain or distress to animals. Most of the attention on alter-
natives has focused on the use of animals in testing and stems from high public awareness
of some tests for pharmacological compounds, especially toxic compounds. In the United
States, the National Institute of Environmental Health Sciences now regulates testing of
such compounds.
In spite of the legislation related to animal use, considerable controversy remains over
using animals in scientific research. At the extremes, people on one side approve any usage
and people on the other side disapprove of using animals for any form of research. Most fall
somewhere in between. The debate centers on issues of philosophy, law, morals, custom,
and biology.
Because researchers in many branches of science experiment with animals to understand
the functions of the human and nonhuman body, brain, and behavior, the issues in this debate
are important to them. Because human and veterinary medicine benefit from this research, as
well as do people and other animals with diseases or damage of the nervous system, this debate
is important. Because many people are philosophically opposed to using animals for work or
food, this debate is important to them. And because you, as a student, encounter many experi-
ments on animals in this book, these issues are important to you as well.
7-7 reVIeW
UsingAnimalsinBrain–BehaviorResearch
Before you continue, check your understanding.
1. Laboratory animals can model such human dysfunctions as and
.
2. One difficulty in using lab animals as models of human disease is determining
.
3. Animal models provide a way to investigate both proposed and
for behavioral disorders.
4. Outline the controversies that surround the use of animals in scientific research on brain
and behavioral relationships.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
Summary 243
Summary
7-1 MeasuringandManipulating Although CT scans are quicker and less expensive, MRI provides
BrainandBehavior exceptionally clear images, both of nuclei and of fiber pathways in the
The brain’s primary function is to produce behavior, so the fundamental brain. MRI also indicates that people’s brain structure varies widely.
research technique in behavioral neuroscience is to study the direct Both CT and MRI can be used to assess brain damage from neurological
relationship between brain and behavior. Investigators study healthy disease or injury, but MRI is more useful as a research tool.
humans and other animals as well as human patients and laboratory Diffusion tensor imaging is a form of MRI that makes it possible
animals with neurological problems. to identify normal or abnormal fiber tracts and myelin in the brain.
Initially, scientists simply observed behavior, but they later Magnetic resonance spectroscopy, another form of MRI, permits
developed neuropsychological testing measures designed to study practitioners to detect brain metabolites, such as those produced
specific functions such as fine movements, memory, and emotion. following concussion.
Today, researchers correlate these behavioral outcomes with 7-4 FunctionalBrainImaging
anatomical, physiological, chemical, genetic, and other molecular
Metabolic imaging shows that any behavior requires the collaboration
measures of brain organization.
of widespread neural circuits. Positron emission tomography records
Brain and behavioral relations can be manipulated by altering brain
blood flow and other metabolic changes in periods measured in
function, either permanently or temporarily. Permanent changes
minutes, and requires complex subtraction procedures and the
involve damaging the brain directly by ablation or neurotoxins that
averaging of responses across multiple subjects. Records of blood
remove or destroy brain tissue. Transient changes in brain activity can
flow obtained using functional magnetic resonance imaging can
be induced either by use of a mild electrical or magnetic current, as in
be combined with anatomical MRI images to locate changes in the
DBS or TMS, or by administration of drugs. Optogenetics, a transgenic
individual brain and to complement ERP results. Resting-state fMRI
technique, employs light-activated ion channels to excite or inhibit
allows investigators to measure connectivity across brain regions.
targeted cells in living tissue. Chemogenetic stimulation combines
Functional near-infrared spectroscopy is the form of optical
designer receptors and synthetic drugs to excite targeted cells in
tomography usually used for functional brain imaging studies. It works on
living tissue.
the principle that an object, including brain tissue, can be reconstructed
by gathering light transmitted through the object. fNIRS is much simpler
7-2 MeasuringtheBrain’sElectricalActivity
to use than PET or fMRI, but because light does not penetrate very far
Recording from single or multiple cells shows that neurons employ a
into the brain, it can be used only to study cortical function.
code and that cortical neurons are organized into functional groups
that work as coordinated networks. Neurons in sensory areas 7-5 ChemicalandGeneticMeasures
respond to specific characteristics of stimuli, such as color or pitch.
Other neurons, such as place cells in the hippocampal formation,
ofBrainandBehavior
Analysis of changes in both genes and neurochemicals provides
can code for more complex information, such as an object’s location
insight into the molecular correlates of behavior. Although genes code
in space.
all the information needed to construct and regulate cells, epigenetic
Electroencephalographic or magnetoencephalographic recordings
research reveals that the environment and life experience can modify
measure electrical or magnetic activity from thousands of neurons at
gene expression. Even identical twins, who have an identical genome
once. EEG can reveal a gross relationship between brain and behavior,
at birth, in adulthood have widely differing patterns of gene expression
as when a person is alert and displays the beta wave pattern versus
and very different brains.
when the person is resting or sleeping, indicated by the slower alpha
wave patterns. Event-related potentials tell us, on the other hand, that 7-6 ComparingNeuroscienceResearchMethods
even though the entire brain is active during waking, certain parts The main consideration in neuroscience research is the question.
are momentarily much more active than others. ERP records how the Whatever the approach, the goal is to understand brain–behavior
location of increased activity changes as information moves from one relationships. Tables 7-1 and 7-2 on pages 238 and 239 summarize the
brain area to another. manipulations and measurements used in behavioral neuroscience.
EEG and ERP are noninvasive methods that record from electrodes Among all the practical issues of measurement resolution and
on the scalp; in the case of MEG, from magnetic detectors above invasiveness, cost may prove the ultimate consideration.
the head. Electrocorticography, by contrast, records via electrodes
attached directly to the cortex. ECoG and single-cell recording 7-7 UsingAnimalsinBrain–BehaviorResearch
techniques are invasive. Understanding brain function, in both the healthy and the disordered
brain, often benefits from animal models. Investigators develop animal
7-3 AnatomicalImaging models to manipulate the brain—to determine how experiential factors
Techniques:CTandMRI and neurological treatments affect brain function.
Computed tomography and magnetic resonance imaging are sensitive Because animal subjects cannot protect themselves from abuse,
to the density of brain structures, ventricles, nuclei, and pathways. governments and researchers have cooperated to develop ethical
CT is a form of three-dimensional X-ray, whereas MRI works on the guidelines for the use of laboratory animals. These guidelines are
principle that hydrogen atoms behave like spinning bar magnets in the designed to ensure that discomfort is minimized, as is the number of
presence of a magnetic field. animals used for invasive procedures.
244 Chapter 7 • HOW DO WE STUDY THE BRAIN’S STRUCTURES AND FUNCTIONS?
Key termS
alpha rhythm, p. 224 diffusion tensor imaging (DTI), hypokinesia, p. 218 place cells, p. 223
behavioral neuroscience, p. 228 magnetic resonance imaging positron emission tomography
p. 214 electrocorticography (ECoG), (MRI), p. 226 (PET), p. 232
cerebral voltammetry, p. 234 p. 223 magnetic resonance resting-state fMRI (rs-fMRI),
chemogenetics, p. 220 event-related potential (ERP), spectroscopy (MRS), p. 228 p. 230
p. 224 magnetoencephalogram (MEG), stereotaxic apparatus, p. 218
compensation, p. 218
functional magnetic resonance p. 226 striatum, p. 234
computed tomography (CT),
imaging (fMRI), p. 230 microdialysis, p. 234
p. 226 synthetic biology, p. 220
functional near-infrared neuropsychology, p. 211
deep-brain stimulation (DBS), transcranial magnetic
spectroscopy (fNIRS), p. 211
p. 218 optogenetics, p. 220 stimulation (TMS), p. 220
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
8 How Does the Nervous ReseaRch Focus 8-1 Linking Socioeconomic StatuS to
corticaL DeveLopment
System Develop
8-1 ThRee PeRsPecTives on BRain DeveloPmenT
correLating emerging Brain StructureS with emerging
BehaviorS
and Adapt? correLating emerging BehaviorS with neuraL maturation
iDentifying infLuenceS on Brain anD Behavior
8-2 neuRoBiology oF DeveloPmenT
groSS DeveLopment of the human nervouS SyStem
originS of neuronS anD gLia
neuronaL growth anD DeveLopment
clinical Focus 8-2 autiSm Spectrum DiSorDer
unique aSpectS of frontaL LoBe DeveLopment
gLiaL DeveLopment
8-3 using emeRging BehavioRs To inFeR neuRal maTuRaTion
motor BehaviorS
Language DeveLopment
DeveLopment of proBLem-SoLving aBiLity
exPeRimenT 8-1 queStion: in what Sequence Do the foreBrain
StructureS requireD for Learning anD memory mature?
a caution aBout Linking correLation to cauSation
8-4 BRain DeveloPmenT anD The enviRonmenT
experience anD corticaL organization
ReseaRch Focus 8-3 increaSeD corticaL activation for
SeconD LanguageS
experience anD neuraL connectivity
criticaL perioDS for experience anD Brain DeveLopment
aBnormaL experience anD Brain DeveLopment
hormoneS anD Brain DeveLopment
clinical Focus 8-4 romanian orphanS
gut Bacteria anD Brain DeveLopment
injury anD Brain DeveLopment
DrugS anD Brain DeveLopment
other SourceS of aBnormaL Brain DeveLopment
clinical Focus 8-5 Schizophrenia
DeveLopmentaL DiSaBiLity
8-5 how Do any oF us DeveloP a noRmal BRain?
Katherine Streeter
245
246 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
ReseaRch F cus 8-1
Linking Socioeconomic Status to Cortical Development
Nobel Prize–winning American economist James Heckman has argued low SES were especially dramatic at the lower end of the family income
passionately about one effective strategy for economic growth: investing spectrum, especially in families with annual incomes less than $30,000.
as early as possible in disadvantaged families promotes optimal develop- Low SES is associated with poor nutrition, high stress, and insuf-
ment of young children at risk. Heckman notes that children from lower ficient prenatal and infant care. Following on Heckman’s thesis, investing
SES families typically develop gaps in knowledge and ability relative to in children from low-income families will increase societal health and
their more advantaged peers. prosperity, because these children can optimize their brain development
These gaps influence health and prosperity, and they persist through- and realize their developmental potential. Policies aimed toward decreas-
out life. Childhood SES correlates with cognitive development, language, ing poverty can lead to clear improvements in children’s cognitive and
memory, social and emotional processing, and ultimately with income brain development.
and health in adulthood. One reason: early experiences related to SES
influence children’s cerebral development.
To examine cerebral development, neuroimaging studies (as shown
children and adolescents” by K. G. Noble et al., 2015, NatureNeuroscience,
in Figure 8-14) visualize differences in brain development that relate
Research from “Family income, parental education, and brain structure in
to growing up in under-resourced environments. As the brain grows
throughout childhood and adolescence, the cortical surface area
expands before declining in adulthood (Schnack et al., 2014). Cortical
surface area reflects the amount of neural tissue available for different
behaviors and correlates positively with cognitive ability. It should be
online doi: 10.1038/nn.3983, Figure 2C, p. 4.
possible to estimate the effect of early experiences on brain and behav- Left hemisphere Right hemisphere
ioral development by comparing the cortical surface area and cognitive
abilities of people raised in lower or higher SES families.
Kimberly Noble and her colleagues (2015) used neuroimaging to
investigate the relationship between SES and cortical surface area in
more than 1000 participants aged 3 to 20. As shown in the illustration,
lower family income, independent of race or sex, was associated with
decreased cortical surface area in widespread regions of frontal, tem-
poral, and parietal lobes, the regions shown in red. After adjusting for age, sex, race, and parental education, Noble and
The investigators also measured participants’ cognitive performance colleagues associated family income with cortical surface area. Areal
on tests of attention, memory, vocabulary, and reading. The larger the brain regions shown in red were significantly smaller in children
cortical surface area, the better the test outcomes. The negative effects of from low-SES families.
to see how scientists go about studying the interconnected processes of brain and
behavioral development, think about all the architectural parallels between how the brain
is constructed and how a house is built. House plans are drawn as blueprints; the plans for a
brain are encoded in genes. Architects do not specify every detail in a blueprint, nor do genes
include every instruction for brain assembly and wiring.
The brain is too complex to be encoded entirely and precisely in genes. This leaves the
fate of billions of brain cells partly undecided, especially in regard to the massive undertaking
of forming appropriate connections between cells.
If the structure and fate of each brain cell are not specified in advance, what controls
brain development? Many factors are at work, and as with house building, brain development
is influenced by the environment in the course of the construction phase and by the quality
of the materials. As we saw in Research Focus 8-1, Linking Socioeconomic Status to Cortical
Development, living in poverty can compromise children’s brain development.
We can shed light on nervous system development by viewing its architecture from dif-
ferent vantage points—structural, functional, and environmental. In this chapter, we con-
sider the neurobiology of development first, explore behavioral correlates of developing brain
functions next, then explore how experiences and environments influence neuroplasticity
over the life-span.
8-1 • Three Perspectives on Brain Development 247
8-1 Three Perspectives on Brain
Development
Brain and behavior develop apace, and scientists thus reason that the two are closely linked.
Events that alter behavioral development should similarly alter the brain’s structural devel-
opment and vice versa. As the brain develops, neurons become more and more intricately
connected, and these increasingly complex interconnections underlie increasingly complex
behaviors. These observations enable neuroscientists to study the relation between brain and
behavioral development from three perspectives:
1. Structural development can be correlated with emerging behaviors.
2. Behavioral development can be predicted by the underlying circuitry that must be
emerging.
3. Research can focus on factors such as language, injury, or socioeconomic status (SES) that
influence both brain structure and behavioral development.
Correlating Emerging Brain Structures with
Emerging Behaviors
We can look at the nervous system’s structural development and correlate it with the emer-
gence of specific behaviors. For example, the development of certain brain structures links
to the motor development of, say, grasping or crawling in infants. As brain structures mature,
their functions emerge and develop, as manifested in behaviors we can observe.
Neural structures that develop quickly—the visual system, for instance—exhibit their
functions sooner than do structures that develop more slowly, such as those used for speech.
Because the human brain continues to develop well into adulthood, some abilities emerge
or mature rather late. Some cognitive behaviors controlled by the frontal lobes are among
the last to develop. One such behavior, the ability to plan efficiently, is a skill vital to many
complexities of life, including organizing daily activities or making travel plans.
The Tower of Hanoi test, illustrated in Figure 8-1, shows how planning skills can be
measured in the laboratory. The task is to plan how to move colored discs one by one, in the
GOAL
minimum number of moves, from one configuration to another. Most 10-year-olds can solve
simple configurations, but more difficult versions of the task, such as shown in Figure 8-1,
cannot be performed efficiently until about age 15 to 17. No surprise then that adolescents
often appear disorganized: their ability to plan has yet to mature.
Mature adults with acquired frontal lobe injuries also fail to perform well on the Tower
of Hanoi test. Such evidence reinforces the idea that children are not miniature adults who
simply need to learn the “rules” of adult behavior. A child’s brain is vastly different from an
adult’s, and the brains of children at different ages are not really comparable either. Move discs on towers below one by one
to match goal above.
Correlating Emerging Behaviors with Neural
Maturation
We can turn our observational sequence around and scrutinize behavior for the emergence
of new abilities, then, inferring underlying neural maturation. For example, as language
emerges in the young child, we expect to find corresponding changes in neural structures Figure 8-1 Testing Cognitive
that control language. In fact, neuroscientists do find such changes. Development The Tower of Hanoi is
At birth, children do not speak, and even extensive training would not enable them to do so. a mathematical puzzle consisting of three
rods and several different-sized discs. The
The neural structures that control speech are not yet ready. Thus, as language emerges, the
task is to match the goal in as few moves
speech-related structures in the brain are undergoing the necessary maturation. as possible, obeying two rules: (1) only one
The same reasoning can be applied to frontal lobe development. As frontal lobe struc- disc may be moved at a time; (2) no disc
tures mature through adolescence and into early adulthood, we look for related changes may be placed on top of a smaller disc.
248 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
in behavior. We can also do the reverse: because we observe new abilities emerging in the
teenage years and even later, we infer that they must be controlled by late-maturing neural
structures and connections.
Identifying Influences on Brain
and Behavior
The third approach to developmental interrelations between brain and behavior is to identify
and study factors that influence both. From this perspective, the mere emergence of a fully
developed brain structure is not enough. We must also know the events that shape how that
structure functions and produces behaviors. Some events that influence brain function are
sensory experience, injuries, and the actions of hormones and genes.
Logically, if one factor influences behavior, then the brain structures changed by that
factor are those responsible for the behavioral outcomes. For example, we might study how
the abnormal secretion of a hormone affects both a certain brain structure and a certain
behavior. We can then infer that because the observed behavioral abnormality results from
the abnormally functioning brain structure, the structure must typically play some role in
controlling the behavior.
8-1 review
Three Perspectives on Brain Development
Before you continue, check your understanding.
1. Structural brain development is correlated with the emergence of .
2. Behavioral development predicts the maturation of .
3. Three factors that influence brain function are , , and
.
4. What important constraint determines when behaviors emerge?
Answers appear at the back of the book.
Salamander Chick Human
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
8-2 Neurobiology of Development
Some 2000 years ago, the Roman philosopher Seneca the Younger proposed that a human
embryo is an adult in miniature, and thus the task of development is simply to grow bigger.
This idea of preformation was so appealing that it was widely believed for centuries. Even
with the development of the microscope, the appeal of preformation proved so strong that
biologists claimed to see microscopic horses in horse semen.
By the mid-1800s, preformation began to lose ground as people realized that embryos look
nothing like the adults they become. In fact, it was obvious that embryos of different species
more closely resemble one another than their respective parents. The top row of Figure 8-2
Figure 8-2 Embryos and Evolution shows the striking similarity among embryos of species as diverse as salamanders, chickens,
The physical similarity of embryos of and humans, each shown in fetal form in the bottom row.
different species is striking in the earliest As embryos, all vertebrate species have a similar-looking primitive head, a region with
stages of development, as the salamander,
bumps or folds, and a tail. Only as an embryo develops does it acquire the distinctive char-
chick, and human embryos in the top row
show. This similarity led to the conclusion acteristics of its species. The similarity of young embryos is so great that many nineteenth-
that embryos are not simply miniature century biologists saw it as evidence for Darwin’s view that all vertebrates arose from a
versions of adults. common ancestor millions of years ago.
Figure 8-3
Embryonic Vertebrate
Nervous System Forebrain, midbrain,
The embryonic nervous systems of vertebrates are as similar structurally as their bodies and hindbrain are visible in the human
are. Figure 8-3 details the three-chambered brain of a young vertebrate embryo: forebrain, embryo at about 28 days, as is the remaining
neural tube, which will form the spinal cord.
midbrain, and hindbrain. The remaining neural tube forms the spinal cord. How do these
three regions develop? We can trace the events as the embryo matures. Hindbrain
Brainstem
Midbrain
Gross Development of the Human Head
Nervous System
When a sperm fertilizes an egg, the resulting human zygote consists of just a single cell. But Forebrain
this cell soon begins to divide. By the fifteenth day after fertilization, the emerging embryo
resembles a fried egg (Figure 8-4), a structure formed by several sheets of cells with a raised
area in the middle called the embryonic disc—essentially the primitive body. Body
Neural tube
Day 1: Fertilization Day 2: Division Day 15 (forms spinal
Embryonic cord)
disc
Figure 8-4 From Fertilization to Embryo
Development begins at fertilization (day 1), with the formation
of the zygote. On day 2, the zygote begins to divide. On day
15, the raised embryonic disc begins to form. Information from K. L.
Moore (1998). The developing human: Clinically oriented embryology (4th ed., p. 61).
Philadelphia: Saunders.
prenatal Stages
By day 21, 3 weeks after conception, primitive neural tissue, the neural plate, occupies
Zygote Fertilization to 2 weeks
part of the outermost layer of embryonic cells. First the neural plate folds to form the neural
Embryo 2 to 8 weeks
groove, detailed in Figure 8-5. The neural groove then curls to form the neural tube, much
Fetus 9 weeks to birth
as you can curl a flat sheet of paper to make a cylinder.
Neural plate Neural Neural
18 days 21 days
(primitive neural tissue) plate groove
neural plate Primitive neural tissue that
gives rise to the neural tube.
Neural groove Anterior neural
(closing to form folds (close to neural tube Structure in the early stage of
22 days neural tube) 23 days
form brain) brain development from which the brain and
spinal cord develop.
Neural tube Ventricle
Neural tube
24 days
Figure 8-5 Formation of the
Neural Neural Tube A long depression, the
tube neural groove, first forms in the neural
Prof. P.M. Motta/Science Source
Developing plate. By day 21, the primitive brain and
forebrain neural groove are visible. On day 23, the
Developing neural tube is forming as the neural plate
heart collapses inward along the length of the
embryo’s dorsal surface. The embryo is
shown in a photograph at 24 days.
249
250 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
(A) Day 9 (B) Day 10 (C) Day 11 The cells that form the neural tube can be regarded as the nursery for
the rest of the central nervous system. The open region in the tube’s center
remains open and matures into the brain’s ventricles and the spinal canal. The
micrographs in Figure 8-6 show the neural tube closing in a mouse embryo.
The human body and nervous system change rapidly in the next
3 weeks (Figure 8-7). By 7 weeks (49 days), the embryo begins to resemble
a miniature person. The brain looks distinctly human by about 100 days
after conception, but it does not begin to form gyri and sulci until about
7 months. By the end of the ninth month, the fetal brain has the gross
appearance of the adult human brain, but its cellular structure is different.
Figure 8-6 Neural Tube Development
Scanning electron micrographs show the
neural tube closing in a mouse embryo.
Reproduced with the permission of Prof. Dr. R. E. Poelmann,
Origins of Neurons and Glia
Dept. Cardiology, Leiden University Medical Center, Institute The neural tube is the brain’s nursery. Neural stem cells lining it have an extensive capacity
of Biology IBL, University of Leiden, Leiden, The Netherlands. for self-renewal. When a stem cell divides, it produces two stem cells; one dies and the other
lives to divide again. This process repeats again and again throughout life. In an adult human,
Adult stem cells that line the subventricular neural stem cells line the ventricles, forming the subventricular zone.
zone also are located in the hippocampus, If lining the ventricles were all that stem cells did throughout the decades of a human life,
spinal cord, and retina. they would seem very odd cells to possess. But neural stem cells have a function beyond self-
renewal: they give rise to progenitor cells (precursor cells), which also can divide. As shown
in Figure 8-8, progenitor cells eventually produce nondividing cells known as neuroblasts
and glioblasts. In turn, neuroblasts and glioblasts mature into neurons and glia. Neural stem
cells, then, are multipotent: they give rise to all the many specialized cell types in the CNS.
Sam Weiss and his colleagues (1996) discovered that stem cells remain capable of
producing neurons and glia not just into early adulthood but even in an aging brain. This
important discovery implies that neurons that die in an adult brain should be replaceable.
But neuroscientists do not yet know how to instruct stem cells to replace them.
One possibility is to make use of signals that the brain typically uses to control stem cell
production in adults. For example, the level of the neuropeptide prolactin increases when
4 weeks 5 weeks 6 weeks 7 weeks 14 weeks
20 weeks 24 weeks 28 weeks 32 weeks
36 weeks
Figure 8-7
Prenatal Brain
Development The developing human
brain undergoes a series of embryonic
and fetal stages. You can identify the Forebrain
forebrain, midbrain, and hindbrain by color Midbrain
(review Figure 8-3) as they develop in Hindbrain
Neural tube
the course of gestation. At 6 months, the
(forms spinal cord)
developing forebrain has enveloped the
midbrain structures. Research from Cowan, W. M.
(1979). The development of the brain. Scientific American,
241(3), p. 116.
8-2 • Neurobiology of Development 251
Cell type Process
neural stem cell Self-renewing
Stem Self-renewal
multipotential cell that gives rise to any of
the different types of neurons and glia in the
nervous system.
Progenitor
Progenitor subventricular zone Lining of neural stem
produced
cells surrounding the ventricles in adults.
progenitor cell (precursor cell) Derived
Neuroblasts from a stem cell; it migrates and produces a
Blast and glioblasts neuron or a glial cell.
produced
neuroblast Product of a progenitor cell that
Neural Glial
gives rise to any of the different types of
neurons.
glioblast Product of a progenitor cell that
gives rise to different types of glial cells.
Neurons
Specialized and glia
differentiate
Interneuron Pyramidal Oligodendroglia Astrocyte
neuron
Figure 8-8 Origin of Brain Cells Cells in the brain begin as multipotential stem cells,
develop into precursor cells, then produce blasts that finally develop into specialized neurons
or glia.
female mice are pregnant and stimulates the fetal brain to produce more neurons (Shingo
et al., 2003). These naturally occurring hormonal signals have been shown to replace lost
neurons in brain-injured laboratory animals.
How does a stem cell know to become a neuron rather than a skin cell? In each cell, cer-
tain genes are expressed (turned on) by a signal, and those genes then produce a particular
cell type. Gene expression means that a formerly dormant gene is activated so that the cell
makes a specific protein. You can easily imagine that certain proteins produce skin cells,
whereas other proteins produce neurons.
The specific signals for gene expression are largely unknown but probably are
chemical, and they form the basis of epigenetics. A common epigenetic mechanism
that suppresses gene expression during development is gene methylation, or DNA
methylation. Here a methyl group (CH3) attaches to the nucleotide base cytosine lying
next to guanine on the DNA sequence. It is relatively simple to quantify gene methyla-
tion in different phenotypes, reflecting either an increase or a decrease in overall gene
expression.
Methylation alters gene expression dramatically during development. Prenatal stress
can reduce gene methylation by 10 percent. This means that prenatally stressed infants Gene Methylation Figure 3-25
contrasts the mechanisms of histone and
express 2000 more genes (of the more than 20,000 in the human genome)
mRNA modification to DNA methylation.
than unstressed infants (Mychasiuk et al., 2011). Other epigenetic
mechanisms, such as histone modification and mRNA modification, Methyl groups (M)
bind to CG base pairs
can regulate gene expression, but these mechanisms are more difficult
to block transcription.
to quantify.
M M
Thus, the chemical environment of a brain cell is different from that of
a skin cell: different genes in these cells are activated, producing different
A C G A A A C G A
proteins and different cell types. The chemical environments needed to
trigger cellular differentiation could be produced by the activity of neigh- T G C T T T G C T
boring cells or by chemicals, such as hormones, that are transported in the DNA
M M
bloodstream.
252 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
The differentiation of stem cells into neurons must require a series of gene-activating
signals. A chemical signal must induce stem cells to produce progenitor cells; another chemi-
cal signal must induce the progenitor cells to produce either neuroblasts or glioblasts. Finally,
a chemical signal—perhaps a set of signals—must induce the genes to make a particular type
of neuron.
Compounds that signal cells to develop in particular ways are neurotrophic factors (-trophic
means nourishing). By removing stem cells from an animal’s brain and placing those cells
in solutions that keep them alive, researchers can study how neurotrophic factors function.
One compound, epidermal growth factor (EGF), when added to the stem cell culture stimu-
lates production of progenitor cells. Another compound, basic fibroblast growth factor (bFGF,
or FGF-2), stimulates progenitor cells to produce neuroblasts.
At this point, the destiny of a given neuroblast is undetermined. The blast can become
any type of neuron if it receives the right chemical signals. The body relies on a general-
purpose neuron that matures into a specific cell type in a particular location when exposed
to certain neurotrophic factors.
This flexibility makes brain development simpler than it would be if each different cell
type, as well as the number of cells of each type, had to be specified precisely in an organ-
ism’s genes. In the same way, building a house from all-purpose two-by-fours that can be cut
to any length as needed is easier than specifying in a blueprint a precise number of precut
pieces of lumber that can be used only in a certain location.
taBLe 8-1 Stages of Brain Development
1 Cell birth (neurogenesis; gliogenesis)
2 Cell migration
Neuronal Growth and Development
The human brain requires approximately 10 billion (1010) cells to form just the cortex that
3 Cell differentiation
blankets a single hemisphere. This means it must produce about 250,000 neurons per minute
4 Cell maturation (dendrite and axon
growth) at the peak of prenatal brain development. But as Table 8-1 shows, this rapid formation of
neurons (neurogenesis) and glia (gliogenesis) is just the first step in brain growth. These new
5 Synaptogenesis (formation of synapses)
cells must travel to the correct destination (migration), they must differentiate into the right
6 Cell death and synaptic pruning
type of neuron or glial cell, and the neurons then must grow dendrites and axons and form
7 Myelogenesis (formation of myelin)
synapses.
The brain also prunes unnecessary cells and connections, sculpting itself according to the
particular person’s experiences and needs. We consider these stages in brain development
In Focus 8-1, investigators used cortical next, focusing on cortical development, because neuroscientists know more about develop-
development as a measure of SES’s effects. ment of the cortex than of any other area of the human brain. The principles derived from
our examination of the cortex, however, apply to neural growth and development in other
brain regions as well.
Neuronal Generation, Migration,
and Differentiation
Figure 8-9 shows that neurogenesis is largely complete after about 5 months of gestation.
(Some growth continues until about 5 years of age.) An important exception is the hippocam-
pus, where new neurons continue to develop throughout life.
Until after full-term birth, however, the fetal brain is especially delicate and extremely
Focus 11-2 describes outcomes resulting vulnerable to injury, teratogens (chemicals that cause malformations), and trauma. Appar-
from cerebral palsy, caused by brain trauma ently, the developing brain can more easily cope with injury earlier, during neurogenesis,
acquired perinatally. than it can during the later stages of cell migration or cell differentiation, when cell matura-
tion begins (see Table 8-1). One reason may be that once neurogenesis has slowed, it is very
hard to start it up again. If neurogenesis is still progressing at a high rate, more neurons can
be made to replace injured ones, or perhaps existing neurons can be allocated differently.
The absence of neurogenesis in adulthood, other than in the hippocampus, also explains
why adult brain tumors arise from glial cells, which are generated throughout adulthood,
rather than from neurons. In contrast, brain tumors in young children are sometimes neu-
ronal, reflecting some lingering neurogenesis.
8-2 • Neurobiology of Development 253
4000 Figure 8-9
Prenatal Development
3000
2000
Body weight of the Human Cerebral
1000 Cortex Brain weight and body weight
500 increase rapidly and in proportion. The
Relative size (in grams)
400 cortex begins to form about 6 weeks after
300 conception, with neurogenesis largely
200 Brain weight complete by 25 weeks. Neural migration
100 and cell differentiation begin at about
50
40
8 weeks and are largely complete by about
30 29 weeks. Neuron maturation, including
20 axon and dendrite growth, begins at about
Neuronal migration Differentiation Neuronal maturation
10 20 weeks and continues until well after
Neurogenesis birth. Information from M. Marin-Padilla (1993).
Pathogenesis of late-acquired leptomeningeal heterotopias
9 18 27 36 38 Birth 40 and secondary cortical alterations: A Golgi study.
Conception Age (in weeks) In A. M. Galaburda (Ed.), Dyslexia and development:
Neurobiological aspects of extraordinary brains.
Cambridge, MA: Harvard University Press.
Cell migration begins shortly after the first neurons are generated and continues for about
6 weeks in the cerebral cortex (and throughout life in the hippocampus). Cell differentiation, The hippocampus (see Figure 2-25) is critical
in which neuroblasts become specific types of neurons, follows migration. Cell differentia- to memory (Section 14-3) and vulnerable to
tion is essentially complete at birth, although neuron maturation, which includes the growth stress (Section 6-5).
of dendrites, axons, and synapses, goes on for years and in some parts of the brain may con-
tinue throughout adulthood.
The cortex is organized into layers distinctly different from one another in their cellular
makeup. How does this arrangement of differentiated areas develop? Neuroscientist Pasko
Rakic and his colleagues (e.g., Geschwind & Rakic, 2013) have been finding answers to this
question for more than four decades. Apparently, the subventricular zone contains a primitive
cortical map that predisposes cells formed in a certain ventricular region to migrate to a cer-
tain cortical location. One subventricular region may produce cells destined to migrate to the neurotrophic factor A chemical compound
visual cortex; another might produce cells destined to migrate to the frontal lobes, for example. that supports growth and differentiation in
How do the migrating cells know where to find these different parts of the cortex? They developing neurons and may act to keep
follow a path made by radial glial cells. A glial fiber from each of these path-making cells certain neurons alive in adulthood.
extends from the subventricular zone to the cortical surface, as illustrated in Figure 8-10A. radial glial cell Path-making cell that a
The close-up views in Figure 8-10B and C show that neural cells from a given subventricular migrating neuron follows to its appropriate
region need only follow the glial road to end up in the correct location. destination.
(A) (B) (C)
Brain surface
Direction of
movement
Brain
surface
Primitive
cortex
Figure 8-10
Neuronal
Nonradially Migration (A) Neuroscientists
Migrating
migrating neuron hypothesize that the cortical map is
neuron
Radial glial process represented in the subventricular
zone. (B) Radial glial fibers extend
from the subventricular zone to
the cortical surface. (c) Neurons
Migrating Radial glial
migrate along the radial glial fibers
neuron processes
that take them from the protomap
Ventricle in the subventricular zone to the
Subventricular Radial glial corresponding region in the cortex.
zone Radial glia cell body Information from P. Rakic (1974). Neurons in
Subventricular rhesus monkey cerebral cortex: Systematic
zone relation between time of origin and eventual
disposition. Science, 183, p. 425.
254 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
As the brain grows, the glial fibers stretch but still go to the same place. Figure 8-10B also
shows a cell moving across the radial glial fibers. Although most cortical neurons follow the
radial glial fibers, a small number appear to migrate by seeking some type of chemical signal.
Researchers do not yet know why these cells function differently.
Figure 2-22 contrasts the sensory and Cortical layers develop from the inside out, much like adding layers to a tennis ball. The
motor cortices’ six distinct layers and their neurons of innermost layer VI migrate to their locations first, followed by those destined for
functions. layer V and so on, as successive waves of neurons pass earlier-arriving neurons to assume pro-
gressively more exterior positions in the cortex. Cortex formation is a bit like building a house
from the ground up until you reach the roof. The materials needed to build
higher floors must pass through lower floors to get to their destinations.
To facilitate house construction, each new story has a blueprint-specified
dimension, such as 10 feet high. How do neurons determine how thick a cor-
tical layer should be? This is a tough question, especially when you consider
that the cortical layers are not all the same thickness.
Local environmental signals—chemicals produced by other cells—likely
influence the way cells form layers in the cortex. These intercellular signals
progressively restrict the choice of traits a cell can express, as illustrated in
Uncommitted Cells with Further Intercellular Diverse Figure 8-11. Thus, the emergence of distinct cell types in the brain results
precursor some segregation segregation environment cells not from the unfolding of a specific genetic program but rather from the
of determinants of determinants interaction of genetic instructions, timing, and signals from other cells in
Figure 8-11 Cellular Commitment the local environment.
As also shown in Figure 8-8, precursor
cells have unlimited possibilities, but Neuronal Maturation
as they develop, interacting genetic, After neurons migrate to their destination and differentiate, they begin to mature by
maturational, and environmental influences (1) growing dendrites to provide surface area for synapses with other cells and (2) extending
increasingly steer them toward developing
their axons to appropriate targets to initiate synapse formation.
into a particular cell type.
Two events take place in dendrite development: dendritic arborization (branching) and
the growth of dendritic spines. As illustrated in Figure 8-12, dendrites in newborn babies
begin as individual processes protruding from the cell body. In the first 2 years of life, den-
drites develop increasingly complex extensions that look much like leafless tree branches:
they undergo arborization. The dendritic branches then begin to form spines, where most
synapses on dendrites are located.
Although dendritic development begins prenatally in humans, it continues for a long time
after birth, as Figure 8-12 shows. Dendritic growth proceeds at a slow rate, on the order of
microns (µm, millionths of a meter) per day. Contrast this with the development of axons,
which grow on the order of a millimeter per day, about a thousand times faster.
Figure 8-12 Neuronal Maturation in
Cortical Language Areas In postnatal
cortical differentiation—shown here around
Broca’s area, which controls speaking—
neurons begin with simple dendritic fields
that become progressively more complex
until a child reaches about 2 years old.
Brain maturation thus parallels a behavioral
development: the emergence of language.
Figure from Biological Foundations of Language Newborn 1 3 6 15 24
(pp. 160–161), by E. Lenneberg, 1967, New York: Wiley. Age (months)
8-2 • Neurobiology of Development 255
The disparate developmental rates of axons and dendrites are important, because the
autism spectrum disorder (AsD) Range
faster-growing axon can reach its target cell before the cell’s dendrites are completely formed.
of cognitive symptoms from mild to severe
Thus the axon may play a role in dendritic differentiation and ultimately in neuron function—
that characterize autism; severe symptoms
for example, as part of the brain’s visual, motor, or language circuitry. Abnormalities in the include greatly impaired social interaction, a
maturation rate can produce abnormalities in patterns of neural connectivity, as explained bizarre and narrow range of interests, marked
in Clinical Focus 8-2, Autism Spectrum Disorder. abnormalities in language and communication,
and fixed, repetitive movements.
clinical F cus 8-2
Autism Spectrum Disorder
In the 1940s, Leo Kanner and Hans Asperger first used the term autism and the social withdrawal component of ASD may be related to the
(from the Greek autos, meaning self) to describe children who seem to enlarged amygdala.
live in their own world. Some were classified as intellectually disabled; Accelerated brain growth associated with enlarged regions suggests
others seemed to function intellectually. that connections between cerebral regions are atypical, which would
The contemporary term, autism spectrum disorder (ASD), accom- in turn produce atypical functioning. What leads to such brain develop-
modates this behavioral range to include children with mild and severe ment? More than 100 genetic differences have been described in chil-
symptoms. Severe symptoms include greatly impaired social interaction, dren with ASD, so it is clear that no “autism gene” is at work.
a bizarre and narrow range of interests, marked abnormalities in lan- The mechanism that translates genetic irregularities into the autistic
guage and communication, and fixed, repetitive movements. brain is unknown but is likely to include epigenetic factors that could be
The autism spectrum includes classic autism and related disorders. prenatal, postnatal, or both. Women have an increased risk of giving birth to
Asperger syndrome, for example, is distinguished by an obsessive inter- a child who develops ASD if they are exposed to rubella (German measles)
est in a single topic or object to the exclusion of nearly any other. Children in the first trimester of pregnancy. Researchers also suspect that industrial
with Asperger are socially awkward and also usually have delayed motor toxins can trigger autism, but the cause or causes remain uncertain.
skill development. Rett syndrome, characterized by poor expressive lan- No medical interventions exist for ASD. Behavioral therapies are the
guage and clumsy hand use, almost exclusively affects girls. most successful, provided they are intense (20 to 40 hours per week)
The rate of ASD has been rising over the past four decades, from and the therapists are trained practitioners. The earlier interventions
fewer than 1 person in 2000 in 1980 to the 2014 estimate of the Centers begin, the better the prognosis. Neuroscience has so far offered little
for Disease Control that as many as 1 in 68 children has some form of insight into why behavioral therapies are effective, although in an animal
autism. The actual incidence may be as high as 1 in 50 (Blumberg et al., model of autism, Raza et al. (2015) showed that tactile stimulation from
2013). The cause of this increased incidence is uncertain. Suggestions birth until weaning reverses many morphological abnormalities in corti-
include changes in diagnostic criteria, diagnosis of children at a younger cal neurons, suggesting a possible mechanism.
age, and epigenetic influences. Although it knows neither racial nor ethnic Autism may appear puzzling because no evolutionary advantage for its
nor social boundaries, ASD is four times as prevalent in boys as in girls. symptoms is apparent, but perhaps one exists. Characteristically, children
The behavior of many children with ASD is noticeable from birth. with ASD are overly focused on specific tasks or information. The ability to
To avoid physical contact, these babies arch their backs and pull away concentrate on a complex problem for extended periods, it is suggested, is
from caregivers or grow limp when held. But approximately one-third the basis for humankind’s development and for cultural advances.. But too
of children develop typically until somewhere between 1 and 3 years of much of such a good thing may lead to conditions such as ASD.
age, when symptoms of autism emerge.
Perhaps the most recognized characteristics of ASD are failure to
interact socially, repetitive rocking or hand flapping, impairments in
language development, and resistance to any change in routine. Some
children on the autism spectrum are severely impaired; others learn
to function quite well. Still others display savant syndrome, a narrow
range of exceptional abilities such as in music, art, or mathematics, often
accompanied by severe cognitive deficits.
The brains of children diagnosed with ASD look remarkably typical.
Kim Gunkel/Getty Images
One emerging view is that these brains are characterized by unusual
neuronal maturation rates. MRI studies show that at about 6 months of
age, the autistic brain’s growth rate accelerates to the point that its total
volume is 6 percent to 10 percent greater than that of typical children.
Excessive brain volume is especially clear in the amygdala (Nordahl Children with ASD often look typical, but some physical anomalies do
et al., 2012) and in the temporal and frontal lobes, the latter show- characterize the condition. The corners of the mouth may be low compared
ing greater gray matter volume (see the review by Chen et al., 2011). with the upper lip (left), and the tops of the ears may flop over (right). The
The subcortical amygdala plays an important role in generating fear, ears may be a bit lower than average and have an almost square shape.
256 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
(A) Growth cone Axon (B)
growth cone Growing tip of an axon.
Target cell Growth cone
filopod (pl. filopodia) Process at the end
of a developing axon that reaches out to
search for a potential target or to sample the
intercellular environment.
Courtesy of Dennis Bray
cell adhesion molecule (cAM) A chemical
molecule to which specific cells can adhere,
thus aiding in migration. Filopodia
tropic molecule Signaling molecule that Increasing concentration of chemical
Filopodia
attracts or repels growth cones.
Figure 8-13 Seeking a Path (A) At the tip of this axon, nurtured in a culture, a growth
netrin Member of the only class of tropic
cone sends out filopodia seeking specific molecules to guide the axon’s direction of growth.
molecules yet isolated.
(B) Filopodia guide the growth cone toward a target cell that is releasing cell adhesion or
neural Darwinism Hypothesis that the tropic molecules, represented in the drawing by red dots.
processes of cell death and synaptic pruning
are, like natural selection in species, the
outcome of competition among neurons for Axon-appropriate connections may be millimeters or even a meter away in the developing
connections and metabolic resources in a brain, and the axon must find its way through complex cellular terrain to make them. Axon
neural environment. connections present a significant engineering problem for the developing brain. Such a task
apoptosis Genetically programmed cell could not possibly be specified in a rigid genetic program. Rather, genetic–environmental
death. interaction is at work again, as various molecules that attract or repel the approaching axon
tip guide the formation of axonic connections.
Santiago Ramón y Cajal was the first scientist to describe this developmental process a
century ago. He called the growing tips of axons growth cones. Figure 8-13A shows that as
growth cones extend, they send out shoots, analogous to fingers reaching out to find a pen
on a cluttered desk. When one shoot, a filopod (pl. filopodia), reaches an appropriate target,
the others follow.
Growth cones are responsive to cues from two types of molecules (Figure 8-13B):
1. Cell adhesion molecules (CAMs) are cell-manufactured molecules that either lie on the
target cell’s surface or are secreted into the intercellular space. Some provide a surface to
which growth cones can adhere, hence the name cellular adhesion molecule; others serve
to attract or repel growth cones.
Do not confuse tropic (guiding) molecules 2. Tropic molecules, produced by the targets the axons’ growth cones are seeking (-tropic means
with the trophic (nourishing) molecules, moving toward; pronounced as trope, not tropical), essentially tell growth cones to come on
discussed earlier, which support neuronal over here. They likely also tell other growth cones seeking different targets to keep away.
growth.
Although Ramón y Cajal predicted them more than 100 years ago, tropic molecules
have proved difficult to find. So far, only one group, netrins (from Sanskrit for to guide),
has been identified in the brain. Given the enormous number of brain connections and the
great complexity in wiring them, many other types of tropic molecules undoubtedly will
be found.
Synaptic Development
The number of synapses in the human cerebral cortex is staggering, on the order of 1014, or
100,000 trillion. A genetic program that assigns each synapse a specific location could not
possibly determine each spot for this huge number. As with all stages of brain development,
only the general outlines of neuronal connections in the brain are likely to be genetically
predetermined. The vast array of specific synaptic contacts is then guided into place by a
variety of local environmental cues and signals.
A human fetus displays simple synaptic contacts in the fifth gestational month. By the sev-
enth gestational month, synaptic development on the deepest cortical neurons is extensive.
After birth, synapse numbers increase rapidly. In the visual cortex, synaptic density almost
doubles between ages 2 months and 4 months and then continues to increase until age 1 year.
8-2 • Neurobiology of Development 257
Cell Death and Synaptic Pruning Figure 8-14
Progressive Changes in
Cortical Thickness MRI scans track
To carve statues, sculptors begin with blocks of stone and chisel away the unwanted pieces. the maturation of gray matter in typical
The brain does something similar during cell death and synaptic pruning. The chisel in development, revealing the length and
the brain could be a genetic signal, experience, reproductive hormones, stress, even SES. pattern of maturation from the back of the
The effect of these chisels can be seen in changes in cortical thickness over time, as illus- cortex to the front. Cortical thinning and
trated in Figure 8-14, an atlas of brain images. The cortex actually becomes measurably increased surface area progress together.
Courtesy Paul M Thompson/Laboratory of Neuro Imaging,
thinner in a caudal–rostral (back-to-front) gradient, a process that is probably due both to
Keck School of Medicine of USC.
synaptic pruning and to white matter expansion. This expansion
stretches the cortex, leading to increased surface area, as illustrated 1.0
in Research Focus 8-1. 0.8
0.6
The graph in Figure 8-15 plots this rise and fall in synaptic den-
0.4
sity. Pasko Rakic (1974) estimated that at the peak of synapse loss, a
0.2
person may lose as many as 100,000 per second. Synapse elimination 5 yrs
0.0
is extensive. Peter Huttenlocher (1994) estimated it at 42 percent in Gray-matter
the human cortex. We can only wonder what the behavioral conse- volume
quence of this rapid synaptic loss might be. It is probably no coin-
cidence that children, especially toddlers and adolescents, seem to Age
change moods and behaviors quickly.
How does the brain eliminate excess neurons? The simplest
explanation is competition, sometimes referred to as neural Darwinism.
Charles Darwin believed that one key to evolution is the variation it
20 yrs
produces in the traits possessed by a species. Those whose traits are best suited
to the local environment are most likely to survive. From a Darwinian perspective,
then, more animals are born than can survive to adulthood, and environmental pressures
weed out the less-fit ones. Similar pressures cause neural Darwinism.
What exactly causes this cellular weeding out in the brain? It turns out that when neu-
rons form synapses, they become somewhat dependent on their targets for survival. In fact,
deprived of synaptic targets, neurons eventually die. They die because target cells produce
neurotrophic (nourishing) factors absorbed by the axon terminals that function to regulate
neuronal survival. Nerve growth factor (NGF), for example, is made by cortical cells and
absorbed by cholinergic neurons in the basal forebrain.
If many neurons compete for a limited amount of a neurotrophic factor, only some can
survive. The death of neurons deprived of a neurotrophic factor is different from the cell
death caused by injury or disease. When neurons are deprived of a neurotrophic
factor, certain genes seem to be expressed, resulting in a message for the cell to die.
This programmed process is called apoptosis.
Striate
Density of synapses
Apoptosis accounts for the death of overabundant neurons, but it does (visual)
not account for the synaptic pruning from cells that survive. In 1976, French cortex
neurobiologist Jean-Pierre Changeux proposed a theory for synapse loss that also
is based on competition (Changeux & Danchin, 1976). According to Changeux,
synapses persist into adulthood only if they have become members of functional
neural networks. If not, they are eventually eliminated from the brain. We can Prefrontal
cortex
speculate that environmental factors such as hormones, drugs, and experience
would influence active neural circuit formation and thus influence synapse Conception Birth Puberty Death
stabilization and pruning. Figure 8-15 Synapse Formation and
In addition to outright errors in synapse formation that give rise to synaptic pruning, Pruning Changes in the relative density
subtler changes in neural circuits may trigger the same process. One such change accounts of synapses in the human visual cortex and
for the findings of Janet Werker and Richard Tees (1992), who studied the ability of infants prefrontal cortex (its frontmost part) as a
function of age. Data from J.-P. Bourgeois (2001).
to discriminate speech sounds taken from widely disparate languages, such as English, Hindi
Synaptogenesis in the neocortex of the newborn: The
(from India), and Salish (a Native American language). Their results show that young infants ultimate frontier for individuation?” In C. A. Nelson and
can discriminate speech sounds of different languages without previous experience, but M. Luciana (Eds.), Handbook of developmental cognitive
their ability to do so declines in the first year of life. An explanation for this declining ability neuroscience. Cambridge, MA: MIT Press.
258 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
Figure 8-16 Gray Matter Thickness Left Right
Brain maps showing the statistical
significance of yearly change in cortical
thickness measures taken from MRIs.
Shading represents increasing (white) or
decreasing (red) cortical thickness. Research
from E. R. Sowell, P. M. Thompson, and A. W. Toga
(2004). Mapping changes in the human cortex throughout
the span of life. The Neuroscientist, 10, 372–392.
Language-related regions Visual cortex
thicken thins
is that synapses encoding speech sounds not typically encountered in an infant’s daily envi-
ronment are not active simultaneously with other speech-related synapses. As a result, they
are eliminated.
Synaptic pruning may also allow the brain to adapt more flexibly to environmental
demands. Human culture is probably the most diverse and complex environment with which
any animal must cope. Perhaps the flexibility in cortical organization achieved by the mecha-
nism of selective synaptic pruning is a necessary precondition for successful development
in a cultural environment.
Synaptic pruning may also be a precursor related to different perceptions that people
develop about the world. Consider, for example, the obvious differences in Eastern and
Western philosophies about life, religion, and culture. Given the cultural differences to
which people in the East and West are exposed as their brain develops, imagine how different
their individual perceptions and cognitions may be. Considered together as a species, how-
ever, we humans are far more alike than we are different.
An important and unique characteristic common to all humans is language. As illus-
trated in Figure 8-14, the cortex generally thins from age 5 to 20. The sole exception: major
language regions of the cortex actually show an increase in gray matter. Figure 8-16 con-
trasts the thinning of other cortical regions with the thickening of language-related regions
(O’Hare & Sowell, 2008). A different pattern of development for brain regions critical in
language processing makes sense, given language’s unique role in cognition and the long
learning time.
Unique Aspects of Frontal Lobe
Development
The imaging atlas in Figure 8-14 confirms that the frontal lobe is the last brain region to
mature. Since the atlas was compiled, neuroscientists have confirmed that frontal lobe matu-
ration extends far beyond its age 20 boundary, including in the dorsolateral prefrontal cortex.
The DLPFC, which comprises Brodmann areas 9 and 46, makes reciprocal connections with
Three-dimensional atlases guide researchers posterior parietal cortex and the superior temporal sulcus: it selects behavior and movement
to brain regions’ precise locations (Section 7-1). with respect to temporal memory. Zdravko Petanjek and colleagues (2011) analyzed synaptic
More in Sections 12-4 and 15-3 on how the spine density in the DLPFC in a large sample of human brains ranging in age at death from
DLPFC functions. newborn to age 91 years.
The analysis confirms that dendritic spine density, a good measure of the number of excit-
atory synapses, is two to three times greater in children than in adults and that spine density
begins to decrease during puberty. The analysis also shows that dendritic spines continue to
be eliminated well beyond age 20, stabilizing at the adult level around age 30. Two important
correlates attend slow frontal lobe development:
1. The frontal lobe is especially sensitive to epigenetic influences (Kolb et al., 2012). In a study
of more than 170,000 people, Robert Anda and colleagues (Anda et al., 2006) show that
8-2 • Neurobiology of Development 259
such aversive childhood experiences (ACEs) as verbal or physical abuse, a family member’s
addiction, or loss of a parent are predictive of physical and mental health in middle You can view and answer the ACE
age. People with two or more ACEs, for example, are 50 times more likely to acquire questionnaire at http://www.theannainstitute.
addictions or attempt suicide. Women with two or more ACEs are 5 times more likely to org/Finding Your ACE Score.pdf
have been sexually assaulted by age 50. We hypothesize that early aversive experiences,
such as sexual assault, promote these ACE-related susceptibilities by compromising
frontal lobe development. Abnormal frontal lobe development would make a person less
likely to judge such a situation as dangerous.
2. The trajectory of frontal lobe development correlates with adult intelligence. Philip Shaw
and his colleagues (2006) used a longitudinal design, administering multiple structural
MRIs to participants over time. The results show that it is not the thickness of the frontal
cortex in adulthood that predicts IQ score but rather the change in trajectory of cortical
thickness (Figure 8-17). Children who score highest in intelligence show the greatest
plastic changes in the frontal lobe over time. These changes are likely to reflect strong
epigenetic influences.
Glial Development
Astrocytes and oligodendrocytes begin to develop after most neurogenesis is complete and
continue to develop throughout life. CNS axons can function before they are myelinated Astrocytes nourish and support neurons;
by oligodendria, but healthy adult function is attained only after myelination is complete. oligodendroglia form myelin in the CNS
Consequently, myelination is a useful rough index of cerebral maturation. (see Table 3-1).
In the early 1920s, Paul Flechsig noticed that cortical myelination begins just after birth
and continues until at least 18 years of age. He also noticed that some cortical regions were
myelinated by age 3 to 4 years, whereas others showed virtually no myelination at that time.
dorsolateral prefrontal cortex (DLPFc)
Figure 8-18 shows one of Flechsig’s cortical maps with areas shaded according to earlier or
Brodmann areas 9 and 46; makes reciprocal
later myelination. connections with posterior parietal cortex
Flechsig hypothesized that the earliest-myelinating areas control simple movements or and the superior temporal sulcus; responsible
sensory analyses, whereas the latest-myelinating areas control the highest mental functions. for selecting behavior and movement with
MRI analyses of myelin development in the cortex show that white matter thickness largely respect to temporal memory.
Light-colored zones
myelinate last.
Frontal Lobe Development
Figure 8-17
and IQ Score The trajectory of frontal lobe
development from ages 7 to 16 years correlates with
dynamic changes in cortical thickness. Colors on the scans
scale to the magnitude of differences between individuals
with average and superior intelligence. Purple shows thinner
cortex in the individuals with higher IQ scores; red, yellow,
and green show progressively increasing cortical thickness
in those individuals. At age 7, they have a thinner frontal
cortex that rapidly thickens to peak at age 13, then wanes Figure 8-18 Progress of Myelination
later in adolescence. P. Shaw, D. Greenstein, J. Lerch, L. Clasen, R. Lenroot The fact that the light-colored zones are
et al. Intellectual ability and cortical development in children and adolescents, very late to myelinate led Flechsig to
Nature, 440, pp. 676–679 Mar 30, 2006, permission conveyed through Copyright propose that they are qualitatively different
Clearance Center, Inc. in function from those that mature earlier.
260 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
(A) Total volume does correspond to the progress of myelination, confirming Flechsig’s ideas. Myelination
continues until at least 20 years of age, as illustrated in Figure 8-19, which contrasts total
1300 brain volume, gray matter volume, and white matter volume during brain development in
females and males.
1200
8-2 review
1100 Neurobiology of Development
Before you continue, check your understanding.
1000 1. The central nervous system begins as a sheet of cells, which folds inward to form the
(B) Gray-matter volume .
Brain volume (cubic centimeters)
800 2. The growth of neurons is referred to as , whereas formation of glial cells is
known as .
750 3. Growth cones are responsive to two types of cues: and .
4. The adolescent period is characterized by two ongoing processes of brain maturation:
700
and .
5. What is the functional significance of the prolonged development of the frontal lobe?
650
Answers appear at the back of the book.
600 For additional study tools, visit :
(C) White-matter volume
www.macmillanhighered.com/launchpad/kolb5e
510
470
8-3 Using Emerging Behaviors
430
to Infer Neural Maturation
390 As brain areas mature, a person’s behaviors correspond to the functions of the maturing
areas. Stated differently, behaviors cannot emerge until the requisite neural machinery has
350 developed. When that machinery is in place, however, related behaviors develop quickly
7 9 11 13 15 17 19
Age
through stages and are shaped significantly by epigenetic factors.
Researchers have studied these interacting changes in the brain and behavior, especially
Figure 8-19
Sex Differences in in regard to the emergence of motor skills, language, and problem solving in children. We
Brain Development Mean brain
now explore development in these three areas.
volume by age in years for males (green)
and females (orange). Arrows above
the curves indicate that females show Motor Behaviors
more rapid growth than males, reaching
Developing locomotion skills are easy to observe in human infants. At first, babies cannot
maximum overall volume (A) and gray
matter volume (B) sooner. Decreasing move about independently, but eventually, they roll over, then crawl, then walk.
gray matter corresponds to cell and Other motor skills develop in less obvious but no less systematic ways. Shortly after
synaptic loss. Increasing white matter birth, infants are capable of flexing their arms in such a way that they can scoop something
volume (c) largely corresponds to myelin toward their body, and they can direct a hand, as toward a breast when suckling. Between
development. Information from R. K. Lenroot,
1 and 3 months of age, babies also begin to make spontaneous hand and digit movements
N. Gogtay, D. K. Greenstein, E. M. Wells, G. L. Wallace,
L. S. Clasen, et al. (2007). Sexual dimorphism of
consisting of almost all the skilled finger movements they will make as an adult, a kind of
brain development trajectories during childhood and motor babbling.
adolescence. NeuroImage, 36, 1065–1073. These movements at first are directed toward handling parts of their body and their clothes
(Wallace & Whishaw, 2003). Only then are reaching movements directed toward objects in
space. Tom Twitchell (1965) studied and described how the ability to reach for objects and grasp
them progresses in stages, illustrated in Figure 8-20.
Between 8 and 11 months, infants’ grasping becomes more sophisticated as the pincer
grasp, employing the index finger and the thumb, develops. The pincer grasp is signifi-
cant developmentally: it allows babies to make the very precise finger movements needed
8-3 • Using Emerging Behaviors to Infer Neural Maturation 261
to manipulate small objects. What we see then, is a sequence in the development of grasping:
first scooping, then grasping with all of the fingers, then grasping with independent finger
movements.
If increasingly well-coordinated grasping depends on the emergence of certain neural
machinery, anatomical changes in the brain should accompany the emergence of these motor
behaviors. Such changes do take place, especially in the development of dendritic arboriza- A classic symptom of motor cortex damage,
tions and in fiber connections between neocortex and spinal cord. And a correlation has detailed in Section 11-1, is permanent loss of
been found between myelin formation and the ability to grasp (Yakovlev & Lecours, 1967). the pincer grasp.
In particular, a group of axons from motor cortex neurons myelinate at about the same
time that whole-hand reaching and grasping develop. Another 2 months 4 months 10 months
group of motor cortex neurons known to control finger movements
myelinates at about the time that the pincer grasp develops. MRI
studies of changes in cortical thickness show that increased motor
dexterity is associated with decreased cortical thickness in the hand
region of the left motor cortex of right-handers (Figure 8-21A).
We can now make a simple prediction. If specific motor cortex
Orients hand toward Grasps appropriately Uses pincer grasp with
neurons are essential for adultlike grasping movements to emerge, an object and gropes shaped object with thumb and index
removing those neurons should make an adult’s grasping ability to hold it. entire hand. finger opposed.
similar to a young infant’s, which is in fact what happens.
Figure 8-20 Development of the
Language Development Grasping Response of Infants
Information from T. E. Twitchell (1965). The automatic
The gradual series of developments that accompanies speech acquisition has usually grasping response of infants. Neuropsychologia, 3, p. 251.
progressed significantly by age 3 or 4. According to Eric Lenneberg (1967), children reach
certain important speech milestones in a fixed sequence and at constant chronological ages.
Children start to form a vocabulary by 12 months. This 5-to-10-word repertoire typically
doubles over the next 6 months. By 2 years, vocabulary will range from 200 to 300 words Figure 8-21 Correlations Between
that include mostly everyday objects. In another year, vocabulary approaches 1000 words Gray Matter Thickness and
and begins to include simple sentences. At 6 years, children boast a vocabulary of about Behavior (A) Red shading corresponds
to regions showing significant cortical
2500 words and can understand more than 20,000 words en route to an adult vocabulary of
thinning correlated with improved motor
more than 50,000 words. skills. (B) White shading corresponds
Although language skills and motor skills generally develop in parallel, the capacity for to regions showing significant cortical
language depends on more than the ability to make controlled movements of the mouth, thickening correlated with improved
lips, and tongue. Precise movements of the muscles controlling these body parts develop well language skills. (c) Red shading shows
regions of decreased cortical thickness
before children can speak. Furthermore, even when children have sufficient motor skill to
correlated with improved vocabulary
articulate most words, their vocabulary does not rocket ahead but rather progresses gradually. scores. (A) and (B) Research from L. H. Lu, C. M.
A small proportion of children (about 1 percent) have typical intelligence and motor skill Leonard, P. M. Thompson, E. Kan, J. Jolley, et al. (2007).
development, yet their speech acquisition is markedly delayed. Such children may not begin Normal developmental changes in inferior frontal gray
to speak in phrases until after age 4, despite an apparently healthy environment and the matter are associated with improvement in phonological
processing: A longitudinal MRI analysis. Cerebral Cortex,
absence of any obvious neurological signs of brain damage. Because the timing of speech
17, pp. 1092–1099. (C) Research from Elizabeth R. Sowell,
onset appears universal in the remaining 99 percent of children across all cultures, some-
Paul M. Thompson, Christiana M. Leonard, Suzanne E.
thing different has likely taken place in the brain maturation of a child with late language Welcome, Eric Kan, and Arthur W. Toga. Longitudinal
acquisition. Specifying what that difference is—that is hard. Mapping of Cortical Thickness and Brain Growth in Normal
Children. J. Neurosci. 2004 24: 8223–8231. Figure 9.
(A) (B) (C)
262 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
Because the age of language onset is usually between 1 and 2 and language acquisition
is largely complete by age 12, the best strategy considers how the cortex is different before
and after these two milestones. By age 2, cell division and migration are complete in the
language zones of the cerebral cortex. The major changes that take place from age 2 to 12
are in neuronal connectivity and myelination of the speech zones.
Changes in dendritic complexity in these areas are among the most impressive in the
brain. Recall from Figure 8-12 that the axons and dendrites of the speech zone called Broca’s
area are simple at birth but grow dramatically denser at age 15 to 24 months. This neuronal
development correlates with an equally dramatic change in language ability, given that a
baby’s vocabulary starts to expand rapidly at about age 2.
Focus 7-1 describes research on newborns’ We can therefore infer that language development may be constrained, at least in part, by
reactions to language. the maturing language areas in the cortex. Individual differences in the speed of language
acquisition may be accounted for by differences in this neural development. Children with
early language ability may have an early-maturating speech zone, whereas it may develop
later in children with delayed language onset.
Results of MRI studies of the language cortex show that, in contrast with the thinning of
motor cortex associated with enhanced dexterity shown in Figure 8-21A, a thickening of the
left inferior frontal cortex areas associated with enhanced phonological processing (under-
standing speech sounds), as shown in Figure 8-21B. The unique association between cortical
thickening and phonological processing is not due to a general relation between all language
functions and cortical thickening, however. Figure 8-21C shows significant thinning of dif-
fuse cortical regions associated with better vocabulary—regions outside the language areas—
and vocabulary is one of the best predictors of general intelligence.
Development of Problem-Solving Ability
The first researcher to try to identify discrete stages of cognitive development was Swiss
psychologist Jean Piaget (1952). He realized that he could infer children’s understanding of
the world by observing their behavior. For example, a baby who lifts a cloth to retrieve a hid-
den toy shows an understanding that objects continue to exist even when out of sight. This
understanding of object permanence is revealed by the behavior of the infant in the upper
row of photographs in Figure 8-22.
Figure 8-22
Two Stages of
Cognitive Development The
infant shows that she understands object
permanence—that things continue to exist
when they are out of sight (top). This girl
does not yet understand the principle of
Doug Goodman/Science Source
conservation of liquid volume. Beakers
with identical volumes but different shapes
seem to her to hold different amounts of
liquid (bottom).
Copyright 2016 Macmillan; Photo by Ellie Miller
8-3 • Using Emerging Behaviors to Infer Neural Maturation 263
An absence of understanding also can be seen in children’s behavior, as shown by the
actions of the 5-year-old girl in the lower row of photographs in Figure 8-22. She was shown
two identical beakers with identical volumes of liquid, then watched as one beaker’s liquid
was poured into a shorter, wider beaker. When asked which beaker contained more liquid,
she pointed to the taller beaker, not understanding that the amount of liquid remains con-
stant despite the difference in appearance. Children display an understanding of this prin-
ciple, the conservation of liquid volume, at about age 7.
By studying children engaged in such tasks, Piaget concluded that cognitive development
is a continuous process. Children’s strategies for exploring the world and their understanding
of it are constantly changing. These changes are not simply the result of acquiring specific
pieces of new knowledge. Rather, at certain points in development, fundamental changes
take place in the organization of a child’s strategies for learning about the world and for solv-
ing problems. With these developing strategies comes new understanding.
Piaget identified four major stages of cognitive development, summarized in Table 8-2:
• Stage I is the sensorimotor period, from birth to about 18 to 24 months of age. During
this time, babies learn to differentiate themselves from the external world, come to
realize that objects exist even when out of sight, and gain some understanding of cause
and effect.
• Stage II, the preoperational period, takes place at age 2 to 6 years. Children gain the
ability to form mental representations of things in their world and to represent those
things in words and drawings.
• Stage III is the period of concrete operations, typically 7 to 11 years. Children learn to
mentally manipulate ideas about material (concrete) things such as volumes of liquid,
dimensions of objects, and arithmetic problems.
• Stage IV, the period of formal operations, is attained sometime after age 11. Children are
now able to reason in the abstract, not just in concrete terms.
If we take Piaget’s stages as rough approximations of qualitative changes that take place in
children’s thinking as they grow older, we can ask what neural changes might underlie them.
One place to look for brain changes is in the relative rate of brain growth.
After birth, brain and body do not grow uniformly but rather during irregularly occur-
ring periods commonly called growth spurts. In his analysis of ratios of brain weight to body growth spurt Sporadic period of sudden
growth that lasts for a finite time.
taBLe 8-2 piaget’s Stages of cognitive Development
approximate typical Developmental
age range (yr) Description of stage phenomena
0–2 I: Sensorimotor Object permanence
Experiences the world through senses Stranger anxiety
and actions (looking, touching, mouthing)
2–6 II: Preoperational Pretend play
Represents things with words and Egocentrism
images but lacks logical reasoning Language development
7–11 III: Concrete operational Conservation
Thinks logically about concrete events; Mathematical
grasps concrete analogies and performs transformations
arithmetical operations
12+ IV: Formal operational Abstract logic
Reasons abstractly Potential for mature moral
reasoning
From: PSYCHOLOGY 11e, by David G. Myers, Copyright 2015 by Worth Publishers. Used with permission of the publisher.
264 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
ExPEriMEnt 8-1 weight, Herman Epstein (1979) found consistent spurts in
brain growth between 3 and 10 months (accounting for an
Question: In what sequence do the forebrain structures required for
learning and memory mature? increase of 30 percent in brain weight by age 18 months) as
well as ages 2 to 4, 6 to 8, 10 to 12, and 14 to 16+ years. The
increments in brain weight were about 5 percent to 10 percent
I. Displacement task in each of these 2-year periods.
Brain growth takes place without a concurrent increase
in the number of neurons, and so it is most likely due to the
growth of glial cells, blood vessels, myelin, and synapses.
Although synapses themselves would be unlikely to add
much weight to the brain, their growth is accompanied by
increased metabolic demands that cause neurons to become
larger, new blood vessels to form, and new astrocytes to be
produced for neuronal support and nourishment.
II. Nonmatching-to-sample learning task We would expect such an increase in cortical complex-
ity to generate more complex behaviors, so we might pre-
Participant is shown object that can
be displaced for a food reward (1). dict significant, perhaps qualitative, changes in cognitive
function during each growth spurt. The first four brain
15 seconds growth spurts Epstein identified coincide nicely with
the four main stages of cognitive development Piaget
described. Such correspondence suggests significant
alterations in neural functioning with the onset of each
cognitive stage.
At the same time, differences in the rate of brain devel-
opment, or perhaps in the rate at which specific groups of
III. Concurrent-discrimination learning task
neurons mature, may account for individual differences in
Day 1 Day 2 Procedure repeated the age at which the various cognitive advances identified by
Piaget emerge. Although Piaget did not identify a fifth stage
Pair 1 By trial and error,
of cognitive development in later adolescence, a growth spurt
participants
determine which that occurs then implies one.
object in each of Growth spurts are superficial measures of changes taking
Pair 2 20 pairs should be place in the brain. To link them to cognitive development,
displaced for a
reward of food. we need to know at a deeper level what neural events are
contributing to brain growth and just where they are tak-
24-hour delay
24-hour delay
Pair 3 ing place. A way to find out is to observe healthy children’s
attempts to solve specific problems that are diagnostic of
In later trials, the
same participants damage to discrete brain regions in adults. If children per-
were presented with form a particular task poorly, then whatever brain region reg-
Pair 4
the pairs from Day 1, ulates that task must not yet be mature. Similarly, if children
both to learn and to
can perform one task but not another, the tasks apparently
recall which object
in each pair should require different brain structures, and these structures must
Pair 20 be displaced for the mature at different rates.
food reward. William Overman and Jocelyne Bachevalier (Overman
et al., 1992) used this logic to study the development of
Results forebrain structures required for learning and memory in
Both human and monkey infants learn the concurrent-discrimination task young children and in monkeys. The Procedure section
at a younger age than the nonmatching-to-sample task.
of Experiment 8-1 shows the three intelligence test items
Conclusion: Neural structures underlying the concurrent-discrimination presented to their participants. The first task was simply to
task mature sooner than those underlying the nonmatching-to-sample task learn to displace an object to obtain a food reward. When
Research from W. H. Overman, J. Bachevalier, M. Turner, and A. Peuster (1992). Object participants had learned the displacement task, they were
recognition versus object discrimination: Comparison between human infants and infant monkeys.
Behavioral Neuroscience, 106, p. 18. trained in two more tasks believed to measure temporal lobe
and basal ganglia functioning, respectively.
8-3 • Using Emerging Behaviors to Infer Neural Maturation 265
In the nonmatching-to-sample task, participants were shown an object they could dis-
place to receive a food reward. After a brief (15-second) delay, two objects were presented:
the first object and a novel object. The participants then had to displace the novel object to
obtain the food reward. Nonmatching to sample is thought to measure object recognition,
which is a temporal lobe function. The participant can find the food only by recognizing
the original object and not choosing it.
In the third task, concurrent discrimination, participants were presented with a pair of
objects and had to learn that one object in that pair was always associated with a food reward,
whereas the other object was never rewarded. The task was made more difficult by sequen-
tially giving participants 20 different object pairs. Each day, they were presented with one
trial per pair. Concurrent discrimination is thought to measure trial-and-error learning of
specific object information, a function of the basal ganglia.
Adults easily solve both the nonmatching and the concurrent tasks but report that the
concurrent task is more difficult because it requires remembering far more information. The
key question developmentally is whether there is a difference in the ages at which children
(or monkeys) can solve these two tasks.
It turns out that children can solve the concurrent task by about 12 months of age, but
not until about 18 months can they solve what most adults believe to be the easier nonmatch-
ing task. These results imply that the basal ganglia, the critical area for the concurrent
discrimination task, mature more quickly than the temporal lobe, the critical region for the
nonmatching-to-sample task.
A Caution about Linking Correlation
to Causation
Throughout this section we have described research results implying that changes in the
brain cause changes in behavior. Neuroscientists assert that by looking at behavioral devel-
opment and brain development in parallel, they can make some inferences regarding the
causes of behavior. Bear in mind, however, that the fact that two things correlate (take place
together) does not prove that one of them causes the other.
The correlation–causation problem raises red flags in brain and behavior studies, because
research in behavioral neuroscience, by its very nature, is often based on correlations.
Nevertheless, correlational studies, especially of development, have proved a powerful source
of insight into the principles of brain and behavior.
8-3 review
Using Emerging Behaviors to Infer Neural Maturation
Before you continue, check your understanding.
1. The last stage in motor development in infants is the ability to make .
2. Language development is correlated with cortical thinning related to and
cortical thickening related to .
3. Brain growth spurts correlate with .
4. The nonmatching-to-sample task is believed to measure the function of the ;
the concurrent-discrimination learning task is believed to measure the function of the
.
5. Describe a major challenge in inferring changes in brain development from the
emergence of behaviors.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
266 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
8-4 Brain Development and
the Environment
Developing behaviors are shaped not only by the maturation of brain structures but also by
each person’s environment and experience. Neuroplasticity suggests that the brain is pliable
and can be molded, at least at the microscopic level. Brains exposed to different environmen-
tal experiences are molded in different ways. Culture is an important aspect of the human
environment, so culture must help to mold the human brain. We would therefore expect
Section 1-5 summarizes humanity’s people raised in widely differing cultures to acquire brain structure differences that have
acquisition of culture. lifelong effects on their behavior.
The brain is plastic in response not only to external events but also to events within a
person’s body, including the effects of hormones, injury, and genetic mutations. The devel-
oping brain early in life is especially responsive to these internal factors, which in turn alter
how the brain responds to external experiences. In this section, we explore a whole range
of external and internal environmental influences on brain development. We start with a
question: Exactly how does experience alter brain structure?
Experience and Cortical Organization
Researchers can study the effects of experience on the brain and behavior by placing labo-
ratory animals in different environments and observing the results. In one of the earliest
The Hebb synapse, diagrammed in Section such studies, Donald Hebb (1947) took a group of young laboratory rats home and let them
15-1, visualizes his predictions about synaptic grow up in his kitchen. A control group grew up in standard laboratory cages at McGill
plasticity. Section 14-4 elaborates Hebb’s University.
contributions to learning theory. The home-reared rats had many experiences that the caged rats did not, including being
chased with a broom by Hebb’s less-than-enthusiastic wife. Subsequently, Hebb gave both
groups a rat-specific intelligence test that consisted of learning to solve a series of mazes, col-
lectively known as Hebb–Williams mazes. Figure 8-23 shows a sample maze. Home-reared
rats performed far better on these tasks than caged rats did. Hebb therefore concluded that
Figure 8-23 Hebb–Williams Maze
In this version of the maze, a rat is placed experience must influence intelligence.
in the start box (S) and must learn to find On the basis of his research, Hebb reasoned that people reared in a stimulating environ-
the food in the goal box (G). Investigators ment will maximize their intellectual development, whereas people raised in impoverished
can reconfigure the walls of the maze to or under-resourced environments, such as those described in the SES study in Research
set new problems. Rats raised in complex Focus 8-1, will not reach their intellectual potential. Although a generalization, Hebb’s reason-
environments solve such mazes much
ing seems logical. How do we define environments that may be stimulating or impoverished?
faster than do rats raised in standard
laboratory cages. People living in slums typically have few formal educational resources—decidedly not
an enriched setting—but that does not mean that the environment offers no cognitive
stimulation or challenge. On the contrary, people raised in slums are better adapted for
survival in a slum than are people raised in upper-class homes. Does this adaptability
make them more intelligent in a certain way? Could it make them more resilient?
Slum dwellers may not be well adapted for college life, however. This is probably
closer to what Hebb had in mind when he referred to a slum environment as limiting
S
intellectual potential. Indeed, Hebb’s logic led to the development of preschool television
programs, such as Sesame Street, that offer enrichment for children who would otherwise
have little preschool exposure to reading.
At 36 months of age, on average, the vocabulary of children from a low-SES envi-
ronment is less than one-third that of high-SES children (400 versus 1200 words). This
difference grows wider as children develop. It is hypothesized to result from less direct
G conversation with caregivers and less reading to the children by caregivers. The weaker
language skills demonstrated by children of low SES is related to the size of cortical lan-
guage areas as early as age 5 years (Raizada et al., 2008). Patricia Kuhl (2011) makes the
important point that SES itself is not the variable driving effects on language and brain
8-4 • Brain Development and the Environment 267
development. Rather, SES is likely a proxy for the opportunity (A) (B)
to learn language, a point that takes us back to James Heckman’s
thesis in Research Focus 8-1.
Seven decades ago, Hebb’s studies used complex stimulat-
ing environments, but much simpler experiences can also influ-
ence brain development. Tactile stimulation of human infants is
important not only for bonding with caregivers but also for stim-
ulating brain development. For example, tactile stimulation of
premature infants in incubators speeds their growth and allows
for quicker release from the hospital. Laboratory studies show
that brushing infant rats for 15 minutes 3 times per day for the
first 3 weeks of life also speeds up growth and development. The
animals show enhanced motor and cognitive skills in adulthood
as well. Tactile stimulation also dramatically improves recovery Laboratory housed Complex-environment
housed
from brain injury incurred early in development.
The idea that early experience can change later behavior
Figure 8-24 Enriched Environment, Enhanced Development
seems sensible enough, but we are left to question why experi-
(A) A complex environment for a group of about six rats allows the
ence should make such a difference. One reason is that experi- animals to move about and to interact with one another and with toys that
ence changes neuronal structure, which is especially evident in are changed weekly. (B) Representative neurons from the parietal cortex
the cortex. Neurons in the brains of animals raised in complex of a laboratory-housed rat and a complex-environment-housed rat; the
environments, such as that shown in Figure 8-24A, are larger latter has about 25 percent more dendritic space for synapses.
and richer in synapses than are those of animals reared in bar-
ren cages (Figure 8-24B). Similarly, 3 weeks of tactile stimulation
increases synapse numbers all over the cortex in adulthood.
Presumably, increased synapse numbers result from increased sensory processing in a Focus 5-5 describes some structural changes
complex and stimulating environment. The brains of animals raised in complex settings neurons undergo as a result of learning.
also display more (and larger) astrocytes. Although complex-rearing studies do not address
the effects of human culture directly, making predictions about human development on
the basis of their findings is easy. We know that experience can modify the brain, so we
can predict that different experiences might modify the brain differently. Take language
development, for example, as Research Focus 8-3, Increased Cortical Activation for Second
Languages, on page 268, explains.
Like early exposure to language during development, early exposure to music alters
the brain. Perfect (absolute) pitch, or the ability to re-create a musical note without exter- Figure 15-11 shows enhanced nerve tract
nal reference is believed to require musical training during an early period, when brain connectivity in people with perfect pitch.
development is most sensitive to this experience. Similarly, adults exposed only to West-
ern music since childhood usually find Eastern music peculiar, even nonmusical, on first
encountering it. Both examples demonstrate that early exposure to music alters neurons
in the auditory system (see Levitin & Rogers, 2005).
Such loss of plasticity does not mean that the adult human brain grows fixed and
unchangeable. Adults’ brains are influenced by exposure to new environments and experi-
ences, although more slowly and less extensively than children’s brains are. In fact, evidence
reveals that experience affects the brain well into old age: good news for those of us who are
no longer children.
It is becoming clear as well that prenatal events can modify brain development. The con-
sensus is that perinatal adversity, such as gestational stress at or near birth, is a significant
risk factor for later behavioral disorders (see Bock et al., 2014). Even events such as stress or
drug use that occur before conception can lead to epigenetic effects in offspring. Examples
include abnormalities in neural organization and behavior (e.g., Harker et al., 2015). Although
such effects are usually presumed to come from maternal exposure before conception,
increasing evidence from research on humans points to paternal preconception experience
also modifying children’s brain development, perhaps including acquisition of fetal alcohol
spectrum disorder (FASD). Focus 6-2 details FASD.
268 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
ReseaRch F cus 8-3
Increased Cortical Activation for Second Languages
Most of the world’s population is bilingual, but people rarely learn their Further support for Klein and colleagues’ conclusions from these
second language as early as their first. Denise Klein and her colleagues imaging studies comes from a review of cortical mapping studies of
(2006) used both PET and fMRI to determine whether native and second bilingual patients undergoing neurosurgery. Carlo Giussani and his
languages differ in cortical activation. colleagues (2007) conclude that although all studies show language
The two languages overlap greatly in neural representation, but when representation grossly located in the same cortical regions, distinct lan-
participants are asked to repeat words, the second language shows greater guage-specific areas exist in the frontal and temporoparietal language
activation in motor regions such as the striatum and cerebellum as well regions. Section 15-6 concludes with updates on these findings.
as in the frontal and temporal language regions. The investigators specu-
late that the second language places greater articulatory demands on the Blue regions show increased activation in neural motor structures when
the person is speaking a second language. Copyright © 2005 Wiley-Liss, Inc.
speaker. These demands correspond to the increased neural involvement
Word and Nonword Repetition in Bilingual Subjects: A PET Study. Denise Klein, Kate E.
in motor as well as language areas, as shown in the illustration.
Watkins, Robert J. Zatorre, and Brenda Milner, Human Brain Mapping 27: 153–161 (2006).
Permission conveyed through Copyright Clearance Center, Inc.
4.00
3.63
3.25
2.88
2.50
Ventral striatum Caudate nucleus Anterior insula Ventral premotor
Experience and Neural Connectivity
Experience can actually sculpt the brain prenatally, as studies of the developing visual sys-
tem illustrate clearly. Consider the anatomical challenge of connecting the eyes to the rest
of the visual system. A simple analogy will help. Imagine that students in a large lecture hall
are each viewing the front of the room (the visual field) through a small cardboard tube, such
as an empty paper towel roll. If each student looks directly ahead, he or she will see only a
small bit of the total visual field.
Essentially, this is how the photoreceptor cells in the eyes act. Each cell sees only a small
bit of the visual field. The problem is putting all of the bits together to form a complete pic-
ture. To do so, analogously to students sitting side by side, receptors that see adjacent views
Section 9-2 describes visual system anatomy. must send their information to adjacent regions in the various parts of the brain’s visual
Figure 2-18 details midbrain structures. system, such as the midbrain. How do they accomplish this feat?
Roger Sperry (1963) suggested the chemoaffinity hypothesis, the idea that specific mol-
ecules in different cells in various midbrain regions give each cell a distinctive chemical iden-
tity. Each cell has an identifiable biochemical label. Presumably, incoming axons seek out a
specific chemical, such as the tropic factors discussed in Section 8-2, and consequently land
in the correct general midbrain region.
Many experiments have shown this process to take place prenatally as the eye and brain
are developing. But the problem is that chemical affinity directs incoming axons only to a
general location. To return to our two adjacent retinal cells, how do they now place them-
selves in the precisely correct position?
Here is where postnatal experience comes in: fine-tuning of neural placement is
believed to be activity-dependent. Because adjacent receptors tend to be activated at the
8-4 • Brain Development and the Environment 269
same time, they tend to form synapses on the same neurons in the midbrain
after chemoaffinity has drawn them to a general midbrain region. Figure 8-25
illustrates this process. Neurons A and G are unlikely to be activated by the same
stimulus, so they seldom fire synchronously. Neurons A and B, in contrast, are
apt to be activated by the same stimuli, as are B and C. Through this simultane-
ous activity and with the passage of time, cells eventually line up correctly in the
connections they form.
Now consider what happens to axons coming from different eyes. Although
the neural inputs from the two eyes may be active simultaneously, cells in the
Eye
same eye are more likely to be active together than are cells in different eyes. Optic tectum
in midbrain
The net effect is that inputs from the two eyes tend to organize themselves into
neural bands, called columns, that represent the same region of space in each eye, Retina Optic tectum
as shown on the left in Figure 8-26 on page 270. Formation of these segregated A
B
cortical columns therefore depends on the patterns of coinciding electrical activ- C
D
E
ity on the incoming axons. F
G
If experience is abnormal—if one eye is covered during a crucial time in
development, for example—then the neural connections will not be guided
Time
appropriately by experience. As shown at the right in Figure 8-26, the effect of
suturing one eye closed has the most disruptive effect on cortical organization
in kittens between 30 and 60 days after birth. In a child who has a lazy eye,
A
visual input from that eye does not contribute to fine-tuning the neural con- B
C
nections as it should. So the details of those connections develop abnormally, D
E
F
much as if the eye had been covered. The resulting loss of sharpness in vision G
is amblyopia.
To summarize, an organism’s genetic blueprint is vague in regard to exactly
Figure 8-25
Chemoaffinity in the Visual
which connections in the brain go to exactly which neurons. Experience fine-tunes
System Neurons A through G project from the
neural connectivity by modifying those details.
retina to the tectum in the midbrain. The activities
of adjacent neurons (C and D, say) are more likely to
Critical Periods for Experience coincide than are the activities of widely separated
neurons such as A and G. As a result, adjacent retinal
and Brain Development neurons are more likely to establish permanent
synapses on the same tectal neurons. By using
The preceding examples of perfect pitch and visual connectivity show that for chemical signals, axons grow to the approximate
healthy development, specific sensory experiences occurring at particular times are location in the tectum (top). The connections become
especially important. A time during which brain development is most sensitive to a more precise with the passage of time (bottom).
specific experience is called either a critical period or a sensitive period.
The absence of appropriate sensory experience during a critical period may result in
abnormal brain development, leading to abnormal behavior that endures even into adult-
hood. Our colleague Richard Tees offered an analogy to help explain the concept. He pic-
tured the developing animal as a little train traveling past an environmental setting, perhaps
the Rocky Mountains. All the windows are closed at the beginning of the journey (pre-
natal development), but at particular stages of the trip, the windows in certain cars open, chemoaffinity hypothesis Proposal that
exposing the occupants (different parts of the brain) to the outside world. Some windows neurons or their axons and dendrites are
open to expose the brain to specific sounds, others to certain smells, others to particular drawn toward a signaling chemical that
sights, and so on. indicates the correct pathway.
This exposure affects the brain’s development, and the absence of any exposure through amblyopia Condition in which vision in one
an open window severely disturbs that development. As the journey continues, the windows eye is reduced as a result of disuse; usually
become harder to open until finally they close permanently. This does not mean that the caused by a failure of the two eyes to look in
brain can no longer change, but changes become much harder to induce. the same direction.
Now imagine two different trains, one headed through the Rocky Mountains and another, critical period Developmental window
the Orient Express, traveling across Eastern Europe. The views from the windows are very during which some event has a long-lasting
different, and the effects on the brain are correspondingly different. In other words, not influence on the brain; also, sensitive period.
270 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
only is the brain altered by the experiences it has during a critical period, but the
In infancy, the projections
from the two eyes overlap. particular kinds of experiences encountered matter too.
An extensively studied, related behavior is imprinting, a critical period during
Typical Restricted
which an animal learns to restrict its social preferences to a specific class of objects,
usually the members of its own species. In birds, such as chickens and waterfowl,
the critical period for imprinting often comes shortly after hatching. Typically, the
Infant first moving object a young hatchling sees is a parent or sibling, so the hatchling’s
brain appropriately imprints to its own species.
Appropriate imprinting is not inevitable. Konrad Lorenz (1970) demonstrated
that if the first animal or object that baby goslings encounter is a person,
Adolescent the goslings imprint to that person as though he or she were their mother.
Figure 8-27 shows a flock of goslings that imprinted to Lorenz and followed
him wherever he went. Incorrect imprinting has long-term consequences for the
hatchlings. They often direct their subsequent sexual behavior toward humans.
Adult A Barbary dove that had become imprinted to Lorenz directed its courtship
L R L R L L R L R L toward his hand and even tried to copulate with the hand if it was held in a
certain orientation.
In adulthood, a If one eyelid of a kitten is sewn
nonoverlapping shut during a critical week of Birds can imprint not just to humans but also to inanimate objects, especially
pattern of terminal development, the terminations moving objects. Chickens have been induced to imprint to a milk bottle sitting on
arborizations from from that eye retract and those the back of a toy train moving around a track. But the brain is not entirely clueless
each eye is normal. from the open eye expand.
when it comes to selecting an imprinting target. Given a choice, young chicks will
Figure 8-26 Ocular Dominance
imprint on a real chicken over any other stimulus.
Columns Typically in the postnatal This quick acquisition and its permanent behavioral consequences suggest that during
development of the cat brain, axons from imprinting, the brain makes a rapid change of some kind, probably a structural change given
each eye enter the cortex, where they the permanence of the new behavior. Gabriel Horn and his colleagues at Cambridge Uni-
grow large terminal arborizations. versity (1985) tried to identify the changes in chicks’ brains during imprinting. The results
(L, left eye; R, right eye).
of Horn’s electron microscopic studies show that synapses in a specific forebrain region
enlarge with imprinting. Thus, imprinting seems a good model for studying brain plasticity
during development, in part because the changes are rapid, related to specific experience,
and localized in the brain.
As noted in Section 8-3, brain development can be affected by either parent’s experiences
before conception or those of the mother or fetus during gestation. Because developmental
events change so dramatically and quickly in utero, we should not be surprised that the
effects of fetal experiences vary with the precise developmental stage. As a rule, the CNS
is especially sensitive during gestational weeks 4 to 8, as the neural tube forms. It remains
sensitive through the period of cerebral neurogenesis, which continues until the end of the
second trimester. Robbin Gibb and her colleagues (2014) have shown that housing pregnant
rats in complex environments, as in Figure 8-24A, results in the offspring showing increased
Thomas D. McAvoy/Time & Life Pictures/Getty Images
dendritic spine density in the cortex, as though the animals had been placed in the environ-
ment in adulthood.
Abnormal Experience and Brain
Development
If complex or enriched experiences can stimulate brain growth and influence later behavior,
severely restricted experiences seem likely to retard both brain growth and behavior. To
study the effects of such restrictions, Donald Hebb and his colleagues (Clarke et al., 1951)
placed young Scottish terriers in the dark with as little stimulation as possible and compared
their behavior to that of dogs raised in a typical environment.
Figure 8-27 Strength of Imprinting When the dogs raised in the barren environment, obviously unethical by today’s stan-
Ethologist Konrad Lorenz followed by
goslings that imprinted on him. He was the dards, were later removed from it, their behavior was highly unusual. They showed virtually
first object that the geese encountered after no reaction to people or other dogs and appeared to have lost any pain sensation. Even stick-
hatching, so he became their “mother.” ing pins in them (equally unethical) produced no response. When given a dog version of the
8-4 • Brain Development and the Environment 271
Hebb–Williams intelligence test for rats, these dogs performed terribly and were unable to
imprinting Formation of an attachment by an
learn some tasks that dogs raised in more stimulating settings learned easily.
animal to one or more objects or animals at a
Results of subsequent studies show specifically that depriving young animals of visual
critical period in development.
input or of maternal contact has devastating consequences for their behavioral develop-
ment and presumably for their brain development. Austin Riesen (1982) and his colleagues
extensively studied animals raised in the dark. They found that even though the animals’
eyes still work, they may be functionally blind after early visual deprivation. An absence of
visual stimulation results in the atrophy of dendrites on cortical neurons, essentially the
opposite of the results observed in the brains of animals raised in complex and stimulating
environments.
Not only does the absence of specific sensory inputs adversely affect brain development;
so do more complex atypical experiences. In the 1950s, Harry Harlow (1971) began the first
systematic laboratory studies of analogous deprivation in laboratory animals. Harlow showed
that infant monkeys raised without maternal (or paternal) contact develop grossly atypical
intellectual and social behaviors in adulthood.
Harlow separated baby monkeys from their mothers shortly after birth and raised them
in individual cages. Perhaps the most stunning effect occurred in adulthood, when these
animals were totally unable to establish normal relations with other animals. Unfortunately,
Harlow did not analyze the deprived monkeys’ brains. We would predict atrophy of corti-
cal neurons, especially in the frontal lobe regions related to social behavior. Harlow’s stu-
dent Stephen Suomi continues to study early experiences in monkeys at the U.S. National
Institute of Child Health and Human Development. He has found a wide variety of hor-
monal and neurological abnormalities among motherless monkeys, including epigenetic
changes (see the review by Suomi, 2011).
Children in a barren environment or abused or neglected are at a serious disadvan-
tage later in life. Proof is the hampered intellectual and motor development displayed by
children raised in dreadful circumstances such as those described in Clinical Focus 8-4,
Romanian Orphans, on page 272. Although some argue that children can succeed in
school and in life if they really want to, abnormal developmental experiences can clearly
alter the brain irrevocably. As a society, we cannot be complacent about the environment
to which our children are exposed.
Early exposure to stress, including prenatally, also has major effects on a child’s later
behavior. Stress can alter the expression of certain genes, such as those related to serotonin
(5-hydroxytryptamine, or 5-HT) reuptake. Early alteration in serotonin activity can severely
alter how the brain responds to stressful experiences later in life.
Stress early in life may predispose people to develop behavioral disorders, such as
depression (Sodhi & Sanders-Bush, 2004). Early stress can also leave a lasting imprint
on brain structure: the amygdala is enlarged and the hippocampus is small (Salm et al.,
2004). Changes in frontal lobe anatomy have been associated with the development of Section 6-5 explains the neurobiology of the
depressive and anxiety disorders and may be linked to the epigenetic effects described stress response. Section 16-4 connects mood
in Section 8-2. and reactivity to stress.
Prenatal experiences also can lead to abnormal behavior in children and adults. Exposing
the fetus to alcohol, especially in the first two trimesters, can lead to FASD, as can exces-
sive alcohol use by either parent before conception. Similarly, children exposed in utero to
radiation in the aftermath of the 1986 accident at the Chernobyl nuclear power plant later
developed a range of cognitive disorders, including lowered IQ scores. Effects were most
severe if they had been exposed during gestational weeks 8 to 25, the critical period of cere-
bral neurogenesis (Nyagu et al., 1998).
Hormones and Brain Development
The determination of sex is largely genetic. In mammals, the Y chromosome in males
controls the process by which an undifferentiated, primitive gonad develops into testes,
272 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
clinical F cus 8-4
Romanian Orphans
In the 1970s, Romania’s Communist regime outlawed all forms of birth Charles Nelson and his colleagues (Berens & Nelson, 2015; Nelson
control and abortion. The natural result was more than 100,000 unwanted et al., 2007; Smyke et al., 2012) analyzed cognitive and social develop-
children in state-run orphanages. The conditions were appalling. ment as well as event-related potential (ERP) measures in a group of
The children were housed and clothed but given virtually no envi- children who had remained in Romania. Whether the children had moved
ronmental stimulation. Mostly they were confined to cots with few, if to foster homes or remained in institutions, the studies reveal severe
any, playthings and virtually no personal interaction with overworked abnormalities at about 4 years of age. The age at adoption was again
caregivers, who looked after 20 to 25 children at once. Bathing often important, but in the Nelson studies the critical age appears to be before
consisted of being hosed down with cold water. 24 months rather than 6 months, as in the earlier studies.
After the Communist government fell, the outside world inter- The inescapable conclusion is that the human brain may be able to
vened. Hundreds of these children were placed in adoptive homes recover from a brief period of extreme deprivation in early infancy, but
throughout the world, especially in the United States, Canada, and periods longer than 24 months produce significant developmental abnor-
the United Kingdom. Studies of these severely deprived children malities that cannot be overcome completely. The studies of Romanian
on arrival in their new homes document malnourishment, chronic orphans make clear that the developing brain requires stimulation for
respiratory and intestinal infections, and severe developmental healthy development. Although the brain may be able to catch up after
impairments. a brief deprivation, severe deprivation lasting many months results in a
A British study by Michael Rutter (1998) and his colleagues assessed small brain and associated behavioral abnormalities, especially in cogni-
the orphans at two standard deviations below age-matched children for tive and social skills.
weight, height, and head circumference (taken as a very rough measure
of brain size). Scales of motor and cognitive development assessed most
of the children in the impaired range.
The improvement these children showed in the first 2 years after
placement in their adoptive homes was nothing short of spectacular.
Average height and weight advanced to nearly normal, although head
circumference remained below normal. Many tested in the normal range
Cynthia Johnson/Liaison/Getty Images
of motor and cognitive development. But a significant number were still
considered intellectually impaired. What caused these individual differ-
ences in recovery from the past deprivation?
The key factor was age at adoption. Children adopted before 6 months of
age did significantly better than those adopted later. In a Canadian study by
Elenor Ames (1997), Romanian orphans who were adopted before 4 months
of age and then tested at age 4½ had an average Stanford–Binet IQ score
of 98. Age-matched Canadian controls had an average score of 109. Brain Romanian orphans warehoused in the 1970s and 1980s endured the
imaging studies showed that children adopted at an older age had a smaller conditions shown in this photograph. The utter absence of stimuli
brain than normal. hampered their normal brain development.
illustrated in Figure 8-28. The genitals begin to form in the seventh week after concep-
tion, but they appear identical (indifferent) in the two sexes at this early stage. No sexual
dimorphism, or structural difference, yet exists. The testes subsequently secrete the sex hor-
mone testosterone, which stimulates development of male reproductive organs and later,
in puberty, the appearance of male secondary sexual characteristics such as facial hair and
deepening of the voice.
Gonadal (sex) hormones change the genetic activity of certain cells, most obviously those
that form the genitals, but neural cells also respond to them. Regions of the embryonic
brain thus also may begin to show sexual dimorphism as testosterone secretion begins,
about 60 days after conception. What does sexual differentiation have to do with brain
development? Although the answer is largely hormonal, genetic influences contribute, too.
Testosterone stimulates sexual differentiation in male embryos. In its absence, female
embryos develop. Prenatal exposure to gonadal hormones shapes male and female brains dif-
ferently, because these hormones activate different genes in the two sexes. Experience, then,
Sections 6-5 and 12-5 detail the actions of affects male and female brains differently. Clearly, genes and experience begin to shape the
gonadal hormones, including testosterone. developing brain very early.
8-4 • Brain Development and the Environment 273
Indifferent stage
Urogenital testosterone Sex hormone secreted by the
membrane testes and responsible for the distinguishing
Anal characteristics of the male.
membrane
androgen Class of hormones that stimulates
or controls masculine characteristics.
masculinization Process by which exposure
to androgens (male sex hormones) alters the
Developing female genitalia Developing male genitalia brain, rendering it identifiably male.
Developing Developing
clitoris
estrogens Variety of sex hormones
penis
responsible for the distinguishing
Urethral
Labial
folds characteristics of the female.
folds
Scrotal
folds
Anus
Anus
Clitoris Penis
Labial
Scrotum
folds
Anus Anus
Figure 8-28 Sexual Differentiation in the Human Infant Early in the indifferent
stage, male and female human embryos are identical (top). In the absence of testosterone,
female structures emerge (left). In response to testosterone, genitalia begin to develop into
male structures at about 60 days (right). Parallel changes take place in the embryonic brain
in response to the absence or presence of testosterone.
Gonadal Hormones and Brain Development
Testosterone, the best-known androgen (the class of hormones that stimulates or con-
trols masculine characteristics), is released during a brief period of prenatal brain devel-
opment. Subsequently, it alters the brain much as it alters the sex organs. This process is Figure 8-29 Sex Differences in Brain
masculinization. Volume Cerebral areas related to sex
Testosterone does not affect all body organs or all brain regions, but it does affect many differences in the distribution of estrogen
(orange) and androgen (green) receptors in
brain regions in many ways. It affects the number of neurons formed in certain brain areas,
the developing brain correspond to areas of
reduces the number of neurons that die, increases cell growth, increases or reduces dendritic relatively larger cerebral volumes in adult
branching and synaptic growth, and regulates synaptic activity, among other effects. women and men. Information from J. M. Goldstein,
Estrogens, the sex hormones responsible for the female’s distinguishing characteristics, L. J. Seidman, N. J. Horton, N. Makris, D. N. Kennedy et
also probably influence postnatal brain development. Jill Goldstein and her colleagues found al. (2001). Normal sexual dimorphism of the adult human
brain assessed by in vivo magnetic resonance imaging.
sex differences in the volume of cortical regions known to have differential levels of recep-
Cerebral Cortex, 11, 490–497.
tors for testosterone (androgen receptors) and estrogen, respectively, as
shown in Figure 8-29 (Goldstein et al., 2001). Orange areas in the figure
are larger in females, and green areas are larger in males. Clearly, a male
brain and a female brain are not the same. Hormones alter brain develop-
ment, and clear sex differences appear in the rate of brain development
(see Figure 8-19).
Testosterone’s effects on brain development were once believed
unimportant, because this hormone was thought primarily to influence
brain regions related to sexual behavior, not regions of higher functions. Lateral view Medial view
274 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
This belief is false. Testosterone changes cell structure in many cortical regions, with diverse
behavioral consequences that include influences on cognitive processes.
Jocelyne Bachevalier adapted her method, shown in Experiment 8-1 on page 264, by
training infant male and female monkeys in the concurrent discrimination task. The
animal has to learn which of two objects in a series of pairs conceals a food reward.
Bachevalier also trained the animals in another task, object reversal learning. The task is
to learn that one object always conceals a food reward, whereas another object never does.
After the animal learns this pattern, the reward contingencies are reversed so that the
particular object that has always been rewarded is now never rewarded, and the formerly
unrewarded object now conceals the reward. When the animal learns this new pattern,
the contingencies are reversed again, and so on for five reversals.
Bachevalier found that 2½-month-old male monkeys were superior to female monkeys on
the object reversal task, but females did better on the concurrent task. Apparently, the dif-
ferent brain areas required for these two tasks mature at different rates in male and female
monkeys. Bachevalier later tested additional male monkeys whose testes had been removed
at birth and so were no longer exposed to testosterone. These animals performed like females
on the tasks, which implies that testosterone was influencing the brain development rate in
areas related to certain cognitive behaviors.
Bachevalier and her colleague William Overman (Overman et al., 1996) repeated the
experiment with children 15 to 30 months old. The results were the same: boys were superior
at the object reversal task and girls were superior at the concurrent task. The investigators
found no such male–female performance differences among children 32 to 55 months of age.
Presumably, the brain regions required for both tasks had matured in both boys and girls.
At the earlier age, however, gonadal hormones seemed to influence the maturation rate in
certain brain regions, just as they had in the baby monkeys.
Lifelong Effects of Gonadal Hormones
Although gonadal hormones’ biggest effects on the brain may come during early develop-
ment, their role there is by no means finished in infancy. Both testosterone and estrogen
(which females’ ovaries produce in large quantities) continue to influence brain structure
throughout an animal’s life. In fact, removal of the ovaries in middle-aged laboratory rats leads
to marked growth of dendrites and glial cells in the cortex. This finding of widespread neural
change in the cortex associated with estrogen loss has implications for treating postmeno-
pausal women with hormone replacement therapy, which may reverse the plastic changes.
Gonadal hormones also affect how the brain responds to environmental events. For
instance, among rats housed in complex environments, males show more dendritic growth
in neurons of the visual cortex than do females (Juraska, 1990). In contrast, females housed
in this setting show more dendritic growth in the hippocampus than males do. Apparently,
the same experience can affect the male and female brain differently owing to the mediating
influence of gonadal hormones.
As females and males develop, then, their brains continue to diverge more and more,
much like a fork in a road. After you set out on one path, your direction is forever changed,
as the roads increasingly course farther apart.
To summarize, gonadal hormones alter basic neuronal development, shape
experience-dependent changes in the brain, and influence neuronal structure throughout
our lifetimes. Those who believe that behavioral differences between males and females
Details on sexual orientation and gender are solely the result of environmental experiences must consider these neural effects of
identity appear in Section 12-5. sex hormones.
In part, it is true that environmental factors exert a major influence. But one reason
they do so may be that male and female brains are different to start with. Even the same
events experienced by structurally different brains may lead to different effects on those
brains. Evidence shows that significant experiences, such as prenatal stress, produce
8-4 • Brain Development and the Environment 275
markedly different changes in gene expression in the frontal cortex of male and female rats
( Mychasiuk et al., 2011).
Another key question related to hormonal influences on brain development is whether
any sex differences in brain organization might be independent of hormonal action. In other
words, are differences in the action of sex chromosome genes unrelated to sex hormones?
Although little is known about such genetic effects in humans, studies of birds clearly show
that genetic effects on brain cells may indeed contribute to sex differentiation.
Songbirds have an especially interesting brain dimorphism: in most species, males sing
and females do not. This behavioral difference between the sexes is directly related to a
neural birdsong circuit present in males but not in females. Robert Agate and his colleagues
(2003) studied the brain of a rare gynandromorph zebra finch, shown in Figure 8-30. This
bird exhibits physical characteristics of both sexes.
Genetic analysis shows that cells on one half of the bird’s brain and body are genetically
female and on the other half are genetically male. The two sides of the gynandromorph’s
body and brain were exposed to the same hormones during prenatal development. Thus, the
effect of male and female genes on the birdsong circuit can be examined to determine how
the genes and hormones might interact.
Figure 8-30 Gynandromorph This
If the sex difference in the birdsong circuit were totally related to the presence of hor- rare zebra finch has dull female plumage
mones prenatally, then the two sides of the brain should be equally masculine or feminine. on one side of the body and bright male
Agate’s results confirm the opposite: the neural song circuit is masculine on the male side of plumage on the other side. Neural, not gonadal,
the brain. Only a genetic difference that was at least partly independent of hormonal effects origin of brain sex differences in a gynandromorphic
finch. Agate RJ, Grisham W, Wade J, Mann S, Wingfield J,
could explain such a structural difference in the brain.
Schanen C, Palotie A, Arnold AP. Proc Natl Acad Sci U S A.
2003 Apr 15; 100 (8): 4873-8. Copyright (2003) National
Adolescent Onset of Mental Disorders Academy of Sciences, U.S.A.
Adolescence is a time of rapid brain change related both to pubertal hormones and to psy-
chosocial stress. Relationships with parents and peers are among the prime stressors, as is
school. Add to this the finding, charted in Figure 8-31, that the peak age of onset for any
mental disorder is estimated at 14 years (Paus et al., 2008).
40
Figure 8-31 reveals that age of onset differs across disorders. However, anxiety disorders,
psychoses (including schizophrenia), bipolar disorder, depression, eating disorders, and sub- 35
stance abuse most commonly emerge by or during adolescence. From an evolutionary per-
30
Age range of onset (years)
spective, neurobiological and associated behavioral changes linked with the period we define
Mood
as adolescence are designed to optimize the brain for challenges that lie ahead in adulthood. 25
But the brain’s plasticity in adolescence can also make it vulnerable to psychopathologies
Schizophrenia
Substance
20
that can endure for the rest of the individual’s life.
use
15
Anxiety
14
Gut Bacteria and Brain Development
Impulse
control
10
We have emphasized factors that affect CNS development directly, but a less direct route 5
exerts itself via the enteric nervous system. The ENS sends information to the brain that
0
affects our mental state. The brain in turn can modify gut function.
Disorder
An important component of the ENS is the microbiome, the bacteria in the gut with
which the ENS interacts. About 1014 microbiota populate the adult gut, which means that Figure 8-31 Emergence of Mental
microbiota outnumber the host body cells by a factor of 10. But in utero, the fetus’s gut is
Disorders in Adolescence Data from
T. Paus, M. Keshavan, and J. N. Giedd (2008). Why do so
sterile. It is only at birth that trillions of microbes from the mother’s vaginal and anal fluids, many psychiatric disorders emerge during adolescence?
and later from her skin, invade the baby’s body and start to grow. Nature Reviews Neuroscience, 9, pp. 947–957.
Many neurodevelopmental disorders, including autism, may be related to an atypical
microbiome early in life (e.g., Finegold et al., 2012). Elaine Hsiao and her colleagues (2013)
studied a mouse model known to display features of ASD. These mice produce few social
auditory vocalizations, about one-third the normal levels. Manipulation of their gut bacteria
restored the vocalizations to normal levels, demonstrating that gut bacteria can alter behav- Section 2-5 introduces the ENS and
ior. Other neurodevelopmental disorders may involve microbiome abnormalities as well. microbiome.
276 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
Frontal cortex
injury
Injury and Brain Development
Dating to the late 1800s, infants and children were generally believed to show better
recovery from brain injury than adults. In the 1930s, Donald Hebb studied children with
major birth-related injuries to the frontal lobes and found them to have severe and per-
manent behavioral abnormalities in adulthood. He concluded that brain damage early in
Cortical neuron
life can alter the brain’s subsequent development and actually may be worse than injury
in adult
later in life.
Have other studies confirmed Hebb’s conclusion? Few anatomical studies of humans with
early brain injuries exist, but we can make some general predictions from studying labora-
tory animals. In general, early brain injuries do produce atypical brains, especially at certain
critical periods in development.
For humans, the worst time appears to be in the last half of the intrauterine period and
the first couple of months after birth. Rats and cats that are injured at a comparable time
have a significantly smaller brain than average, and their cortical neurons show general atro-
Damage on day 1 Damage on day 10
phy relative to healthy brains, as illustrated on the left in Figure 8-32. Behaviorally, these
Figure 8-32 Time-Dependent animals appear cognitively deficient over a wide range of skills.
Effects Damage to the rat’s frontal Injury to the developing brain is not always devastating. For example, researchers have
cortex on the day of birth leads to cortical known for more than 100 years that children with brain injuries in the first couple of years
neurons with simple dendritic fields and
after birth almost never have the severe language disturbances common to adults with equiv-
sparse growth of spines in the adult (left).
In contrast, damage to the frontal cortex alent injuries. Animal studies help explain why.
at 10 days of age leads to cortical neurons Whereas damage to the rat brain in the developmental period comparable to the last
with expanded dendritic fields and denser few months of gestation in humans produces widespread cortical atrophy, damage at a time
spines than normal in adults (right). in rat brain development roughly comparable to ages 6 months to 2 years in humans actu-
Information from B. Kolb and R. Gibb (1993). Possible
ally produces more dendritic development in rats (Figure 8-32 at right). Furthermore, these
anatomical basis of recovery of function after neonatal
frontal lesions in rats. Behavioral Neuroscience, 107, p. 808.
animals show dramatic recovery of functions, which implies that during development the
brain has a capacity to compensate for injury. Parallel studies in cats have shown extensive
reorganization of cortex-to-cortex connections after early injury to the visual cortex (see the
review by Payne and Lomber, 2001).
Drugs and Brain Development
The U.S. National Institute on Drug Abuse (2012) estimates that 16 percent of babies born
alive in the United States today are exposed to nicotine in utero. Similar statistics on alcohol
consumption by pregnant mothers are not available, but the effects of alcohol on the fetus
are well documented. Even low doses of commonly prescribed drugs, including antidepres-
sants, antipsychotics, and pain-killers, appear to alter prenatal neuron development in the
prefrontal cortex. It manifests after birth in abnormalities in behaviors controlled by the
affected regions (see the review by Halliwell et al., 2009).
NIDA also estimates that 5.5 percent of expectant mothers, approximately 221,000 preg-
nant women each year in the United States, use an illicit drug at least once in the course
of their pregnancy. Among pregnant teenagers aged 15 to 17, that figure climbs to 16%, or
about 14,000 women. And what about caffeine and nicotine? More than likely most children
were exposed to caffeine (from coffee, tea, cola, energy drinks, and chocolate) in utero and
Section 6-3 reviews nicotine’s prominence as about 16% were exposed to nicotine. Laboratory animal studies have shown that prenatal
a gateway drug. exposure to nicotine alters the brain’s response to complex housing: the brain appears less
plastic (e.g., Mychasiuk et al., 2014).
The precise effects of prenatal drug intake on brain development are poorly understood,
but the overall conclusion from current knowledge is that children with prenatal exposure
to a variety of psychoactive drugs have an increased likelihood of later drug use (e.g., Minnes
et al., 2014). Although, again, childhood disorders are poorly studied, many experts sug-
Focus 7-4 details ADHD and Focus 14-1 gest that they—learning disabilities and ADHD are examples—may be related to prenatal
details dyslexia. exposure to drugs such as nicotine or caffeine or both. As Carl Malanga and Barry Kosofsky
8-4 • Brain Development and the Environment 277
(2003) note poignantly, society at large does not yet fully appreciate the impact that prenatal
drug exposure can have on the lives of its children.
Other Sources of Abnormal Brain
Development
The nervous system need not be damaged by external forces to develop abnormally. Many
anencephaly Failure of the forebrain to
genetic aberrations are believed to result in abnormalities in brain development and ulti-
develop.
mately brain structure. Spina bifida, in which the genetic blueprint goes awry and the neural
tube does not close completely, leads to an incompletely formed spinal cord. After birth, sudden infant death syndrome (siDs)
Unexplained death while asleep of a
unless treated with folic acid, children with spina bifida usually have serious motor problems.
seemingly healthy infant less than 1 year old.
Imagine what happens if some genetic aberration causes improper closure of the front end
of the neural tube. Because the front end of the neural tube forms the brain (see Figure 8-5),
this failure results in gross abnormalities in brain development known as anencephaly. Affected
infants die soon after birth.
Atypical brain development can be much subtler than anencephaly. For example, if cells
do not migrate to their correct locations, and if these mispositioned cells do not subsequently
die, they can disrupt brain function and may lead to disorders ranging from seizures to
schizophrenia (see review by Guerrini et al., 2007). In a variety of conditions, neurons fail
to differentiate normally. In certain cases, neurons fail to produce long dendrites or spines,
which results in abnormal brain connectivity and developmental disabilities.
The opposite condition also is possible: neurons continue to make dendrites and form
connections with other cells until the neurons are extraordinarily large. The functional
consequences of all the newly formed connections can be devastating. Excitatory synapses
in the wrong location effectively short-circuit a neuron’s function.
Subtle abnormal events also can be devastating, even terminal. Sudden infant death
syndrome (SIDS), the unexplained death while asleep of a seemingly healthy infant less than
1 year old, kills about 2500 babies yearly in the United States alone. Postmortem studies
reveal that SIDS victims are more likely than other babies to have a particular gene variation
that makes the serotonin transporter unusually efficient. Normally, the serotoninergic sys-
tem helps to stimulate a respiratory mechanism that responds to high carbon dioxide levels
in the blood and acts to expel the gas.
In babies who die of SIDS, serotonin is cleared from the synapse more rapidly than normal.
This action makes 5-HT less effective in regulating life-threatening events such as carbon
dioxide buildup during sleep. Babies can breathe excessive levels of carbon dioxide that is
trapped in their bedding, for example, and suffocate.
In addition to the serotonin transporter abnormality, David Paterson and his col-
leagues (2006) found an abnormally low occurrence of 5-HT1A receptors in SIDS victims’
brains. The researchers found that boys have significantly fewer 5-HT1A receptors than
do females, a result consistent with higher SIDS mortality in boys. Hannah Kinney (2009)
speculates that the primary defect is increased numbers of 5-HT cells, possibly arising dur-
ing fetal development and owing to unknown causes, but augmented by adverse prenatal
exposure to alcohol, nicotine, and/or other factors. This defect leads to the changes in
5-HT1A receptors.
A curious consequence of abnormal brain development is that behavioral effects may
emerge only as the brain matures and the maturing regions begin to play a greater role in
behavior. This consequence is true especially of frontal lobe injuries. The frontal lobes con-
tinue to develop into early adulthood (see Figure 8-17), and often not until adolescence do
the effects of frontal lobe abnormalities become noticeable.
Schizophrenia is a disease characterized by its slow development, usually not becoming Section 16-4 describes the schizophrenic
obvious until late adolescence. Clinical Focus 8-5, Schizophrenia on page 278, relates disease brain and Section 5-3 a possible relation to
progress and its possible origin. excessive DA or 5-HT activity in that brain.
278 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
clinical F cus 8-5
Schizophrenia enlarged ventricles. Research findings also suggest that brains affected
by schizophrenia have smaller frontal lobes (or at least a reduction in
When Mrs. T. was 16 years old, she began to experience her first symptom
the number of neurons in the prefrontal cortex) and thinner parahip-
of schizophrenia: a profound feeling that people were staring at her.
These bouts of self-consciousness soon forced her to end her public
pocampal gyri.
piano performances. Her self-consciousness led to withdrawal, then to Joyce Kovelman and Arnold Scheibel (1984) found abnormalities in
fearful delusions that others were speaking about her behind her back, the orientation of hippocampal neurons in people with schizophrenia.
and finally to suspicions that they were plotting to harm her. Rather than the consistently parallel orientation of neurons in this region
At first Mrs. T.’s illness was intermittent, and the return of her characteristic of healthy brains, schizophrenic brains have a more hap-
intelligence, warmth, and ambition between episodes allowed her to hazard organization, as shown in the accompanying drawings.
complete several years of college, to marry, and to rear three children. Evidence is increasing that the abnormalities observed in schizo-
She had to enter a hospital for her illness for the first time at age 28, after phrenic brains are associated with disturbances of brain development.
the birth of her third child, when she began to hallucinate. William Bunney and his colleagues (1997) suggested that at least a
Now, at 45, Mrs. T. is never entirely well. She has seen dinosaurs
subgroup of those with schizophrenia underwent either environmental
on the street and live animals in her refrigerator. While hallucinating,
insults or some type of abnormal gene activity in the fourth to sixth
she speaks and writes in an incoherent, but almost poetic way. At other
times, she is more lucid, but even then the voices she hears sometimes
month of fetal development.
lead her to do dangerous things, such as driving very fast down the These events are thought to result in abnormal cortical development,
highway in the middle of the night, dressed only in a nightgown. . . . particularly in the frontal lobes. Later in adolescence, as the frontal lobes
At other times and without any apparent stimulus, Mrs. T. has bizarre approach maturity, the person begins to have symptoms deriving from
visual hallucinations. For example, she saw cherubs in the grocery this abnormal prenatal development.
store. These experiences leave her preoccupied, confused, and
frightened, unable to perform such everyday tasks as cooking or
playing the piano. (Gershon & Rieder, 1992, p. 127)
It has always been easier to identify schizophrenic behav- Pyramidal cell orientation in the hippocampus
ior than to define schizophrenia. Perhaps the one universally of (A) a healthy brain and (B) a schizophrenic
accepted criterion for its diagnosis is the absence of other neu- brain. Research from J. A. Kovelman and A. B. Scheibel
rological disturbances or affective (mood) disorders that could (1984.) A neurohistologic correlate of schizophrenia.
Hippocampus Biological Psychiatry, 19, p. 1613.
cause a person to lose touch with reality—a definition by default.
Symptoms of schizophrenia vary, suggesting that biological
abnormalities also vary from person to person. Most patients (A) (B)
appear to stay at a fairly stable level after the first few years of
symptoms, with little evidence of a decline in neuropsychologi-
cal functioning. Symptoms come and go, much as for Mrs. T.,
but the severity is relatively constant after the first few episodes.
Numerous studies have investigated the brains of schizo-
phrenia patients, both in MRI and CT scans and in autop-
sies. Although the results vary, most neuroscientists agree
that schizophrenic brains weigh less than normal and have Organized (healthy) pyramidal neurons Disorganized (schizophrenic) pyramidal neurons
Developmental Disability
Impaired cognitive functioning accompanies abnormal brain development. Impairment may
range from mild, allowing an almost normal lifestyle, to severe, requiring constant care. As
summarized in Table 8-3, such developmental disability can result from chronic malnutrition,
Figure 3-22 illustrates trisomy, the genetic abnormalities such as Down syndrome, hormonal abnormalities, brain injury, or neu-
chromosomal abnormality that causes rological disease. Different causes produce different abnormalities in brain organization, but
Down syndrome. the critical similarity across all types of developmental disability is that the brain is not normal.
Dominique Purpura (1974) conducted one of the few systematic investigations of devel-
opmentally disabled children’s brains. Purpura used Golgi stain to examine the neurons
of children who had died of accident or disease unrelated to the nervous system. When he
examined the brains of children with various forms of intellectual disability, he found that
dendrite growth was stunted and the spines very sparse relative to dendrites from children
of typical intelligence, as illustrated in Figure 8-33.
8-5 • How Do Any of Us Develop a Normal Brain? 279
taBLe 8-3 causes of Developmental Disability Typical Developmentally
child disabled child
cause example mechanism example condition
Abnormal embryonic Exposure to a toxin FASD
development
Birth trauma Anoxia (oxygen deprivation) Cerebral palsy
Chronic malnutrition Abnormal brain development Kwashiorkor
Drugs (e.g., valproate) Neural tube defects Spina bifida
ASD
Environmental abnormality Sensory deprivation Children in Romanian
orphanages
Genetic abnormality Error of metabolism Phenylketonuria
Chromosomal abnormality Down syndrome
Prenatal disease Infection Rubella (German measles)
Retardation
Figure 8-33 Neuronal Contrast
Representative dendritic branches from
The simpler neuronal structure probably indicates a marked reduction in the number cortical neurons in a child of typical
intelligence (left) and a developmentally
of brain connections, which presumably caused the developmental disability. Variation in
disabled child (right), whose neurons are
both the nature and the extent of neuronal abnormality in different children would lead to thinner and have far fewer spines. Information
different behavioral syndromes. from D. P. Purpura (1974). Dendritic spine “dysgenesis”
and mental retardation. Science, 186, p. 1127.
8-4 review
Brain Development and the Environment
Before you continue, check your understanding.
1. The idea that specific molecules in different cells in various midbrain regions give each
cell a distinctive chemical identity is known as the .
2. Subnormal visual stimulation to one eye during early development can lead to a loss of
acuity, known as .
3. The hormone masculinizes the brain during development.
4. The brain’s sensitivity to experience is highest during .
5. Why do so many mental disorders appear during adolescence?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
8-5 How Do Any of Us Develop
a Normal Brain?
When we consider the brain’s complexity, the less-than-precise process of brain development,
and the myriad factors—from SES to gut bacteria—that can influence development, we are
left to marvel at how so many of us end up with brains that pass for normal. We all must have
had neurons that migrated to wrong locations, made incorrect connections, were exposed to
viruses or other harmful substances. If the brain were as fragile as it might seem, to end up
with a normal brain would be almost impossible.
Apparently, animals have evolved a substantial capacity to repair minor abnormalities in
brain development. Most people have developed in the range that we call normal because the
human brain’s plasticity and regenerative powers overcome minor developmental deviations.
280 Chapter 8 • HOW DOES THE NERVOUS SYSTEM DEVELOP AND ADAPT?
By initially overproducing neurons and synapses, the brain gains the capacity to correct
errors that might have arisen accidentally.
These same plastic properties later allow us to cope with the ravages of aging. Neurons are
dying throughout our lifetime. By age 60, investigators ought to see significant effects from
all this cell loss, especially considering the cumulative results of exposure to environmental
toxins, drugs, traumatic brain injuries, and other neural insults. But this is not what happens.
Although some teenagers may not believe it, relatively few 60-year-olds are demented.
By most criteria, the 60-year-old who has been intellectually active throughout adulthood
is likely to be much wiser than the 18-year-old whose brain has lost relatively few neurons.
A 60-year-old chess player will have a record of many more chess matches from which to draw
game strategies than does an 18-year-old, for example.
Clearly, some mechanism must enable us to compensate for loss and minor injury
to our brain cells. This capacity for plasticity and change, for learning and adapting, is
We return to learning, memory, and arguably the most important characteristic of the human brain during development and
neuroplasticity in Chapter 14. throughout life.
Summary
8-1 Three Perspectives on Brain Development cognitive development. Each stage can be identified by specific
Nervous system development entails more than the unfolding of a behavioral tests.
genetic blueprint. Development is a complex dance of genetic and Behaviors emerge as the neural systems that produce them
environmental events that interact to sculpt the brain to fit within develop. Matching the median timetables of neurodevelopment with
a particular cultural and environmental context. We can approach observed behavior infers the hierarchical relation between brain
this dance from three perspectives: (1) correlating emerging brain structure and brain function. Motor behaviors emerge in synchrony
structures with emerging behaviors, (2) correlating new behaviors with maturating motor circuits in the cerebral cortex, basal ganglia,
with neural maturation, and (3) identifying influences on brain and and cerebellum, as well as in the connections from these areas to
behavior. the spinal cord. Similar correlations between emerging behaviors
and neuronal development accompany the maturation of cognitive
8-2 Neurobiology of Development behavior as neural circuits in the frontal and temporal lobes mature
Human brain maturation is a long process, lasting as late as age 30. in early adulthood.
Neurons, the units of brain function, develop a phenotype, migrate,
and, as their processes elaborate, establish connections with other
8-4 Brain Development and the Environment
The brain is most plastic during its development, and neuronal
neurons even before birth. The developing brain produces many
structures and their connections can be molded by various factors
more neurons and connections than it needs and then prunes back
throughout development. The brain’s sensitivity to factors such as
in toddlerhood and again in adolescence and early adulthood to a
external events, quality of environment, tactile stimulation, drugs,
stable level maintained by some neurogenesis throughout the life-
gonadal hormones, stress, and injury varies over time. At critical
span. Experiences throughout development can trigger epigenetic
periods in the course of development, beginning prenatally, different
mechanisms, such as gene methylation, that alter gene expression.
brain regions are particularly sensitive to different events.
Brain perturbations in the course of development from, say,
8-3 Using Emerging Behaviors to Infer Neural anoxia, trauma, or toxins can alter brain development significantly;
Maturation can result in severe behavioral abnormalities, including intellectual
Throughout the world, across the cultural spectrum, from newborn disability; and may be related to such disorders as ASD or SIDS. Other
to adult, we all develop through similar behavioral stages. As behavioral disorders emerge in adolescence, a time of prolonged
infants develop physically, motor behaviors emerge in a predictable frontal lobe change.
sequence from gross, poorly directed movements toward objects to
controlled pincer grasps to pick up objects as small as pencils by 8-5 How Do Any of Us Develop a Normal Brain?
about 11 months. Cognitive behaviors also develop through stages of The brain has a substantial capacity to repair or correct minor
logic and problem solving. Beginning with Jean Piaget, researchers abnormalities, allowing most people to develop normal behavioral
have identified and characterized four or more distinct stages of repertoires and to maintain brain function throughout life.
Key Terms 281
Key termS
amblyopia, p. 269 critical period, p. 269 imprinting, p. 271 neurotrophic factor, p. 253
androgen, p. 273 dorsolateral prefrontal cortex masculinization, p. 273 progenitor cell (precursor cell),
anencephaly, p. 277 (DLPFC), p. 259 netrin, p. 256 p. 251
apoptosis, p. 256 estrogens, p. 273 neural Darwinism, p. 256 radial glial cell, p. 253
autism spectrum disorder filopod (pl. filopodia), neural plate, p. 249 subventricular zone, p. 251
(ASD), p. 255 p. 256 sudden infant death syndrome
neural stem cell, p. 251
cell adhesion molecule (CAM), glioblast, p. 251 (SIDS), p. 277
neural tube, p. 249
p. 256 growth cone, p. 256 testosterone, p. 273
neuroblast, p. 251
chemoaffinity hypothesis, p. 269 growth spurt, p. 263 tropic molecule, p. 256
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
this page left intentionally blank
ch a p te r
9 How Do We Sense, CliniCal FoCus 9-1 MigraineS and a CaSe of BlindSight
9-1 nature oF sensation and PerCePtion
Perceive, and See the SenSory reCeptorS
neural relayS
World? SenSory Coding and repreSentation
perCeption
9-2 the Visual system’s FunCtional anatomy
StruCture of the retina
THE BASICS ViSiBle light and the StruCture of the eye
photoreCeptorS
CliniCal FoCus 9-2 ViSual illuMinanCe
typeS of retinal neuronS
ViSual pathwayS
dorSal and Ventral ViSual StreaMS
9-3 loCation in the Visual World
Coding loCation in the retina
loCation in the lateral geniCulate nuCleuS and region V1
ViSual CorpuS CalloSuM
9-4 neuronal aCtiVity
Seeing Shape
Seeing Color
researCh FoCus 9-3 Color-defiCient ViSion
neuronal aCtiVity in the dorSal StreaM
9-5 the Visual Brain in aCtion
injury to the ViSual pathway leading to the Cortex
injury to the What pathway
CliniCal FoCus 9-4 CarBon Monoxide poiSoning
injury to the hoW pathway
Katherine Streeter
283
284 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
CliniCal F cus 9-1
Migraines and a Case of Blindsight
D. B.’s recurring headaches began at about age 14. A visual aura warned D. B.’s attacks continued at intervals of about 6 weeks for 10 years.
of a headache’s approach: an oval area of flashing (scintillating) light After one attack, he was left with a small blind spot, or scotoma, illustrated
appeared just left of center in his field of vision. Over the next few min- in the accompanying photographs. When D. B. was 26 years old, a neurolo-
utes, the oval enlarged. After about 15 minutes, the flashing light van- gist found that a collection of abnormal blood vessels at the back of his right
ished, and D. B. was blind in the region of the oval. occipital lobe was causing the migraine attacks—a most unusual cause.
D. B. described the oval as an opaque white area surrounded by a By the time he was 30, the migraines had begun to interfere with
rim of color. A headache on the right side of his head followed and could his family life, social life, and job. No drug treatment was effective,
persist for as long as 48 hours. D. B. usually fell asleep before that much so D. B. had the malformed blood vessels surgically removed. The
time elapsed. When he awakened, the headache was gone and his vision operation relieved his pain and generally improved his life, but a part
was normal again. of his right occipital lobe, deprived of blood, had died. D. B. was blind
D. B. was subject to severe migraine, a recurrent headache usu- in the left half of his visual field: as he looks at the world through
ally on one side of the head. Migraines vary in severity, frequency, and either eye, he is unable to see anything left of the midline.
duration and are often accompanied by nausea and vomiting. Migraine is Lawrence Weizkrantz (1986) made a remarkable discovery about
perhaps the most common of all neurological disorders, affecting some D. B.’s blindness. D. B. could not identify objects in his blind area but
5 to 20 percent of the population at some time in their life. could very accurately tell whether a light had blinked on there and even
Auras may be auditory or tactile as well as visual and may result where the light was. Apparently, D. B.’s brain knew when a light blinked
in an inability to move or to talk. After an aura passes, most have a and where it appeared. This phenomenon is called blindsight. D. B.’s
severe headache caused by a dilation of cerebral blood vessels. The brain knew more than he was aware of consciously. D. B.’s case pro-
headache is usually limited to one side of the head, just as the aura is vides an excellent example of the parallel streams of visual processing
on one side of the visual field. Left untreated, migraines may last for in the cortex. His system for processing objects was impaired, but his
hours or even days. system for locating objects in space was not.
tyler olson/Shutterstock
X X X X X
X = Fixation point As a typical migraine scotoma develops, a person looking at the small white × in the photograph
at the far left would first see a small patch of lines. This striped area continues growing outward,
leaving an opaque area (scotoma) where the stripes were, almost completely blocking the visual
field within 15 to 20 minutes. Normal vision returns shortly thereafter.
as you look at the photograph in Clinical Focus 9-1, Migraines and a Case of Blindsight,
you see three people—two women and a man—who appear to be walking and talking on a
warm summer day. Trees appear in the background, clearly behind the people. It is tempting
to believe that this visual image is transferred whole to the brain, where we see it.
But how could the nervous system do this? There is no viewing screen in the brain.
Instead, the nervous system must construct the image from bits of information, such as
shape and color. Then the brain must put it all together to form what we perceive as a com-
plete image. The neural reconstruction is not a passive image such as a TV screen projects.
Rather, the brain continuously employs memories, both to interpret moment-to-moment
sensory information and to predict the immediate future.
D. B.’s case demonstrates that we are consciously aware of only part of the visual infor-
mation our brain is processing. This selective awareness is an important working principle
behind human sensation and perception. Weizkrantz, a world-renowned visual neuroscien-
tist at Oxford University, detected it in the visual system only because of D. B.’s injury.
9-1 • Nature of Sensation and Perception 285
We are in fact unaware of much of the sensory processing that takes place in the neural Vision is this chapter’s main topic; hearing
pathways for vision, hearing, touch, taste, and smell. All our senses convert energy into is Chapter 10’s. Section 11-4 covers body
neural activity that has meaning for us. We begin this chapter with a general summary of senses and balance. Section 12-2 explains
sensation and perception that explores how this energy conversion takes place. smell and taste.
The ability to lose conscious visual perception while retaining unconscious vision, as
D. B. did, leads us to the chapter’s central question: How do we see the world? We begin
by overviewing visual system anatomy. Next we consider the connections between the
eyes and the sections of the brain that process visual information.
Turning to the perceptual experience of sight, we focus on how neurons respond to visual
input and enable the brain to perceive features such as color, shape, and movement. At the
chapter’s end, we explore vision’s culmination: understanding what we see. How do we infuse
light energy with meaning to grasp the content of written words or to see the beauty in a
painting? Read on.
9-1 Nature of Sensation
and Perception
We may believe that we see, hear, touch, smell, and taste real things in a real world. In fact,
the only input our brain receives from the “real” world is a series of action potentials passed
along the neurons that form our various sensory pathways. Although we experience visual and
body sensations as fundamentally different from one another, the nerve impulses coursing
in the neurons of these two sensory systems are quite similar, as are the neurons themselves.
Neuroscientists understand how nerves can turn energy, such as light waves, into nerve
impulses. They also know the pathways those nerve impulses take to reach the brain. But
they do not know how we end up perceiving one set of nerve impulses as what the world
looks like and another set as what makes us move.
How much of what you know comes through your senses? Taken at face value, this ques-
tion seems reasonable. At the same time, we realize that our senses can deceive us—that
two people can look at the same optical illusion and see very different images, that a person
dreaming typically does not think that the dream images are real, that you often do not think
that a picture of you looks like you. Many scientists think that much of what we know comes
to us through our senses, but they also think that our brains actively transform sensory infor-
mation into forms that help us to adapt and are thus behaviorally useful.
Our sensory systems appear to be extremely diverse: vision, audition, touch, taste, and
olfaction appear to have little in common at first glance. Although our perceptions and
behaviors in relation to them differ, each sensory system is organized on a similar hierarchi-
cal plan. We now consider the features common to the sensory systems—receptors, neural
relays between receptor and neocortex, sensory coding and representation, and perception.
Sensory Receptors
Sensory receptor neurons are specialized to transduce (convert) sensory energy—light, for
example—into neural activity. If we put flour into a sieve and shake it, the more finely milled
particles fall through the holes, whereas the coarser particles and lumps do not. Sensory
receptors are designed to respond only to a narrow band of energy—analogous to particles
Spl/Science Source
of certain sizes—within each modality’s energy spectrum. Each sensory system’s receptors
are specialized to filter a different form of energy:
• For vision, the photoreceptors in the retina convert light energy into chemical energy,
which is in turn converted into action potentials.
Vision begins in the photoreceptor cells,
• In the auditory system, air pressure waves are first converted into mechanical energy, which the rods and cones shown here. Section
activates the auditory receptors that produce action potentials in auditory receptor neurons. 9-2 details how they work.
286 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
• In the somatosensory system, mechanical energy activates receptors sensitive to touch,
receptive field Sensory region that
pressure, or pain. These somatosensory receptors in turn generate action potentials in
stimulates a receptor cell or neuron.
somatosensory receptor neurons.
optic flow Streaming of visual stimuli that
accompanies an observer’s movement • For taste and olfaction, various chemical molecules in the air or in food fit themselves
through space. into receptors of various shapes to activate action potentials in the respective
receptor neurons.
auditory flow Change heard as a person
and a source of sound move relative to one Were our visual receptors somewhat different, we would be able to see in the ultraviolet
another. as well as the visible parts of the electromagnetic spectrum, as honeybees and butterflies
can. Receptors in the human ear respond to a wide range of sound waves, but elephants
and bats can hear and produce sounds far below and above, respectively, the range humans
can hear. In fact, in comparison with those of other animals, human sensory abilities are
about average.
Even our pet dogs have “superhuman” powers: they can detect trace odors; hear low-range
An animal’s perception of the world depends sounds, as elephants do; and see in the dark. We can hold up only our superior color vision.
on its nervous system’s complexity and Thus, for each species and its individual members, sensory systems filter the inputs to pro-
organization. duce an idiosyncratic representation of reality.
Receptive Fields
Every sensory receptor organ and cell has a receptive field, a specific part of the world to
which it responds. If you fix your eyes on a point directly in front of you, for example, what
you see of the world is the scope of your eyes’ receptive field. If you close one eye, the visual
world shrinks. What the remaining eye sees is the receptive field for that eye.
Each photoreceptor cell in the eye points in a slightly different direction and so has a unique
receptive field. You can grasp the conceptual utility of the receptive field by considering that
the brain uses information from each sensory receptor’s receptive field not only to identify
sensory information but also to contrast the information each receptor field is providing.
Receptive fields not only sample sensory information but also help locate events in space.
Because adjacent receptive fields may overlap, the contrast between their responses to events
help us localize sensations. This spatial dimension of sensory information produces cortical
patterns and maps that form each person’s sensory reality.
Our sensory system is organized to tell us both what is happening in the world around
us and what in the world we are doing ourselves. When you move, you change the per-
ceived properties of objects, and you sense things that have little to do with the external
world. When we run, visual stimuli appear to stream by us, a stimulus configuration called
optic flow. When you move past a sound source, you hear an auditory flow, a gradual shift in
sound intensity that takes place because of your changing location. Optic flow and auditory
tyler olson/Shutterstock
flow are useful for telling us how fast we are going, whether we are going in a straight line or
up or down, and whether we or an object in the world is moving.
Try this experiment. Slowly move your hand back and forth before your eyes and gradu-
ally increase its speed. Eventually, your hand will get a little blurry, because your eye move-
ments are not quick enough to follow its movement. Now keep your hand still and move your
Receptive Fields In vision, each head back and forth. The image of your hand remains clear. When receptors in the inner ear
photoreceptor neuron has a unique inform your visual system that your head is moving, the visual system compensates for the
receptive field that partially overlaps
head movements, and you observe the hand as a stationary image.
adjacent fields, diagrammed for another
class of retinal neurons in Figure 9-27.
Receptor Density and Sensitivity
Receptor density is particularly important for determining a sensory system’s sensitivity. For
example, tactile receptors on the fingers are numerous compared with those on the arm. The
difference explains why fingers can discriminate touch remarkably well and the arm cannot.
Our sensory systems use different receptors to enhance sensitivity under different condi-
tions. For example, the visual system uses different sets of receptors to respond to light and
color. Color photoreceptors are small and densely packed to make sensitive color discriminations
9-1 • Nature of Sensation and Perception 287
in bright light. Receptors for black–white vision are larger and more scattered, but their sensitiv-
ity to light—say, a lighted match at a distance of 2 miles on a dark night—is truly remarkable.
Differences in density of sensory receptors determine many animals’ special abilities—
dogs’ excellent olfactory ability and the excellent tactile ability of raccoons’ digits. Variations
in receptor density in the human auditory receptor organ may explain such abilities as per-
fect pitch, displayed by some musicians.
Neural Relays
Craig lovell/eagle Visions photography/alamy
Inasmuch as receptors are common to each sensory system, all receptors connect to the cor-
tex through a sequence of three or four intervening neurons. The visual and somatosensory
systems have three relays, and the auditory system has four. Information can be modified at
various stages in the relay, allowing the sensory system to mediate different responses. Once
again, this is very different from the sensory images on a TV screen or from an audio system:
information is being modified repeatedly as the brain constructs the image or sound.
Neural relays also allow sensory systems to interact. There is no straight-through point-
to-point correspondence between one neural relay and the next; rather, each successive
relay recodes the activity. Sensory neural relays are central to the hierarchy of motor
Section 10-4 explains how we perceive
responses in the brain. music.
Some of the three or four relays in each sensory system are in the spinal cord; others, in
the brainstem; and still others, in the neocortex. At each level, the relay allows a sensory
system to produce relevant actions that define the hierarchy of our motor behavior. For Recall the principle from Section 2-6: brain
example, the first relay for pain receptors in the spinal cord is related to reflexes that produce systems are organized hierarchically and in
withdrawal of a body part from a painful stimulus. Thus, even after section of the spinal cord parallel.
from the brain, a limb still withdraws from a painful stimulus.
A dramatic effect of sensory interaction is the visual modification of sound. If a person
hears a speech syllable such as ba while observing someone who is articulating ga, the listener
hears not the actual sound ba but a hybrid sound, da. The viewed lip movements modify the
listener’s auditory perception.
This interaction effect is potent: it highlights the fact that a speaker’s facial gestures influ-
ence our perception of speech sounds. As Roy Hamilton and his coworkers (2006) described,
synchrony of gestures and sounds is an important aspect of language acquisition. The dif-
ficulty of learning a foreign language can relate to the difficulty of blending a speaker’s
articulation movements with the sounds the speaker produces.
Sensory Coding and Representation
After it has been transduced, all information from all sensory systems is encoded by action
potentials that travel along peripheral nerves in the somatic nervous system until they enter
the spinal cord or brain. From there the action potentials travel on nerve tracts within the
central nervous system. Every bundle carries the same kind of signal. How do action poten-
tials encode different sensations? (How does vision differ from touch?) How do they encode
the features of particular sensations? (How does purple differ from blue?)
Parts of these questions seem easy to answer; others pose a fundamental challenge to
neuroscience. The presence of a stimulus can be encoded by an increase or decrease in a
neuron’s discharge rate, and the amount of increase or decrease can encode stimulus inten-
sity. As detailed in Section 9-4, qualitative visual changes, such as from red to green, can be Recall the principle from Section 2-6: the
encoded by activity in different neurons or even by different levels of discharge in the same nervous system works by juxtaposing
neuron. (For example, more activity might signify redder and less activity, greener.) excitation and inhibition.
What is less clear is how we perceive such sensations as touch, sound, and smell as dif-
ferent from one another. Part of the explanation is that each sensation is processed in its
own distinct cortical region. Also, we learn through experience to distinguish them. Third,
each sensory system has a preferential link with certain reflexive movements, constituting
a separate wiring that helps keep each system distinct at all levels of neural organization.
288 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
For example, pain stimuli produce withdrawal responses, and fine-touch and pressure
Sensory homunculus (plaster), english School, (20th century)/natural
stimuli produce approach responses.
The distinctions among the sensory systems, however, are not always clear: some people
hear in color or identify smells by how the smells sound to them. This mixing of the senses
history Museum, london, uK/the Bridgeman art library
is called synesthesia. Anyone who has shivered when hearing a piece of music or at the noise
chalk or fingernails can make on a blackboard has felt sound.
In most mammals, the neocortex represents the sensory field of each modality—vision,
hearing, touch, smell, or taste—as a spatially organized neural representation of the external
world. This topographic map is a neural–spatial representation of the body or of the areas
of the sensory world perceived by a sensory organ. All mammals have at least one primary
cortical area for each sensory system. Additional areas are usually referred to as secondary,
because most of the information that reaches these areas is relayed through the primary
area. Each additional representation is probably dedicated to encoding one specific aspect
of the sensory modality. For vision, different additional representational areas may take part
This curious figure reflects the topographic
in perceiving color, movement, and form.
map in the sensorimotor cortex.
Disproportionately large areas control
body parts we use to make the most- Perception
skilled movements. See Sections 11-2 and
Sensation is far more than the simple registration of physical stimuli from the environment
11-6. Section 15-6 details synesthesia.
by the sensory organs. Compared with the richness of actual sensation, our description of
sensory neuroanatomy and function is bound to seem sterile. Part of the reason for the dis-
parity is that our sensory impressions are affected by the context in which they take place, by
our emotional state, and by our past. All these factors contribute to perception, the subjec-
tive experience of sensation—how we interpret what we sense. Perception is more interesting
Figure 9-1 Perceptual Illusions to neuropsychologists than is sensation.
(A) Edgar Rubin’s ambiguous reversible Clear proof that perception is more than sensation lies in the fact that different people
image can be perceived as a vase or transform the same sensory stimulation into totally different perceptions. The classic dem-
as two faces. (B) Likewise ambiguous onstration is an ambiguous image such as the well-known Rubin’s vase shown in Figure 9-1A.
in the photo, each cheetah’s head can
This image may be perceived either as a vase or as two faces. If you fix your eyes on the
be perceived as belonging to either
cheetah’s body. center of the picture, the two perceptions will alternate, even though the sensory stimula-
tion remains constant.
(A) Similarly, the photograph of two cheetahs in Figure 9-1B is ambiguous. Which head goes
with which cheetah? As with the Rubin’s vase, the two perceptions may alternate. Such
ambiguous images and illusions demonstrate the workings of complex perceptual phenom-
ena and enlighten our insight into our cognitive processes.
9-1 review
Nature of Sensation and Perception
Before you continue, check your understanding.
(B)
1. are energy filters that transduce incoming physical energy into
neural activity.
2. fields locate sensory events. Receptor determines
sensitivity to sensory stimulation.
3. We distinguish one sensory modality from another by its .
4. Sensation registers physical stimuli from the environment by the sensory organs.
Perception is the .
5. How is the anatomical organization similar for each sense?
Answers appear at the back of the book.
© gerry lemmo
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
9-2 • The Visual System’s Functional Anatomy 289
9-2 The Visual System’s topographic map Spatially organized neural
representation of the external world.
Functional Anatomy sensation Registration by the sensory
organs of physical stimuli from the
Our primary sensory experience is visual. Far more of the human brain is dedicated to
environment.
vision than to any other sense. Understanding the visual system’s organization, then, is key
to understanding human brain function. To build this understanding, we begin by following perception Subjective interpretation of
the routes visual information takes into and within the brain. This exercise is a bit like travel- sensations by the brain.
ing a road to discover where it goes. As you trace the route, keep in mind the photograph in retina Light-sensitive surface at the
Focus 9-1 (page 284) and what the different levels of the visual system are doing to capture back of the eye consisting of neurons and
that image in the brain. photoreceptor cells.
photoreceptor Specialized retinal neuron
that transduces light into neural activity.
Structure of the Retina
Light energy travels from the outside world through the pupil and into the eye, where it
strikes a light-sensitive surface, the retina, at the back of the eye (Figure 9-2). From this Virtually all retinal neurons are insensitive
stimulation of photoreceptor cells on the retina, we begin to construct a visual world. If you to light so are unaffected by light passing
are familiar with the properties of the electromagnetic spectrum and with the structure of through them.
the eye, read on. To refresh your knowledge of these topics, read The Basics: Visible Light
and the Structure of the Eye on pages 290–291 before you continue.
Figure 9-2 includes a photograph of the retina, which is composed of photoreceptors
beneath a layer of neurons connected to them. The neurons lie in front of the photorecep- Figure 9-2 Central Focus This cross
section through the retina (A) shows the
tor cells, but they do not prevent incoming light from being absorbed by those receptors,
depression at the fovea—also shown in the
because the neurons are transparent and the photoreceptors are extremely sensitive to light. scanning electron micrograph (B)—where
In addition, special glial cells in the retina called Müller cells span from the retina’s inner photoreceptors are packed most densely
membrane at the front to the photoreceptors at the back of the retina and act as optical and where our vision is clearest.
fibers, channeling light to the buried photoreceptors.
Together, the photoreceptor cells and the retinal neurons perform some amazing func-
tions. They translate light into action potentials, discriminate wavelengths so that we can
distinguish colors, and work in a range of light intensities from bright to dim. These cells
afford visual precision sufficient for us to see a human hair lying on the page of this book
from a distance of 18 inches.
As in a camera, the image of objects projected onto the retina is upside down and back-
ward. This flip-flopped orientation poses no problem for the brain. Remember, the brain is
constructing the outside world, so it does not really care how
the image is oriented initially. In fact, the brain can make adjust- Fovea Light
ments regardless of the orientation of the images that it receives.
Rod-free area
If for several days you were to wear glasses that invert vis- (cones are most Fovea
ual images, the world would first appear upside down but then Optic dense in this area)
would suddenly appear right side up again because your brain nerve
would correct the distortion (Held, 1968). Curiously, when you Blind spot
(optic disc)
removed the glasses, the world would temporarily seem upside
down once more, because your brain at first would be unaware
that you had tricked it again. Eventually, though, your brain
would solve this puzzle too, and the world would flip back to
the correct orientation.
Fovea
Try this experiment. Focus on the print at the left edge of this
page. The words will be clearly legible. Now, while holding
Spl/Science Source
your eyes still, try to read the words on the right side of the Ganglion Bipolar Cone Rod
page. It will be very difficult, even impossible, even though you cell cell
can see that words are there. Retina
290 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
THE BASICS
Visible Light and the Structure of the Eye
The brain’s visual system analyzes visible light—the part of the electro- retina in the eye or the light-sensitive material in the camera. If the
magnetic (EM) spectrum that the human eye evolved to capture and focus. focal point of the light falls slightly in front of the receptor surface or
slightly behind it, a refractive error causes objects to appear blurry.
Light: The Stimulus for Vision Refractive errors in the eye are of two basic types, diagrammed in
Light can enter the eye directly from a source that produces it—a lamp, Refractive Errors.
for example, or the sun—or indirectly after reflecting from a surface— Myopia (nearsightedness) afflicts about 50 percent of young people in
the pages of a book, for example, or the surface of water. As illustrated the developed world. Hyperopia (farsightedness) is a less common refrac-
in Electromagnetic Spectrum, not all light waves are the same length, tive error, but as people age, the lens loses its elasticity and consequently
and only a sliver of the EM spectrum is visible to us. If our photorecep- becomes unable to refract light from nearby objects correctly. This form
tors could detect light in the shorter ultraviolet or longer infrared wave- of hyperopia, called presbyopia (old-sightedness), is so common that you
lengths, we would see additional colors. rarely find people older than 50 who do not need glasses to see up close,
especially for reading.
Structure of the Eye It is also common to see young children wearing corrective lenses. The
The range of light visible to humans is constrained not by the proper- incidence of myopia in the United States has doubled in the past 40 years
ties of light waves but rather by the properties of our visual receptors. to about 42 percent. It is even higher in Northern Europe (50 percent)
How do photoreceptor cells in the retina absorb light energy and initiate and Asia (50 percent to 80 percent). Two factors probably account for the
the processes leading to vision? How the Eye Works illustrates the eye’s increase.
structure and shows how its design captures and focuses light. First, more young people are attending school longer and thus are
doing more close work, especially reading. Close work strains the eye
Optical Errors of Refraction muscles. Second, people are spending less and less time outdoors in
A web of muscles adjusts the shape of the eye’s lens to bend light to greater bright light. Bright light makes the pupil contract, which improves vi-
or lesser degrees, which allows near or far images to be focused on the sual depth of field: your eyes focus better. Children should probably
retina. When images are not properly focused, we need corrective lenses. spend at least 2 hours each day outside in bright light. Consider that
The eye, like a camera, works correctly only when sufficient light myopia is less common in countries such as Australia (17 percent),
passes through the lens and is focused on the receptor surface—the where bright light is plentiful.
The electromagnetic energy visible to humans varies in wavelength from about 400 to 700 nanometers.
We perceive the shortest visible wavelengths as deep purple. As wavelength increases, perceived color
morphs from violet to blue to green to yellow, orange, and red: the colors of the rainbow.
400 500 600 700
Visible light
Shorter waves Longer waves
Gamma rays X rays Ultraviolet Infrared Microwaves Radio waves
10–4 10–3 10–2 10–1 1 10 102 103 104 105 106 107 108 109 1010 1011 1012 1013 1014
Wavelength (nm)
Butterflies and honeybees Electromagnetic wavelength is Night-vision devices make
detect light in the ultraviolet measured in nanometers, use of infrared light waves.
range and so have a broader abbreviated nm. One
range of color perception nanometer equals one-
than we do. billionth of a meter.
Electromagnetic Spectrum
9-2 • The Visual System’s Functional Anatomy 291
How the Eye Works A photograph of the retina’s surface shows
blood vessels emerging from the blind spot
and their near absence around the fovea.
Fovea
Blind spot
The sclera forms the eyeball, the white In the retina, light energy initiates
ralph eagle/Science Source
of the eye. The cornea is the eye’s clear neural activity. At the center of the
outer covering. The colored iris opens retina, the fovea is the region of
and closes to allow more or less light sharpest vision and has the densest
through a hole, the pupil. The lens distribution of photoreceptors
focuses light. specialized for color.
Retina Retina
Fovea
Chetty thomas/
Sclera
Shutterstock
Optic disc The optic disc, where blood vessels
Cornea (blind spot) enter the eye and the axons that form
Iris
Lens the optic nerve leave the eye, has no
Pupil Blood vessels receptors and thus forms a blind spot.
Optic nerve The optic nerve conveys information
from the eye to the brain.
The cornea and lens of
the eye, like the lens of a
camera, focus light rays As light enters the eye, it is bent first by the cornea,
to project a backward, travels through the pupil, and is then bent again
inverted image on a by the lens. The curvature of the cornea is fixed,
light-receptive surface. whereas small muscles adjust the curvature of the
lens to focus nearby or far away.
Lenses
Normal
In normal vision, the lens focuses incoming light directly on the retina.
Retina
Myopia
People with myopia cannot bring distant objects into clear focus
because the focal point of light falls short of the retina. Most
commonly caused by the normally round eyeball being elongated,
nearsightedness can also be caused by excessive curvature of the front
of the cornea.
Hyperopia
People with hyperopia cannot focus on nearby objects because the
focal point of light falls beyond the retina. Whereas the myopic
eyeball may be too long, the hyperoptic eyeball may be too short.
Farsightedness may also be due to the fact that the lens is too flat to
refract light adequately.
Refractive Errors
292 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
Y
The lesson is that our vision is better in the center of the visual field
than at the margins, or periphery. Letters at the periphery must be much
larger than those in the center for us to see them as well. Figure 9-3
shows how much larger. The difference is due partly to the fact that
E S
M
photoreceptors are more densely packed at the center of the retina, in a
D
region known as the fovea. Figure 9-2 shows that the retinal surface is
T depressed at the fovea. This depression is formed because many optic
nerve fibers skirt the fovea to facilitate light access to its receptors.
C E
J Blind Spot
H
Z W
Now try another experiment. Stand with your head over a tabletop and
Q B G
hold a pencil in your hand. Close one eye. Stare at the edge of the table-
I F
top nearest you. Now hold the pencil in a horizontal position and move
R X it along the edge of the table, with the eraser on the table. Beginning at
A U
L P
a point approximately below your nose, move the pencil slowly along the
table in the direction of the open eye.
N When you have moved the pencil about 6 inches, the eraser will vanish.
V O
You have found your blind spot, a small area of the retina also known as
the optic disc. This is the area where blood vessels enter and exit the eye and
K
where fibers leading from retinal neurons form the optic nerve, which goes
to the brain. There are therefore no photoreceptors in this part of the ret-
ina. You can use Figure 9-4 to demonstrate the blind spot in another way.
Fortunately, your visual system solves the blind spot problem: your
Figure 9-3 Acuity Across the Visual optic disc is in a different location in each eye. The optic disc is lateral to the fovea in each
Field Focus on the star in the middle eye, which means that it is left of the fovea in the left eye and right of the fovea in the right
of the chart to demonstrate the relative
eye. Because the two eyes’ visual fields overlap, the right eye can see the left eye’s blind spot
sizes of letters legible in the central field of
vision compared with the peripheral field. and vice versa.
Using both eyes together, then, you can see the whole visual world. For people blind in
one eye, the sightless eye cannot compensate for the blind spot in the functioning eye. Still,
the visual system compensates for the blind spot in several
other ways, and so these people have no sense of a hole in
their field of vision.
The blind spot is of particular importance in neurology.
It allows neurologists to indirectly view the condition of the
optic nerve while providing a window on events in the brain.
If intracranial pressure increases, as occurs with a tumor
or brain abscess (an infection), the optic disc swells, leading
to papilledema (swollen disc). The swelling occurs in part
because, like all neural tissue, the optic nerve is surrounded
by cerebrospinal fluid. Pressure inside the cranium can dis-
place CSF around the optic nerve, causing swelling at the
optic disc.
Another cause of papilledema is inflammation of the
optic nerve itself, a condition known as optic neuritis. What-
Figure 9-4 Find Your Blind Spot Hold ever the cause, a person with a swollen optic disc usually loses vision owing to pressure on the
this book 30 centimeters (about 12 inches) optic nerve. If the swelling is due to optic neuritis, probably the most common neurological
away from your face. Shut your left eye visual disorder, the prognosis for recovery is good.
and look at the cross with your right eye.
Slowly bring the page toward you until the
red spot in the center of the yellow disc Photoreceptors
disappears and the entire disc appears
The retina’s photoreceptor cells convert light energy first into chemical energy and then into
yellow. The red spot is now in your blind
spot. Your brain replaces the area with the neural activity. Light striking a photoreceptor triggers a series of chemical reactions that lead
surrounding yellow to fill in the image. Turn to a change in membrane potential (electrical charge) that in turn leads to a change in the
the book upside down to test your left eye. release of neurotransmitter onto nearby neurons.
9-2 • The Visual System’s Functional Anatomy 293
Cones are responsive to bright light.
Fovea They are responsible for color vision
and our ability to see fine detail.
Cone
Light
Synaptic Inner Outer
terminal segment segment
Rod
Spl/Science Source
Retina
Rods are more numerous than cones
and are more sensitive to dim light.
They are mainly used for night vision.
Figure 9-5 Photoreceptor Cells Rods and cones are tubelike structures, as the
scanning electron micrograph at right shows. They differ, especially in the outer segment
that contains the light-absorbing visual pigment. Rods are especially sensitive to broad-
spectrum luminance; and cones, to particular wavelengths of light.
Rods and cones, the two types of photoreceptors shown in Figure 9-5, differ in many ways.
fovea Central region of the retina specialized
They are structurally different. Rods are longer than cones and cylindrical at one end, whereas
for high visual acuity; its receptive fields are at
cones have a tapered end. Rods are more numerous than cones; are sensitive to low levels of
the center of the eye’s visual field.
brightness (luminance), especially in dim light; and function mainly for night vision (see Clinical
blind spot Retinal region where axons
Focus 9-2, Visual Illuminance). Cones do not respond to dim light, but they are highly responsive
forming the optic nerve leave the eye and
to bright light. Cones mediate both color vision and our ability to see fine detail (visual acuity).
blood vessels enter and leave; has no
Rods and cones are unevenly distributed over the retina. The fovea has only cones, but
photoreceptors and is thus said to be blind.
their density drops dramatically beyond the fovea. For this reason, our vision is not so sharp
rod Photoreceptor specialized for functioning
at the edges of the visual field, as demonstrated in Figure 9-3.
at low light levels.
A final difference between rods and cones is in their light-absorbing pigments. All rods
have the same pigment. Each cone has one of three pigments. These four pigments, one in cone Photoreceptor specialized for color and
the rods and three in the cones, form the basis for our vision. high visual acuity.
As shown on the spectrum in Figure 9-6, the three cone pigments absorb light across a
range of visible frequencies, but each is most responsive to a small range of wavelengths—
short (bluish light), medium (greenish light), and long (reddish light). As you can see on the
background spectrum in Figure 9-6, however, if you were to look at lights with wavelengths
of 419, 531, and 559 nanometers (nm), they would not appear blue, green, and red but rather A nanometer (nm) is one-billionth of a meter.
blue-green, yellow-green, and orange. Remember, though, that you are looking at the lights
with all three of your cone types and that each cone pigment responds to light across a range
of frequencies, not just to its frequency of maximum absorption.
Both the presence of three cone receptor types and their relative numbers and distribution
across the retina contribute to our perception of color. As Figure 9-7 shows, the three cone
types are distributed more
or less randomly across the Peak sensitivity
retina, making our ability
to perceive different colors S cone Rod M cone L cone
Range and Peak
Figure 9-6
419 496 531 559 Sensitivity Our color perception
fairly constant across the vis-
100
corresponds to the summed activity of
Maximum response (%)
ual field. The numbers of red the three cone types: S cones, M cones,
and green cones are approxi- 75 and L cones (for short, medium, and long
mately equal, but blue cones wavelengths). Each type is most sensitive
are fewer. As a result, we 50 to a narrow range of the visible spectrum.
Rods (white curve) prefer a range of
are not as sensitive to wave- 25 wavelengths centered on 496 nm but do
lengths in the blue part of the not contribute to our color perception. Rod
visible spectrum as we are to 400 450 500 550 600 650 activity is not summed with the cones in
red and green wavelengths. Wavelength (nm) the color vision system.
294 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
CliniCal F cus 9-2
Visual Illuminance
The eye, like a camera, works correctly only when sufficient light passes estimated that between ages 20 and 40, people’s ability to see in dim
through the lens and is focused on the receptor surface—the retina of light drops by 50 percent; and by a further 50 percent over every 20
the eye or the light-sensitive surface in the camera. Too little light enter- additional years. As a result, seeing in dim light becomes increasingly
ing the eye or the camera produces a problem of visual illuminance: it is difficult, especially at night.
hard to see any image at all. The only solution to compensate for visual illuminance is to increase
Visual illuminance is typically a complication of aging eyes, It cannot lighting. Night vision is especially problematic. Not surprisingly, statistics
be cured by corrective lenses. As we age, the eye’s lens and cornea show a marked drop in the number of people driving at night in each
allow less light through, so less light strikes the retina. Don Kline (1994) successive decade after age 40.
photo Courtesy of dr. donald Kline, university of Calgary
These photographs represent the typical drop in luminance between age 20 (left) and age 60 (right).
Other species that have color vision similar to humans’ also have three types
of cones with three color pigments. Because of slight variations in these pigments,
Cones Rod the exact frequencies of maximum absorption differ among species. For humans,
the exact frequencies are not identical with the numbers given earlier, which are
an average across mammals. They are actually 426 and 530 nm for the blue and
green cones, respectively, and 552 or 557 nm for the red cone. The two peak sen-
sitivity levels of red cones represent the two variants that humans have evolved.
The difference in these two red cones appears minuscule, but it does make a
functional difference in some females’ color perception.
The gene for the red cone is carried on the X chromosome. Males have only
Figure 9-7 Retinal Receptors The one X chromosome, so they have only one of these genes and only one type of red cone. The
retinal mosaic of rods and three cone
situation is more complicated for females, who possess two X chromosomes. Although most
types. This diagram represents the
distribution near the fovea, where cones women have only one type of red cone, those who have both are more sensitive than the rest
outnumber rods. Red and green cones of us to color differences at the red end of the spectrum. We could say that women who have
outnumber the blue. both red cone types have a slightly rosier view of the world: their color receptors construct a
world with a richer range of red experiences. But they also have to contend with seemingly
peculiar color coordination by others.
Types of Retinal Neurons
Photoreceptors are connected to two layers of retinal neurons. In the procession from the
rods and cones toward the brain shown in Figure 9-8, the first layer contains three cell
types: bipolar, horizontal, and amacrine. Horizontal cells link photoreceptors with bipolar
cells, whereas amacrine cells link bipolar cells with cells in the second neural layer, the
retinal ganglion cells (RGCs). RGC axons collect in a bundle at the optic disc and leave the
eye to form the optic nerve.
9-2 • The Visual System’s Functional Anatomy 295
Figure 9-8 Retinal Cells Neurons in
Retina the retina—bipolar, horizontal, amacrine,
and ganglion cells—form two layers
moving outward from the rods and cones
Light at the retinal surface. Light must pass
through both transparent neuron layers to
Optic reach the photoreceptors.
nerve
Axons of Ganglion Amacrine Bipolar Horizontal Cone Rod
ganglion cells cell cell cell cell
Retinal ganglion cells fall into two major categories, called M and P cells in the primate ret-
ina. The designations derive from the distinctly different cell populations in the visual thalamus
to which these two classes of RGCs send their axons. As shown in Figure 9-9, one population
consists of magnocellular cells (hence M); the other consists of parvocellular cells (hence P). In Latin, magno means large and parvo
The larger M cells receive their input primarily from rods and so are sensitive to light but not to means small.
color. The smaller P cells receive their input primarily from cones and so are sensitive to color.
M cells are found throughout the retina, including the periphery, where we are sensitive
to movement but not to color or fine detail. P cells are found largely in the region of the
fovea, where we are sensitive to color and fine details. As we follow the ganglion cell axons
into the brain, you will see that these two categories of RGCs maintain their distinctiveness
throughout the visual pathways.
Figure 9-9 Visual Thalamus The optic
nerves connect with the lateral geniculate
nucleus of the thalamus. The LGN has six
layers: two magnocellular layers, which
receive input mainly from rods, and four
Parvocellular
parvocellular layers, which receive input
layers mainly from cones.
Magnocellular retinal ganglion cell (RGc) One of a group
LGN layers
Thalamus Optic of retinal neurons with axons that give rise to
nerve the optic nerve.
magnocellular (M) cell Large visual system
neuron sensitive to moving stimuli.
parvocellular (P) cell Small visual system
neuron sensitive to differences in form and
color.
Visual Pathways optic chiasm Junction of the optic nerves,
RGCs form the optic nerve, the road into the brain. This road forks off to several places. The one from each eye, at which the axons from
destinations of these branches give us clues to what the brain is doing with visual input and the nasal halves of the retinas cross to the
how the brain constructs our visual world. brain’s opposite side.
Crossing the Optic Chiasm
We begin with the optic nerves, one exiting from each eye. Just before entering the brain,
the optic nerves partly cross, forming the optic chiasm. The optic chiasm gets its name from the
About half the fibers from each eye cross in such a way that the left half of each optic shape of the Greek letter chi (χ)
nerve goes to the left side of the brain, and the right half goes to the brain’s right side, as (pronounced ki).
diagrammed in Figure 9-10. The medial path of each retina, the nasal retina, crosses to the
opposite side. The lateral path, the temporal retina, travels straight back on the same side.
296 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
By connecting both eyes with both Because light that falls on the right half of each retina actually comes from the left side of
hemispheres, our visual system represents the visual field, information from the left visual field goes to the brain’s right hemisphere,
the world seen through two eyes as a single and information from the right visual field goes to the left hemisphere. Thus, half of each
perception. retina’s visual field is represented on each side of the brain.
Three Routes to the Visual Brain
Two main pathways lead to the visual cortex in the occipital lobe: the
geniculostriate pathway for processing the object’s image and the tectopul-
Lateral Optic Primary visual vinar pathway for directing rapid eye movements. Another smaller path-
geniculate radiations cortex (region V1)
way tracks into the hypothalamus.
nucleus
Optic tract
Optic chiasm GeniCulostriate system On entering the brain, the RGC axons
Optic nerve separate, forming the two distinct pathways shown in Figure 9-11. All of
Nasal retina the P ganglion axons and some of the M ganglion axons form a pathway
Temporal retina called the geniculostriate system. This pathway goes from the retina to
Eye the lateral geniculate nucleus (LGN) of the thalamus and then to layer IV
of the primary visual cortex in the occipital lobe.
When stained, the primary visual cortex shows a broad stripe across it
in layer IV and so is known as striate (striped) cortex (Figure 9-12). The
Vis geniculostriate system therefore bridges the thalamus (geniculate) and
ual f
ield the striate cortex. From the striate cortex, the axon pathway divides. One
route goes to vision-related regions of the parietal lobe, and another route
goes to vision-related regions of the temporal lobe.
teCtopulvinar system The second pathway leading from the eye
is formed by the axons of the remaining M ganglion cells. These cells
Crossing the Optic
Figure 9-10 send their axons to the midbrain’s superior colliculus, which sends connections to the pulvi-
Chiasm This dorsal view shows the nar region of the thalamus. This pathway is therefore known as the tectopulvinar system
visual pathway from each eye to the
because it runs from the eye through the midbrain tectum to the pulvinar (see Figure 9-11).
primary visual cortex of each hemisphere.
Information from the right side of the visual The pulvinar sends connections to the parietal and temporal lobes, bypassing the occipital
field (blue) moves from the two left halves visual areas.
of the retinas, ending in the left hemisphere.
Information from the left side of the visual retinohypothalamiC traCt Between 1 percent and 3 percent of RGCs are unique in
field (red) hits the right halves of the retinas that they are photosensitive: they act as photoreceptors. These pRGCs, which contain the
and travels to the right side of the brain. pigment melanopsin, absorb blue light at a wavelength (between 460 and 480 nm) different
from the wavelengths of rods or cones (see Figure 9-6). Axons of pRGCs form a small third
visual pathway, the retinohypothalamic tract.
Figure 13-6 maps the retinohypothalamic tract The retinohypothalamic tract synapses in the tiny suprachiasmatic nucleus (SCN) in the
into the SCN. hypothalamus, next to the optic chiasm. Photosensitive RGCs participates both in regulat-
ing circadian rhythms and in the pupillary reflex that expands and contracts the pupil in
response to the amount of light falling on the retina. Farhan
Brain
Zaidi and colleagues (2007) studied two profoundly blind
Geniculostriate system
subjects who lack functional rods and cones. The research-
Optic nerve Other
Lateral
Striate visual ers found that stimulation with 480-nm (blue) light increases
geniculate
cortex cortical alertness and appears to play some rudimentary role in visual
nucleus
Visual areas
Eye awareness.
information Tectopulvinar system
Superior
Pulvinar
colliculus
Dorsal and Ventral Visual
Streams
Figure 9-11 Main Visual Pathways into the Brain The optic
The geniculostriate and tectopulvinar pathways extend into
nerve follows (1) the geniculostriate path to the primary visual cortex and
(2) the tectopulvinar path to the temporal and parietal lobes. (The LGN of the visual brain. Each eventually leads to either the parietal
the thalamus is part of the diencephalon, shown in Figure 2-19; the superior lobe or the temporal lobe. Our next task is to determine the
colliculus in the tectum is part of the midbrain, shown in Figure 2-18.) role each lobe plays in building our visual world. As we look at
9-2 • The Visual System’s Functional Anatomy 297
Parietal lobe
Striate cortex geniculostriate system Projections from the
retina to the lateral geniculate nucleus to the
visual cortex.
Occipital lobe
striate cortex Primary visual cortex (V1) in
the occipital lobe; shows stripes (striations)
on staining.
Temporal lobe
tectopulvinar system Projections from the
retina to the superior colliculus to the pulvinar
(thalamus) to the parietal and temporal visual
Bryan Kolb
areas.
retinohypothalamic tract Neural route
Figure 9-12 Striate Cortex Area V1 is also called the striate cortex because sections formed by axons of photosensitive retinal
appear striated (striped) when stained with either a cell body stain (left) or a myelin stain ganglion cells (pRGCs) from the retina to
(right). The sections shown here come from a rhesus monkey’s brain. the suprachiasmatic nucleus; allows light to
entrain the SCN’s rhythmic activity.
ventral stream Visual processing
the photograph in Clinical Focus 9-1, we can identify objects, and we can point to them. pathway from V1 to the temporal lobe for
Identifying and pointing are different functions. object identification and perceiving related
Having identified the temporal lobe and parietal lobe visual pathways, researchers movements.
went searching for their possible functions. Why would evolution produce two different dorsal stream Visual processing pathway
destinations for these neural pathways? Each route must produce visual knowledge for a from V1 to the parietal lobe; guides
different purpose. movements relative to objects.
David Milner and Mel Goodale (2006) proposed that these two purposes are to identify a
stimulus (the what function) and to control movement to or away from the stimulus (the how
function). This what–how distinction came from an analysis of the routes visual information
takes when it leaves the striate cortex. Figure 9-13 shows the two distinct visual pathways
that originate in the striate cortex, one progressing to the temporal lobe and the other to the
parietal lobe. The pathway to the temporal lobe is the ventral stream, whereas the pathway Parietal
to the parietal lobe is the dorsal stream. lobe
Both the geniculostriate and the tectopulvinar pathways contribute to the dorsal and
Occipital
ventral streams. To understand how the two streams function, we return to the details of lobe
Do
how visual input from the eyes contributes to them. rsa
ls
tr e
am
Geniculostriate Pathway
Ventral stream
The RGC fibers from the two eyes distribute their connections to the two lateral geniculate
nuclei (left and right) of the thalamus. At first glance, this appears to be an unusual arrange- Temporal
ment. As seen in Figure 9-10, the fibers from the left half of each retina go to the left LGN; lobe
Striate
those from the right half of each retina go to the right LGN. But the fibers from each eye do cortex (region V1)
not go to exactly the same LGN location.
Figure 9-13 Visual Streaming
Each LGN has six layers, and the projections from the two eyes go to different layers, as
Information travels from the occipital visual
illustrated in anatomical context in Figure 9-9 and diagrammed in Figure 9-14. Layers 2, 3, areas to the parietal and temporal lobes,
and 5 receive fibers from the ipsilateral eye (the eye on the same side), whereas layers 1, 4, forming the dorsal (how) and ventral (what)
and 6 receive fibers from the contralateral eye (the eye on the opposite side). This arrange- streams, respectively.
ment provides both for combining the information from the two eyes and for segregating the
information from the P and M ganglion cells.
Axons from the P cells go only to layers 3 through 6 (the parvocellular layers). Axons
from the M cells go only to layers 1 and 2 (the magnocellular layers). Because the P cells
are responsive to color and fine detail, LGN layers 3 through 6 must be processing infor-
mation about color and form. In contrast, the M cells mostly process information about
movement, so layers 1 and 2 must deal with movement.
Just as there are six layers in the thalamic LGN (numbered 1 through 6), there are also Figure 2-22 maps layers I through VI in the
six layers in the striate cortex (numbered I through VI). That there happen to be six layers in primary motor and sensory cortices.
298 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
Information travels from the right each location is an accident of evolution found in all primate brains. Let us now see where
side of each retina to the right LGN. these LGN cells from the thalamus send their connections within the visual cortex.
Layer IV is the main afferent (incoming) layer of the cortex. In the visual cortex, layer IV
Left eye Right eye
has several sublayers, two of which are known as IVCα and IVCβ. LGN layers 1 and 2 go to
(contralateral) (ipsilateral)
IVCα, and layers 3 through 6 go to IVCβ. A distinction between the P and M functions thus
continues in the striate cortex.
As illustrated in Figure 9-15, input from the two eyes also remains separated in the
cortex. The input from the ipsilaterally and contralaterally connected parts of the LGN
Nasal Temporal go to adjacent strips of occipital cortex. These strips, which are about 0.5 mm across, are
projection projection
known as cortical columns.
In summary, P and M retinal ganglion cells send separate pathways to the thalamus, and
this segregation continues in the striate cortex. The left and right eyes also send separate
pathways to the thalamus, and these pathways, too, remain segregated
Information from the Information from the in the striate cortex.
contralateral side goes ipsilateral side goes to
to layers 1, 4, and 6. layers 2, 3, and 5.
1 Tectopulvinar Pathway
2 To review, magnocellular RGCs found throughout the retina receive
4 3 Layers of LGN input primarily from the rods and so are sensitive to light but not to
6 5 color. M cells in the periphery of the retina are sensitive to movement
Left LGN Right LGN
but not to color or fine details. In the brain, some M cells join P cells
Layers 1 and 2 receive input from Layers 3 through 6 receive input to form the geniculostriate pathway. The tectopulvinar pathway is
the magnocellular pathway. from the parvocellular pathway. formed by the axons of the remaining M cells.
These M cells send their axons to the superior colliculus in the
Figure 9-14 Geniculostriate Pathway
midbrain’s tectum. One function of the tectum is to produce orienting movements—to
detect stimuli and shift the eyes toward them. The superior colliculus sends connections
to the pulvinar region of the thalamus. The medial pulvinar sends connections to the
parietal lobe, and the lateral pulvinar sends connections to the temporal lobe. One type of
Many textbooks emphasize the how pathway information that these connections are conveying is related to where. Where is important
as a where function. Because where is both a in both the what and how visual streams.
property of what a stimulus is and a cue for The where function of the tectopulvinar system is useful in understanding D. B.’s blind-
how to control movement, we use Milner and sight, described in Clinical Focus 9-1. His geniculostriate system was disrupted by surgery,
Goodale’s what–how distinction. but his tectopulvinar system was not, which allowed him to identify the location of stimuli
(where) that he could not identify (what).
Lateral geniculate Horizontal section
nucleus of striate cortex
Right Left
eye eye
Left 1
eye M layers
2
3
4
P layers
5
6
Ocular dominance columns
I
II
III Figure 9-15 Maintaining Separate Visual Input
IVCa Left: Information from the eyes is segregated by layers in the
IVCb LGN, which maintains this segregation in its projections from
the thalamus to the primary visual cortex. Information from
V
each eye travels to adjacent regions in cortical layer IV. Right:
VI A horizontal plane through striate cortex shows a zebralike
Cortical visual area 1 effect of alternating left and right eye regions.
9-2 • The Visual System’s Functional Anatomy 299
Occipital Cortex cortical column Anatomic organization that
Our route down the visual pathways has led us from the retina all the way back to the occipital represents a functional unit six cortical layers
lobe and into the parietal and temporal lobes. Now we explore how visual information proceeds deep and approximately 0.5 mm square,
from the striate cortex through the rest of the occipital lobe to the dorsal and ventral streams. perpendicular to the cortical surface.
primary visual cortex (V1) Striate cortex in
(A) Medial view of functional areas (B) Lateral view of functional areas the occipital lobe that receives input from the
lateral geniculate nucleus.
extrastriate (secondary visual) cortex
V3A V3A
(V2–V5) Visual cortical areas in the occipital
V3 V3
lobe outside the striate cortex.
V2 V2
V1 blob Region in V1 that contains color-
V1 V2 sensitive neurons, as revealed by staining for
V2 V3
V3A cytochrome oxidase.
V4
V4
V3 V5
V3A
V1 = Primary visual cortex
V2–V5 = Extrastriate cortex
Figure 9-16 Visual Regions of the Occipital Lobe
As shown in Figure 9-16, the occipital lobe is composed of at least six visual regions: V1,
V2, V3, V3A, V4, and V5. The striate cortex is region V1, the primary visual cortex. The All mammals have at least one primary
remaining occipital visual areas form the extrastriate cortex, with each region processing cortical area for each sensory system. The
specific features of visual information. Because each occipital region has a unique cytoar- primary area relays most information that
chitecture (cellular structure) and unique inputs and outputs, we can infer that each must reaches secondary areas.
be doing something different from the others.
As shown in Figures 9-12 and 9-15, a remarkable feature of region V1 is its striations—its
distinctly visible layers. When Margaret Wong-Riley and her colleagues (1993) stained region
VI for the enzyme cytochrome oxidase, which has a role in cell metabolism, they found an
unexpected heterogeneity. So they sectioned the V1 layers in such a way that each cortical
layer was in one plane of section, much like peeling off the layers of an onion and laying them
flat on a table. The surface of each flattened layer can then be viewed from above.
The heterogeneous cytochrome staining now appears as random blobs in the V1 lay-
ers, as diagrammed in Figure 9-17. These darkened regions have in fact become known as
blobs, the less-dark regions separating them as interblobs. Blobs and interblobs serve differ-
ent functions. Neurons in the blobs take part in color perception; neurons in the interblobs
participate in perception of form and motion. Within region V1, then, input arriving from
the P cell and M cell pathways of the geniculostriate system is segregated into three separate
types of information: color, form, and motion.
All three types of information move from region V1 to the adjoining region V2. Here,
the color, form, and motion inputs remain segregated, again seen through the pattern of
cytochrome oxidase staining. But as Figure 9-17 shows, the staining pattern in region V2
differs from that in region V1. Region V2 has a pattern of thick and thin stripes intermixed
with pale zones. The thick stripes receive input from the movement-sensitive neurons in
Stripes Thin
Thick
Pale zones
Blobs Figure 9-17 Heterogeneous Layering Blobs in region V1 and
stripes in region V2 are illustrated in this drawing of a flattened
Interblobs
section through the visual cortex of a monkey. The blobs and
V2 stripes are revealed by a special stain for cytochrome oxidase, a
marker for mitochondria, the organelles in cells that gather, store,
V1 and release energy.
300 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
V3A (form)
Striate T Parietal lobe (PG)
T V5 (motion)
cortex (V1) h Dorsal
i h Extrastriate stream
Blobs c i
Lateral (color) k n cortex
geniculate
nucleus Interblob regions
V3 (dynamic form)
Form Movement Temporal lobe (TE)
Extrastriate V4 (color form)
Ventral
cortex (V2) Extrastriate stream
cortex
Parietal-lobe Figure 9-18 Charting the Visual Streams The dorsal stream, which controls
area PG visual action (top), begins in region V1 and flows through V2 to the other occipital areas
Dorsal stream and finally to the parietal cortex, ending in area PG. The ventral stream, which controls
object recognition (bottom), begins in region V1 and flows through V2 to the other
Ventral stream occipital areas and finally to the temporal cortex, ending in area TE. Information from
the blobs and interblobs in V1 flows to the thick, thin, and pale zones of V2 and then to
Temporal-lobe regions V3 and V4 to form the ventral stream. Information in the thick and pale zones
area TE goes to regions V3A and V5 to form the dorsal stream.
region V1; the thin stripes receive input from V1’s color-sensitive neurons; and the pale zones
receive input from V1’s form-sensitive neurons.
As charted in Figure 9-18, the visual pathways proceed from region V2 to the other
occipital regions and then to the parietal and temporal lobes, forming the dorsal and ven-
tral streams. Although many parietal and temporal regions take part, the major regions
are region G in the parietal lobe (thus called region PG) and region E in the temporal
lobe (thus called region TE).
The simple records of color, form, and motion from the occipital regions are assembled
in the dorsal and ventral streams to produce a rich, unified visual world of complex objects,
such as faces and paintings, and complex skills, such as bike riding and ball catching. We can
think of the complex representations of the dorsal and ventral streams as consisting of how
functions and what functions. How is looking at, reaching for, and grasping; what is the spoon.
Vision Beyond the Occipital Cortex
Visual processing that begins in occipital cortex continues via the ventral and dorsal streams
into the temporal and parietal visual cortex. Each region has multiple areas specialized for
specific visual functions. For example, Figure 9-19A shows two regions on the ventral surface
(A) (B)
AIP
PRR
LIP
FFA PPA
Figure 9-19 Vision Beyond the Occipital Cortex (A) In the temporal lobe, the fusiform face area (FFA)
processes faces, and the parahippocampal place area (PPA) processes scenes. (B) In the parietal lobe, the
lateral intraparietal area (LIP) contributes to eye movements; the anterior intraparietal area (AIP) is involved
in visual control of grasping; and the parietal reach region (PRR) participates in visually guided reaching.
(A) Republished with permission of Hasson, U., Y. Nir, I. Levy, G. Fuhrmann, and R. Malach. Intersubject synchronization of cortical activity during
natural vision. Science 303:1634–1640, 2004, permission conveyed through Copyright Clearance Center, Inc.
9-3 • Location in the Visual World 301
of the temporal lobes. One is specialized for recognizing faces (fusiform face area, or FFA),
the other for analyzing landmarks such as buildings or trees (parahippocampal place area,
or PPA). As we gaze at the photograph in Clinical Focus 9-1 (p. 284), then, the three faces
activate the FFA and the trees engage the PPA. Figure 9-19B shows three regions in the
parietal lobe related to eye movements (lateral intraparietal area, or LIP) and visual control
of grasping (anterior intraparietal area, or AIP). The parietal reach region (PRR) has a role in
visually guided reaching movements.
Damage to these regions can produce surprisingly specific deficits. For example, dam-
age to the FFA leads to facial agnosia, or prosopagnosia, a condition in which an individual Literally, agnosia means not knowing. Section
cannot recognize faces. We saw one patient with prosopagnosia so severe that she could not 15-7 ties conditions like agnosia to the search
recognize her identical twin sister’s face. Curiously, her other visual functions seemed to for a neural basis of consciousness.
be normal.
9-2 review
The Visual System’s Functional Anatomy
Before you continue, check your understanding.
1. Neurons that project into the brain from the retina and form the optic nerve are called
.
2. retinal ganglion cells receive input mostly from cones and carry
information about color and fine detail, whereas retinal ganglion cells
receive input mostly from rods and carry information about light but not color.
Left visual field Right visual field
3. The two major pathways from the retina into the brain are and
.
4. Damage to the fusiform face area in the temporal lobe can produce .
5. Contrast the paths and functions of the dorsal and ventral streams.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
9-3 Location in the Visual World
As we move about from place to place, we encounter objects in specific locations. If we had
no awareness of location, the world would be a bewildering mass of visual information. The Visual-Field
Figure 9-20
next leg of our journey down the neural roads traces how the brain constructs a spatial map. Demonstration As you focus on the
In Clinical Focus 9-1, the photograph has a left and a right, an up and a down. All these ele- cross at center, information at the left of
this focal point forms the left visual field
ments must be coded separately in the brain.
(red) and travels to the right hemisphere.
Neural coding of location begins in the retina and is maintained throughout all visual Information to the right of the focal point
pathways. To understand how this spatial coding is accomplished, imagine your visual world forms the right visual field (blue) and
as seen by your two eyes. Imagine the large red and blue rectangles in Figure 9-20 as a wall. travels to the left hemisphere. The visual
Focus your gaze on the black cross in the middle of the wall. field can be split horizontally as well:
information above the focal point is in the
The part of the wall that you can see without moving your head is your visual field. It can
upper visual field and that below the focal
be divided into two halves, the left and right visual fields, by drawing a vertical line through point is in the lower visual field.
the middle of the black cross. Now recall from Figure 9-10 that the left half of each retina
looks at the right side of the visual field, whereas the right half of each retina looks at the
visual field’s left side. Thus, input from the right visual field goes to the left hemisphere, and
input from the left visual field goes to the right hemisphere. facial agnosia Face blindness—the inability
Therefore, the brain can easily determine whether visual information lies to the left or to recognize faces; also called prosopagnosia.
right of center. If input goes to the left hemisphere, the source must be in the right visual visual field Region of the visual world seen
field; if input goes to the right hemisphere, the source must be in the left visual field. This by the eyes.
302 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
arrangement tells you nothing about the precise location of an object in the left or right side
of the visual field, however. To understand how precise spatial localization is accomplished,
we must return to the retinal ganglion cells.
Coding Location in the Retina
Look again at Figure 9-8 and you can see that each RGC receives input through bipolar
cells from several photoreceptors. In the 1950s, Stephen Kuffler, a pioneer in visual system
physiology, made an important discovery about how photoreceptors and retinal ganglion
cells are linked (Kuffler, 1952). By shining small spots of light on the receptors, he found that
each ganglion cell responds to stimulation on just a small circular patch of the retina—the
ganglion cell’s receptive field.
A ganglion cell’s receptive field is therefore the retinal region on which it is possible to
influence that cell’s firing. Stated differently, the receptive field represents the outer world
as seen by a single cell. Each RGC sees only a small bit of the world, much as you would if
you looked through a narrow cardboard tube. The visual field is composed of thousands of
such receptive fields (illustrated on page 286).
Now let us consider how receptive fields enable the visual system to interpret an object’s
location. Imagine that the retina is flattened like a piece of paper. When a tiny light shines
Like a camera lens, the lens in the eye focuses on different parts of the retina, different ganglion cells respond. For example, when a light
light rays to project a backward, inverted shines on the top left corner of the flattened retina, a particular RGC responds because that
image on a light-receptive surface (see How
light is in its receptive field. Similarly, when a light shines on the top right corner, a different
the Eye Works in The Basics, p 291).
RGC responds.
By using this information, we determine the location of a light on the retina by the gan-
glion cell it activates. Another location device is determining where the light must come from
to hit a particular place on the retina. Light coming from above hits the bottom of the retina
after passing through the eye’s lens, and light from below hits the top of the retina. Infor-
mation at the top of the visual field stimulates ganglion cells on the bottom of the retina;
information at the bottom of the field stimulates ganglion cells on the top of the retina.
Retina
Location in the Lateral Geniculate
Nucleus and Region V1
Now consider the connection from the ganglion cells to the lateral geniculate nucleus. In
contrast to the retina, the LGN is not a thin sheet; it is shaped more like a sausage. We can
compare it to a stack of sausage slices, with each slice representing a layer of cells.
Figure 9-21 shows how the connections from the retina to the LGN can represent loca-
LGN tion. A retinal ganglion cell that responds to light in the top left region of the retina connects
to the left side of the first card. A retinal ganglion cell that responds to light in the bottom
right region of the retina connects to the right side of the last card. In this way, the location
LGN
of left–right and top–bottom information is maintained in the LGN.
Like the ganglion cells, each LGN cell has a receptive field—the region of the retina that
influences its activity. If two adjacent retinal ganglion cells synapse on a single LGN cell, the
receptive field of that LGN cell will be the sum of the two ganglion cells’ receptive fields. As
a result, the receptive fields of LGN cells are bigger than those of RGCs.
Receptive Field
Figure 9-21
Projection Information from a The LGN projection to the striate cortex (region V1) also maintains spatial information.
receptive field in the retina retains its As each LGN cell, representing a particular place, projects to region V1, a spatially organ-
spatial relation when sent to the lateral ized neural representation—a topographic map—is produced in the cortex. As illustrated in
geniculate nucleus. Information at the top Figure 9-22, this representation is essentially a map of the visual world.
of the visual field goes to the top of the
The central part of the visual field is represented at the back of the brain, whereas the
LGN; information from the bottom of the
visual field goes to the bottom of the LGN; periphery is represented more anteriorly. The upper part of the visual field is represented
and information from the left or right goes at the bottom of region V1 and the lower part at the top of V1. The other regions of the
to the left or right of the LGN, respectively. visual cortex (such as V3, V4, and V5) have topographical maps similar to that of V1.
9-3 • Location in the Visual World 303
Left visual field (projecting Topographic
Figure 9-22
to right visual cortex) Organization of Region V1
The fovea sends information to a
disproportionately large part of the
occipital cortex, which is why visual acuity
is best in the central part of the visual field.
Fovea
Periphery
Right visual
cortex
The central part of the visual field is represented at the
back of the brain.
The peripheral areas of the visual field are located
more anteriorly.
The top part of the visual field is represented in the
lower part of the occipital lobe.
Receptive-Field
Figure 9-23
Hierarchy
Thus the V1 neurons must project to the other regions The receptive fields …combine to form The receptive fields of many
in an orderly manner, just as the LGN neurons project to of many retinal the receptive field LGN cells combine to form the
region V1 in an orderly way. ganglion cells… of a single LGN cell. receptive field of a single V1 cell.
Within each visual cortical area, each neuron’s receptive
field corresponds to the part of the retina to which the neu-
ron is connected. As a rule of thumb, cells in the cortex have
much larger receptive fields than RGCs do. This large field
size means that the receptive field of a cortical neuron must
be composed of the receptive fields of many RGCs, as illus-
trated in Figure 9-23.
One additional wrinkle pertains to the organization of topographic maps. Harry
Jerison (1973) proposed the principle of proper mass, which states that the amount of In Figure 1-14, we apply Jerison’s ideas
neural tissue responsible for a particular function is proportional to the amount of to relative differences in overall brain size
neural processing that function requires. The more complex a function is, the larger across mammals.
a specific region performing that function must be. The visual cortex provides some
good examples.
You can see in Figure 9-22 that not all parts of the visual field are equally represented
in region V1. The small central part of the visual field seen by the fovea is represented by a
larger area in the cortex than the visual field’s periphery, even though the periphery covers
a much larger area. In accord with Jerison’s principle, we would predict more processing
of foveal information than of peripheral information in region V1. This prediction makes
intuitive sense because we can see more clearly in the center of the visual field than at the
periphery (see Figure 9-3). In other words, sensory areas that have more cortical representa-
tion provide a more detailed construct of the external world.
304 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
Corpus callosum
Visual Corpus Callosum
Topographic mapping based on neuronal receptive fields is an effective way for the brain
to code object location. But if the left visual field is represented in the right cerebral hemi-
sphere and the right visual field is represented in the left cerebral hemisphere, how are the
two halves of the visual field ultimately merged into a unified representation? After all, we
have the subjective impression not of two independent visual fields but rather of a single,
continuous field of vision.
The answer to how this unity is accomplished lies in the corpus callosum, which binds the
two sides of the visual field together at the midline. Until the 1950s, its function was largely
Section 15-4 describes the revelations a mystery. Physicians had occasionally cut the corpus callosum to control severe epilepsy or
learned from studying split-brain patients, to reach a very deep tumor, but patients did not appear much affected by this surgery. The
whose corpus callosa have been severed.
corpus callosum clearly linked the two hemispheres of the brain, but exactly which parts
were connected was not yet known.
Figure 9-24 Callosal Connections We now realize that the corpus callosum connects only certain brain structures. As shown
Darker areas show regions of the rhesus in Figure 9-24, the frontal lobes have many callosal connections, but the occipital lobes have
monkey cortex that receive projections
almost none. If you think about it, there is no reason for a neuron in the visual cortex that
from the opposite hemisphere through the
corpus callosum. is looking at one place in the visual field to be concerned with what another neuron in the
opposite hemisphere is looking at in another part of the visual field.
Most of the two …whereas the Cells that lie along the midline of the visual field are an exception, however. These
frontal lobes occipital lobes cells look at adjacent places in the visual field, one slightly to the left of center and one
have callosal have almost no
connections,... Parietal connections. slightly to the right. Callosal connections between such cells zip the two visual fields
lobe together by combining their receptive fields to overlap at the midline. The two fields
thus become one.
Frontal Occipital
lobe lobe
9-3 review
Temporal
lobe Location in the Visual World
Before you continue, check your understanding.
1. The characteristic of visual receptive fields that allows us to detect exactly where a light
source is coming from is their .
2. List four types of cells that have visual receptive fields: , ,
, and .
3. Inputs to different parts of cortical region V1 from different parts of the retina essentially
form a of the visual world within the brain.
4. The two sides of the visual world are bound together as one perception by the
.
5. How does Jerison’s principle of proper mass apply to the visual system?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
9-4 Neuronal Activity
Individual neurons make up the visual system pathways. By studying how these cells behave
when their receptive fields are stimulated, we can begin to understand how the brain pro-
cesses the features of the visual world beyond the location of a light. We first examine how
neurons in the ventral stream respond to objects’ shapes and colors, then briefly consider
how neurons in the dorsal stream direct vision for action.
9-4 • Neuronal Activity 305
Seeing Shape
Imagine a microelectrode placed near a neuron somewhere in the visual pathway from retina Figure 4-6 diagrams how microelectrodes
to cortex. The microelectrode is recording changes in the neuron’s firing rate. This cell occa- work.
sionally fires spontaneously, producing action potentials with each discharge. Assume that
the neuron discharges, on average, once every 0.08 second. Each action potential is brief, on
the order of 1 millisecond.
If we plot action potentials spanning 1 s, we see only spikes in the record because the (A) Baseline (12 per second)
action potentials are so brief. Figure 9-25A is a single cell recording of 12 spikes in the span
of 1 second. If the firing rate of this cell increases, we see more spikes (Figure 9-25B). If the
firing rate decreases, we see fewer spikes (Figure 9-25C). The increase in firing is the result of 0 0.25 0.50 0.75 1.0
Time (seconds)
neuronal excitation, whereas the decrease indicates inhibition. Excitation and inhibition, of
course, are the principal information transfer mechanisms in the nervous system.
(B) Excitation
Now suppose we present a stimulus to the neuron by illuminating its receptive field in the
retina, perhaps by shining a light on a blank screen within the cell’s visual field. We might
place before the eye a straight line positioned at a 45° angle. The cell could respond to this 0 0.25 0.50 0.75 1.0
stimulus either by increasing or decreasing its firing rate. In either case, we would conclude Time (seconds)
that the cell is generating information about the line.
The same cell could show excitation to one stimulus, inhibition to another stimulus, and (C) Inhibition
no reaction at all to a third. The cell could be excited by lines oriented 45° to the left and
inhibited by lines oriented 45° to the right. Similarly, the cell could be excited by stimulation
0 0.25 0.50 0.75 1.0
in one part of its receptive field (such as the center) and inhibited by stimulation in another Time (seconds)
part (such as the periphery).
Figure 9-25 Recording Neuronal
Finally, we might find that the cell’s response to a particular stimulus is selective.
Stimulation Each action potential is
Such a cell would be telling us about the importance of the stimulus to the animal. For
represented by a spike. (A) In a 1-s period
instance, the cell might be excited when a stimulus is presented with food but inhibited at this neuron’s baseline firing rate,
when the same stimulus is presented alone. In each case, the cell is selectively sensitive 12 spikes were recorded. (B) A firing rate
to characteristics in the visual world. over baseline signals excitation. (c) A firing
Neurons at each level of the visual system have distinctly different characteristics and rate under baseline signals inhibition.
functions. Our goal is not to look at each neuron type but rather to consider generally how
some typical neurons at each level differ from one another in their contributions to process-
ing shape. We focus on neurons in three areas: the ganglion cell layer of the retina, the
primary visual cortex, and the temporal cortex.
Processing in RGCs
Neurons in the retina do not detect shape, because their receptive fields are minuscule dots.
Each retinal ganglion cell responds only to the presence or absence of light in its receptive
field, not to shape. Shape is constructed by processes in the cortex from the information that
those ganglion cells pass on about events in their receptive fields.
The receptive field of a ganglion cell has a concentric circle arrangement, as illustrated in
Figure 9-26A. A spot of light falling in the receptive field’s central circle excites some of these
cells, whereas a spot of light falling in the receptive field’s surround (periphery) inhibits the
cell. A spot of light falling across the entire receptive field weakly increases the cell’s firing rate.
This type of neuron is called an on-center cell. Other RGCs, called off-center cells,
have the opposite arrangement, with light in the center of the receptive field inhibiting,
light in the surround exciting, and light across the entire field producing weak inhibition
(Figure 9-26B). The on–off arrangement of RGC receptive fields makes these cells especially
responsive to tiny spots of light.
This description of ganglion cell receptive fields might mislead you into thinking that
they form a mosaic of discrete little circles on the retina. In fact, neighboring retinal ganglion
cells receive their inputs from an overlapping set of photoreceptors. As a result, their recep-
tive fields overlap, as illustrated in Figure 9-27. In this way, a small spot of light shining on
the retina is likely to produce activity in both on-center and off-center RGCs.
306 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
(A) On-center cell’s receptive field (B) Off-center cell’s receptive field
Response of cell to stimulus at left
Light strikes Light strikes
center center
ON OFF
OFF 0 1 Excitation 2 3 ON 0 1 Inhibition 2 3
Time (seconds) Time (seconds)
Light strikes Light strikes
surround surround
ON OFF
0 1 Inhibition 2 3 0 1 Excitation 2 3
OFF Time (seconds) ON Time (seconds)
Figure 9-26 On–Off Receptivity (A) In the receptive field of an RGC with an on-center
and off-surround, a spot of light shining on the center excites the neuron, but a spot of light
in the surround inhibits it. When the light in the surround is turned off, firing rate increases
briefly—an offset response. A light shining in both the center and the surround would
produce a weak increase in firing. (B) In the receptive field of an RGC with an off-center
and on-surround, light in the center produces inhibition, light on the surround produces
excitation, and light across the entire field produces weak inhibition.
How can on-center and off-center ganglion cells tell the brain anything about shape? The
luminance contrast Amount of light an
answer is that a ganglion cell tells the brain about the amount of light hitting a certain spot
object reflects relative to its surroundings.
on the retina compared with the average amount of light falling on the surrounding retinal
region. This comparison is known as luminance contrast. Luminance is the amount of vis-
ible light reflected to the eye from a surface, and contrast is the difference in luminance
between adjacent parts of that surface. The photograph in Focus 9-1 (p. 284) shows
The receptive fields of …so any two adjacent us two clear differences in luminance contrast. On the left, the woman’s pink top
retinal ganglion cells fields look at almost the contrasts sharply with her black slacks, but the sleeve on the right contrasts far less
overlap extensively,… same part of the world.
with the background. It does not appear as bright.
To understand how luminance contrast tells the brain about shape, consider
the hypothetical population of on-center ganglion cells represented in Figure 9-28.
Their receptive fields are distributed across the retinal image of a light–dark edge.
Some of the ganglion cells’ receptive fields are in the dark area, others are in the light
area, and still others’ fields straddle the edge of the light.
The ganglion cells with receptive fields in the dark or light areas are least affected
because they receive either no stimulation or stimulation of both the excitatory and
Receptive fields of Two overlapping On-center ganglion cells
neighboring ganglion cells receptive fields
A
Figure 9-27 Overlapping Receptive Fields Light–dark edge B
C
D
E
Figure 9-28 Activity at the Margins Responses of a
hypothetical population of on-center ganglion cells whose
receptive fields (A–E) are distributed across a light–dark
edge. The activity of the cells along the edge is most
affected relative to those away from the edge. Information
Cell response rate
from D. Purves, G. J. Augustine, D. Fitzpatrick, L. C. Katz, A.-S. LaMantia, &
J. O. McNamara (Eds.). (1997). Neuroscience, (1st ed., p. 195). Sunderland, MA: Level of spontaneous activity
Sinauer. Position
9-4 • Neuronal Activity 307
(A) Horizontally aligned preferred orientation (B) Oblique preferred orientation
No stimulus OFF Baseline response No stimulus Baseline response
F
OF
Simple cell's ON ON
receptive F
field OFF OF
OFF Strong response No response
F
Light Light OF
ON
ON
F
OFF OF
OFF No response Strong response
F
OF
ON
ON
F
OFF OF
Light Light
Figure 9-29 Typical Receptive Fields for Simple V1 Cells Simple
cells respond to a bar of light in a particular orientation, such as (A) horizontal
or (B) oblique. The position of the bar in the visual field is important, because
the cell either responds (ON) or does not respond (OFF) to light in adjacent
visual field regions.
Complex cell’s
receptive field
the inhibitory regions of their receptive fields. The ganglion cells most affected
No stimulus Baseline response
by the stimulus are those lying along the edge. Ganglion cell B is inhibited
because the light falls mostly on its inhibitory surround, and ganglion cell D is
excited because its entire excitatory center is stimulated but only part of its inhibi-
tory surround is.
Consequently, information transmitted from retinal ganglion cells to the visual Stimulus at 45˚ Strong response
areas in the brain does not give equal weight to all visual field regions. Rather, it Light
emphasizes regions containing differences in luminance—areas along the edges.
So RGCs are really sending signals about edges, and edges form shapes.
Stimulus at 45˚ Strong response
Processing Shape in the Primary Visual Cortex
Now consider cells in region V1 that receive their visual inputs from LGN cells,
which in turn receive theirs from retinal ganglion cells. As you read on, think
about how these cortical cells are responding to the Clinical Focus 9-1 photograph.
Stimulus at 60˚ Weak response
Because each V1 cell receives input from multiple RGCs, the receptive fields of the
V1 neurons are much larger than those of retinal neurons. Consequently, V1 cells
respond to stimuli more complex than simply light on or light off. In particular,
these cells are maximally excited by bars of light oriented in a particular direction
rather than by spots of light. These V1 cells are therefore called orientation detectors. Stimulus at 15˚ No response
Like the ganglion cells, some orientation detectors have an on–off receptive-
field arrangement, but the arrangement is rectangular rather than circular. Visual
cortex cells with this property are known as simple cells. Typical receptive fields
for simple cells in V1 are shown in Figure 9-29. Figure 9-30 Receptive Field of a
Simple cells are not the only kind of orientation detector in the primary visual cortex; Complex Cell Unlike a simple cell’s
several functionally distinct types of neurons populate region V1. For instance, the receptive on–off response pattern, a complex cell in
fields of complex cells, such as those in Figure 9-30, are maximally excited by bars of light V1 shows the same response throughout
its circular receptive field, responding best
moving in a particular direction through the visual field. A hypercomplex cell, like a complex
to bars of light moving at a particular angle.
cell, is maximally responsive to moving bars but also has a strong inhibitory area at one end The response is reduced or absent with
of its receptive field. As illustrated in Figure 9-31, a bar of light landing on the right side of the bar of light at other orientations.
308 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
Hypercomplex cell’s the hypercomplex cell’s receptive field excites the cell; but if, for example, the bar
receptive field
lands mainly on the inhibitory area to the left, the cell’s firing is inhibited.
No stimulus Baseline response Each class of V1 neurons responds to bars of light in some way, yet this response
OFF ON results from input originating in retinal ganglion cells that respond maximally not
to bars but to spots of light. How does this conversion from responding to spots to
responding to bars take place? An example will help explain the process.
ON Strong response A thin bar of light falls on the retinal photoreceptors, striking the receptive fields
OFF of perhaps dozens of retinal ganglion cells. The input to a V1 neuron comes from a
group of ganglion cells that happen to be aligned in a row, as in Figure 9-32. That
V1 neuron is activated (or inhibited) only when a bar of light hitting the retina strikes
that particular row of ganglion cells. If the bar of light shines at a slightly different
ON Strong response
angle, only some of the retinal ganglion cells in the row are activated, so the V1
OFF
neuron is excited only weakly.
Figure 9-32 illustrates the connection between light striking the retina in a cer-
tain pattern and the activation of a simple cell in the primary visual cortex, one that
Weak response responds to a bar of light in a particular orientation. Using the same logic, we can
ON also diagram the retinal receptive fields of complex or hypercomplex V1 neurons.
Try it as an exercise yourself by adapting the format in Figure 9-32.
A characteristic of cortical structure is that the neurons are organized into func-
tional columns. The connectivity pattern in a column is vertical: inputs arrive in
No response
layer IV, then connect with cells in the other layers. Figure 9-33 shows such a col-
ON
umn, a 0.5-mm-diameter strip of cortex that includes representative neurons and
their connections.
Neurons within a cortical column have similar functions. For example,
Receptive Field of a
Figure 9-31
Figure 9-34A shows that neurons within the same column respond to lines oriented
Hypercomplex Cell A hypercomplex
cell in V1 responds to a moving bar of light in the same direction. Adjacent columns house cells responsive to different line
in a particular orientation (horizontal, e.g.) orientations. Figure 9-34B shows the cortical columns of input coming from each
anywhere in the excitatory (ON) part of its
receptive field. If most of the bar extends
into the inhibitory area (OFF), however, the Each circle Stimulation of a subset of
response is inhibited. represents the on-center ganglion cells
receptive field of a excites a V1 neuron
ganglion cell. through connections in
the LGN (not shown here).
OFF
Strong response
+ +
+
+
+ V1 neuron
+ +
ON
OFF
Weak response
– –
+
+
Figure 9-32 V1 Receptivity A V1 cell responds to
a row of ganglion cells in a particular orientation on + V1 neuron
the retina. The bar of light strongly activates a row
– –
of ganglion cells, each connected through the LGN
to a V1 neuron. The activity of this V1 neuron is most ON
affected by a bar of light at a 45° angle.
9-4 • Neuronal Activity 309
eye, discussed earlier, called ocular dominance columns. So V1 has both ori-
Visual cortex
entation columns housing neurons of similar sensitivity and ocular dominance
columns with input from one eye or the other.
Processing Shape in the Temporal Cortex
Consider neurons along the ventral stream in temporal lobe region TE. Rather
than being responsive to spots or bars of light, TE neurons are maximally
excited by complex visual stimuli, such as faces (see Figure 9-19A) or hands,
and can be remarkably specific in their responsiveness. They may be responsive I
to particular faces seen head-on, to faces viewed in profile, to the posture of the
head, or even to particular facial expressions. II
How far does this specialized responsiveness extend? Would it be practical
to have visual neurons in the temporal cortex specialized to respond to every Vertical
column
conceivable feature of objects? Keiji Tanaka (1993) approached this question by III
presenting monkeys with many three-dimensional representations of animals
and plants to find stimuli that are effective in activating particular neurons of
the inferior temporal cortex.
Having identified stimuli that were especially effective, such as faces or IV Stellate
hands, he then wondered which specific features of those stimuli are criti- cells
cal to stimulating the neurons. Tanaka found that most neurons in area TE
require rather complex features for their activation. These features include a V Pyramidal
combination of characteristics such as orientation, size, color, and texture. Fur- cell
thermore, neurons with similar but not identical responsiveness to particular
features tend to cluster in columns, as shown in Figure 9-35.
Apparently, then, an object is represented not by the activity of a single neu- VI
ron but rather by the activity of many neurons with slightly varying stimulus
specificity. These neurons are grouped in a column. This finding is important
because it provides an explanation for stimulus equivalence, recognizing an
Output Input destined
object as remaining the same despite being viewed from different orientations. for layer IV
Think of how the representation of objects by multiple neurons in a column can produce
stimulus equivalence. If each neuron in the column module varies slightly in regard to the Figure 9-33 Neural Circuit in a
features to which it responds but the effective stimuli largely overlap, the effect of small
Column in the Visual Cortex In
this three-dimensional view, sensory
inputs enter the cortical column at layer VI
(bottom) and terminate on stellate cells in
(A) (B) layer IV that synapse with pyramidal cells
Adjacent columns house neurons Ocular dominance columns receive in layers III and V. The information flow
that are responsive to slightly input from the right or left eye. is vertical. Axons of the pyramidal cells
different line orientations, forming leave the column to join other columns
an array of 180˚. or structures. Information from J. Szentagothai
(1975). The “module-concept” in cerebral architecture.
Brain Research, 95, p. 490.
I
II & III
IV
V R
L
VI R
L
Every neuron in the same column
has the same orientation bias. ocular dominance column Functional
column in the visual cortex maximally
Figure 9-34 Organization of Functional Columns in V1 responsive to information coming from one eye.
310 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
changes in incoming visual images will be minimized and we will continue to perceive
Neurons in the an object as itself.
temporal lobe form The stimulus specificity of neurons in the inferior temporal cortex in monkeys shows
columns that respond
to categories of remarkable neuroplasticity. If monkeys are trained to discriminate particular shapes to
shapes. obtain a food reward, not only do they improve their discriminatory ability but neurons
in the temporal lobe also modify their preferred stimuli to fire maximally to some of the
Temporal stimuli used in training. This result shows that the temporal lobe’s role in visual process-
lobe ing is not determined genetically but is instead subject to experience, even in adults.
We can speculate that this neuroplastic characteristic evolved because it allows the
visual system to adapt to a changing visual environment. Think of how different the
demands on your visual recognition abilities are when you move from a dense forest to
a treeless plain to a city street. The visual neurons of your temporal cortex can adapt
I
II & III to these differences (Tanaka, 1993). Experience-dependent visual neurons ensure in
IV addition that people can identify visual stimuli that were never encountered as the
V human brain evolved.
VI The preferred stimuli of neurons in the primary visual cortex are not modified by
experience. This implies that the stimulus preferences of V1 neurons are genetically
programmed. Regardless, the functions of the V1 neurons underlie the more complex
and flexible characteristics of the inferior temporal cortex neurons.
Columnar Organization
Figure 9-35
of Area TE Neurons with similar but Seeing Color
slightly different pattern selectivity cluster Scientists have long wondered why—and how—we see a world so rich in color. One hypothesis
in vertical columns, perpendicular to the on the why is that color vision evolved first in the great apes, specifically in apes that eat fruit.
cortical surface.
Chimpanzees and humans are members of this family. Over their evolution, both species
Section 1-4 recounts several ideas on how the have faced plentiful competition for ripe fruits—from other animals, insects, and each other.
primate lifestyle, including diet, encouraged Scientists suspect that color vision gave the great apes a competitive evolutionary advantage.
the evolution of complex nervous systems. An explanation of color vision has its roots in the Renaissance 600 years ago in Italy. Paint-
ers of the time discovered that they could obtain the entire range of colors in the visual world
by mixing only three colors of paint (red, blue, and yellow). This is the process of subtractive
(A)
color mixing shown in Figure 9-36A.
We now know that such trichromatic color mixing is a property of the cones in the retina.
Subtractive color mixing works by removing light from the mix. This is why matte black
surfaces reflect no light: the darker the color, the less light it contains.
Conversely, additive color mixing increases light to make color (Figure 9-36B). The lighter
the color, the more light it contains, which is why a white surface reflects the entire visible
spectrum. Unlike those of paint, the primary colors of light are red, blue, and green. Light
of different wavelengths stimulates the three cone receptor types in different ways. It is the
ratio of activity of these three receptor types that forms our impressions of colors.
Trichromatic Theory
According to the trichromatic theory, the color we see—say, blue at short 400-nanometer
(B) wavelengths, green at medium 500 nm, and red at long 600 nm—is determined by the relative
responses of the corresponding cone types (see Figure 9-6). If all three types are equally
active, we see white.
Trichromatic theory predicts that if we lack one cone receptor type, we cannot process as
fritz goro/time & life pictures/getty images
many colors as we could with all three. This is exactly what happens when a person is born
with only two cone types. The colors this person cannot perceive depend on which receptor
type is missing, as illustrated in Research Focus 9-3, Color-Deficient Vision.
Figure 9-36 Color Mixing (A) Subtractive color mixing absorbs light waves that we see
as red, blue, or yellow. When all visible wavelengths are absorbed, we see black. (B) Additive
color mixing reflects light waves that we see as red, blue, and green. When all visible
wavelengths are reflected, we see white.
9-4 • Neuronal Activity 311
ReseaRCh F cus 9-3
Color-Deficient Vision
Most people’s retinas contain three cone types. These people have tritanopia. The frequency of each condition is about 1 percent in men and
trichromatic vision. But some people are missing one or more cone 0.01 percent in women. Having only a partial lack of one cone type, most
types and are thus often mistakenly said to be color-blind. Mistakenly, commonly the green cone, also is possible. This condition afflicts about
because people who have two types of cones still can distinguish lots of 5 percent of men and 0.4 percent of women.
colors, just not as many as people with three cones can. The illustration provides a simple approximation, compared with
To have no color vision at all, one would have to have only one type of trichromats (left), of what people with protanopia (center) or deuter-
photoreceptor, rods. This is a rare occurrence, but we do have a friend anopia (right) see. They still see plenty of color, but that color is largely
who has no concept of color. It has led to a lifetime of practical jokes, different from the color trichromats see. Many domestic animals (dogs,
because others (especially his wife) must choose clothing colors that cats, and horses among them) have deuteranopia, which actually gives
coordinate for him to wear. them an advantage in seeing objects that appear camouflaged to trichro-
The complete lack of red cones leads to a condition called protano- mats. In fact, the military often use humans with deuteranopia to help
pia; the lack of green cones is deuteranopia; the lack of blue cones is see through camouflage.
dr. terrace l. waggoner/www.ColorVisiontesting.com
Image as viewed by a trichromat Protanopia: image as viewed by an Deuteranopia: image as viewed by an
observer observer lacking red cones observer lacking green cones
The mere presence of cones in an animal’s retina does not mean that the animal has color
trichromatic theory Explanation of color
vision. It simply means that the animal has photoreceptors particularly sensitive to light.
vision based on the coding of three primary
Many animals lack color vision as we know it, but the only animal with eyes known to have
colors: red, green, and blue.
no cones at all is a fish, the skate.
Opponent Processes
Although the beginning of color perception in the cones follows the trichromatic model, suc-
ceeding levels of color processing use a different strategy. Try staring first at the red and blue
box in Figure 9-37 for about 30 seconds then at the white box next to it. When you shift your
Demonstrating
Figure 9-37
Opposing Color Pairs Stare at the
rectangle on the left for about 30 seconds.
Then stare at the white box on the right.
You will see an afterimage of green on the
red side and of yellow on the blue side.
312 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
gaze to the white surface, you will see an afterimage in the colors opposite to red
(A) White light Baseline response
and blue—green and yellow. Conversely, if you stare at a green and yellow box and
then shift to white, you will see a red and blue afterimage. Such afterimages lead
to the sense that there are actually four basic colors (red, green, yellow, and blue).
A characteristic of RGCs explains the two opposing pairs of four basic colors.
(B) Red light Strong response Remember that RGCs have an on–off and center–surround organization. Stimu-
lation to the center of the cell’s receptive field is either excitatory (in some cells)
or inhibitory (in other cells), whereas stimulation to the periphery of the recep-
tive field has the opposite effect (see Figure 9-26).
This arrangement can be adapted to produce color-opponent cells. If one
Strong response
wavelength of light produced excitation and another inhibition, cells would
(C)Green light evolve that are excited by red and inhibited by green (or vice versa), as would
cells that are excited by blue and inhibited by yellow (or vice versa). Red–green
and blue–yellow would therefore be linked to each other as color opposites, or
(C) Green light Weak response opponents.
In fact, about 60 percent of human retinal ganglion cells are color-sensitive
in this way, with the center responsive to one wavelength and the surround to
another. The most common opponent-process pairing, shown in Figure 9-38,
is medium-wavelength (green) versus long-wavelength (red), but we also have
(D) Red and Very strong response
blue versus yellow RGCs. Most likely, opponent-process cells evolved to
green light
enhance the relatively small differences in spectral absorption among the three
cone types.
Cortical neurons in region V1 also respond to color in an opponent-process
manner reminiscent of retinal ganglion cells. Recall that color inputs in the pri-
(E) Green and No response
red light mary visual cortex go to the blobs that appear in sections stained for cytochrome
oxidase (see Figure 9-17). These blobs are where the color-sensitive cells are found.
Figure 9-39 models how the color-sensitive cells in the blobs are inserted amid
the orientation-sensitive and ocular dominance columns. The primary visual cor-
Figure 9-38 Opponent-Color tex thus appears to be organized into modules that include ocular dominance and
Contrast Response (A) A red–green orientation-sensitive columns as well as blobs. Think of V1 as composed of several thousand
color-sensitive RGC responds weakly to modules, each analyzing color and contour for a particular visual region. This organization
white light on its center and surround allows the primary visual cortex to perform several functions concurrently.
because red and green cones absorb
How do neurons in the visual system beyond V1 process color? You have already learned
white light to similar extents, so their
inputs cancel out. (B) The cell responds that cells in region V4 respond to color, but in contrast with the cells in region V1, these
strongly to a spot of red light in its center
as well as to red’s paired wavelength,
green, in the surround. (c) It is strongly
inhibited by a small spot of green in
its center. (D) The RGC responds very
strongly to simultaneous illumination of Striate cortex
the center with red and the surround with
green. (E) It is completely inhibited by the Color-sensitive
simultaneous illumination of the center blobs
with green and the surround with red.
Hypercolumn
Figure 9-39 V1 Modules A model of striate cortex showing the orientation-
R
sensitive columns, ocular dominance columns, and color-sensitive blobs as L
Orientation R
composed of two hypercolumns. Each consists of a full set (red and blue) of columns L
orientation-sensitive columns spanning 180° of preferred angle as well as a pair Ocular dominance
of blobs. All cells in the hypercolumn share the same receptive field. columns
9-4 • Neuronal Activity 313
V4 cells do not respond to particular wavelengths. Rather, they are
responsive to different perceived colors, with the center of the field
being excited by a certain color and the surround being inhibited.
Speculation swirls about the function of these V4 cells. One idea
is that they are important for color constancy, the property of percep-
tion whereby colors appear to remain the same relative to one another
despite changes in light. For instance, were you to look at a bowl of
wired.com via tumblr
fruit through light-green glasses, the fruit would take on a greenish
tinge, but bananas would still look yellow relative to red apples. If you
removed all the fruit except the bananas and looked at them through
the tinted glasses, the bananas would appear green because the color
you perceive is isolated relative to any other. Monkeys with V4 lesions Color Constancy Depending on the viewer, the dress in the
lose color constancy, though they can discriminate different color center photo is perceived as either white and gold or blue and
black. The image is color-balanced, at left, to show the dress as
wavelengths.
white and gold, at right, as blue and black. Which is the original?
Neuronal Activity in the Dorsal Stream
A striking characteristic of many cells in the visual areas of parietal cortex is that they are vir-
tually silent to visual stimulation when a person is under anesthesia. This is true of neurons
in the posterior parietal regions of the dorsal stream. In contrast, cells in the visual temporal
cortex do respond to visual stimulation when a person is anesthetized.
The silence on the part of neurons in the posterior parietal cortex under anesthesia makes
sense if their role is to process visual information for action. In the absence of action when a
person is unconscious, there is no need for processing. Hence, the cells are quiescent.
Cells in the dorsal stream are of many types, their details varying with the nature of
the movement in which a particular cell takes part. One interesting cell category processes
the visual appearance of an object to be grasped. If a monkey is going to pick up an apple,
for instance, these cells respond even when the monkey is only looking at the apple. The opponent process Explanation of color
cells do not respond when the monkey encounters the same apple if no movement is to vision that emphasizes the importance of the
be made. apparently opposing color pairs: red versus
These dorsal stream cells also respond if the monkey merely watches another monkey green and blue versus yellow.
making movements to pick up the apple. Apparently, the cells have some understanding of color constancy Phenomenon whereby
what is happening in the external world. But that understanding is always related to action an object’s perceived color tends to remain
performed with respect to visually perceived objects. These cells led David Milner and constant relative to other colors, regardless of
Mel Goodale (2006) to conclude that the dorsal stream is a how visual system. changes in illumination.
9-4 review
Neuronal Activity
Before you continue, check your understanding.
1. Neurons in the primary visual cortex respond to properties of shapes, especially to
oriented in a certain direction.
2. Recognition of complex visual stimuli such as faces is completed in the
lobe.
3. The idea that the color we see is determined by the relative responses of the three cone
types in the retina is called .
4. Retinal ganglion cells mediate color vision by processes.
5. Describe the opponent process in the retinal ganglion cells.
Answers appear at the back of the book.
For additional study tools, visit : The blue and black dress at right is the
www.macmillanhighered.com/launchpad/kolb5e original.
314 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
9-5 The Visual Brain in Action
Anatomical and physiological studies of brain systems leave one key question unanswered:
How do all of the cells in these systems act together to produce a particular function? One
way to answer this question is to evaluate what happens when parts of the visual system are
dysfunctional. Then we can see how these parts contribute to the workings of the whole.
We use this strategy to examine the neuropsychology of vision—the study of the visual brain
Consequences of
Figure 9-40 in action.
Lesions in Region V1 The shaded
areas indicate regions of visual loss.
(A) A complete lesion of V1 in the left
Injury to the Visual Pathway Leading
hemisphere results in hemianopia affecting to the Cortex
the right visual field. (B) A large lesion What happens when parts of the visual pathway leading from the eye to the cortex are
of the lower lip of the calcarine fissure
injured? For instance, destruction of the retina or optic nerve of one eye produces monocular
produces quadrantanopia that affects
most of the upper right visual quadrant. blindness, the loss of sight in that eye. Partial destruction of the retina or optic nerve pro-
(c) A smaller lesion of the lower lip of duces a partial loss of sight in one eye, restricted to the visual field region that has severed
the calcarine fissure results in a smaller connections to the brain.
scotoma. Injuries to the visual pathway beyond the eye also produce blindness. For example, com-
plete cuts of the optic tract, the LGN, or cortical region V1 result in homonymous hemianopia,
Left visual
cortex blindness of one entire side of the visual field, as shown in Figure 9-40A. We encountered
this syndrome in Focus 9-1, the story of D. B.’s lesion in region V1. Should a lesion in one of
these areas be partial, as is often the case, the result is quadrantanopia, destruction of only
a part of the visual field, illustrated in Figure 9-40B.
Figure 9-40C shows that small lesions in V1 often produce small
Calcarine fissure blind spots, or scotomas, in the visual field. Focus 9-1 observes that
(A) Hemianopia Left visual field Right visual field scotomas can be a warning symptom for migraine sufferers. But
brain-injured people are often totally unaware of them. One reason
is that the eyes are usually moving.
We make tiny, involuntary eye movements almost constantly.
Because of this usually constant eye motion, called nystagmus, a sco-
toma moves about the visual field, allowing the intact brain regions
to perceive all the information in that field. If the eyes are temporar-
ily held still, the visual system actually compensates for a scotoma
Injury through pattern completion—filling in the hole, so to speak—so that
(B) Quadrantanopia the people and objects in the visual world are perceived as whole.
The result: a seemingly normal set of perceptions.
The visual system may cover up a scotoma so successfully that
its presence can be demonstrated to the patient only by tricking
the visual system. The trick is to place an object entirely within
the scotoma and without allowing the patient to shift gaze, asking
what the object is. If the patient reports seeing nothing, to confirm
the existence of a blind area the examiner moves the object out of
Injury the scotoma so that it suddenly appears in the intact region of the
(C) Scotoma visual field.
This technique is similar to demonstrating the presence of the
blind spot that is due to the optic disc (as in Figure 9-4). When a per-
son is looking at an object with only one eye, the brain compensates
glowimages/getty images
for the scotoma in the same way as for the optic disc’s blind spot. As
a result, the person does not notice the scotoma.
Thus the type of blindness offers clues about where in the vis-
ual pathway the cause of the problem lies. If the loss of vision is
Injury in one eye only, the problem must be in that eye or its optic nerve;
9-5 • The Visual Brain in Action 315
if the vision loss affects both eyes, the problem most likely is in the brain. Many people
homonymous hemianopia Blindness of an
have difficulty understanding why a person with damage to the visual cortex has diffi-
entire left or right visual field.
culty with both eyes. They fail to realize that the visual field, not the eye, is represented
in the brain. quadrantanopia Blindness of one quadrant
of the visual field.
Beyond region V1, the nature of visual loss caused by injury is considerably more com-
plex. It is also very different in the ventral and dorsal streams. We therefore look at each scotoma Small blind spot in the visual field
pathway separately. caused by migraine or by a small lesion of the
visual cortex.
visual-form agnosia Inability to recognize
Injury to the What Pathway objects or drawings of objects.
We have encountered an example of damage to the what pathway: the case of D. B. in Focus
9-1. He appeared to be blind in his affected visual field but could point to the location of
blinking lights in that field, suggesting that some part of his visual system was working.
An even more dramatic example of ventral stream injury comes from the case of D. F., a
35-year-old woman who, while taking a shower, was poisoned by carbon monoxide (CO)
from a faulty gas-fueled water heater. The length of her exposure is unclear, but when her
roommate found her, the shower was running cold. CO poisoning can cause several kinds of
neurological damage, as discussed in Clinical Focus 9-4, Carbon Monoxide Poisoning; the
result for D. F. was an extensive lesion of the lateral occipital region, including cortical tissue
in the ventral visual pathway.
D. F.’s principal deficit was visual-form agnosia, an inability to recognize objects, Section 9-2 describes damage to the
real or drawn (see Farah, 1990). Not only was D. F. unable to recognize objects, especially temporal lobe area that causes facial agnosia.
line drawings of objects, she could neither estimate their size and their orientation nor
CliniCal F cus 9-4
Carbon Monoxide Poisoning
Brain damage from carbon monoxide (CO) poisoning is usually caused Postmortem examination of this woman’s brain found that although
either by a faulty furnace or by motor vehicle exhaust fumes. The blood the parietal and temporal lobes were damaged extensively, as shown in
absorbs carbon monoxide gas, resulting in swelling and bleeding of the accompanying diagram, her speech areas were intact. Geschwind
the lungs and anoxia (loss of oxygen) in the brain. The cerebral cortex, proposed that she could not comprehend speech because the words she
hippocampus, cerebellum, and striatum are especially sensitive to CO- heard did not arouse associations in other parts of her cortex.
induced anoxia. She could, however, repeat sentences because the internal connections
Only a small proportion of people who are subjected to CO poison- of the speech regions were undamaged. Geschwind did not comment on
ing have permanent neurological symptoms. Among those who do, the whether this woman had agnosia, but it is likely that she did. The difficulty
symptoms are highly variable. Most common are cortical blindness would be in diagnosing agnosia in a person who is unable to communicate.
and various agnosias, as seen in case D. F. Many also have language
difficulties.
The peculiarities of the language difficulties are shown clearly in a Parietal
Frontal lobe
young woman whose case was described by Norman Geschwind (1972). lobe
Geschwind studied this patient for 9 years after her accidental poison-
ing. She required complete nursing care during this time, never uttered
spontaneous speech, and did not comprehend spoken language. None- Speech
Speach
theless, she could repeat with perfect accuracy sentences that had just
been said to her.
She could also complete certain well-known phrases. For example,
if she heard “Roses are red,” she would say, “Roses are red, violets are Temporal Occipital
lobe lobe
blue, sugar is sweet, and so are you.” She could also learn new songs.
She did not appear to understand the content of the songs, yet with only
a few repetitions, she began to sing along. Eventually, she could sing the Areas damaged by carbon monoxide poisoning are shown in red in
song spontaneously, making no errors in either words or melody. this postmortem diagram of Geschwind’s patient’s brain.
316 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
Original J. W.'s copy copy drawings. Likewise, as Figure 9-41 illustrates, patient J. W. also fails to recognize or
copy simple drawings.
Marlene Behrmann, director Cognitive neuroscience lab,
Clearly, D. F.’s lesion interfered with her ventral stream what pathway. Remarkably,
despite her inability to identify objects or to estimate their size and orientation, D. F. retained
the capacity, illustrated in Figure 9-42, to appropriately shape her hand when reaching out to
grasp something. Goodale, Milner, and their research colleagues (1991) studied D. F. exten-
sively for years and devised a way to demonstrate D. F.’s skill at reaching for objects.
Carnegie Mellon university
The middle column in Figure 9-43 shows the grasp patterns of a control participant
(S. H.) when she picks up something irregularly shaped. S. H. grasps the object along which-
ever of the two axes makes it easier to pick up. When D. F. is presented with the same task,
shown in the left-hand column, she is as good as S. H. at placing her index finger and thumb
on appropriately opposed grasp points.
Injury to the Ventral
Figure 9-41
Clearly, D. F. remains able to use the structural features of objects to control her visually
Stream J. W. survived a severe heart guided grasping movements, even though she is unable to interpret these same features.
attack while exercising and later, anoxia. This result demonstrates once more that we are consciously aware of only a small part of the
Subsequently, he was unable to recognize sensory processing that goes on in the brain. Furthermore, D. F.’s ability to use structural
the simple line drawings on the left and features of objects for guiding movement but not for perceiving shapes again shows us that
copied them poorly (right).
the brain has separate systems for each type of visual operation.
D. F.’s lesion is quite far back in the ventral visual pathway. More anterior lesions pro-
duce other deficits, depending on the exact location. For example, J. I., described by Oliver
Sacks and Robert Wasserman (1987), was an artist who developed complete color deficiency
owing to a cortical lesion presumed to be in region
V4. His principal symptom was achromatopsia, or
color agnosia. Despite his inability to distinguish
any colors whatsoever, J. I.’s vision appeared other-
wise unaffected.
Figure 9-42 Visual Guidance You may
Similarly, L. M., a woman described by Josef
consciously reach for an object such as
a pen or a mug, but your hand forms the Zihl and his colleagues (1983), lost her ability to
appropriate posture automatically, without detect movement after a lesion presumed to be
your conscious awareness. Figure 11-1 in region V5. In her case, objects either vanished
details this type of sequentially organized when they moved or appeared frozen despite their
movement.
movement. L. M. had particular difficulty pouring
tea into a cup, because the fluid appeared to be fro-
zen in midair. Yet she could read, write, and recognize objects, and she appeared to have
normal form vision—until objects moved.
These varied cases demonstrate that cortical injuries in the ventral stream all somehow
interfere with determining what things are or are like or are doing. In each case, the symp-
toms are somewhat different, however, which is thought to be indicative of damage to differ-
ent subregions or substreams of the ventral visual pathway.
Injury to the How Pathway
In 1909, R. Bálint described a rather peculiar set of visual symptoms associated with a bilat-
eral parietal lesion. The patient had full visual fields and could recognize, use, and name
objects, pictures, and colors normally. But he had a severe deficit in visually guided reach-
ing, even though he could still make accurate movements directed toward his own body
Section 11-5 details the somatic senses, (presumably guided by tactile or proprioceptive feedback from his joints). Bálint called this
including proprioception, or body awareness. syndrome optic ataxia.
Since Bálint’s time, many descriptions of optic ataxia associated with parietal injury have
been recorded. Goodale has studied several such patients, one of whom is a woman identi-
fied as R. V. (Milner & Goodale, 2006). In contrast with patient D. F.’s visual form agnosia,
optic ataxia Deficit in the visual control of R. V.’s perception of drawings and objects was normal, but she could not guide her hand to
reaching and other movements. reach for objects.
9-5 • The Visual Brain in Action 317
Each line passes through
the points where the index
finger and thumb first
contacted the perimeter of
the shape on individual
trials in which the subjects
and the control were
instructed to pick up the
shape.
2 …but she and S. H. both
place finger and thumb on
appropriately opposed points
on either side of the shapes.
Grasp
Figure 9-43
Patterns The Milner–Goodale
experiments confirm that the brain
3 R. V., whose object has different systems for visual
recognition is unimpaired, object recognition and visual
chooses unstable grasp
1 D. F. cannot recognize guidance of movement. Information
points that often do not
these shapes,… from A. D. Milner & M. A. Goodale (1995). The
pass through the object’s
D. F. S. H. R. V. center of mass.
Visual Brain in Action (p. 127). Oxford: Oxford
(ventral-stream (control) (dorsal-stream University Press.
deficit) deficit)
The rightmost column in Figure 9-43 shows that, when asked to pick up the same irregu-
larly shaped objects that D. F. could grasp normally, R. V. often failed to place her fingers on
the appropriate grasp points, even though she could distinguish the objects easily. In other
words, although R. V.’s perception of an object’s features was normal for the task of describ-
ing that object, her perception was not normal for the task of visually guiding her hand to
reach for the object.
To summarize, people with damage to the parietal cortex in the dorsal visual stream can
see perfectly well, yet they cannot accurately guide their movements on the basis of visual
information. Guidance of movement is the dorsal stream’s function. In contrast, people with
damage to the ventral stream cannot perceive objects, because object perception is a ventral
stream function. Yet these same people can guide their movements to objects on the basis
of visual information.
The first kind of patient, like R. V., has an intact ventral stream that analyzes the visual
characteristics of objects. The second kind of patient, like D. F., has an intact dorsal stream
that visually directs movements. Comparing the two types of cases enables us to infer the
visual functions of the dorsal and ventral streams.
9-5 review
The Visual Brain in Action
Before you continue, check your understanding.
1. Cuts completely through the optic tract, LGN, or V1 produce .
2. Small lesions of V1 produce small blind spots called .
3. Destruction of the retina or the optic nerve of one eye produces .
4. The effect of severe deficits in visually guided reaching is called .
5. Contrast the effects of injury to the dorsal stream and the effects of injury to the ventral
stream.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
318 Chapter 9 • HOW DO WE SENSE, PERCEIVE, AND SEE THE WORLD?
summary
9-1 Nature of Sensation and Perception produces our visual experience. Each functional column in the cortical
Sensory systems allow animals, including ourselves, to adapt. Animals visual regions is about 0.5 mm in diameter and extends to the depth
adapted to different environments vary widely in their sensory abilities. of the cortex. The visual system cortical columns are specialized for
What is distinctive about humans is the extent to which we can transform processes such as analyzing line orientation or comparing similar
sensations into perceptual information to mediate aspects of language, shapes as complex as faces.
music, and culture. For each sense, mammals represent the world in
topographic maps that form neural–spatial representations in the cortex. 9-4 Neuronal Activity
Neurons in the ventral stream are selective for aspects of shape.
9-2 The Visual System’s Function Anatomy Those in the visual cortex are maximally responsive to lines of different
Like all sensory systems, vision begins with receptor neurons. The orientations. Upstream, cells in the inferior temporal cortex are
visual photoreceptors (rods and cones) at the back of the eye in the responsive to shapes, some abstract, and in other cases, to concrete
retina transduce the physical energy of light waves into neural activity. forms as complex as hands or faces.
Rods are sensitive to dim light. Cones, which are sensitive to bright light, Cones in the retina are maximally responsive to different light
mediate color vision. Each of the three cone types is maximally sensitive to wavelengths, roughly corresponding to colors we perceive as green,
a different wavelength—short, medium, or long. We see these wavelengths, blue, and red. At the next level, RGCs’ center–surround organization
respectively, as the colors blue, green, or red; thus the short, medium, and facilitates their opponent-process function: the cells are excited by one
long cone receptors often are referred to as blue, green, or red. hue and inhibited by another, as for example, red versus green; blue
Retinal ganglion cells receive input from photoreceptors through versus yellow.
bipolar cells and send their axons out from the retinas to form the optic Color-sensitive cells in V1, located in the blobs, also have opponent-
nerve. P ganglion cells receive input mostly from cones and convey process properties. Cells in region V4 respond to colors that we perceive
information about color and fine detail. M cells receive input from rods rather than to particular visible light wavelengths. Both the luminance
and convey information about luminance and movement but not color. and the color of nearby objects influence the colors we perceive.
The optic nerve forms two distinct major routes into the brain. The
geniculostriate pathway synapses first in the thalamic LGN nucleus, 9-5 The Visual Brain in Action
then in V1. The tectopulvinar pathway synapses first in the midbrain’s Upon entering the brain, information from the left and right visual fields
tectum (superior colliculus), then in the pulvinar of the thalamus, and proceeds on the optic nerve to the brain’s right and to its left sides,
finally in the temporal and parietal visual cortex areas. A few optic respectively. As a result of these contralateral connections, damage to
nerve fibers also form the retinohypothalamic tract, which functions the visual areas on one side of the brain results in visual disturbance
in part to control circadian rhythms. in both eyes, because half of each retina’s visual field is represented
Among the visual regions in the occipital cortex, V1 and V2 carry on each side of the brain.
out multiple functions; the remaining regions (V3, V3A, V4, and V5) Specific visual functions are localized to different brain regions, so
are specialized. Visual information flows from the thalamus to V1 and local damage results in the loss of a particular function. Damage to region
V2, then divides to form the visual stream pathways. The unconscious V4 produces a loss of color constancy, for example; damage to regions
dorsal stream aids in guiding movements visually, whereas the in the parietal cortex inhibits the contralateral hand’s grasping ability.
conscious ventral stream aids in visual object perception. As summarized in the illustration, the visual streams perform
distinct functions: (A) object recognition (the what) in the ventral
9-3 Location in the Visual World stream and (B) visual action (the how) in the dorsal stream. We are
At each step along the visual pathways, neuronal activities are largely unconscious of the dorsal stream’s ongoing online analyses,
distinctly different; it is the summed neural activity in all regions that that allow us to make accurate movements in relation to objects.
(A) Object recognition (what) (B) Action (how)
Temporal visual Parietal visual
areas areas
Ventral stream Dorsal stream
V3 V4
V5 V3A
(dynamic (color
(motion) (form)
(A) The ventral stream begins in V1 and flows form) form)
through V2 to V3 and V4, then into the temporal
visual areas. (B) The dorsal stream begins
in V1 and flows through V5 and V3A to the V2 V2
posterior parietal visual areas. Double-headed
arrows show information flow between the
two streams—between recognition and action,
V1 V1
perception and behavior.
Key Terms 319
Key terms
auditory flow, p. 286 geniculostriate system, p. 297 parvocellular (P) cell, p. 295 rod, p. 293
blind spot, p. 293 homonymous hemianopia, perception, p. 289 scotoma, p. 315
blob, p. 299 p. 315 photoreceptor, p. 289 sensation, p. 289
color constancy, p. 313 luminance contrast, p. 306 primary visual cortex (V1), striate cortex, p. 297
cone, p. 293 magnocellular (M) cell, p. 295 p. 299 tectopulvinar system, p. 297
cortical column, p. 299 ocular dominance column, quadrantanopia, p. 315 topographic map, p. 289
p. 309 receptive field, p. 286
dorsal stream, p. 297 trichromatic theory, p. 311
opponent process, p. 313 retina, p. 289
extrastriate (secondary visual) ventral stream, p. 297
cortex (V2–V5), p. 299 optic ataxia, p. 316 retinal ganglion cell (RGC), visual field, p. 301
facial agnosia, p. 301 optic chiasm, p. 295 p. 295
visual-form agnosia, p. 315
fovea, p. 293 optic flow, p. 286 retinohypothalamic tract, p. 297
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
this page left intentionally blank
ch a p te r
10 How Do We Hear, ReseaRch Focus 10-1 Evolution of languagE and Music
10-1 sound Waves: stimulus FoR audition
Speak, and Make Physical ProPErtiEs of sound WavEs
PErcEPtion of sound
Music? 10-2
ProPErtiEs of languagE and Music as sounds
Functional anatomy oF the auditoRy system
structurE of thE Ear
auditory rEcEPtors
clinical Focus 10-2 otoacoustic EMissions
PathWays to thE auditory cortEx
auditory cortEx
ReseaRch Focus 10-3 sEEing With sound
10-3 neuRal activity and heaRing
hEaring Pitch
dEtEcting loudnEss
dEtEcting location
dEtEcting PattErns in sound
10-4 anatomy oF language and music
ProcEssing languagE
clinical Focus 10-4 lEft-hEMisPhErE dysfunction
ProcEssing Music
clinical Focus 10-5 cErEbral anEurysMs
ReseaRch Focus 10-6 thE brain’s Music systEM
10-5 auditoRy communication in nonhuman species
birdsong
Echolocation in bats
Katherine Streeter
321
322 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
ReseaRch F cus 10-1
Evolution of Language and Music
The finding that modern humans (Homo sapiens) made music early on about 30,000 years ago. During some of that time they coexisted in
implies that music has been important in our evolution. Behavioral sci- Europe and the Middle East with Homo sapiens, whom they resembled
entists have shown that music plays as central a role in our social and in many ways because they shared a common ancestor. In some locales,
emotional lives as language does. the two species may have shared resources and tools.
Thomas Geissmann (2001) noted that among most of the 26 species Researchers long hypothesized that Neanderthal culture was
of singing primates, males and females sing duets. All singing primates significantly less developed than that of early modern humans. Yet
are monogamous, suggesting that singing may somehow relate to sexual Neanderthals had a brain as large as or larger than that of Homo
behaviors. Music may also play a role in primates’ parenting behaviors. sapiens, with whom they appear to have shared many cultural simi-
The human brain is specialized for analyzing certain aspects of music larities. Neanderthals buried their dead with artifacts, which implies that
in the right temporal lobe, which complements the left temporal lobe they held spiritual beliefs, but we have no conclusive evidence that they
specialization for analyzing aspects of speech. Did music and language made visual art. In contrast, Homo sapiens began painting on cave walls
evolve simultaneously in our species? Possibly. some 30,000 years ago, near the end of the Neanderthal era.
Neanderthals (Homo neanderthalensis) have long fascinated research- Anatomically, some skeletal analyses of the larynx suggest that
ers. The species originated about 300,000 years ago and disappeared Neanderthals’ articulated language ability was less well developed than
their Homo sapiens contemporaries’. What about music? It appears that
Neanderthals did make music.
Shown in the accompanying photo is the bone flute found in 1995
Czech Poland by Ivan Turk, a paleontologist at the Slovenian Academy of Sciences
Germany Republic
Slovakia in Ljubljana. Turk was excavating a cave in northern Slovenia used by
Neanderthals long ago as a hunting camp. Buried in the cave among a
Austria
Hungary cache of stone tools was the leg bone of a young bear that looked as if it
had been fashioned into a flute.
Croatia The bone has holes aligned along one side that could not have been
Italy Bosnia Serbia made by gnawing animals. Rather, the holes’ spacing resembles posi-
tions found on a modern flute. But the bone flute is at least 43,000 years
Archive of the Institute of Archaeology ZRC SAZU,
photo: Marko Zaplatil
old—perhaps as old as 82,000 years. All the evidence suggests that
Neanderthals, not modern humans, made the instrument.
Bob Fink, a musicologist, analyzed the flute’s musical qualities. He
found that an eight-note scale similar to a do-re-mi scale could be played
on the flute, but compared with the scale most familiar in European
music, one note was slightly off. That blue note, a staple of jazz, is stan-
dard in musical scales throughout Africa and India today.
The similarity between Neanderthal and contemporary musical
scales encourages us to speculate about the brain that conceived this
ancient flute. Like modern humans, Neanderthals probably had comple-
Ancient Bone Flute The hole alignment in this piece of mentary hemispheric specialization for language and music. This may
bear femur, found in a cave in northern Slovenia, suggests that have contributed to the two species cohabitating and to interbreeding
Neanderthals made a flute from the bone and made music with that led to 1 to 4 percent of alleles being of Neanderthal origin in humans
the flute. whose lineages, in the last 30,000 years, come from outside of Africa.
Language and music are universal among humans. The oral language of every known
Language is independent of making or culture follows similar basic structural rules, and people in all cultures make and enjoy
perceiving sounds, as sign language music. Music and language allow us both to organize and to interact socially. Like music,
demonstrates. In this chapter, however, language probably improves parenting. People who can communicate their intentions to one
language refers to speech. another and to their children presumably are better parents.
Humans’ capacities for language and music are linked conceptually because both are
based on sound. Understanding how and why we engage in speech and music is this chapter’s
goal. We first examine the physical energy that we perceive as sound, then how the human
ear and nervous system detect and interpret sound. We next examine the complementary
10-1 • Sound Waves: Stimulus for Audition 323
neuroanatomy of human language and music processing. Finally, we investigate how two
other species, birds and bats, interpret and utilize auditory stimuli.
10-1 Sound Waves: Stimulus for
Audition
What we experience as sound is the brain’s construct, as is what we see. Without a brain, The nervous system produces movement
sound and sight do not exist. When you strike a tuning fork, the energy of its vibrating prongs within a perceptual world the brain
displaces adjacent air molecules. Figure 10-1 shows how, as one prong moves to the left, air constructs.
molecules to the left compress (grow more dense) and air molecules to the right become more
rarefied (grow less dense). The opposite happens when the prong moves to the right. The
undulating energy generated by this displacement of molecules causes compression waves of
changing air pressure to emanate from the fork. These sound waves move through compress-
ible media—air, water, ground—but not through the vacuum of outer space.
sound wave Mechanical displacement of
The top graph in Figure 10-2 represents waves of changing air pressure emanating from a molecules caused by changing pressure
tuning fork by plotting air molecule density against time at a single point. The bottom graph that possesses the physical properties of
shows how the energy from the right-hand prong of the tuning fork moves to make the air frequency, amplitude, and complexity. Also
pressure changes associated with a single cycle. A cycle is one complete peak and valley on compression wave.
the graph—the change from one maximum or minimum air pressure level of the sound wave frequency Number of cycles a wave
to the next maximum or minimum level, respectively. completes in a given time.
hertz (Hz) Measure of sound wave
Physical Properties of Sound Waves frequency (repetition rate); 1 hertz equals
Light is electromagnetic energy we see; sound is mechanical energy we hear. Sound wave 1 cycle per second.
energy has three physical attributes—frequency, amplitude, and complexity—produced by
the displacement of air molecules and summarized in Figure 10-3. The auditory system ana-
lyzes each property separately, just as the visual system analyzes color and form separately. Section 9-4 explains how we see shapes and
colors.
Sound Wave Frequency
Sound waves in air travel at a fixed speed of 1100 feet (343 meters) per second and more than
four times faster in water, but sound energy varies in wavelength. Frequency is the number
of cycles a wave completes in a given amount of time. Sound wave frequencies are measured
in cycles per second, called hertz (Hz), for the German physicist Heinrich Rudolph Hertz.
One hertz is 1 cycle per second, 50 hertz is 50 cycles per second, 6000 hertz is 6000 cycles
per second, and so on. Sounds we perceive as low pitched have fewer wave frequencies
(A) (B) Compression (C) Rarefication
Rarefication Compression
Waves of pressure
changes in air molecules
are sound waves.
Figure 10-1 How a Tuning Fork Produces Sound Waves (A) The fork is still, and
air molecules are distributed randomly. (B) When struck, the fork’s right arm moves to the
left; air on the leading edge compresses and air on the trailing edge rarefies. (c) As the arm
rebounds, air to the right compresses and air to the left rarefies.
324 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
One cycle Properties of Sound Waves
Normal air pressure Frequency and pitch perception
The rate at which sound waves vibrate is
(molecule density)
+ measured as cycles per second, or hertz (Hz).
Air pressure
Low frequency High frequency
(low-pitched sound) (high-pitched sound)
– Amplitude and perception of loudness
Intensity of sound is usually measured in
decibels (dB).
0 1 2 3 4 High amplitude Low amplitude
Time (s) (loud sound) (soft sound)
Complexity and timbre (perception of
sound quality)
+ Unlike the pure tone of a tuning fork, most
(molecule density)
sounds are a mixture of frequencies. A
Air pressure
sound's complexity determines its timbre, Simple Complex
allowing us to distinguish, for example, a (pure tone) (mix of frequencies)
trombone from a violin playing the same note.
– Figure 10-3 Physical Dimensions of Sound Waves The frequency, amplitude,
and complexity of sound wave sensations correspond to the perceptual dimensions of pitch,
loudness, and timbre.
Fork moves Fork moves
right left
(fewer cycles per second), whereas sounds that we perceive as high pitched have more wave
frequencies (many cycles per second), as shown in the top panel of Figure 10-3.
Just as we can perceive light only at visible wavelengths, we can perceive sound waves
only in the limited range of frequencies plotted in Figure 10-4. Healthy young adult humans’
hearing range is from about 20 to 20,000 hertz. Many animals communicate with sound:
their auditory system is designed to interpret their species-typical sounds. After all, what is
Visualizing a Sound
Figure 10-2 the point in making complicated songs or calls if other members of your species cannot hear
Wave Air molecule density plotted and interpret them?
against time at a single point relative to the The range of sound wave frequencies heard by different species varies extensively. Some
tuning fork’s right prong. Physicists call (such as frogs and birds) have a rather narrow hearing range; others (such as dogs, whales,
the resulting cyclical waves sine waves. and humans) have a broad range. Some species use extremely high frequencies (bats are off
the scale in Figure 10-4); others (fish, for example) use the low range.
The auditory systems of whales and dolphins are responsive to a remarkably wide range
of sound waves. Characteristics at the extremes of these frequencies allow marine mam-
mals to use them in different ways. Very low frequency sound waves travel long distances in
water. Whales produce them for underwater communication over hundreds of miles. High-
frequency sound waves echo and form the basis of sonar. Dolphins produce them in bursts,
listening for the echoes that bounce back from objects. The echoes help the dolphins to
navigate and locate prey.
Differences in sound wave frequencies become differences in pitch when heard. Each
note in a musical scale must have a different frequency, because each has a different pitch.
Middle C on the piano, for instance, has a frequency of 264 hertz.
Section 8-4 suggests a critical period in Most people can discriminate between one musical note and another, but some can actu-
brain development most sensitive to musical ally name any note they hear (A, B flat, C sharp, and so forth). This perfect (or absolute) pitch
training. Figure 15-11 shows enhanced runs in families, suggesting a genetic influence. On the side of experience, most people who
connectivity in people with perfect pitch. develop perfect pitch also receive musical training in matching pitch to note from an early age.
Sound Wave Amplitude
Sound waves vary not only in frequency, which causes differences in perceived pitch, but
also in amplitude (strength), which causes differences in perceived intensity, or loudness. If
you hit a tuning fork lightly, it produces a tone with a frequency of, say, 264 hertz (middle C).
10-1 • Sound Waves: Stimulus for Audition 325
Hearing Ranges among
Figure 10-4
Humans Animals Frogs and birds hear a
relatively narrow range of frequencies;
Whales and whales’ and dolphins’ ranges are extensive,
dolphins as are dogs’. Humans’ hearing range is
broad, yet we do not perceive many sound
Seals and frequencies that other animals can both
sea lions make and hear.
Dogs
Rodents
Bats
Birds
Frogs
Fish
0 20 50 100 200 500 1000 2000 5000 10,000 20,000 50,000 100,000
Frequency (Hz)
If you hit it harder, the frequency remains 264 hertz, but you also transfer more energy into
amplitude Stimulus intensity; in audition,
the vibrating prong, increasing its amplitude.
roughly equivalent to loudness, graphed by
The fork now moves farther left and right but at the same frequency. Increased air mol-
the increasing height of a sound wave.
ecule compression intensifies the energy in a sound wave, which amps the sound—makes
decibel (dB) Measure of the relative physical
it louder. Differences in amplitude are graphed by increasing the height of a sound wave, as
intensity of sounds.
shown in the middle panel of Figure 10-3.
Sound wave amplitude is usually measured in decibels (dB), the strength of a sound rela-
tive to the threshold of human hearing as a standard, pegged at 0 decibels (Figure 10-5). Typi-
cal speech sounds, for example, measure about 40 decibels. Sounds that register more than
about 70 dB we perceive as loud; those of less than about 20 dB we perceive as soft, or quiet.
The human nervous system evolved to be sensitive to soft sounds and so is actually blown
away by extremely loud ones. People regularly damage their hearing through exposure to
very loud sounds (such as rifle fire at close range) or even by prolonged exposure to sounds
that are only relatively loud (such as at a live concert). Prolonged exposure to sounds louder
than 100 decibels is likely to damage our hearing.
Rock bands, among others, routinely play music that registers higher than 120 decibels
and sometimes as high as 135 decibels. Drake-Lee (1992) found that rock musicians had a
significant loss of sensitivity to sound waves, especially at about 6000 hertz. After a typical
90-minute concert, this loss was temporarily far worse—as much as a 40-fold increase in
Threshold Normal speech Chainsaw Rock band Rocket
0 20 40 60 80 100 120 140 160 180 200
Loudness (dB) Figure 10-5 Sound Intensity
326 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
sound pressure was needed to reach a musician’s hearing threshold. But rock concerts are
not the only music venue that can damage hearing. Teie (1998) reports that symphony or-
chestras also produce dangerously high sound levels and that hearing loss is common among
symphony musicians. Similarly, prolonged listening through headphones or earbuds to music
played loudly on personal music players is responsible for significant hearing loss in many
young people (Daniel, 2007).
Sound Wave Complexity
Sounds with a single frequency wave are pure tones, much like those that emanate from a
tuning fork or pitch pipe, but most sounds mix wave frequencies together in combinations
called complex tones (see Figure 10-3, bottom panel). To better understand the blended na-
ture of a complex tone, picture a clarinetist, such as Don Byron in Figure 10-6, playing a
steady note. The upper graph in Figure 10-6 represents the sound wave a clarinet produces.
The waveform pattern is more complex than the simple, regular waves visualized in
Figures 10-2 or 10-3. Even when a musician plays a single note, the instrument is making
a complex tone. Using a mathematical technique known as Fourier analysis, we can break
down this complex tone into its many component pure tones, the numbered waves traced at
the bottom of Figure 10-6.
The fundamental frequency (wave 1) is the rate at
which the complex waveform pattern repeats. Waves
Waveform from clarinet
2 through 20 are overtones, a set of higher-frequency
sound waves that vibrate at whole-number (integer)
multiples of the fundamental frequency. Different mu-
sical instruments sound unique because they produce
Breaking Down a
Figure 10-6
Complex Tone The waveform of overtones of different amplitudes. Among the clarinet’s
a single note (top) from Don Byron’s overtones, represented by the heights of the blue waves
clarinet and the simple sound waves— in Figure 10-6, wave 5 is low amplitude, whereas wave 2
the fundamental frequency (middle) is high amplitude.
and overtones (bottom)—that make up Fundamental As primary colors blend into near-infinite variety,
the complex tone. frequency
so pure tones blend into complex tones. Complex
tones emanate from musical instruments, from the
1
human voice, from birdsong, and from machines or
repetitive mechanisms that make rhythmic buzzing
Simple waves that or humming sounds. A key feature of complex tones,
make up sound Overtones besides being made up of two or more pure tones, is
of clarinet
periodicity: the fundamental frequency repeats at reg-
2
ular intervals. Sounds that are aperiodic, or random,
we call noise.
4
Perception of Sound
Visualize what happens when you toss a pebble into a
5 pond. Waves of water emanate from the point where
6 the pebble enters the water. These waves produce no
7 audible sound. But if your skin were able to convert the
craig lovell/Eagle visions Photography/alamy
8 water wave energy (sensation) into neural activity that
9
10
stimulated your auditory system, you would hear the
11 waves when you placed your hand in the rippling water
12
13 (perception). When you removed your hand, the sound
14
15 would stop.
16
17 The pebble hitting the water is much like a tree fall-
18
19 ing to the ground, and the waves that emanate from
20
the pebble’s entry point are like the air pressure waves
10-1 • Sound Waves: Stimulus for Audition 327
that emanate from the place where the tree strikes the ground. The frequency of the waves
determines the pitch of the sound heard by the brain, whereas the height (amplitude) of the
waves determines the sound’s loudness.
Our sensitivity to sound waves is extraordinary. At the threshold of human hearing, we
can detect the displacement of air molecules of about 10 picometers. We are rarely in an en- 1 picometer = one-trillionth of a meter
vironment where we can detect such a small air pressure change: there is usually too much
background noise. A quiet, rural setting is probably as close as we ever get to an environment
suitable for testing the acuteness of our hearing. The next time you visit the countryside,
take note of the sounds you can hear. If there is no sound competition, you can often hear
a single car engine miles away.
In addition to detecting minute changes in air pressure, the auditory system is also adept
at simultaneously perceiving different sounds. As you read this chapter, you can differenti-
ate all sorts of sounds around you—traffic on the street, people talking next door, your air
conditioner humming, footsteps in the hall. As you listen to music, you detect the sounds of
different instruments and voices.
You can perceive more than one sound simultaneously because each frequency of change
in air pressure (each different sound wave) stimulates different neurons in your auditory
system. Sound perception is only the beginning of your auditory experience. Your brain
interprets sounds to obtain information about events in your environment, and it analyzes
a sound’s meaning. Your use of sound to communicate with other people through both lan-
guage and music clearly illustrate these processes.
Properties of Language and Music
as Sounds
Language and music differ from other auditory sensations in fundamental ways. Both convey
meaning and evoke emotion. Analyzing meaning in sound is a considerably more complex
behavior than simply detecting a sound and identifying it. The brain has evolved systems
that analyze sounds for meaning, speech in the left temporal lobe and music in the right.
Infants are receptive to speech and musical cues before they have any obvious utility,
which suggests both the innate presence of these skills and the effects of prenatal experi-
ences. Humans have an amazing capacity for learning and remembering linguistic and musi-
cal information. We are capable of learning a vocabulary of tens of thousands of words, often
in many languages, and a capacity for recognizing thousands of songs.
Language facilitates communication. We can organize our complex perceptual worlds
by categorizing information with words. We can tell others what we think and know and
imagine. Imagine the efficiency that gestures and language added to the cooperative food
hunting and gathering behaviors of early humans.
All these benefits of language seem obvious, but the benefits of music may seem less
straightforward. In fact, music helps us to regulate our own emotions and to affect the emo-
tions of others. After all, when do people most commonly make music? We sing and play
loomis dean/time life Pictures/getty images
music to communicate with infants and put children to sleep. We play music to enhance so-
cial interactions and gatherings and romance. We use music to bolster group identification—
school songs and national anthems are examples. Music as we know it is unique to humans.
Studies of nonhumans provide little evidence for preferences for human music over other
sounds.
Another characteristic that distinguishes speech and musical sounds from other audi-
tory inputs is their delivery speed. Nonspeech and nonmusical noise produced at a rate of
about five segments per second is perceived as a buzz. (A sound segment is a distinct unit of
sound.) Normal speed for speech is on the order of 8 to 10 segments per second, and we are
Elvis Presley’s memory for lyrics suits his
capable of understanding speech at nearly 30 segments per second. Speech perception at legend: while serving in the U.S. Army, he
these higher rates is astounding, because the input speed far exceeds the auditory system’s wagered all comers that he could sing any
ability to transmit all the speech segments as separate pieces of information. song they named. Elvis never lost a bet.
328 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
Properties of Language
Experience listening to a particular language helps the brain to analyze rapid speech, which
is one reason people who are speaking languages unfamiliar to you often seem to be talking
incredibly fast. Your brain does not know where the foreign words end and begin, so they
seem to run together in a rapid-fire stream.
A unique characteristic of our perception of speech sounds is our tendency to hear varia-
Auditory constancy is reminiscent of the tions of a sound as if they were identical, even though the sound varies considerably from one
visual system’s capacity for object constancy; context to another. For instance, the English letter d is pronounced differently in the words
see Section 9-4. deep, deck, and duke, yet a listener perceives the pronunciations to be the same d sound.
The auditory system must therefore have a mechanism for categorizing sounds as being
the same despite small differences in pronunciation. Experience must affect this mecha-
nism, because different languages categorize speech sounds differently. A major obstacle to
mastering a foreign language after age 10 is the difficulty of learning which sound categories
are treated as equivalent.
Properties of Music
As with other sounds, the subjective properties that people perceive in musical sounds differ
from one another. One subjective property is loudness, the magnitude of the sound as judged
University of New Brunswick
by a person. Loudness is related to the amplitude of a sound wave measured in decibels, but
Courtesy Drew Rendall,
loudness is also subjective. What is very loud music for one person may be only moderately
loud for another, whereas music that seems soft to one listener may not seem at all soft to
someone else. Your perception of loudness also changes with context. After you’ve slowed
down from driving fast on a highway, for example, your car’s music system seems louder.
C E G The reduction in road noise alters your perception of the music’s loudness.
Another subjective property of musical sounds is pitch, the position of each tone on a
musical scale as judged by the listener. Although pitch is clearly related to sound wave fre-
C
quency, there is more to it than that. Consider the note middle C as played on a piano. This
note can be described as a pattern of sound frequencies, as is the clarinet note in Figure 10-6.
Amplitude
Like the note played on the piano, any musical note is defined by its fundamental
frequency—the lowest frequency of the sound wave pattern, or the rate at which the overall
pattern repeats. For middle C, the fundamental frequency is 264 Hertz, and the sound waves
for notes C, E, and G, as measured by a spectrograph, are shown in Figure 10-7. Notice that
E by convention sound wave spectrographs are measured in kilohertz (kHz), or thousands of
hertz. Thus, if we look at the fundamental frequency for middle C, it is the first large wave
Amplitude
on the left, at 0.264 kilohertz. The fundamental frequencies for E and G are 0.330 and
0.392 kilohertz, respectively.
An important feature of the human brain’s analysis of music is that middle C is per-
ceived as being the same note whether it is played on a piano or on a guitar, even though
the sounds of these instruments differ widely. The right temporal lobe extracts pitch from
G
sound, whether the sound is speech or music. In speech, pitch contributes to the perceived
melodic tone of a voice, or prosody.
Amplitude
A final property of musical sound is quality, or timbre, the perceived characteristics that
distinguish a particular sound from all others of similar pitch and loudness. We can easily
distinguish the timbre of a violin from that of a trombone, even if both instruments are play-
0 1.0 2.0 ing the same note at the same loudness. The quality of their sounds differs.
Frequency (kHz)
Fundamental
Figure 10-7
Frequencies of Piano Notes 10-1 reVieW
Waveforms of the notes C, E, and G as Sound Waves: Stimulus for Audition
played on a piano and recorded on a
Before you continue, check your understanding.
spectrograph. The first wave in each
graph is the fundamental frequency; the 1. The physical stimulus for audition, produced by changes in , is a form of
secondary waves are the overtones. mechanical energy converted in the ear to neural activity.
10-2 • Functional Anatomy of the Auditory System 329
2. Sound waves have three physical attributes: , , and
.
3. Four properties of musical sounds are , , , and
.
4. Sound is processed in the lobes.
5. What distinguishes speech and musical sounds from other auditory inputs?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
10-2 Functional Anatomy
of the Auditory System
To understand how the nervous system analyzes sound waves, we begin by tracing the path-
way sound energy takes to and through the brain. The ear collects sound waves from the
surrounding air and converts their mechanical energy to electrochemical neural energy,
which begins a long route through the brainstem to the auditory cortex.
Before we can trace the journey from ear to cortex, we must ask what the auditory system
is designed to do. Because sound waves have the properties frequency, amplitude, and com-
plexity, we can predict that the auditory system is structured to decode these properties. Most
animals can tell where a sound comes from, so some mechanism
Cerebrum Cerebrum
must locate sound waves in space. Finally, many animals, including
humans, not only analyze sounds for meaning but also make sounds.
Because the sounds they produce are often the same as the ones they
hear, we can infer that the neural systems for sound production and
analysis must be closely related. Temporal
In humans, the evolution of sound-processing systems for both lobe Brainstem
language and music was accompanied by enhancement of special- Monkey
ized cortical regions, especially in the temporal lobes. In fact, a Temporal
lobe Brainstem
major difference between the human and the monkey cortex is a
marked expansion of auditory areas in humans. Human
Structure of the Ear
The ear is a biological masterpiece in three acts: outer ear, middle ear, and inner ear, all il-
lustrated in Figure 10-8.
Processing Sound Waves
Both the pinna, the funnel-like external structure of the outer ear, and the external ear
canal, which extends a short distance from the pinna inside the head, are made of cartilage
and flesh. The pinna is designed to catch sound waves in the surrounding environment and
deflect them into the external ear canal. To enhance sound detection when we want to hear
better, we often cup a hand around the pinna.
Because it narrows from the pinna, the external canal amplifies sound waves and directs
them to the eardrum at its inner end. When sound waves strike the eardrum, it vibrates, the
rate of vibration varying with the frequency of the waves. On the inner side of the eardrum, prosody Melodic tone of the speaking voice.
as depicted in Figure 10-8, is the middle ear, an air-filled chamber that contains the three ossicle Bone of the middle ear; includes
smallest bones in the human body, connected in a series. malleus (hammer), incus (anvil), and stapes
These three ossicles are called the hammer, the anvil, and the stirrup because of their (stirrup).
distinctive shapes. The ossicles attach the eardrum to the oval window, an opening in the cochlea Inner ear structure containing the
bony casing of the cochlea, the inner ear structure containing the auditory receptor cells. auditory receptor cells.
330 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
Middle ear
and inner ear
Middle Inner
Outer ear ear ear Ossicles Stirrup Semicircular
Anvil canals
Pinna Auditory
Semicircular Hammer nerve
canals
Ossicles Cochlea Auditory
nerve
Eardrum Oval
window
Cochlea
External Eardrum
Sound ear canal
wave
2 Waves are 3 …which in 4 Ossicles amplify
amplified and turn vibrates and convey
1 The pinna catches directed to the ossicles. vibrations to the
Figure 10-8 Anatomy of sound waves and eardrum, causing oval window.
the Human Ear Sound deflects them into the it to vibrate,…
waves gathered into the external ear canal. Cross section
outer ear are transduced Inner Cilia through cochlea
from air pressure into hair cell Organ of Corti
mechanical energy in the Outer Inner Tectorial
middle ear ossicles then into hair cells hair cell membrane
electrochemical activity in
the inner ear cochlea. Inner
hair cells embedded in the
basilar membrane (the organ
of Corti) are tipped by cilia.
Movements of the basilar and Nerve Basilar
tectorial membranes displace fibers membrane
Axons of
the cilia, leading to changes auditory nerve
in the inner hair cells’
membrane potentials and 7 …which in turn cause cilia of inner hair cells to 6 …causing the basilar 5 Vibration of oval
bend. This bending generates neural activity in and tectorial membranes window sends waves
resultant activity of auditory
hair cells. to bend,… through cochlear fluid,…
bipolar neurons.
These receptor cells and the cells that support them are collectively called the organ of Corti,
shown in detail in Figure 10-8.
When sound waves vibrate the eardrum, the vibrations are transmitted to the ossicles.
The leverlike action of the ossicles amplifies the vibrations and conveys them to the mem-
brane that covers the cochlea’s oval window. As Figure 10-8 shows, the cochlea coils around
Cochlea actually means snail shell in Latin. itself and looks a bit like a snail shell. Inside its bony exterior, the cochlea is hollow, as the
cross-sectional drawing reveals.
The hollow cochlear compartments are filled with lymphatic fluid, and floating in its
midst is the thin basilar membrane. Embedded in a part of the basilar membrane are outer
and inner hair cells. At the tip of each hair cell are several filaments called cilia, and the cilia
of the outer hair cells are embedded in the overlying tectorial membrane. The inner hair cells
loosely contact this tectorial membrane.
Pressure from the stirrup on the oval window makes the cochlear fluid move because
a second membranous window in the cochlea (the round window) bulges outward as the
stirrup presses inward on the oval window. In a chain reaction, the waves traveling through
the cochlear fluid bend the basilar and tectorial membranes, and the bending membranes
stimulate the cilia at the tips of the outer and inner hair cells.
Transducing Sound Waves into Neural Impulses
How does the conversion of sound waves into neural activity code the various properties of
sound that we perceive? In the late 1800s, the German physiologist Hermann von Helmholtz
10-2 • Functional Anatomy of the Auditory System 331
(A) Uncoiling of cochlea (B) Uncoiled cochlea
A narrow, thick base is tuned A wide, thin apex is tuned
Cochlear for high frequencies. for low frequencies.
Basilar
base
membrane
20,000 4000 1000 100 Basilar membrane
Hertz
Sound waves at medium frequencies cause peak
bending of the basilar membrane at this point.
Figure 10-9 Anatomy of the
Cochlea (A) The basilar membrane
proposed that sound waves of different frequencies cause different parts of the basilar mem- is maximally responsive to frequencies
brane to resonate. Von Helmholtz was partly correct. Actually, all parts of the basilar mem- mapped as the cochlea uncoils. (B) Sound
brane bend in response to incoming waves of any frequency. The key is where the peak waves of different frequencies produce
maximal displacement of the basilar
displacement takes place (Figure 10-9).
membrane (shown uncoiled) at different
This solution to the coding puzzle was determined in 1960, when George von Békésy locations.
observed the basilar membrane directly. He saw a traveling wave moving along the mem-
brane all the way from the oval window to the membrane’s apex. The coiled cochlea in
Figure 10-9A maps the frequencies to which each part of the basilar membrane is most
responsive. When the oval window vibrates in response to the vibrations of the ossicles,
shown beside the uncoiled membrane in Figure 10-9B, it generates waves that travel
through the cochlear fluid. Békésy placed little grains of silver along the basilar mem-
brane and watched them jump in different places to different frequencies of incoming
waves. Higher wave frequencies caused maximum peaks of displacement near the base
of the basilar membrane; lower wave frequencies caused maximum displacement peaks
near the membrane’s apex.
As a rough analogy, consider what happens when you shake a rope. If you shake it
quickly, the waves in the rope are small and short and the peak of activity remains close
to the base—the hand holding the rope. But if you shake the rope slowly, with a broader
movement, the longer waves reach their peak farther along the rope—toward the apex. The
key point is that, although both rapid and slow shakes produce movement along the rope’s
entire length, the point of maximum displacement depends on whether the wave move-
ments are rapid or slow.
This same response pattern holds for the basilar membrane and sound wave frequency.
All sound waves cause some displacement along the entire length of the membrane, but the
amount of displacement at any point varies with the sound wave’s frequency. In the human
cochlea, shown uncoiling in Figure 10-9A, the basilar membrane near the oval window
is maximally affected by frequencies as high as about 20,000 hertz, the upper limit of our
hearing range. The most effective frequencies at the membrane’s apex register less than
100 hertz, closer to our lower limit of about 20 Hz (see Figure 10-4).
Intermediate frequencies maximally displace points on the basilar membrane between
its ends, as shown in Figure 10-9B. When a wave of a certain frequency travels down the
basilar membrane, hair cells at the point of peak displacement are stimulated, resulting in
a maximal neural response in those cells. An incoming signal composed of many frequen-
cies causes several points along the basilar membrane to vibrate and excites hair cells at all basilar membrane Receptor surface in the
these points. cochlea that transduces sound waves into
Not surprisingly, the basilar membrane is much more sensitive to changes in frequency neural activity.
than is the rope in our analogy, because the basilar membrane varies in thickness along its hair cell Specialized neurons in the cochlea
entire length. It is narrow and thick at the base, near the oval window, and wider and thin- tipped by cilia; when stimulated by waves in
ner at its tightly coiled apex. The combination of varying width and thickness enhances the cochlear fluid, the cilia bend and generate
the effect of small frequency differences. As a result, the cochlear receptors can code small graded potentials in inner hair cells, the
differences in sound wave frequency as neural impulses. auditory receptor cells.
332 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
Cochlea Auditory Receptors
Two kinds of hair cells transform sound waves into neural activity. Figure 10-8 (bottom left)
shows the anatomy of the inner hair cells; Figure 10-10 illustrates how sound waves stimulate
them. A young person’s cochlea has about 12,000 outer and 3500 inner hair cells. The num-
bers fall off with age. Only the inner hair cells act as auditory receptors, and their numbers
are small considering how many different sounds we can
hear. As diagrammed in Figure 10-10, both outer and inner
hair cells are anchored in the basilar membrane. The tips
of the cilia of outer hair cells are attached to the overlying
Tectorial tectorial membrane, but the cilia of the inner hair cells only
membrane Inner
hair cell loosely touch that membrane. Nevertheless, the movement
Outer
hair of the basilar and tectorial membranes causes the cochlear
cells fluid to flow past the cilia of the inner hair cells, bending
Basilar them back and forth.
membrane Axons of Displacement Animals with intact outer hair cells but no inner hair
cochlear nerve cells are effectively deaf. That is, they can perceive only
...creates a shearing force that bends cilia in very loud, low-frequency sounds via the somatosensory sys-
Movement of the basilar contact with and near the overlying tectorial tem. You may have experienced this feeling when a sub-
membrane in response to membrane. This bending generates neural activity woofer or a passing truck caused vibrations in your chest.
sound waves… in the hair cells from which the cilia extend.
Inner hair cells can be destroyed by prolonged exposure to
Figure 10-10 Transducing Waves intense sound pressure waves, infections, diseases, or cer-
into Neural Activity Movement of tain chemicals and drugs. Inner hair cells do not regenerate; thus once the inner hair cells
the basilar membrane produces a shearing have died hearing loss is permanent.
force in the cochlear fluid that bends the Outer hair cells function by sharpening the cochlea’s resolving power, contracting or
cilia, leading to the opening or closing of
relaxing and thereby changing tectorial membrane stiffness. That’s right: the outer hair cells
calcium channels in the outer hair cells.
An influx of calcium ions leads the inner have a motor function. While we typically think of sensory input preceding motor output,
hair cells to release neurotransmitter, in fact, motor systems can influence sensory input. The pupil contracts or dilates to change
stimulating increased action potentials in the amount of light that falls on the retina, and the outer hair cells contract or relax to alter
auditory neurons. the physical stimulus detected by the inner hair cells.
How this outer hair cell function is controlled is puzzling. What stimulates these cells to
contract or relax? The answer seems to be that through connections with axons in the audi-
tory nerve, the outer hair cells send a message to the brainstem auditory areas and receive a
reply that causes the cells to alter tension on the tectorial membrane. In this way, the brain
helps the hair cells to construct an auditory world. The outer cells are also part of a mecha-
nism that modulates auditory nerve firing, especially in response to intense sound pressure
waves, and thus offers some protection against their damaging effects.
A final question remains: How does movement of the inner hair cell cilia alter neural
activity? The neurons of the auditory nerve have a spontaneous baseline rate of firing ac-
tion potentials, and this rate is changed by the amount of neurotransmitter the hair cells
release. It turns out that movement of the cilia changes the inner hair cell’s polarization
and its rate of neurotransmitter release. Inner hair cells continuously leak calcium, and
this leakage causes a small but steady amount of neurotransmitter release into the synapse.
Movement of the cilia in one direction results in depolarization: calcium channels open
and release more neurotransmitter onto the dendrites of the cells that form the auditory
Section 4-2 reviews phases of the action nerve, generating more nerve impulses. Movement of the cilia in the other direction hyper-
potential and its propagation as a nerve polarizes the cell membrane and transmitter release decreases, thus decreasing activity in
impulse. auditory neurons.
Inner hair cells are amazingly sensitive to the movement of their cilia. A movement
sufficient to allow sound wave detection is only about 0.3 nm, about the diameter of
a large atom! Such sensitivity helps to explain why our hearing is so incredibly sensi-
tive. Clinical Focus 10-2, Otoacoustic Emissions, describes a consequence of cochlear
function.
10-2 • Functional Anatomy of the Auditory System 333
ReseaRch F cus 10-2
Otoacoustic Emissions
While the ear is exquisitely designed to amplify and convert sound waves sound waves, are important because evoked emissions are useful for
into action potentials, it is unique among the sensory organs. The ear assessing hearing impairments.
also produces the physical stimulus it is designed to detect! A healthy A simple, noninvasive test can detect and evaluate evoked otoacoustic
cochlea produces sound waves called otoacoustic emissions. emissions in newborns and children who are too young to take conven-
The cochlea acts as an amplifier. The outer hair cells amplify sound tional hearing tests, as well as in people of any age. A small speaker and
waves, providing an energy source that enhances cochlear sensitivity microphone are inserted into the ear. The speaker emits a click sound,
and frequency selectivity. Not all the energy the cochlea generates is and the microphone detects the resulting evoked emission without dam-
dissipated within it. Some escapes toward the middle ear, which works aging the delicate workings of the inner ear. Missing or abnormal evoked
efficiently in both directions, thus setting the eardrum in motion. The ear- emissions predict a hearing deficit. Many wealthy countries now spon-
drum then acts as a loudspeaker, radiating sound waves—the otoacoustic sor universal programs to test the hearing of all newborn babies using
emissions—out of the ear. otoacoustic emissions.
Sensitive microphones placed in the external ear canal can detect Otoacoustic emissions serve a useful purpose, but even so, they play
both types of otoacoustic emissions, spontaneous and evoked. As the no direct role in hearing. They are considered an epiphenomenon—a
name implies, spontaneous otoacoustic emissions occur without exter- secondary phenomenon that occurs in parallel with or above (epi) a
nal stimulation. Evoked otoacoustic emissions, generated in response to primary phenomenon.
Pathways to the Auditory Cortex
Inner hair cells in the organ of Corti synapse with neighboring bipolar cells, the axons that
form the auditory (cochlear) nerve. The auditory nerve in turn forms part of the eighth cra-
nial nerve, the auditory vestibular nerve that governs hearing and balance. Whereas ganglion Figure 2-27 lists and locates the cranial
cells in the eye receive inputs from many receptor cells, bipolar cells in the ear receive input nerves, and in its caption is a mnemonic for
from but a single inner hair cell receptor. remembering them in order.
Cochlear-nerve axons enter the brainstem at the level of the medulla and synapse in the
cochlear nucleus, which has ventral and dorsal subdivisions. Two nearby structures in the
hindbrain (brainstem), the superior olive (a nucleus in the olivary complex) and the trapezoid
body, receive connections from the cochlear nucleus, as charted in Figure 10-11. Projections
from the cochlear nucleus connect with cells on the same side of the brain as well as with
cells on the opposite side. This arrangement mixes the inputs from the two ears to form a
single sound perception.
Both the cochlear nucleus and the superior olive send projections to the inferior colliculus
otoacoustic emissions Spontaneous or
in the dorsal midbrain. Two distinct pathways emerge from the inferior colliculus, coursing
evoked sound waves produced within the ear
to the medial geniculate nucleus in the thalamus. The ventral region of the medial genicu-
by the cochlea and escape from the ear.
late nucleus projects to the primary auditory cortex (area A1), whereas the dorsal region
medial geniculate nucleus Major thalamic
projects to the auditory cortical regions adjacent to area A1.
region concerned with audition.
Analogous to the two distinct visual pathways—the ventral stream for object recognition and
the dorsal stream for visual control of movement—a similar distinction exists in the auditory primary auditory cortex (area A1)
cortex (Romanski et al., 1999). Just as we can identify objects by their sound characteristics, we Asymmetrical structures within Heschl’s
gyrus in the temporal lobes; receive input
can direct our movements by the sound we hear. The role of sound in guiding movement is less
from the ventral region of the medial
familiar to sight-dominated people than it is to the blind. Nevertheless, the ability exists in us
geniculate nucleus.
all. Imagine waking up in the dark and reaching to pick up a ringing telephone or to turn off an
alarm clock. Your hand automatically forms the appropriate shape in response to just the sound
you have heard. That sound is guiding your movements much as a visual image guides them.
Relatively little is known about the what–how auditory pathways in the cortex. One Figure 9-13 maps the visual pathways through
appears to continue through the temporal lobe, much like the ventral visual pathway, and the cortex.
plays a role in identifying auditory stimuli. A second auditory pathway apparently goes to the
posterior parietal region, where it forms a dorsal route for the auditory control of movement.
It appears as well that auditory information can gain access to visual cortex, as illustrated in
Research Focus 10-3, Seeing with Sound.
334 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
Cochlea of Figure 10-11 Auditory Pathways Auditory inputs cross to the
left ear Left hemisphere Right hemisphere hemisphere opposite the ear in the hindbrain and midbrain, then recross
Hindbrain in the thalamus. In this way, the information from each ear reaches both
Ventral Olivary Olivary Ventral hemispheres. Multiple nuclei process inputs en route to the auditory
cochlear complex complex cochlear cortex, charted here for the left ear.
Auditory nucleus nucleus
(cochlear) Trapezoid Trapezoid
nerve body body
Dorsal Dorsal
cochlear
nucleus
cochlear
nucleus Auditory Cortex
In humans, the primary auditory cortex (A1) lies within Heschl’s gyrus,
Midbrain surrounded by secondary cortical areas (A2), as shown in Figure 10-12A.
Inferior Inferior The secondary cortex lying behind Heschl’s gyrus is called the planum
colliculus colliculus temporale (Latin for temporal plane).
In right-handed people, the planum temporale is larger on the left than
Thalamus
it is on the right side of the brain, whereas Heschl’s gyrus is larger on the
right side than on the left. The cortex of the left planum forms a speech
Medial Medial zone known as Wernicke’s area (the posterior speech zone), whereas the
geniculate geniculate
nucleus nucleus cortex of the larger right-hemisphere Heschl’s gyrus has a special role in
analyzing music.
Cerebral These hemispheric differences mean that the auditory cortex is ana-
cortex Auditory Auditory tomically and functionally asymmetrical. Although cerebral asymmetry
cortex cortex
is not unique to the auditory system, it is most obvious here because audi-
tory analysis of speech takes place only in the left hemisphere of right-
handed people. About 70 percent of left-handed people have the same
anatomical asymmetries as right-handers, an indication that speech organization is not
strictly related to hand preference. Language, including speech and other functions such as
reading and writing, also is asymmetrical, although the right hemisphere also contributes to
these broader functions.
The remaining 30 percent of left-handers fall into two distinct groups. The organization
in about half of these people is opposite that of right-handers. The other half has some
(A) Auditory cortex (B) Insula Corpus
Thalamus callosum
Lateral
Retractor opens lateral fissure ventricle
to reveal auditory cortex.
Right hemisphere Gustatory
cortex
Primary Secondary
Lateral auditory cortex auditory Heschl’s gyri
sulcus cortex Auditory
Insula cortex
Amygdala Hippocampus
Thalamus
Secondary
auditory cortex Wernicke’s
area Figure 10-12 Human Auditory Cortex (A) The left
hemisphere, showing the lateral fissure retracted to reveal
the primary auditory cortex buried within Heschl’s gyrus; and
Secondary Primary Wernicke’s adjacent secondary auditory regions. In cross section, the
auditory auditory cortex area (planum posterior speech zone (Wernicke’s area) is larger on the left,
cortex (Heschl’s gyrus) temporale) and Heschl’s gyrus is larger in the right hemisphere.
(B) Frontal view showing the extent of the multifunctional
Left hemisphere insular cortex buried in the lateral fissure.
10-2 • Functional Anatomy of the Auditory System 335
ReseaRch F cus 10-3
Seeing with Sound
As detailed in Section 10-5, echolocation, the ability to use sound to versus those that did not, the auditory activity disappeared. By contrast,
locate objects in space, has been extensively studied in species such as as illustrated in the figure, the blind echolocators showed activity only in
bats and dolphins. But it was reported more than 50 years ago that some the visual cortex when sounds with and without echoes were compared.
blind people also echolocate. Sighted controls (findings not shown) showed no activity in either the
More recently, anecdotal reports have surfaced of blind people visual or auditory cortex in this comparison.
who navigate around the world using clicks made with their tongues These results suggest that blind echolocation experts process click–
and mouths then listening to the returning echoes. Videos, such echo information using brain regions typically devoted to vision. Thaler
as the 45- minute documentary at https://www.youtube.com/ and his colleagues propose that the primary visual cortex is performing
watch?v=AiBeLoB6CKE, show congenitally blind people riding a bicycle a spatial computation using information from the auditory cortex.
down a street with silent obstacles such as parked cars. But how do they Future research may determine how this process works. More im-
do this, and what part of the brain enables it? mediately, the study suggests that echolocation could be taught to blind
Behavioral studies of blind people reveal that echolocators make and visually impaired people to provide them increased independence
short, spectrally broad clicks by moving the tongue backward and down- in their daily life.
ward from the roof of the mouth directly behind the teeth. Skilled echo-
locators can identify properties of objects that include position, distance,
size, shape, and texture (Teng & Whitney, 2011).
Thaler and colleagues (2011) investigated the neural basis of this abil-
ity using fMRI. They studied two blind echolocation experts and com-
pared brain activity for sounds that contain both clicks and returning
echoes with brain activity for control sounds that did not contain the
echoes. The participants use echolocation to localize objects in the en-
vironment, but more important, they also perceive the object’s shape,
motion—even its identity!
Seeing with Sound When cortical activation for sound with and
When the blind participants listened to recordings of their echoloca- without echoes is imaged in a blind echolocator, only the visual cortex
tion clicks and echoes compared to silence, both the auditory cortex shows activation (left) relative to the auditory cortex (right). Research from
and the primary visual cortex showed activity. Sighted controls showed Thaler, L., Arnott, S. R., & Goodale, M. A. (2011), Neural correlates of natural human
activation only in the auditory cortex. Remarkably, when the investigators echolocation in early and late blind echolocation experts. PLoS ONE, 6, (5)e20162.
compared the controls’ brain activity to recordings that contained echoes doi:10.1371/journal.pone.0020162
idiosyncratic bilateral speech representation. That is, about 15 percent of all left-handed
Wernicke’s area Secondary auditory cortex
people have some speech functions in one hemisphere and some in the other hemisphere.
(planum temporale) lying behind Heschl’s
Localization of language on one side of the brain is an example of lateralization. Note here
gyrus at the rear of the left temporal lobe;
simply that, in neuroanatomy, if one hemisphere is specialized for one type of analysis—as, regulates language comprehension. Also
for example, the left hemisphere is for language—the other hemisphere has a complementary posterior speech zone.
function: the right hemisphere appears to be lateralized for music.
lateralization Localization of function
The temporal lobe sulci enfold a volume of cortical tissue far more extensive than the
primarily on one side of the brain.
auditory cortex (Figure 10-12B). Buried in the lateral fissure, cortical tissue called the insula
contains not only lateralized regions related to language but also areas controlling taste per- insula Multifunctional cortical tissue located
within the lateral fissure; contains language-
ception (the gustatory cortex) and areas linked to the neural structures underlying social
and taste perception–related regions and
cognition. As you might expect, injury to the insula can produce such diverse deficits as
neural structures underlying social cognition.
disturbance of both language and taste.
10-2 reVieW
Functional Anatomy of the Auditory System
Before you continue, check your understanding.
1. Incoming sound wave energy vibrates the eardrum, which in turn vibrates the
.
2. The auditory receptors are the , found in the .
336 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
3. The motion of the cochlear fluid causes displacement of the and
membranes.
4. The axons of bipolar cells from the cochlea form the nerve, which is part
of the cranial nerve.
5. The auditory nerve originating in the cochlea projects to various nuclei in the brainstem;
then it projects to the in the midbrain and the in the
thalamus.
6. Describe the asymmetrical structure and functions of the auditory cortex.
Answers appear at the back of the book
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
10-3 Neural Activity and Hearing
We now turn to the neuronal activity in the auditory system that produces our percep-
tion of sound. Neurons at different levels in this system serve different functions. To get
an idea of what individual hair cells and cortical neurons do, we consider how the audi-
tory system codes sound wave energy so that we perceive pitch, loudness, location, and
pattern.
Hearing Pitch
Recall that perception of pitch corresponds to the frequency (repetition rate) of sound
waves measured in hertz (cycles per second). Hair cells in the cochlea code frequency as
Tonotopic literally means of a tone place. a function of their location on the basilar membrane. In this tonotopic representation,
hair cell cilia at the base of the cochlea are maximally displaced by high-frequency waves,
which we hear as high-pitched sounds; those at the apex are displaced the most by low-
frequency waves, which we hear as low-pitched sounds. Because each bipolar-cell axon
that forms the cochlear nerve is connected to only one inner hair cell, the bipolar cells
convey information about the spot on the basilar membrane, from apex to base, that is
being stimulated.
Recordings from single fibers in the cochlear nerve reveal that although each axon trans-
mits information about only a small part of the auditory spectrum, each cell does respond to
a range of sound wave frequencies—if the wave is sufficiently loud. That is, each hair cell is
A hair cell’s frequency range parallels maximally responsive to a particular frequency and also responds to nearby frequencies, but
a photoreceptor’s response to light the sound wave’s amplitude must be greater (louder) for those nearby frequencies to excite
wavelengths. See Figure 9-6. the receptor’s membrane potential.
We can plot this range of hair cell responses to different frequencies at different
amplitudes as a tuning curve. As graphed in Figure 10-13, each hair cell receptor is
maximally sensitive to a particular wavelength but still responds somewhat to nearby
wavelengths.
Tuning Curves Graphs plotted by the High High
Sound amplitude (dB)
Figure 10-13
sound wave frequency and amplitude energy required to
increase the firing rate of two axons in the cochlear nerve.
The lowest point on each tuning curve is the frequency
to which that hair cell is most sensitive. The curve at
left is centered on a frequency of 1000 Hz, the midrange Low Low
of human hearing; the curve at right is centered on a 0 100 1000 10,000 0 100 1000 10,000
frequency of 10,000 Hz, in the high range. Frequency (Hz)
10-3 • Neural Activity and Hearing 337
Figure 10-14 Tonotopic
Retractor Representation of Area A1 A
retractor holds the lateral fissure open to
8000 Hz
z
16,000
reveal the underlying primary auditory
4000 H
Hz
Hz
cortex. The anterior end of area A1
2000
Hz
1000
corresponds to the apex of the cochlea,
500
hence low frequencies. The posterior end
corresponds to the base of the cochlea,
hence high frequencies.
Primary auditory
cortex (A1) Corresponds to Corresponds to
apex of cochlea base of cochlea
Bipolar cell axons in the cochlea project to the cochlear nucleus in an orderly manner (see
Figure 10-11). Axons entering from the base of the cochlea connect with one location; those tonotopic representation In audition,
structural organization for processing
entering from the middle connect to another location; and those entering from the apex
of sound waves from lower to higher
connect to yet another. Thus the basilar membrane’s tonotopic representation is reproduced
frequencies.
in the hindbrain cochlear nucleus.
This systematic representation is maintained throughout the auditory pathways and into cochlear implant Electronic device
implanted surgically into the inner ear to
the primary auditory cortex. Figure 10-14 shows the distribution of projections from the base
transduce sound waves to neural activity and
and apex of the cochlea across area A1. Similar tonotopic maps can be constructed for each
allow a deaf person to hear.
level of the auditory system.
This systematic auditory organization has enabled the development of cochlear implants—
electronic devices surgically inserted in the inner ear that serve as prostheses to allow deaf
people to hear (see Loeb, 1990). Cochlear implants are no cure for deafness but rather are
a hearing substitute. In Figure 10-15, a miniature microphonelike processor secured to the
skull detects the component frequencies of incoming sound waves and sends them to the
appropriate place on the basilar membrane through tiny wires. The nervous system does not
distinguish between stimulation coming from this artificial device and stimulation coming
through the middle ear.
As long as appropriate signals go to the correct locations on the basilar membrane, the
brain will hear. Cochlear implants work well, allowing the deaf to detect even the fluctuat-
ing pitches of speech. Their success corroborates the tonotopic representation of pitch in
the basilar membrane.
Coil
Implant
Semicircular
canals Ossicles
Auditory Microphone
nerve
Audio
Cochlea processor
Electrode
Pinna Figure 10-15 Tonotopic
contacts Technology A cochlear implant
Wire captures incoming sound wave stimulation
Eardrum via a microphone worn behind the ear. An
External audio processor converts the frequencies
ear canal into electric current and stimulates
the correct locations on the basilar
membrane.
338 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
Even so, the quality of sound cochlear implants create is impoverished relative to natural
hearing. Adults who lose their hearing and then get cochlear implants describe the sounds as
“computerized” and “weird.” Many people with implants find music unpleasant and difficult
to listen to. Graeme Clark (2015) developed a prototype high-fidelity cochlear implant with
50 electrodes to increase basilar membrane stimulation. His goal is achieving better music
perception and enhanced ability to discern specific voices in noisy rooms.
One minor difficulty with frequency detection is that the human cochlea does not re-
spond in a tonotopic manner to frequencies below about 200 Hz, yet we can hear frequencies
as low as 20 Hz. At its apex, all the cells respond to movement of the basilar membrane, but
they do so in proportion to the frequency of the incoming wave (see Figure 10-9B). Higher
rates of bipolar cell firing signal a higher frequency, whereas lower rates of firing signal a
lower frequency.
Why the cochlea uses a different system to differentiate pitch within this range of very
low frequency sound waves is not clear. It probably has to do with the physical limitations
of the basilar membrane. Discriminating among low-frequency sound waves is vital to ani-
mals such as elephants and whales, which depend on these frequencies to communicate.
These species most likely have more neurons at the apex of the basilar membrane than we
humans do.
Detecting Loudness
The simplest way for cochlear (bipolar) cells to indicate sound wave intensity is to fire at
a higher rate when amplitude is greater, which is exactly what happens. More intense air
pressure changes produce more intense basilar membrane vibrations and therefore greater
shearing of the cilia. Increased shearing leads to more neurotransmitter released onto bipolar
cells. As a result, the bipolar axons fire more frequently, telling the auditory system that the
sound is getting louder.
Detecting Location
Psychologist Albert Bregman devised a visual analogy to describe what the auditory system
is doing when it detects sound location:
Imagine a game played at the side of a lake. Two small channels are dug, side by side, leading
away from the lake, and the lake water is allowed to fill them up. Partway up each channel, a cork
floats, moving up and down with the waves. You stand with your back to the lake and are allowed
to look only at the two floating corks. Then you are asked questions about what is happening on
the lake. Are there two motorboats on the lake or only one? Is the nearer one going from left to
right or right to left? Is the wind blowing? Did something heavy fall into the water? You must
answer these questions just by looking at the two corks. This would seem to be an impossible
task. Yet consider an exactly analogous problem. As you sit in a room, a lake of air surrounds
you. Running off this lake, into your head, are two small channels – your ear canals. At the end
of each is a membrane (the ear drum) that acts like the floating corks in the channels running
off the lake, moving in and out with the sound waves that hit it. Just as the game at the lakeside
offered no information about the happenings on the lake except for the movements of the corks,
the sound-producing events in the room can be known by your brain only through the vibrations
of your two eardrums. (Bregman, 2005, p. 35)
We estimate the location of a sound both by taking cues derived from one ear and by
comparing cues received at both ears. The fact that each cochlear nerve synapses on both
sides of the brain provides mechanisms for locating a sound source. In one mechanism, neu-
rons in the brainstem compute the difference in a sound wave’s arrival time at each ear—the
interaural time difference (ITD). Differences in arrival time need not be large to be detected. If
two sounds presented through earphones are separated in time by as little as 10 microseconds,
the listener will perceive that a single sound came from the leading ear.
This computation of left-ear–right-ear arrival times is carried out in the medial part of the
superior olivary complex (see Figure 10-11). Because these hindbrain cells receive inputs from
each ear, they can compare exactly when the signal from each ear reaches them.
10-3 • Neural Activity and Hearing 339
Figure 10-16 shows how sound waves originating on the left reach the left ear Extra distance that
slightly before they reach the right ear. As the sound source moves from the side of sound must travel to
the head toward the middle, a person has greater and greater difficulty locating it: the reach the right ear.
ITD becomes smaller and smaller until there is no difference at all. When we detect
no difference, we infer that the sound is either directly in front of us or directly behind
us. To locate it, we turn our head, making the sound waves strike one ear sooner. We
have a similar problem distinguishing between sounds directly above and below us.
Again, we solve the problem by tilting our head, thus causing the sound waves to strike
one ear before the other.
Another mechanism used by the auditory system to detect the source of a sound is
the sound’s relative loudness on the left and the right—the interaural intensity differ-
ence (IID). The head acts as an obstacle to higher-frequency sound waves, which do
not easily bend around the head. As a result, higher-frequency waves on one side of the
head are louder than on the other. The lateral part of the superior olive and the trap-
ezoid body detect this difference. Again, sound waves coming from directly in front or
behind or from directly above or below require the same solution: tilting or turning the head.
Head tilting and turning take time, which is important for animals, such as owls, that
hunt using sound. Owls need to know the location of a sound simultaneously in at least two
directions—right or left and above or below. Owls, like humans, can orient in the horizontal Figure 10-16 Locating a Sound
plane to sound waves by using ITD. Additionally, the owl’s ears have evolved to detect the Compression waves originating on the left
relative loudness of sound waves in the vertical plane. As diagrammed in Figure 10-17, owls’ side of the body reach the left ear slightly
ears are slightly displaced vertically. This solution allows owls to hunt entirely by sound in before the right. The ITD is small, but the
auditory system can discriminate it and
the dark. Bad news for mice.
fuse the dual stimuli so that we perceive
a single, clear sound coming from the left.
Detecting Patterns in Sound Horizontal orienting is azimuth detection;
vertical orienting is elevation detection.
Music and language are perhaps the primary sound wave patterns that humans recognize.
Perceiving sound wave patterns as meaningful units thus is fundamental to our auditory
analysis. Because music perception and language perception are lateralized in the right and
left temporal lobes, respectively, we can guess that neurons in the right and left temporal
cortex take part in pattern recognition and analysis of both auditory experiences. Studying
the activities of auditory neurons in humans is not easy, however.
Most of what neuroscientists know comes from studies of how individual neurons re-
spond in nonhuman primates. Both human and nonhuman primates have a ventral and
Facial Ear-canal
ruff opening Ear opening
Wayne lynch/all canada
Photos/getty images
Ear opening
Figure 10-17 Hunting by Ear Left: In the dark, a barn owl aligns its talons
with the body axis of the mouse it is about to catch. Center: The owl’s facial
ruff collects and funnels sound waves into ear canal openings through tightly
feathered troughs above and below the eyes. The owl’s left ear is more
sensitive to sound waves from the left and below because the ear canal is
art Wolfe/getty images
higher on the left side and the trough is tilted down. The right-side ear canal
is lower and the trough tilts up, making the right ear more sensitive to sound
waves from the right and above. Right: The boreal owl’s asymmetric skull
produces a similar auditory asymmetry. Information from E. I. Knudsen (1981). The hearing
of the barn owl. Scientific American, 245(6), p. 115.
340 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
dorsal cortical pathway for audition. Neurons in the ventral pathway decode spectrally com-
plex sounds—referred to by some investigators as auditory object recognition—including the
meaning of speech sounds for people and species-typical vocalizations in monkeys (for a
Audition for action parallels unconscious review, see Rauschecker, 2012). Less is known about the properties of neurons in the dorsal
visually guided movements by the dorsal auditory stream, but this path clearly has a role in integrating auditory and somatosensory
stream; see Figure 9-42. information to control speech production. We could call it audition for action.
10-3 reVieW
Neural Activity and Hearing
Before you continue, check your understanding.
1. Bipolar neurons in the cochlea form maps that code sound wave
frequencies.
2. Loudness is decoded by the firing rate of cells in the .
3. Detecting the location of a sound is a function of neurons in the and
of the brainstem.
4. The function of the dorsal auditory pathway can be described as .
5. Explain how the brain detects a sound’s location.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
10-4 Anatomy of Language and Music
This chapter began with the evolutionary implications of discovering a flute made by Nean-
derthals (see Focus 10-1). That Neanderthals made flutes implies not only that they processed
musical sound wave patterns but also that they made music. In our brain, musical ability is
generally a right-hemisphere specialization complementary to language ability, lateralized to
the left hemisphere in most people.
No one knows whether these complementary systems evolved together in the hominid
brain, but it is highly likely. Language and music abilities are highly developed in the mod-
ern human brain. Although little is known about how each is processed at the cellular level,
Section 7-4 surveys functional brain imaging electrical stimulation and recording and blood flow imaging studies yield important insights
methods; Section 7-2 reviews methods for into the cortical regions that process them. We investigate such studies next, focusing first
measuring its electrical activity. on how the brain processes language.
Processing Language
An estimated 5000 to 7000 human languages are spoken in the world today, and probably
many more have gone extinct in past millennia. Researchers have wondered whether the
brain has a single system for understanding and producing any language, regardless of its
structure, or whether disparate languages, such as English and Japanese, are processed dif-
ferently. To answer this question, it helps to analyze languages to determine just how funda-
mentally similar they are, despite their obvious differences.
Uniformity of Language Structure
Foreign languages often seem impossibly complex to those who do not speak them. Their
sounds alone may seem odd and difficult to make. If you are a native English speaker, for
instance, Asian languages, such as Japanese, probably sound especially melodic and almost
without obvious consonants to you, whereas European languages, such as German or Dutch,
may sound heavily guttural.
10-4 • Anatomy of Language and Music 341
Even within such related languages as Spanish, Italian, and French, marked differences can
make learning one of them challenging, even if the student already knows another. Yet as real as all
these linguistic differences may be, they are superficial. The similarities among human languages,
although not immediately apparent, are actually far more fundamental than their differences.
Noam Chomsky (1965) is usually credited as the first linguist to stress similarities over dif-
ferences in human language structure. In a series of books and papers written over the past
half-century, Chomsky has made a sweeping claim, as have researchers such as Steven Pinker
(1997) more recently. They argue that all languages have common structural characteristics
stemming from a genetically determined constraint, and these common characteristics form
the basis of universal grammar theory. Humans, apparently, have a built-in capacity for learn-
ing and using language, just as we have for walking upright.
Chomsky was greeted with deep skepticism when he first proposed this idea in the 1960s,
but it has since become clear that the capacity for human language is indeed genetic. An ob-
vious piece of evidence: language is universal in human populations. All people everywhere
use language.
A language’s complexity is unrelated to its culture’s technological complexity. The lan-
guages of technologically unsophisticated peoples are every bit as complex and elegant as
the languages of postindustrial cultures. Nor is the English of Shakespeare’s time inferior or
superior to today’s English; it is just different.
Another piece of evidence that Chomsky adherents cite for the genetic basis of human A 1-year-old’s 5- to 10-word vocabulary
language is that humans learn language early in life and seemingly without effort. By about doubles in the next 6 months and by
12 months of age, children everywhere have started to speak words. By 18 months, they are 36 months mushrooms to 1000 words;
combining words, and by age 3 years, they have a rich language capability. see Section 8-3.
Perhaps the most amazing thing about language development is that children are not
formally taught the structure of their language, just as they are not taught to crawl or walk.
They just do it. As toddlers, they are not painstakingly instructed in the rules of grammar.
In fact, their early errors—sentences such as “I goed to the zoo”—are seldom even corrected
by adults. Yet children master language rapidly. They also acquire language through a series
of stages that are remarkably similar across cultures. Indeed, the process of language acquisi-
tion plays an important role in Chomsky’s theory of its innateness—which is not to say that
language development is not influenced by experience.
At the most basic level, children learn the language or languages that they hear spoken.
In an English household, they learn English; in a Japanese home, Japanese. They also pick
up the language structure—the vocabulary and grammar—of the people around them, even
though that structure can vary from one speaker to another. Children go through a sensi-
tive period for language acquisition, probably from about 1 to 6 years of age. If they are not
exposed to language throughout this critical period, their language skills are severely com- Focus 8-3 describes how cortical activation
promised. If children learn two languages simultaneously, the two share the same part of differs for second languages learned later in
Broca’s area. In fact, their neural representations overlap (Kim et al., 1997). life and Section 15-6, research on bilingualism
Both its universality and natural acquisition favor the theory for a genetic basis of human and intelligence.
language. A third piece of evidence is the many basic structural elements common to all lan-
guages. Granted, every language has its own particular grammatical rules specifying exactly
how various parts of speech are positioned in a sentence (syntax), how words are inflected
to convey different meanings, and so forth. But an overarching set of rules also applies to all
human languages, and the first rule is that there are rules.
For instance, all languages employ parts of speech that we call subjects, verbs, and direct
objects. Consider the sentence Jane ate the apple. Jane is the subject, ate is the verb, and apple
is the direct object. Syntax is not specified by any universal rule but rather is a characteristic
of the particular language. In English, syntactical order (usually) is subject, verb, object; in
Japanese, the order is subject, object, verb; in Gaelic, the order is verb, subject, object. None-
theless, all have both syntax and grammar.
The existence of these two structural pillars in all human languages is seen in the phe-
nomenon of creolization—the development of a new language from what was formerly
342 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
a rudimentary language, or pidgin. Creolization took place in the seventeenth century in the
Americas when slave traders and colonial plantation owners brought together, from various
parts of West Africa, people who lacked a common language. The newly enslaved needed to
communicate, and they quickly created a pidgin based on whatever language the plantation
owners spoke—English, French, Spanish, or Portuguese.
The pidgin had a crude syntax (word order) but lacked a real grammatical structure. The
children of the slaves who invented this pidgin grew up with caretakers who spoke only
pidgin to them. Yet within a generation, these children had developed their own creole, a
language complete with a genuine syntax and grammar.
Clearly, the pidgin invented of necessity by adults was not a learnable language for chil-
dren. Their innate biology shaped a new language similar in basic structure to all other
human languages. All creolized languages seem to evolve in a similar way, even though the
base languages are unrelated. This phenomenon can happen only because there is an innate
biological component to language development.
Localizing Language in the Brain
Finding a universal basic language structure set researchers on the search for an innate brain
system that underlies language use. By the late 1800s, it had become clear that language
functions were at least partly localized—not just within the left hemisphere but to specific
areas there. Clues that led to this conclusion began to emerge early in the nineteenth century,
when neurologists observed patients with frontal lobe injuries who had language difficulties.
Then, in 1861, the French physician Paul Broca confirmed that certain language func-
tions are localized in the left hemisphere. Broca concluded, on the basis of several post-
Section 7-1 links Broca’s observations to his mortem examinations, that language is localized in the left frontal lobe, in a region just
contributions to neuropsychology. anterior to the central fissure. A person with damage in this area is unable to speak despite
both an intact vocal apparatus and normal language comprehension. The confirmation of
Broca’s area was significant because it triggered the idea that the left and right hemispheres
might have different functions.
Figure 10-18 Neurology of Language
(A) In Wernicke’s model of speech Other neurologists of the time believed that Broca’s area might be only one of several left-
recognition, stored sound images are hemisphere regions that control language. In particular, they suspected a relation between
matched to spoken words in the left hearing and speech. Proving this suspicion correct, Karl Wernicke later described patients
posterior temporal cortex, shown in who had difficulty comprehending language after injury to the posterior region of the left
yellow. (B) Speech is produced through temporal lobe, identified as Wernicke’s area in Figure 10-18.
the connection that the arcuate fasciculus
makes between Wernicke’s area and
Broca’s area.
(A) (B)
Contains motor Connects Wernicke’s Contains sound
programs for speech and Broca’s areas images of words
Motor area Arcuate
for face fasciculus
A1 Wernicke’s area
Wernicke’s area
Broca’s area
Cranial nerves
Wernicke’s area Broca’s area
Spoken (contains Comprehend Wernicke’s (stores motor Facial area Cranial
A1 Thought programs for Speak
word sound images word heard area of motor cortex nerves
of words) speaking
words)
10-4 • Anatomy of Language and Music 343
In Section 10-2 we identified Wernicke’s area as a speech zone (see Figure 10-12A). Dam-
Broca’s area Anterior left hemisphere
age to any speech area produces some form of aphasia, the general term for any inability to
speech area that functions with the motor
comprehend or produce language despite the presence of otherwise normal comprehension
cortex to produce movements needed for
and intact vocal mechanisms. At one extreme, people who suffer Wernicke’s aphasia can speaking.
speak fluently, but their language is confused and makes little sense, as if they have no idea
aphasia Inability to speak or comprehend
what they are saying. At the other extreme, a person with Broca’s aphasia cannot speak de-
language despite the presence of normal
spite normal comprehension and intact physiology.
comprehension and intact vocal mechanisms.
Wernicke went on to propose a model, diagrammed in Figure 10-18A, for how the two Broca’s aphasia is the inability to speak
language areas of the left hemisphere interact to produce speech. He theorized that images fluently despite the presence of normal
of words are encoded by their sounds and stored in the left posterior temporal cortex. When comprehension and intact vocal mechanisms.
we hear a word that matches one of those sound images, we recognize it, which is how Wernicke’s aphasia is the inability to
Wernicke’s area contributes to speech comprehension. understand or to produce meaningful
To speak words, Broca’s area in the left frontal lobe must come into play, because the language even though word production
motor program to produce each word is stored in this area. Messages travel to Broca’s area remains intact.
from Wernicke’s area through the arcuate fasciculus, a fiber pathway that connects the two
regions. Broca’s area in turn controls articulation of words by the vocal apparatus, as dia-
grammed in Figure 10-18B.
Wernicke’s model provided a simple explanation both for the existence of two major lan-
guage areas in the brain and for the contribution each area makes to the control of language.
But the model was based on postmortem examinations of patients with brain lesions that
were often extensive. Not until neurosurgeon Wilder Penfield’s pioneering studies, begun in
the 1930s, were the left hemisphere language areas clearly and accurately mapped.
Auditory and Speech Zones Mapped by Brain
Stimulation
It turns out, among Penfield’s discoveries, that neither is Broca’s area the independent site of
speech production nor is Wernicke’s area the independent site of language comprehension.
Electrical stimulation of either region disrupts both processes.
Penfield took advantage of the chance to map the brain’s auditory and language areas when
he operated on patients undergoing elective surgery to treat epilepsy unresponsive to antisei-
zure medication. The goal of this surgery is to remove tissues where the abnormal discharges
are initiated without damaging the areas responsible for linguistic ability or vital sensory or
motor functioning. To determine the locations of these critical regions, Penfield used a weak
electrical current to stimulate the brain surface. By monitoring the patient’s responses during Section 7-1 describes brain stimulation
stimulation in different locations, Penfield could map brain functions along the cortex. techniques used in neuroscience research.
Typically, two neurosurgeons perform the operation under local anesthesia applied to the
skin, skull, and dura mater (Penfield is shown operating in Figure 10-19A) as a neurologist
analyzes the electroencephalogram in an adjacent room. Patients, who are awake, are asked
to contribute during the procedure, and the effects of brain stimulation in specific regions
can be determined in detail and mapped. Penfield placed tiny numbered tickets on differ-
ent parts of the brain’s surface where the patient noted that stimulation had produced some
noticeable sensation or effect, producing the cortical map shown in Figure 10-19B.
When Penfield stimulated the auditory cortex, patients often reported hearing such
sounds as a ringing that sounded like a doorbell, a buzzing noise, or a sound like birds chirp-
ing. This result is consistent with later single-cell recordings from the auditory cortex in non-
human primates. Findings in these later studies showed that the auditory cortex participates
in pattern recognition.
Penfield also found that stimulation in area A1 seemed to produce simple tones—ringing
sounds, and so forth—whereas stimulation in the adjacent auditory cortex (Wernicke’s area)
was more apt to cause some interpretation of a sound—ascription of a buzzing sound to
a familiar source such as a cricket, for instance. There was no difference in the effects of
stimulation of the left or right auditory cortex, and the patients heard no words when the
brain was stimulated.
344 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
(A)
(B)
Central
courtesy Penfi eld archive, Montreal neurological
institute, Mcgill university
sulcus
Lateral
fissure
Figure 10-19 Mapping Cortical Functions (A) Neurosurgery for eligible epilepsy
patients who failed to respond to antiseizure medications. The patient is fully conscious,
lying on his right side, and kept comfortable with local anesthesia. Wilder Penfield stimulates
discrete cortical areas in the patient’s exposed left hemisphere. In the background, a
neurologist monitors an EEG recorded from each stimulated area to help identify the
epileptogenic focus. The anesthetist (seated) observes the patient’s responses to the cortical
stimulation. (B) A drawing overlies a photograph of the patient’s exposed brain. The numbered
tickets identify points Penfield stimulated to map the cortex in this patient’s brain. At points
26, 27, and 28, a stimulating electrode disrupted speech. Point 26 presumably is in Broca’s
area, 27 is the motor cortex facial control area, and 28 is in Wernicke’s area.
Sometimes, however, stimulation of the auditory cortex produced effects other than
sound perceptions. Stimulation of one area, for example, might cause a patient to feel deaf,
whereas stimulation of another area might produce a distortion of sounds actually being
heard. As one patient exclaimed after a certain region had been stimulated, “Everything you
said was mixed up!”
Supplementary Areas controlling
speech area facial movement or Penfield was most interested in the effects of brain stimulation not on simple sound wave
(vocalization or sensation (vocalization processing but on language. He and later researchers used electrical stimulation to identify
speech arrest) or speech arrest)
four important cortical regions that control language. The two classic regions—Broca’s area
Aphasia
and Wernicke’s area—are left-hemisphere regions. Located on both sides of the brain are
the other two major language use regions: the dorsal area of the frontal lobes and the areas
of the motor and somatosensory cortex that control facial, tongue, and throat muscles and
sensations. Although the effects on speech vary depending on the region, stimulating any
of them disrupts speech in some way.
Clearly, much of the left hemisphere takes part in audition. Figure 10-20 shows those
areas that Penfield found engaged in some way in processing language. In fact, Penfield
mapped cortical language areas in two ways, first by disrupting speech, then by eliciting
Broca’s A1
Wernicke’s
area (sounds speech. Not surprisingly, damage to any speech area produces some form of aphasia.
area
(aphasia) heard)
(aphasia) Disrupting speeCh Penfield expected that electrical current might disrupt ongoing
Cortical Regions That
Figure 10-20 speech by effectively short-circuiting the brain. To test his hypothesis, he stimulated dif-
Control Language This map, based ferent cortical regions while the patient was speaking. In fact, the speech disruptions took
on Penfield’s extensive study, summarizes several forms, including slurring, word confusion, and difficulty in finding the right word.
the left-hemisphere areas where direct
Such aphasias are detailed in Clinical Focus 10-4, Left-Hemisphere Dysfunction.
stimulation may disrupt speech or elicit
vocalization. Information from W. Penfield & Electrical stimulation of the supplementary speech area on the dorsal surface of the
L. Roberts (1956). Speech and brain mechanisms (p. 201). frontal lobe (shown in Figure 10-20) can even stop ongoing speech completely, a reaction that
London: Oxford University Press. Penfield called speech arrest. Stimulation of other cortical regions far removed from
10-4 • Anatomy of Language and Music 345
clinical F cus 10-4
Left-Hemisphere Dysfunction
Susan S., a 25-year-old college graduate and mother of two, had epi- remainder of her left temporal lobe, including the auditory cortex and
lepsy. When she had a seizure, which was almost every day, she lost Wernicke’s area. The extent of lost brain tissue resembles that shown in
consciousness for a short period during which she often engaged in the accompanying MRI.
repetitive behaviors, such as rocking back Susan no longer understood language, ex-
and forth. cept to respond to the sound of her name and
Courtesy of George Jallo/
Johns Hopkins Hospital
Medication can usually control such sei- to speak just one phrase: I love you. Susan
zures, but the drugs were ineffective for Susan. was also unable to read, showing no sign that
The attacks disrupted her life: they prevented she could even recognize her own name in
her from driving and restricted the types of jobs writing.
she could hold. So Susan decided to undergo To find ways to communicate with Susan,
neurosurgery to remove the region of abnor- Bryan Kolb tried humming nursery rhymes
mal brain tissue that was causing the seizures. to her. She immediately recognized them and
The procedure has a high success rate. Su- could say the words. We also discovered that
san’s surgery entailed removal of a part of the her singing skill was well within the normal
left temporal lobe, including most of the cortex range and she had a considerable repertoire
in front of the auditory areas. Although it may of songs.
seem a substantial amount of the brain to cut Postoperative MRI of a patient who has lost Susan did not seem able to learn new
away, the excised tissue is usually abnormal, so most of the left hemisphere. songs, however, and she did not understand
any negative consequences typically are minor. messages that were sung to her. Apparently,
After the surgery, Susan did well for a few days; then she started Susan’s musical repertoire was stored and controlled independently of
to have unexpected and unusual complications. As a result, she lost the her language system.
the temporal and frontal speech areas has no effect on ongoing speech, with the exception
supplementary speech area Speech
of motor cortex regions, shown in Figure 10-20, that control facial movements. This excep-
production region on the left frontal lobe
tion makes sense because talking requires movement of facial, tongue, and throat muscles.
dorsal surface.
eliCiting speeCh The second way Penfield mapped language areas was to stimulate the
cortex when a patient was not speaking. Here the goal was to see if stimulation caused the
person to utter a speech sound. Penfield did not expect to trigger coherent speech; cortical
electrical stimulation is not physiologically normal and so probably would not produce actual
words or word combinations. His expectation was borne out.
Stimulation of regions on both sides of the brain—for example, the supplementary speech
areas—produces a sustained vowel cry, such as Oooh or Eee. Stimulation of the facial areas
in the motor and somatosensory cortices produces some vocalization related to mouth and
tongue movements. Stimulation outside these speech-related zones produces no such effects.
Auditory Cortex Mapped by
Positron Emission Tomography
To study the metabolic activity of brain cells engaged in tasks such as processing language,
researchers use PET, a brain-imaging technique that detects changes in brain blood flow. Section 7-4 details procedures used to obtain
Among the many PET studies of auditory stimulation, a series conducted by Robert Zatorre a PET scan.
and his colleagues (1992, 1996) serves as a good example. These researchers hypothesized
that simple auditory stimulation, such as bursts of noise, are analyzed by area A1, whereas
more complex auditory stimulation, such as speech syllables, are analyzed in adjacent sec-
ondary auditory areas.
The researchers also hypothesized that performing a discrimination task for speech
sounds would selectively activate left-hemisphere regions. This selective activation is exactly
what they found. Figure 10-21A shows increased activity in the primary auditory cortex
346 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
Area A1 Wernicke’s area Broca’s area
Figure 10-21 Cortical Activation in
Language-Related Tasks
(A) Passively listening to noise bursts
in response to bursts of noise, whereas secondary auditory areas are activated by speech
activates the primary auditory cortex.
(B) Listening to words activates the syllables (Figure 10-21B and C).
posterior speech zone, including Both types of stimuli produced responses in both hemispheres but with greater activation
Wernicke’s area. (c) Making a phonetic in the left hemisphere for the speech syllables. These results imply that area A1 analyzes all
discrimination activates the frontal region, incoming auditory signals, speech and nonspeech, whereas the secondary auditory areas are
including Broca’s area.
responsible for some higher-order signal processing required for analyzing language sound
patterns.
As Figure 10-21C shows, the speech sound discrimination task yielded an intriguing addi-
tional result: Broca’s area in the left hemisphere was also activated. This frontal lobe region’s
involvement during auditory analysis may seem surprising. In Wernicke’s model, Broca’s area
is considered the storage area for motor programs needed to produce words. It is not usually
a region thought of as a site of speech sound discrimination.
A possible explanation is that to determine that the g in bag and the one in pig are the
same speech sound, the auditory stimulus must be related to how the sound is actually
articulated. That is, speech sound perception requires a match with the motor behaviors
associated with making the sound.
This role for Broca’s area in speech analysis is confirmed further when investigators ask
people to determine whether a stimulus is a word or a nonword (e.g., tid versus tin or gan
versus tan). In this type of study, information about how the words are articulated is irrel-
evant, and Broca’s area need not be recruited. Imaging reveals that it is not.
Processing Music
Although Penfield did not study the effect of brain stimulation on musical analysis, many
researchers study musical processing in brain-damaged patients. Clinical Focus 10-5, Cere-
bral Aneurysms, describes one such case. Collectively, the results of these studies confirm
that musical processing is in fact largely a right-hemisphere specialization, just as language
processing is largely a left-hemisphere one.
Localizing Music in the Brain
A famous patient, the French composer Maurice Ravel (1875–1937), provides an excellent
example of right-hemisphere predominance for music processing. Boléro is perhaps Ravel’s
best-known work. At the peak of his career, Ravel had a left-hemisphere stroke and devel-
oped aphasia. Yet many of his musical skills remained intact post-stroke because they were
localized to the right hemisphere. He could still recognize melodies, pick up tiny mistakes in
music he heard, and even judge the tuning of pianos. His music perception was largely intact.
Skills that had to do with producing music, however, were among those destroyed. Ravel
could no longer recognize written music, play the piano, or compose. This dissociation of
music perception and music production may parallel the dissociation of speech comprehension
and speech production in language. Apparently, the left hemisphere plays at least some role
in certain aspects of music processing, especially those that have to do with making music.
10-4 • Anatomy of Language and Music 347
clinical F cus 10-5
Cerebral Aneurysms
C. N. was a 35-year-old nurse described by Isabelle Peretz and an aneurysm in the middle cerebral artery on the right side of her
her colleagues (1994). In December 1986, C. N. suddenly developed brain.
severe neck pain and headache. A neurological examination revealed An aneurysm is a bulge in a blood vessel wall caused by weakening
of the tissue, much like the bulge that appears in a bicycle tire at a weak-
ened spot. Aneurysms in a cerebral artery are dangerous: if they burst,
Aneurysm in middle Bulge in severe bleeding and consequent brain damage result.
cerebral artery bicycle tire
In February 1987, C. N.’s aneurysm was surgically repaired, and she
appeared to have few adverse effects. Postoperative brain imaging re-
vealed, however, that a new aneurysm had formed in the same location
but in the middle cerebral artery on the opposite side of the brain. This
second aneurysm was repaired 2 weeks later.
After her surgery, C. N. had temporary difficulty finding the right
word when she spoke, but more important, her perception of music was
deranged. She could no longer sing, nor could she recognize familiar
tunes. In fact, singers sounded to her as if they were talking instead of
singing. But C. N. could still dance to music.
A brain scan revealed damage along the lateral fissure in both tem-
poral lobes. The damage did not include the primary auditory cortex, nor
did it include any part of the posterior speech zone. For these reasons,
C. N. could still recognize nonmusical sound patterns and showed no
evidence of language disturbance. This finding reinforces the hypothesis
that nonmusical sounds and speech sounds are analyzed in parts of the
brain separate from those that process music.
To find out more about how the brain carries out the perceptual side of music process-
ing, Zatorre and his colleagues (1994) conducted PET studies. When participants listened
simply to bursts of noise, Heschl’s gyrus became activated (Figure 10-22A), but perception
of melody triggers major activation in the right-hemisphere auditory cortex lying in front
of Heschl’s gyrus (Figure 10-22B), as well as minor activation in the same left-hemisphere
region (not shown).
In another test, participants listened to the same melodies. The investigators asked them
to indicate whether the pitch of the second note was higher or lower than that of the first
note. During this task, which necessitates short-term memory of what was just heard, blood
flow in the right frontal lobe increased (Figure 10-22C). As with language, then, the frontal Cortical Activation in
Figure 10-22
lobe plays a role in auditory analysis when short-term memory is required. People with en- Music-Related Tasks (A) Passively
hanced or impaired musical abilities show differences in frontal lobe organization, as dem- listening to bursts of noise activates
onstrated in Research Focus 10-6, The Brain’s Music System. Heschl’s gyrus. (B) Listening to a melody
activates the secondary auditory cortex.
As noted earlier, the capacity for language is innate. Sandra Trehub and her colleagues (1999)
(c) Making relative pitch judgments about
showed that music may be innate as well, as we hypothesized at the beginning of the chapter. two notes in each melody activates a right
frontal lobe area.
(A) Listening to bursts of noise (B) Listening to melodies (C) Comparing pitches
Heschl‘s gyrus A2 Frontal lobe
348 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
ReseaRch F cus 10-6
The Brain’s Music System
Nonmusicians enjoy music and have musical ability. Musicians show an led to an excess of neurons in the right frontal–temporal music pathway
enormous range of ability: some have perfect pitch and some do not, for of the amusics. Their impaired music cognition is the result.
example. About 4 percent of the population is tone deaf. Their difficulties,
characterized as amusia—an inability to distinguish between musical
notes—are lifelong.
Right hemisphere
Robert Zatorre and his colleagues (Bermudez et al., 2009; Hyde
et al., 2007) have used MRI to look at differences among the brains of
musicians, nonmusicians, and amusics. MRIs of the left and right hemi-
spheres show that compared to nonmusicians, musicians’ cortical thick-
ness is greater in dorsolateral frontal and superior temporal regions.
Curiously, musicians with perfect pitch have thinner cortex in the pos-
terior part of the dorsolateral frontal lobe. Thinner appears to be better
for some music skills.
Compared to nonmusicians then, musicians with thicker than Left hemisphere
normal cortex must have enhanced neural networks in the right-
hemisphere frontal–temporal system linked to performing musical
Compared to nonmusicians and amusics, musicians' thicker cortex,
tasks. But thicker than normal cortex can bestow both advantage and shown in the green, yellow, and red areas, contributes to performance.
impairment. Focus 14-5 describes how playing music can affect sensorimotor maps in
Analysis of amusic participants’ brains showed thicker cortex in the the cortex. Research from P. Bermudez, J. P. Lerch, A. C. Evans, & R. J. Zatorre (2009).
right frontal area and in the right auditory cortex regions. Some abnor- Neuroanatomical correlates of musicianship as revealed by cortical thickness and
mality in neuronal migration during brain development is likely to have voxel-based morphometry. Cerebral Cortex, 7, 1583–1596.
Trehub found that infants show learning preferences for musical scales versus random
amusia Tone deafness—inability to
notes. Like adults, children are sensitive to musical errors, presumably because they are
distinguish between musical notes.
biased for perceiving regularity in rhythms. Thus, it appears that the brain is prepared at
The brain may be tuned prenatally to the birth for hearing both music and language, and presumably it selectively attends to these
language it will hear at birth; see Focus 7-1. auditory signals.
Music as Therapy
The power of music to engage the brain has led to its use as a therapeutic tool for brain dys-
functions. The best evidence of its effectiveness lies in studies of motor disorders such as
At: https://www.youtube.com/watch?v= stroke and Parkinson disease (Johansson, 2012). Listening to rhythm activates the motor and
eNpoVeLfMKg, watch as Parkinson patients premotor cortex and can improve gait and arm training after stroke. Musical experience re-
step to the beat of music to improve their gait portedly also enhances the ability to discriminate speech sounds and to distinguish speech
length and walking speed. from background noise in patients with aphasia.
Music therapy also appears to be a useful complement to more traditional therapies, especially
when there are problems with mood, such as in depression or brain injury. This may prove im-
portant in the treatment of stroke and traumatic brain injury, with which depression is a common
More on music as therapy in Focus 5-2 complication in recovery. Music therapy also has positive effects following major surgery, both in
and the dance class for Parkinson patients adults and children, by reducing both their pain perception and the amount of pain medication
pictured on page 160. Sections 16-2 and 16-3 they use (Sunitha Suresh et al., 2015). With all these applications, perhaps researchers will decide
revisit music therapy. to use noninvasive imaging to determine which brain areas music therapy recruits.
10-4 reVieW
Anatomy of Language and Music
Before you continue, check your understanding.
1. The human auditory system has complementary specialization for the perception of
sounds: left for and right for .
10-5 • Auditory Communication in Nonhuman Species 349
2. The three frontal lobe regions that participate in producing language are ,
, and .
3. area identifies speech syllables and words and stores their representations
in that location.
4. area matches speech sounds to the motor programs necessary to
articulate them.
5. At one end of the spectrum for musical ability are people with and at the
other are people who are .
6. What evidence supports the idea that language is innate?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
10-5 Auditory Communication
in Nonhuman Species
Sound has survival value. You will appreciate this if you’ve ever narrowly escaped becoming
an accident statistic by crossing a busy intersection on foot while listening to a music player
or talking on a cell phone. Audition is as important a sense to many animals as vision is to
humans. Many animals also communicate with other members of their species by using
sound, as humans do.
Here we consider just two types of auditory communication in nonhumans: birdsong and
echolocation. Each provides a model for understanding different aspects of brain–behavior
relations in which the auditory system plays a role.
Birdsong
Of about 8500 living bird species, about half are considered songbirds. Birdsong has many
functions, including attracting mates (usually employed by males), demarcating territories,
and announcing location or even just presence. Although all birds of the same species have
a similar song, the song’s details vary markedly from region to region, much as dialects of
the same human language vary.
Parallels Between Birdsong and Language
Figure 10-23 shows sound wave spectrograms for the songs of male white-crowned sparrows
that live in three localities near San Francisco. These songs differ markedly from region to
region. The differences stem from the fact that song development in young birds is influenced
not just by genes but also by early experience and learning. Young birds that have a good tutor
can acquire more elaborate songs than can other members of their species (Marler, 1991).
These gene–experience interactions are the result of epigenetic mechanisms. For example,
brain areas that control singing in adult song sparrows show altered gene expression in spring
as the breeding—and singing—season begins (Thompson et al., 2012). Such studies have not
yet targeted young birds, but it is safe to predict that researchers will find parallel changes.
Birdsong and human language have broad similarities beyond regional variation. Both
appear to be innate yet are sculpted by experience. Both are diverse and can vary in complex-
ity. Humans seem to have a basic template for language that is programmed into the brain,
and experience adds a variety of specific structural forms to this template.
If a young bird is not exposed to song until it is a juvenile and then listens to recordings of
birdsongs of various species, the young bird shows a general preference for its own species’
song. This preference must mean that each bird has a species-specific song template in the
brain. As for language, experience modifies the details of this birdsong template.
350 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
Another broad similarity between birdsong
White-crowned
and human language is their great diversity.
sparrow
Among birds, diversity is apparent in the sheer
number of songs that a species possesses. Species
such as the white-crowned sparrow have but a
Point Reyes
single song; the marsh wren has as many as 150.
Berkeley The number of syllables in birdsong also varies
greatly, ranging from 30 for the canary to about
San Francisco
Bay 2000 for the brown thrasher. Similarly, even
Sunset Beach though all modern human languages are equally
complex, they vary significantly in the type and
number of elements they employ. The number of
meaningful patterns in speech sounds in human
Figure 10-23 Birdsong Dialects The
songs of male white-crowned sparrows languages ranges from about 15 for some Polynesian languages to about 100 for some dialects
recorded in three locales around San spoken in the Caucasus Mountains. English has 24.
Francisco Bay are similar, but sound wave A final broad similarity between birdsong and human language lies in how they develop.
spectrograms reveal that the dialects In many bird species, song development is heavily influenced by experience during a criti-
differ. Like humans, birds acquire regional
cal period, just as language development is in humans. Birds also go through stages in song
dialects. Information from P. Marler (1991). The instinct
to learn. In S. Carey & R. German (Eds.), The epigenesis
development, just as humans go through stages in language development. Hatchlings make
of mind: Essays on biology and cognition (p. 39), Hillsdale, noises that attract their parents’ attention, usually for feeding, and human babies emit cries
NJ: Erlbaum. to signal hunger, among other things.
The fledgling begins to make noises that Charles Darwin compared to the prespeech
babbling of human infants. These noises, called subsong, are variable in structure, low in
volume, and often produced as the bird appears to doze. Presumably, subsong, like human
babbling, is practice for the later development of adult communication after the bird has
left the nest.
As a young bird matures, it starts to produce sound wave patterns that contain recogniz-
able bits of the adult song. Finally, the adult song emerges. In most species, the adult song
remains remarkably stable, although a few species, such as canaries, can develop a new song
every year that replaces the previous year’s song.
Neurobiology of Birdsong
The neurobiology of birdsong has been a topic of intense research, partly because it pro-
vides an excellent model of brain changes that accompany learning and partly because it
offers insight into how sex hormones influence behavior. In the 1970s, Fernando Nottebohm
and his colleagues first identified the major structures controlling birdsong, illustrated in
Figure 10-24 (Nottebohm & Arnold, 1976). The largest structures are the higher vocal con-
trol center (HVC) and the nucleus robustus archistriatalis (RA). The axons of the HVC con-
nect to the RA, which in turn sends axons to the 12th cranial nerve. This nerve controls the
muscles of the syrinx, the structure that actually produces the song.
The HVC and RA have several important and some familiar characteristics:
• The structures are asymmetrical in some bird species, with those in the left hemisphere
larger than those on the right. In many cases, this asymmetry is similar to the
lateralized control of language in humans: if the left-hemisphere pathways are damaged,
the bird stops singing, but similar injury in the right hemisphere has no effect on song.
• Birdsong structures are sexually dimorphic, that is, much larger in males than in
Shown in Figure 8-30, a rare gyandromorph females. In male canaries, the structures are five times as large as in the female. This
zebra finch exhibits physical characteristics of sex difference is due to the hormone testosterone in males. Injection of testosterone
both sexes. into female birds causes the song-controlling nuclei to increase in size.
• The size of the birdsong-controlling nuclei is related to singing skill. Unusually talented
singers among male canaries tend to have larger HVCs and RAs than do less-gifted
singers.
10-5 • Auditory Communication in Nonhuman Species 351
• The HVC and RA contain cells that produce birdsong as well as
Canary brain HVC
cells responsive to hearing song, especially the song of a bird’s own
species.
Ad RA
The same structures therefore play a role in both song production
Area X
and song perception. This avian neural anatomy is comparable to the LMAN DLM
overlapping roles of Broca’s and Wernicke’s areas in language perception HYP
and production in humans.
Syrinx
(vocal organ) Trachea
Echolocation in Bats Muscle
12th cranial
nerve
Next to rodents, bats are the most numerous mammalian order. The two KEY
general groups, or suborders, are the smaller bats (Microchiroptera) and Cell groups specialized
for vocal learning
the larger fruit-eating and flower-visiting bats (Megachiroptera), some-
Cell groups specialized
times called flying foxes. Each uses a form of echolocation. Using their for vocal learning
wings to make clicking sounds, Megachiroptera can detect large surfaces and adult song
and orient in complete darkness. This rudimentary form of echolocation
Figure 10-24 Avian Neuroanatomy Lateral view of the
may be the forerunner of the highly evolved throat (laryngeal) system
canary brain shows several left-hemisphere nuclei that control
used in a sophisticated way by the Microchiroptera to navigate, hunt, song learning. Two that are necessary both for adult singing and
and communicate using sound waves (Boonman et al., 2014). for learning the song are the higher vocal control center (HVC)
Most of the 680 species of Microchiroptera feed on insects. Others and the nucleus robustus archistriatalis (RA). Other regions
live on blood (vampire bats), and some catch frogs, lizards, fishes, birds, necessary for learning the song during development but not
and small mammals. These bats’ auditory system is highly specialized required for adult singing include the dorsal archistriatum (Ad),
the lateral magnocellular nucleus of the anterior neostriatum
to use echolocation not only to locate targets in the dark but also to ana-
(LMAN), area X of the avian striatum, and the medial dorsolateral
lyze the targets’ features as well as environmental features in general. nucleus of the thalamus (DLM).
Through echolocation, these bats identify prey, navigate through the
leaves of trees, and locate suitable landing surfaces. Echolocation in the Microchiroptera
Dolphins use an auditory strategy similar to
works rather like sonar. The bat larynx emits bursts of sound waves at ultrasonic frequencies.
bats, but in water. Focus 10-2 profiles human
The waves bounce off objects and return to the bat’s ears, allowing the animal to identify echolocators.
what is in the surrounding environment. The bat, in other words, navigates by the echoes it
hears, differentiating among the various characteristics of the echoes.
Moving objects (such as insects) give off a moving echo, smooth objects a different echo
Microchiroptera
from rough objects, and so on. A key component of the bats’ echolocation system is analysis of
differences in echo return times. Close objects return echoes sooner than more distant objects
do, and the textures of various objects’ surfaces impose minute differences in return times.
A bat’s cries are short (ranging from 0.3 to 200 milliseconds) and high frequency (12,000
to 200,000 Hz, charted in Figure 10-4). Most of this range lies at too high a frequency for the
human ear to detect. Different bat species produce sound waves of different frequencies that
depend on the animal’s ecology. Bats that catch prey in the open use different frequencies
from those used by bats that catch insects in foliage and from those used by bats that hunt
prey on the ground.
The echolocation abilities of bats are phenomenal, as shown in Figure 10-25. Bats in the
wild can be trained to catch small food particles thrown up into the air in the dark. These
echolocating skills make the bat a most efficient hunter. The little brown bat, for instance,
can capture tiny flying insects, such as mosquitoes, at the remarkable rate of two per second.
Researchers have considerable interest in the neural mechanisms of bat echolocation.
Each species emits sound waves in a relatively narrow frequency range, and a bat’s auditory Megachiroptera
pathway has cells specifically tuned to echoes in its species’ frequency range. For example,
the mustached bat sends out sound waves ranging from 60,000 to 62,000 Hz, and its audi-
tory system has a cochlear fovea (a maximally sensitive area in the organ of Corti) that cor-
responds to that frequency range. echolocation Identifying and locating an
In this way, more neurons are dedicated to the frequency range used for echolocation object by bouncing sound waves off it.
than to any other range of frequencies. Analogously, our visual system dedicates more neu-
rons to the retina’s fovea, the area responsible for our most detailed vision. In the cortex of Figure 9-2 details the fovea’s structure.
352 Chapter 10 • HOW DO WE HEAR, SPEAK, AND MAKE MUSIC?
Figure 10-25 Born with
Sonar Based entirely on
auditory information,
© rolf nussbaumer/imagebroKEr
a bat with a 40-centimeter
wingspan can navigate
through openings in a
14-by-14-centimeter mesh
made of 80-millimeter nylon
thread while flying in total
darkness.
the bat’s brain, several distinct areas process complex echoic inputs. One area computes the
distance of given targets from the animal, for instance, whereas another area computes the
velocity of a moving target. This neural system makes the bat exquisitely adapted for night-
time navigation.
10-5 reVieW
Auditory Communication in Nonhuman Species
Before you continue, check your understanding.
1. Song development in young birds is influenced both by genes and by early experience and
learning, interactions indicative of .
2. In many bird species the control of song in the brain is lateralized to the
hemisphere.
3. Bats use to locate prey in the dark. This system is much like the
that ships use to locate underwater objects.
4. What does the presence of dialects in birdsong in the same species demonstrate?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
summary
Although we take language and music for granted, both play central 10-2Functional Anatomy of the
roles in our mental lives and in our social lives. Language and music Auditory System
provide us ways to communicate with other people—and with ourselves. Beginning in the ear, mechanical and electrochemical systems
They facilitate social identification, parenting, and cultural transmission. combine to transform sound waves into auditory perceptions—what
we hear. Changes in air pressure are conveyed in a mechanical chain
10-1 Sound Waves: The Stimulus for Audition reaction from the eardrum to the bones of the middle ear to the oval
The stimulus for the auditory system is the mechanical energy of window of the cochlea and the cochlear fluid that lies behind it in
sound waves that results from changes in air pressure. The ear the inner ear. Movements of the cochlear fluid produce movements
transduces three fundamental physical qualities of sound wave in specific regions of the basilar membrane, leading to changes in
energy: frequency (repetition rate), amplitude (size), and complexity. the electrochemical activity of the auditory receptors, the inner hair
Perceptually, neural networks then translate these energies into the cells on the basilar membrane that send neural impulses through the
pitch, loudness, and timbre of the sounds that we hear. auditory nerve into the brain.
Key Terms 353
10-3 Neural Activity and Hearing Among several left-hemisphere language-processing areas,
The basilar membrane has a tonotopic organization. High-frequency Wernicke’s area identifies speech syllables and words and so is
sound waves maximally stimulate hair cells at the base, whereas low- critically engaged in speech comprehension. Broca’s area matches
frequency sound waves maximally stimulate hair cells at the apex, speech sound patterns to the motor behaviors necessary to make
enabling cochlear neurons to code sound frequencies. them and so plays a major role in speech production. Broca’s area
Tonotopic organization analyzes sound waves at all levels of the also discriminates between closely related speech sounds. Aphasias
auditory system, which also detects both amplitude and location. The are an inability to speak (Broca’s aphasia) or to comprehend language
firing rate of cochlear neurons codes sound amplitude, with louder (Wernicke’s aphasia) despite the presence of normal cognition and
sounds producing higher firing rates than softer sounds do. Location intact vocal mechanisms.
is detected by structures in the brainstem that compute differences in Auditory analysis of music draws more on right-hemisphere
the arrival times and loudness of a sound in the two ears. activity than on the left. Nor is music production localized to the right
Cochlear hair cells synapse with bipolar neurons that form the hemisphere: it recruits the left hemisphere as well. Music perception
cochlear nerve, which in turn forms part of the eighth cranial nerve. engages both the right temporal and frontal regions.
The cochlear nerve takes auditory information to three structures Music’s power to engage both right- and left-hemisphere activity
in the hindbrain: the cochlear nucleus, the superior olive, and the makes it a powerful tool for engaging the injured or dysfunctioning
trapezoid body. Cells in these areas are sensitive to differences in brain. Music therapy is playing an increasingly important role in
both sound wave intensity and arrival times at the two ears. In this treatment.
way, they enable the brain to locate a sound.
The auditory pathway continues from the hindbrain areas to the
10-5 Auditory Communication
inferior colliculus of the midbrain, then to the medial geniculate in Nonhuman Species
nucleus in the thalamus, and finally to the auditory cortex. As for Nonhuman animals have evolved specialized auditory structures
vision, dorsal and ventral pathways exist in the auditory cortex, one and behaviors. Regions of songbirds’ brains are specialized for
for pattern recognition and the other for controlling movements in producing and comprehending song. In many species, these regions
auditory space. Cells in the cortex are responsive to specific sound are lateralized to the left hemisphere, analogous in a way to how
categories, such as species-specific communication. language areas are lateralized to the left hemisphere in most humans.
Similarities in the development of song in birds and the development of
10-4 Anatomy of Language and Music language in humans, as well as similarities in the neural mechanisms
Despite differences in the patterns and structures of speech sounds, underlying both the production and the perception of birdsong and
all human languages have the same basic foundation: syntax and language, are striking.
grammar, which implies an innate template for creating language. Both owls and bats can fly and catch prey at night using only
Auditory areas of the left hemisphere cortex play a special role in auditory information to guide their movement. Bats evolved a type of
analyzing language-related information, whereas those in the right biosonar that allows them to map the objects in their auditory world,
hemisphere play a special role in analyzing music-related information. as humans map their visual worlds. Although some blind humans
The right temporal lobe also analyzes prosody, the melodic qualities employ this strategy, the mainly auditory reality of bats, dolphins, and
of speech. other echolocators is one most people can only try to imagine.
Key terms
aphasia, p. 343 decibel (dB), p. 325 medial geniculate sound wave, p. 323
amplitude, p. 325 echolocation, p. 351 nucleus, p. 333 supplementary speech area,
amusia, p. 348 frequency, p. 323 ossicle, p. 329 p. 345
basilar membrane, p. 331 hair cell, p. 331 otoacoustic emissions, p. 333 tonotopic representation, p. 337
Broca’s area, p. 343 hertz (Hz), p. 323 primary auditory cortex (area Wernicke’s area, p. 335
A1), p. 333
cochlea, p. 329 insula, p. 335
prosody, p. 329
cochlear implant, p. 337 lateralization, p. 335
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
this page left intentionally blank
ReseaRch Focus 11-1 NeuroproStheticS
ch a p te r 11-1 a hieRaRchy oF MoveMent contRol
11 How Does the Nervous THE BASICS relatiNg the SomatoSeNSory aNd motor SyStemS
ForebraiN: iNitiatiNg movemeNt
System Respond experimeNtal evideNce For a movemeNt hierarchy
braiNStem: SpecieS-typical movemeNt
to Stimulation and expeRiMent 11-1 QueStioN: What are the eFFectS
oF braiNStem StimulatioN uNder diFFereNt coNditioNS?
Produce Movement?
clinical Focus 11-2 cerebral palSy
SpiNal cord: executiNg movemeNt
clinical Focus 11-3 SpiNal cord iNjury
11-2 MotoR systeM oRganization
motor cortex
motor cortex aNd SKilled movemeNt
expeRiMent 11-2 QueStioN: hoW doeS the motor cortex
taKe part iN the coNtrol oF movemeNt?
plaSticity iN the motor cortex
expeRiMent 11-3 QueStioN: What iS the eFFect
oF rehabilitatioN oN the cortical repreSeNtatioN
oF the Forelimb aFter braiN damage?
corticoSpiNal tractS
motor NeuroNS
coNtrol oF muScleS
11-3 Basal ganglia, ceReBelluM, and MoveMent
baSal gaNglia aNd the Force oF movemeNt
clinical Focus 11-4 tourette SyNdrome
cerebellum aNd movemeNt SKill
expeRiMent 11-4 QueStioN: doeS the cerebellum help
to maKe adjuStmeNtS reQuired to Keep
movemeNtS accurate?
11-4 soMatosensoRy systeM ReceptoRs and pathways
SomatoSeNSory receptorS aNd perceptioN
poSterior root gaNglioN NeuroNS
SomatoSeNSory pathWayS to the braiN
SpiNal reFlexeS
FeeliNg aNd treatiNg paiN
ReseaRch Focus 11-5 phaNtom limb paiN
veStibular SyStem aNd balaNce
11-5 exploRing the soMatosensoRy coRtex
SomatoSeNSory homuNculuS
ReseaRch Focus 11-6 ticKliNg
Katherine Streeter
eFFectS oF SomatoSeNSory cortex damage
SomatoSeNSory cortex aNd complex movemeNt
355
356 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
RESEARCH F cus 11-1
Neuroprosthetics
Most of us seamlessly control the approximately 650 muscles that move
our bodies. But if the motor neurons that control those muscles no lon-
ger connect to them, as happens in amyotrophic lateral sclerosis (ALS,
or Lou Gehrig disease), movement, and eventually breathing, become
impossible.
This happened to Scott Mackler, a neuroscientist and marathon run-
ner, in his late 30s. Dependent on a respirator to breathe, he developed
locked-in syndrome: Mackler lost virtually all ability to communicate.
ALS has no cure, and death often occurs within 5 years of diagnosis.
Yet Scott Mackler beat the odds: he survived for 17 years before he died
in 2013 at age 55. Mackler beat locked-in syndrome too, by learning to
translate his mental activity into movement. He returned to work at the
University of Pennsylvania, stayed in touch with family and friends, and
even gave an interview to CBS’s 60 Minutes in 2008.
Mackler was a pioneer in brain–computer interface (BCI) technology.
BCIs employ the brain’s electrical signals to direct computer-controlled
devices. BCIs are one area of neuroprosthetics, development of computer-
assisted devices to replace lost biological function.
A computer–brain interface (CBI) employs electrical signals from a com-
puter to instruct the brain. Cochlear implants that deliver sound-related
signals to the inner ear to allow hearing are CBIs. Brain–computer–brain
interfaces (BCBIs) combine the BCI and CBI approaches. BCBIs enable
the brain to command robotic devices that provide it sensory feedback.
© lifehand2, patriziatocci
In 2008, Mackler’s BCI took up to 20 s to execute a single command.
Today’s devices enhance processing speed and increase signal preci-
sion by using electrodes placed directly adjacent to brain cells in arrays
that interface with thousands of cells. Experimental approaches use
optogenetics, incorporating light-sensitive channels into cortical motor
Brain–computer–brain interfaces such as the robotic limb
and sensory neurons. Light signals are faster than electrical signals and
shown here enable the brain to command robotic devices that
produce less tissue damage. provide it sensory feedback.
BCBIs command robotic hands to grasp objects while tactile recep-
tors on the robot are delivering touch and other sensory information
to the user. BCBIs in development also control exoskeletal devices CNS activity to generate signals. It is unlikely, however, that in doing
that reach and walk and return touch, body position, and balance so they employ the signaling codes normally used by the brain in
information to guide movement. In essence, BCBIs use variations in producing behavior (Daly & Huggins, 2015).
Movement is a defining feature of animals, and this chapter explores how the ner-
vous system produces movement. The body senses are more closely related to movement
Section 1-1 offers a simple definition of than are the other senses. This chapter also describes how somatic sensation and movement
behavior: any movement in a living organism. interact at different levels of the nervous system.
At the level of the spinal cord, somatosensory information contributes to motor reflexes.
In the brainstem, it contributes to movement timing and control. In the cerebrum, it con-
tributes to complex voluntary movements. Indeed, for many functions, the other senses work
through the somatosensory system to produce movement. If the motor system is a vehicle and
the somatosensory system is the driver, the other sensory systems act like backseat drivers.
We first consider how movement is organized in the central nervous system, then turn to
We begin here with movement and end with how the somatic senses contribute to movement and balance. If you want to review how the
sensation. Section 4-4 begins with sensation motor system and somatic sensation interact before you read on, turn to The Basics: Relating
and ends with movement. the Somatosensory and Motor Systems, on pages 358–359.
11-1 • A Hierarchy of Movement Control 357
11-1 A Hierarchy of Movement neuroprosthetics Field that develops
computer-assisted devices to replace lost
Control biological function.
Our movements feature at least two categories of action. First we decide on a goal and choose
how to achieve it; then we make moves to reach the goal. As we move, we correct movement
errors that direct us away from our goal. What are the neural bases of these choices? What
neural bases enable the motor system to produce our movements?
The major components of our motor system are the cerebrum (forebrain), the brainstem,
and the spinal cord. The cerebrum contributes to our conscious control of movement, while
the brainstem and spinal cord direct our movements. In the face of impaired brainstem or
spinal cord function, the forebrain can imagine movement but can no longer produce it.
Neuroprosthetic devices, described in Research Focus 11-1, can replace the movement pro-
duction function provided by the brainstem and spinal cord and restore forebrain control.
Getting from decisions to movements involves most of our nervous system. Figure 11-1
illustrates the stepwise sequence your CNS performs in the seemingly simple act of directing
your hand to pick up a cup. Once you decide to pick it up, you visually inspect it to determine
what part to grasp. The visual cortex relays this information through the cortical somatosen-
sory regions to the motor regions that plan and initiate the movement. Only then does the
brain send instructions to the spinal cord segments that control your arm and hand muscles.
As you grasp the cup’s handle, information from sensory receptors in your fingers aids in
adjusting your grip and sends information back through the spinal cord to the somatosensory For now, remember that the entire
cortex and from there to the motor cortex to confirm that the act is complete—you are hold- sensorimotor system is organized
ing the cup. Other brain regions also participate in controlling the movement. The subcorti- hierarchically. When you reach the chapter’s
cal basal ganglia help to produce the appropriate amount of force for grasping the cup handle, end, review Figure 11-1 to reinforce what
while in the brainstem, the cerebellum helps to regulate the movement‘s timing and accuracy. you’ve learned.
Clearly, the movement involved in picking up a cup involves widespread CNS regions.
The action also requires that higher-function regions, including those that participate in de-
ciding to pick up the cup, work through and influence the actions of lower functional areas.
Remarkably, once you have made the decision to pick up the cup, most of the movement
happens automatically, without conscious control. Few of us can describe the sequence of
actions or produce an accurate pantomime of the movements we make to actually grasp a
1 Visual information 8 Sensory cortex receives
required to locate the target. message that the cup has
been grasped.
2 Frontal-lobe motor
areas plan the reach and 7 Basal ganglia judge
command the movement. grasp forces, and
cerebellum corrects
movement errors.
3 Spinal cord carries
information to the hand.
6 Spinal cord carries
Motor sensory information
4 Motor neurons carry nerve to the brain.
message to muscles of
the hand and forearm.
Sensory
nerve
5 Sensory receptors on the fingers send message to sensory Sequentially Organized
Figure 11-1
cortex saying that the cup has been grasped. Movement
358 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
THE BASICS
Relating the Somatosensory and Motor Systems
The intimate relationship between the motor and somatosensory systems
Sensory pathways
is apparent in their close anatomical relationships. Afferent somatosensory
are afferent.
information travels from the body inward via the somatic nervous system.
Movement information travels out of the central nervous system via a paral-
lel efferent motor system.
As diagrammed in Information Flow, when you step on a tack, the sen-
sory signals transmitted by the SNS from the body through the spinal cord
and into the brain are afferent. Efferent signals from the CNS trigger a
motor response: you lift your foot.
The spinal cord connects the somatosensory and motor systems
Motor pathways
throughout the CNS. Connections Between the Nerves and the Spine
are efferent.
shows the spinal cord in cross section. In the outer part, which consists
of white matter, posterior tracts are sensory and anterior tracts are motor, Sensory
with some exceptions. The inner cord is gray matter composed largely of endings
cell bodies and shaped like a butterfly.
SNS nerves entering the spinal cord’s posterior side carry information Information Flow
inward from the body’s sensory receptors and merge into a posterior root muscles. They, too, bundle together as the fibers exit the spinal cord, form-
as the fibers enter a spinal cord segment of the CNS. Fibers leaving the ing an anterior root. (Bundles of nerve fibers within the CNS are called tracts;
spinal cord’s anterior side carry information out from the spinal cord to the outside the CNS they are called nerves.)
3 Collateral branches of
sensory neurons may cross to
the other side and influence
motor neurons there.
1 Fibers entering the Posterior root
posterior root bring (sensory)
sensory information Sensory
from sensory receptors. neuron
Motor
neuron Anterior
root (motor)
Gray White
matter matter
2 Fibers leaving the anterior
root carry motor information 4 White-matter fiber tracts carry
to the muscles. information to and from the brain.
Connections Between the Nerves and the Spine
cup, although we have performed the action thousands of times (Davarpanah et al., 2015).
Recall the principle from Section 2-6: The To understand how these CNS regions work together to produce decisions and movements,
CNS functions on multiple levels. we now consider the major components of the hierarchy, starting with the forebrain.
Forebrain: Initiating Movement
Complex movements consist of many acts. Consider playing basketball. At every moment,
players must make decisions and perform actions. Dribble, pass, and shoot are different
movement categories, and each can be performed in many ways. Skilled players choose
among the categories effortlessly and blend them together seemingly without thought.
11-1 • A Hierarchy of Movement Control 359
The spinal cord lies within a series of small bones called vertebrae cat- and lumbar dermatomes represent the human forelimbs and hind limbs.
egorized into the five anatomical regions diagrammed on the left in Spinal Their arrangement is sequential if you imagine a human on all fours.
Segments and Dermatomes. Each spinal segment corresponds to a region Layering in the Neocortex plumbs the depths of the primary motor
of body surface called a dermatome (literally, skin cut), shown on the right. cortex (shown in blue) and adjacent sensory (red) cortical regions. Viewed
From top to bottom, the cervical, thoracic, lumbar, sacral, and coccygeal through a microscope, the six cortical layers differ in appearance, charac-
regions are identified by spinal segment number: C5 (cervical segment 5) at teristics, and functions. Layer IV is relatively thick in the sensory cortex but
the base of the neck, for example, and L2 in the lower back. relatively thin in the motor cortex. Layer V is relatively thick in the motor
Body and nervous system segmentation has a long evolutionary history cortex and relatively thin in the sensory cortex. Cortical layer IV is afferent
that can be seen in spineless worms as well as in vertebrates. The cervical and layer V is efferent, and that makes sense: sensory regions have a large
input layer and motor regions, a large output layer.
Dermatomes
Spinal cord Vertebrae C3
(spinal column) C4
C5 The motor cortex lies in the The sensory cortex lies posterior
C1 C2 C6 frontal lobe just anterior to to the central fissure and extends
C2 C7
C3 C8 the brain’s central fissure. into the parietal lobe.
Cervical C4 T1
C5 Central fissure
nerves C6 T2
C7 T3
C8 T4
T1 T5
T2 T6
T3 T7
T4 T8
T5 T9
Thoracic T6 C7 T10
T7 T11
nerves T8 T12
T9 L1
T10 L2 Motor cortex Sensory cortex
T11 L3
L4
T12 L5 I I
L1 S1
S2 II II
L2 S3 Integrative
S4 functions
Lumbar L3 S5
nerves S2 III III
L4
S1 Sensory
IV input (afferent)
L5 IV
S1 V Output to V
S2 other parts of
Sacral brain (efferent) VI
nerves S3 Coccygeal VI
segment L5
S4 L5
S5
Spinal Segments and Dermatomes Layering in the Neocortex
An early explanation for control of such complex movements centered on feedback: after
we act, we wait for feedback about how well the action has succeeded, then make the next Lashley experimented for three decades
movement. The pioneering neuroscience researcher Karl Lashley (1951), in the article “The to find the location of memory in the brain.
Problem of Serial Order in Behavior,” found fault with this explanation. He failed.
Lashley realized that we perform skilled movements too quickly to rely on feedback about
one movement before shaping the next. The time required to receive feedback about the first
movement combined with the time needed to develop a plan for the subsequent movement
and send a corresponding message to muscles is simply too long for effective action. Lashley motor sequence Movement modules
argued that movements must be performed as motor sequences, with the next sequence held preprogrammed by the brain and produced
in readiness while the ongoing one is under way. as a unit.
360 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
All complex behaviors, including speaking, piano playing, and playing basketball, require
2 Premotor cortex organizes
movement sequences. selecting and executing multiple movements as sequences. Most of our motor learning is
mastering sequences of action. As one sequence is being executed, the next sequence is
3 Motor cortex being prepared to follow the first smoothly. The act of speaking illustrates this activity.
produces specific
1 Prefrontal When people use complex rather than simple word sequences, they are more likely to pause
movements.
cortex plans and make umm and ahh sounds, suggesting that it is taking them more time than usual to
movements.
organize their speech sequences.
Initiating a Motor Sequence
The frontal lobes are responsible for planning and initiating motor sequences. Each frontal
lobe is divided into several hierarchically arranged motor regions, including the three illus-
trated in Figure 11-2. From front to back, they are prefrontal cortex, premotor cortex, and
primary motor cortex.
prefrontal Cortex Atop the hierarchy, the prefrontal cortex (PFC) plans our behavior.
Prefrontal Premotor Motor cortex Deciding to get up at a certain hour to arrive at work on time, to stop at the library to return
cortex cortex executes
plans sequences actions a book, even whether a behavior is right or wrong and whether it should be performed at all
are examples. Humans with PFC injury often break social and legal rules not because they
Initiating a Motor
Figure 11-2
do not know the rules or the consequences of breaking them but because their decision
Sequence
making is faulty. The PFC does not specify the precise movements to be made. It simply
Sections 12-4 and 15-2 explore cognitive specifies the goal.
deficits caused by frontal lobe injury.
premotor Cortex To bring a plan to completion, the prefrontal cortex sends instruc-
tions to the premotor cortex, which produces movements coordinating many body parts. If
the premotor cortex is damaged, sequences cannot be coordinated and goals cannot be ac-
complished. For example, the monkey on the right in Figure 11-3 has a lesion in the dorsal
premotor cortex. The monkey has been given the task of extracting a piece of food wedged
in a hole in a table (Brinkman, 1984).
The monkey simply pushes the food with a finger. The food drops to the floor and is lost.
The monkey has to catch the food by holding a palm beneath the hole as the food is being
Recall the principle from Section 2-6: Brain pushed out. But this brain-injured animal is unable to make the two complementary move-
circuits process information hierarchically and ments together. It can push the food with a finger and extend an open palm, but it cannot
in parallel. coordinate the action of its two hands, as the healthy monkey on the left can.
primary motor Cortex The primary motor cortex (area M1) specializes in producing
focal skilled movements, such as those involving our arms, hands, and mouth. To understand
its role, consider the rich array of movements we can use to grasp objects. We can hold them
in one hand, with two hands, or between a hand and another part of the body, for example.
In using the precision pincer grip (Figure 11-4A), we hold an object between the thumb
and index finger. We can perform many precision grips using the thumb and other fingers in
opposition. The pincer grip not only allows us to pick up small objects easily but also allows
Healthy animal 5 months Premotor cortex Primary motor
after lesion (area of lesion) cortex
Prefrontal
Figure 11-3 Premotor Control On a cortex
task requiring both hands, the healthy
monkey can push the peanut out of a hole
with one hand and catch it in the other, but
5 months after receiving a lesion of the
premotor cortex, the brain-injured monkey
cannot. Information from C. Brinkman (1984).
Supplementary motor area of the monkey’s cerebral
cortex: Short- and long-term effects after unilateral
ablation and the effects of subsequent callosal section.
Journal of Neuroscience, 4, p. 925.
11-1 • A Hierarchy of Movement Control 361
us to use them with considerable skill. In contrast, when using a power (A) Pincer grip (B) Whole-hand grip
grip (Figure 11-4B), we hold an object with all our fingers and with more
power but fewer skilled options.
People with damage to M1 have difficulty performing reaching
movements and shaping their fingers correctly to perform various hand
grasps. They also have difficulty performing many skilled hand, arm,
ian Whishaw
and trunk movements, bringing the hand to the mouth to feed them-
selves, and in talking (Lang & Schieber, 2004).
Figure 11-4 Getting a Grip Figure 8-20
illustrates the development of grasping
Experimental Evidence for a responses in infants, from the whole-hand
Movement Hierarchy to the pincer grip.
The frontal lobe regions in each hemisphere that plan, coordinate, and execute different
kinds of movements are hierarchically related. After the prefrontal cortex formulates a plan
of action, it instructs the premotor cortex to organize the appropriate movement sequence,
which the primary motor cortex executes. This hierarchy is supported by findings from stud-
ies of cerebral blood flow, which serves as an indicator of neural activity. Figure 11-5 shows Section 7-4 describes imaging methods that
the brain regions that were active as the participants in one such study performed various record and measure blood flow in the brain.
tasks (Roland, 1993).
As the participants use a finger to push a lever, increased blood flow is limited to the pri-
mary somatosensory and primary motor cortex (Figure 11-5A). As the participants execute a
sequence of finger movements, blood flow also increases in the premotor cortex (Figure 11-5B).
And as the participants use a finger to trace their way through a maze, a task that requires
coordinated movements in relation to a goal, blood flow increases in the prefrontal cortex
as well (Figure 11-5C). Notice that as the participants were performing these tasks, relative
blood flow increased most in the regions taking part in the required movements rather than
throughout the frontal lobe.
(A) Simple movement (B) Movement sequence (C) Complex movement Figure 11-5 Hierarchical Movement
Blood flow increases in hand Blood flow increases in When participants use a Control in the Brain Research from
area of primary somatosensory premotor cortex when finger to find a route P. E. Roland (1993). Brain Activation (p. 63). New York:
and primary motor cortex participants perform a through a maze, blood flow Wiley-Liss.
when participants use a finger sequence of movements. also increases in prefrontal,
to push a lever. temporal, and parietal cortex.
Dorsal premotor
Motor cortex Sensory cortex cortex
Brainstem: Species-Typical Movement
In a series of studies, the Swiss neuroscientist Walter Hess (1957) found that the brainstem
controls species-typical behaviors, actions displayed by every member of a species—the Section 1-5 introduces species-typical
pecking of a robin, the hissing of a cat, or the breaching of a whale. Species-typical move- behavior, noting that evolutionary principles
ments, then, are mainly innate and organized by brainstem neurons. Hess developed the apply across species but not to individuals
technique of implanting electrodes into the brains of cats and other animals and cementing within a species.
them in place. These electrodes could then be attached to stimulating leads in the freely
moving animal without causing it much discomfort.
362 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
ExpErimEnt 11-1 By stimulating the brainstem, Hess elicited the innate
movements that the animal might be expected to make. A
Question: What are the effects of brainstem stimulation under different
resting cat could be induced to suddenly leap up with an
conditions?
arched back and erect hair as though frightened, for exam-
Procedures Results ple, by an approaching dog. The elicited movements began
Stimulating electrode abruptly when the stimulating current was turned on and
in brainstem
ended equally abruptly when it was turned off. An animal
Electrical stimulation alone
produces restless behavior.
performed such species-typical behaviors in a subdued man-
ner when the stimulating current was low and displayed in-
creased vigor as the stimulating current was turned up.
The actions varied, depending on the brainstem site
that was stimulated. Stimulating some sites produced head
turning; others, walking or running; and still others elicited
displays of aggression or fear. The animal’s response to a par-
ticular stimulus could be modified accordingly. For instance,
when shown a stuffed toy, a cat responded to electrical stimu-
Electrical stimulation in lation of some brainstem sites by stalking it and to stimula-
the presence of a fist
produces slight threats. tion of other sites by showing fear and withdrawing.
Hess’s experiments have been confirmed and expanded
on by other researchers using many animal species.
Experiment 11-1 shows the effects of brainstem stimu-
lation on a chicken under various conditions (von Holst,
1973). Notice the effect of context: how the neural site
Electrical stimulation in
stimulated interacts both with the object presented and
the presence of a stuffed
polecat (a type of weasel) with the stimulation’s duration.
produces vigorous threat. With stimulation at a certain site alone, the chicken dis-
plays only restless behavior. When a fist is displayed, the
same stimulation elicits slightly threatening behavior. When
the display switches from a fist to a stuffed polecat, the
chicken responds with vigorous threats. Finally, with contin-
ued stimulation in the presence of the polecat, the chicken
flees, screeching.
Such experiments show that producing complex pat-
terns of adaptive behavior is an important brainstem func-
Continued electrical stimulation in
the presence of the stuffed polecat tion. These adaptive patterns include movements used in
produces flight and screeching. eating and drinking and in sexual behavior. Animals can be
induced to display survival-related behaviors when certain
brainstem areas are stimulated. An animal can even be in-
duced to eat nonfood objects, such as chips of wood, if the
part of the brainstem that triggers chewing is stimulated.
Grooming illustrates how the brainstem coordinates com-
plex action patterns (Kalueff et al., 2007). A grooming rat sits
back on its haunches, licks its paws, wipes its nose with its
paws, then wipes its paws across its face, and finally turns
Conclusion: Stimulation of some brainstem sites produces behavior that to lick the fur on its body. These movements are always per-
depends on context, suggesting that an important function of the brainstem formed in the same order, from the face to the shoulders and
is to produce appropriate species-typical behavior. then toward the rear of the body. The next time you dry off
Information from The Collected Papers of Erich von Holst (p. 121), translated by R. Martin, 1973, after a shower or swimming, note the grooming sequence
Coral Gables, FL: University of Miami Press.
you use. Humans’ grooming sequence is very similar to the
one rats use.
The brainstem is also important for maintaining posture, standing upright, coordinating
Focus 4-4 details ALS. limb movements, swimming and walking, grooming the fur, and making nests. The effects
11-1 • A Hierarchy of Movement Control 363
of damage to brainstem regions that organize many adaptive movements can be seen in the
locked-in syndrome Condition in which a
effects of locked-in syndrome, similar to those Scott Mackler experienced in connection
patient is aware and awake but cannot move
with ALS (see Research Focus 11-1, Neuroprosthetics). The patient with locked-in syndrome
or communicate verbally because of complete
is aware and awake but cannot move or communicate verbally because nearly all voluntary paralysis of nearly all voluntary muscles
muscles except those of the eyes are completely paralyzed. except the eyes.
The effects of brainstem damage on behavior can also be seen in cerebral palsy (CP),
cerebral palsy Group of disorders that result
a disorder primarily of motor function: making voluntary movements becomes difficult,
from brain damage acquired perinatally (at or
whereas many aspects of conscious behavior controlled by the cortex may remain intact. CP near birth).
is often caused by brainstem trauma before or shortly after birth. As described in Clinical
connectome Comprehensive map of the
Focus 11-2, Cerebral Palsy, trauma leading to cerebral palsy can sometimes happen in early
structural connectivity (the physical wiring)
infancy as well. Advances in neuroprosthetic technology, touch-screen technology, and re-
of an organism’s nervous system.
motely controlled computers all signal important steps toward allowing people with physical
disabilities to become more independent.
CliniCAl F cus 11-2
Cerebral Palsy
E. S. had a cold and infection when he was about 6 months old. Most children with cerebral palsy appear healthy in the first few
Subsequently, he had great difficulty coordinating his movements. As months of life, but as the nervous system develops, motor distur-
he grew up, his hands and legs were almost useless and his speech bances become progressively more noticeable. Common symptoms
was extremely difficult to understand. E. S. was considered intellectually include spasticity, an exaggerated contraction of muscles when they are
disabled and spent most of his childhood in a custodial school. stretched; dyskinesia, involuntary extraneous movements such as trem-
When E. S. was 13 years old, the school bought a computer. One ors and uncontrollable jerky twists (athetoid movements); and rigidity,
teacher attempted to teach E. S. to use it by pushing the keys with a or resistance to passive movement. Everyday movements are abnormal,
pencil held in his mouth. Within a few weeks, the teacher realized that and the affected person may be confined to a wheelchair.
E. S. was extremely intelligent and could communicate and complete As a means for investigating the relationship between brain develop-
school assignments on the computer. He eventually received a motor- ment and susceptibility to brain injury, investigators can use an MRI-
ized wheelchair that he could control with finger movements of his derived baby connectome that maps changing brain connections during
right hand. development. A connectome is a comprehensive map of the structural
Assisted by the computer and the wheelchair, E. S. soon became connectivity (the physical wiring) of an organism’s nervous system. The
almost self-sufficient and eventually attended college, where he achieved baby connectome can reveal developmental abnormalities in brain con-
excellent grades and became a student leader. On graduation with a nections even at very early ages, thus expanding the time window to
degree in psychology, he became a social worker and worked with initiate therapeutic strategies (Castellanos et al., 2014).
children with cerebral palsy.
William Little, an English physician, first noticed in 1853
that difficult or abnormal births could lead to later motor dif-
ficulties in children. The disorder that Little described was
cerebral palsy (also called Little disease), a group of dis-
orders that result from brain damage acquired perinatally
(at or near birth). Cerebral palsy is common worldwide,
with an incidence estimated to be 1.5 in every 1000 births.
Among surviving babies who weigh less than 2.5 kilograms
at birth, the incidence is much higher—about 10 in 1000.
The most common causes of cerebral palsy are birth
injury, especially due to anoxia, a lack of oxygen, and
ap photo/tony dejak
genetic defects. Anoxia may result from a defect in the
placenta, the organ that allows oxygen and nutrients to
pass from mother to child in utero, or it may be caused
by a tangled umbilical cord that reduces the oxygen sup-
ply to the infant during birth. Other causes include infec- Many people with cerebral palsy have successful professional careers.
tions, hydrocephalus, seizures, and prematurity. All may Dr. John Melville, second from right, monitors a CT scan and discusses the patient’s
produce a defect in the immature brain before, during, or progress with a colleague. Cerebral palsy has not impeded—and may have inspired—his
just after birth. medical career.
364 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Spinal Cord: Executing
Movement
The late actor Christopher Reeve, who portrayed
Superman in three 1980s films, was thrown from a
horse during a riding competition in 1995. Reeve’s
spinal cord was severed near its upper end, at the
C1–C2 level (see Spinal Segments and Derma-
tomes, page 359). The injury left Reeve’s brain in-
tact and functioning and his remaining spinal cord
the Kobal collection at art resource
intact and functioning too, but his brain and spinal
pavel Wolberg/epa/ corbis
cord were no longer connected.
Other than head movements and slight move-
ment in his shoulders, Reeve’s body was com-
pletely paralyzed. He was even unable to breathe
without assistance. A century ago such a severe in-
Christopher Reeve (left) portraying jury would have been fatal, but modern and timely
Superman in 1984 and (right) in 2004, medical treatment allowed Reeve to survive for nearly a decade.
9 years after his spinal cord injury. A cut high on the spinal cord, such as Christopher Reeve survived, entails paralysis and
loss of sensation in the arms and legs, a condition called quadriplegia. If the cut is low,
paraplegia results: paralysis and loss of sensation are confined to the legs and lower body,
as described in Clinical Focus 11-3, Spinal Cord Injury, on page 365. Christopher Reeve and
his late wife Dana founded the Christopher and Dana Reeve Foundation for spinal cord
research. It is dedicated to improving the life and function of spinal cord–injured people and
also to searching for cures for spinal cord injury.
Far from being a mere relay between the body and brain, the spinal cord contains complex
motor programs. A spinal cord patient can walk on a conveyor belt if the body is supported.
Indeed, Christopher Reeve was able to walk in a swimming pool, where his body was sup-
ported by water.
When a spinal cord patient’s leg is moved backward on a conveyor belt, causing the foot
to lose support, the limb reflexively lifts off the belt and swings forward underneath the
body. As the foot touches the surface of the belt again, tactile receptors initiate the reflex
that causes the foot to push against the surface and support the body’s weight. In this way,
Scratch reflex several spinal reflexes work together to facilitate the complex movement of walking. Walk-
ing’s reflexive organization can even be obtained in a premature or newborn baby: when held
upright, the baby will perform stepping movements.
Among the complex reflexes observed in other vertebrates is the scratch reflex. Here,
an animal reflexively scratches a part of its body in response to a stimulus from the body
surface. The complexity of the scratch reflex is revealed in the movement’s accuracy.
quadriplegia Paralysis of the legs and arms Absent the brain’s direction, the tip of a limb, usually a hind limb in a quadruped, can
due to spinal cord injury. be correctly directed to the irritated body part. Typically, itching is the sensation that
paraplegia Paralysis of the legs due to spinal elicits scratching; it is likely that the sensory receptors on the skin that produce itch
cord injury. evolved for detecting parasites and other foreign objects. We return to itching sensations
scratch reflex Automatic response in which in Section 11-4.
an animal’s hind limb reaches to remove a In humans and other animals with a severed spinal cord, spinal reflexes still function,
stimulus from the surface of its body. even though the spinal cord is cut off from communication with the brain. As a result, the
paralyzed limbs may display spontaneous movements or spasms. But the brain can no longer
guide the timing of these movements. Consequently, reflexes related to bladder and bowel
control may have to be artificially stimulated by caregivers.
11-1 • A Hierarchy of Movement Control 365
CliniCAl F cus 11-3
Spinal Cord Injury
Each year, on average, about 11,000 people in the United States and substances between 1 and 100 nanometers (nm) in size. (A nanometer
1000 people in Canada undergo spinal cord injury (as reported by is one billionth, or 10–9, of a meter.)
the Foundation for Spinal Cord Injury). Nearly 40 percent of these Nanotubes, or nanovesicles, can be engineered to transport drugs,
injuries occur in traffic accidents and another 40 percent occur as RNA, or new stem cells into the area of injury, where they can arrest
a result of falls. Often the spinal cord is completely severed, leaving degenerative changes and help form neural bridges across the injury
an individual with no sensation or movement from the site of the cut (Sharma & Sharma, 2012). Nanotubes that can carry chemicals or con-
downward. duct electrical impulses can be threaded into the injury through blood
Although 12,000 annual spinal cord injuries may seem like a large vessels and then into the very small capillaries within the spinal cord. Or
number, it is small relative to the number of people in the United States they can be injected as molecules that self-assemble into scaffolding or
and Canada who undergo other kinds of nervous system damage each tubes when they reach a target area.
year. To increase public awareness of their condition and promote Nanoscaffolding, introduced into the injury to form a bridge, can aid
research into possible treatments, some, like Christopher Reeve and the regrowth of axons across the injury (Imani et al., 2015). Nanoaxons
Canadian Rick Hansen, have been especially active. can be introduced into the region of injury to synapse with neurons
Hansen’s paraplegia resulted from a lower thoracic spinal injury in on both sides of the injury and to carry messages across the injury.
1975. Twelve years later, to raise public awareness of the potential of Because they are small, nanomedicinal substances can interface with
people with disabilities, he wheeled himself 40,000 kilometers around spinal cord cells on both sides of an injury.
the world to raise funds for the Man in Motion Legacy Trust Fund. The
fund contributes to rehabilitation, wheelchair sports, and public aware-
ness programs. In 2008 it sponsored the Blusson Spinal Cord Centre in
Vancouver, Canada, the largest institution in the world dedicated to spinal
cord research, housing over 300 investigators.
Spinal cord injury is usually due to trauma to the cord that results
in a number of secondary degenerative processes. These processes
increase the size of the lesion. Thereafter, the formation of scar tis-
Stacy pearsall/getty images/aurora creative
sue, a cavity, and cysts block communication between the two sev-
ered sides. Research on spinal cord injury is directed at minimizing
the acute changes that take place after the insult, devising ways to
facilitate neural communication across the injury, and improving
mobility and home care.
Nanotechnology, the science of making and using molecular-sized
tools, holds promise for both decreasing the acute effects of injury
and bridging the two sides of the injury. Nanotechnology works with
11-1 review
A Hierarchy of Movement Control
Before you continue, check your understanding.
1. The motor system is organized as a .
2. The cortex plans movements, the cortex organizes
movement sequences to carry out the plan, and the cortex executes
precise movements.
3. The is responsible for species-typical movements, for survival-related
actions, and for posture and walking.
4. In addition to serving as a pathway between the brain and the rest of the body, the
independently produces reflexive movements.
5. Explain what happens when the brain is disconnected from the spinal cord and why.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
366 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
11-2 Motor System Organization
Although we humans tend to rely primarily on our hands for manipulating objects, we can
still learn to handle things with other body parts, such as the mouth or a foot, if we have to.
Some people without arms become proficient at using a foot for writing or painting or even
for driving. What properties of the motor system allow such versatility in carrying out such
skilled movements? In this section we examine first the organization of the motor cortex,
then the descending pathways from the motor cortex to the brainstem and spinal cord, and
finally the motor neurons that in turn connect with the body’s muscles.
Motor Cortex
Section 4-1 describes the milestones that led In 1870, two Prussian physicians, Gustav Fritsch and Eduard Hitzig, discovered that they
to understanding how the nervous system could electrically stimulate the neocortex of an anesthetized dog to produce movements of
uses electrical charge to convey information. the mouth, limbs, and paws on the opposite side of the dog’s body. They provided the first
direct evidence that the neocortex controls movement. Later researchers confirmed the find-
ing by experimenting with a variety of animals as subjects, including rats, monkeys, and apes.
Figure 10-19 shows Penfield using brain Based on this research background, beginning in the 1930s Wilder Penfield (Penfield &
stimulation to map the cortex. Boldrey, 1958) used electrical stimulation to map the cortices of conscious human patients
who were about to undergo neurosurgery. Penfield’s aim was to use the results to assist in
surgery. He and his colleagues confirmed that movements in humans are triggered mainly
in response to stimulation of the premotor and primary motor cortices.
Motor cortex
Mapping the Motor Cortex
Penfield summarized his results by drawing cartoons of body parts to represent the areas
of the motor cortex that produce movement in those parts. The result was a homunculus
(pl. homunculi; Latin for little person) that could be spread out across the primary motor
cortex, as illustrated in Figure 11-6. Because the body is symmetrical, an equivalent motor
homunculus is discernible in the primary motor cortex of each hemisphere, and each motor
cortex mainly controls movement in the opposite side of the body. Penfield also identified
another, smaller motor homunculus in the dorsal premotor area of each frontal lobe, a region
sometimes referred to as the supplementary motor cortex.
Electrical stimulation
of the motor cortex… The striking feature of the homunculus shown in Figure 11-7 is the disproportionate
relative sizes of its body parts compared with the relative sizes of actual parts of the human
Homunculus
body. The homunculus has huge hands with an especially large thumb. Its lips and tongue
are also prominent. By contrast, the trunk,
arms, and legs—most of the area of a real
Sensory homunculus (plaster), english School, (20th century)/Natural
Stimulating body—are small.
electrode
These distortions illustrate that extensive
history museum, london, uK / the bridgeman art library
areas of M1 allow precise regulation of the
hands, fingers, lips, and tongue (see Figure 11-6).
Body areas over which we have relatively little
motor control have a much smaller representa-
tion in the motor cortex.
Movement of …elicits movements Another curious feature of the homuncu-
body parts of body parts
lus as laid out across the motor cortex is that
corresponding to the
map of the body. the body parts are discontinuous—arranged
differently from those of an actual body. The
Figure 11-6 Penfield’s Homunculus cortical area that produces eye movements is
Movements are topographically organized in front of the homunculus head on the motor
in M1. Stimulation of dorsal medial regions Figure 11-7 Homuncular Man
cortex (see the top drawing in Figure 11-6),
produces movements in the lower limbs. An artist’s representation illustrates the
and the head is oriented with the chin up and
Stimulation in ventral regions of the cortex disproportionate areas of the sensory
produces movements in the upper body, and motor cortices that control different the forehead down (bottom drawing). The
hands, and face. body parts. tongue is below the forehead.
11-2 • Motor System Organization 367
Modeling Movement homunculus Representation of the human
The motor homunculus shows at a glance that relatively large areas of the brain control the body in the sensory or motor cortex; also any
body parts we use to make the most skilled movements—our hands, mouth, and eyes. This topographical representation of the body by a
makes it useful for understanding M1’s topographic organization (functional layout). Debate neural area.
over how the motor areas represented by Penfield’s homunculus might produce movement topographic organization Neural spatial
has been considerable. representation of the body or areas of the
An early idea was that each part of the homunculus controls muscles in that part of sensory world perceived by a sensory organ.
the body. Information from other cortical regions could be sent to the motor homunculus,
and neurons in the appropriate part of the homunculus could then activate body muscles
required for producing the movement. If you wanted to pick up a coin, for example, messages
from the M1 finger area would instruct the fingers. More recent experiments suggest that
the motor cortex represents not muscles but rather a repertoire of fundamental movement
categories (Grazaino, 2006).
The drawings in Figure 11-8 illustrate several movement categories elicited in monkeys
by electrical stimulation. They include (A) ascend, descend, or jump, (B) reach to clasp,
(C) defensive posture or expression, (D) hand toward mouth, (E) masticate or lick, (F) control
centrally, and (G) control distally. Whole-body movements are elicited from premotor cortex,
and more precise hand and mouth movements are elicited from M1. All these movements
occur only when the electrical stimulation lasts long enough for the movement to take place.
Each observed movement has the same end regardless of the starting location of a
monkey’s limb or its other ongoing behavior. Electrical stimulation that results in the hand Natural Movement
Figure 11-8
coming to the mouth always recruits the hand. If a weight is attached to the monkey’s arm,
Categories Movement categories
evoked by electrical stimulation of the
the evoked movement compensates for the added load. monkey cortex and the primary motor
But categorized movements are inflexible: when an obstacle is placed between the and premotor regions from which the
hand and the mouth, the hand hits the obstacle. If stimulation continues after the hand categories were elicited. Research from
has reached the mouth, the hand remains there for the duration of the stimulation. M. S. A. Graziano and T. N. Aflalo (2007). Mapping
behavioral repertoire onto the cortex. Neuron 56:
Figure 5, p. 243.
Ascend or Control distally
A descend, jump
A G G
B
F
C
D
E
B
F
Reaching to
clasp Handle/control
centrally
KEY
Primary motor cortex
Premotor motor cortex
Prefrontal cortex
C E
D Masticate/lick
Defensive posture/
expression Bring hand
toward mouth
368 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Further, broad movement categories—for example, reaching—cluster together on the motor
cortex, but reaching directed to different parts of space is elicited from slightly different
cortical points in the topographic reaching map.
MRI studies on human subjects suggest that the human motor cortex, like the monkey
motor cortex, is organized in terms of functional movement categories (Meier et al., 2008).
The motor cortex maps appear to represent basic types of movements that learning and prac-
tice can modify. In other words, the motor cortex encodes not muscle twitches but a lexicon,
or dictionary, of movements. As with words and sentences, these few movements used in
ExpErimEnt 11-2 different combinations produce all the movements you are
Question: How does the motor cortex take part in the control of capable of, even in activities as complex as playing basketball.
movement?
Procedure
Motor Cortex and Skilled
Electrode from motor-cortex
neurons to recording Movement
device In a study designed to investigate how neurons in the motor
Monkey flexes wrist cortex control movement, Edward Evarts (1968) used the
to rotate lever.
simple procedure illustrated in Experiment 11-2. He trained
Pulley Lever a monkey to flex its wrist to move a bar. Different weights
could be attached to the bar. An electrode implanted in the
wrist region of the monkey’s motor cortex recorded the activ-
ity of neurons there.
Evarts discovered that the neurons began to discharge
Restraint even before the monkey began the movement, as shown in
Wrist the Results section of Experiment 11-2. Thus, they take part
movement in planning the movement as well as initiating it. The neu-
Weight rons continued to discharge as the wrist moved, confirming
that they play a role in producing the movement. Finally, the
neurons discharged at a higher rate when the bar was loaded
Attached weight can
be changed to vary with a weight. This finding shows that motor cortex neurons
force of movement. increase a movement’s force by increasing their firing rate
and its duration, as stated in the experiment’s Conclusion.
Results Evarts’s findings also reveal that the motor cortex has a
Response of motor-cortex neurons to wrist movement
role in specifying the end point of a movement. Motor cortex
No neurons in the wrist might discharge when the monkey flexed
weight
its wrist inward but not when the wrist was extended back to
its starting position. These on–off neuronal responses are a
Neural activity increases Neural activity continues simple way of coding a desired final position of a movement.
before movement, throughout movement, Evart’s finding that motor cortex neurons are involved in
suggesting motor-cortex suggesting motor-cortex planning movements is confirmed in much less formal situa-
participation in planning. participation in execution.
tions. For example, recordings of a monkey’s biceps muscle,
which produces arm flexion, and from motor cortex neurons
Weight that produce arm flexion when stimulated, show correlated
added activity during a monkey’s spontaneous behaviors.
The activity of motor neurons in freely moving monkeys
suggests that the neurons, depending upon their location, move
Movement
Neural activity increases over
no-weight condition, suggesting the body or parts of the body to specific positions (Aflalo &
begins
that motor-cortex neurons code Graziano, 2007). For example, if some neurons are very active
force of movement. when a hand is moved to a specific location, they are progres-
sively less active when the hand is moved away from that posi-
Conclusion: The motor cortex takes part in planning movement, executing tion. Thus, the neurons in the motor cortex regions illustrated
movement, and adjusting the force and duration of a movement.
in Figure 11-8 are responsible for configuring movements that
Research from E. V. Evarts (1968). Relation of Pyramidal Tract Activity to Force Exerted During
Voluntary Movement. Journal of Neurophysiology, 31, p. 15.
achieve the same end point produced when those same neu-
rons are electrically stimulated (Aflalo & Graziano, 2007).
11-2 • Motor System Organization 369
Nevertheless, studies using human participants reveal situations in which motor cor-
tex neurons can be active even when no overt movement occurs (Schieber, 2011). These
situations include planning a movement, withholding a movement on instruction, and
mental imagery. Such subthreshold activity in motor cortex neurons may underlie our abil-
ity to imagine movements without actually producing them. Subthreshold activity may also
allow motor cortex neurons to control brain–computer interfaces (see Research Focus 11-1).
In keeping with this idea, monkeys that are controlling an external device using brain activity
are described as displaying a nearly complete absence of movement.
Plasticity in the Motor Cortex
An intimate relationship connects the activity of M1 neurons with movement of the body.
The studies just described show that flexibility is part of the relationship. Flexibility underlies
another property of the motor cortex: its plasticity, which contributes both to motor learning Section 14-4 explores how motor maps
and to recovery after the motor cortex is damaged, as the following example explains. change in response to learning.
A study by Randy Nudo and his coworkers (1996), summarized in the Procedure section of
Experiment 11-3, illustrates change due to cortical damage. These researchers mapped the
ExpErimEnt 11-3
Question: What is the effect of rehabilitation on the cortical representation of the Focus 2-3 describes motor disruptions that
forelimb after brain damage? stroke causes; Section 16-3 reviews stroke
treatments.
Procedure
Areas of motor cortex that produce
digit, wrist, and forearm movement.
Elbow and
shoulder
Hand and digits
Small lesion is made with Experimental lesion
electrical current.
Results
3 months postlesion 3 months postlesion
with no rehabilitation with rehabilitation
Elbow and Elbow and
shoulder shoulder
Hand and digits
Lesion Lesion
Without rehabilitation, the area regulating the With rehabilitation, the area
hand becomes smaller and the area regulating regulating the hand retains its large
the elbow and shoulder becomes larger. cortical representation.
Conclusion: Rehabilitation prevents both a loss of movement in the hand and a decrease in
the hand’s cortical representation.
Research from R. J. Nudo, B. M. Wise, F. SiFuentes, & G. W. Milliken (1996). Neural Substrates for the Effects of
Rehabilitative Training on Motor Recovery after Ischemic Infarct. Science, 272, p. 1793.
370 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Section 7-1 describes ablation techniques motor cortices of monkeys to identify the hand and digit areas. They then surgically removed
used by neuroscience researchers to a small part of the cortex that represents the digit area. After undergoing this electrolytic
manipulate the brain. lesion, the monkeys used the affected hand much less, relying mainly on the good hand.
When the researchers stimulated the cortex of the monkeys 3 months later, the animals
were unable to produce many lower-arm movements—including the wrist, hand, and digits—
that they produced prior to the lesion. Much of the area representing the hand and lower arm
had disappeared from the animals’ cortical maps. The shoulder, upper arm, and elbow areas
had spread out to take up what had formerly been space representing the hand and digits.
The Results section of Experiment 11-3 shows this topographic change.
The experimenters wondered whether the change could have been prevented had they
forced the monkeys to use the affected arm. To find out, they used the same procedure on
other monkeys, except that during the postsurgery period they forced the animals to rely on
the bad arm by binding the good arm in a sling.
When the experimenters reexamined these monkeys’ motor maps 3 months later, they
found that the hand and digit area retained its larger size. Even though no neural activity
Left-Hemisphere
Figure 11-9 occurred in the spot with the lesion, the monkeys had gained some function in the digits
Corticospinal Tract Nerve fibers that used to be connected to the damaged spot. Apparently, the remaining cortical digit area
descend from the left-hemisphere motor
cortex to the brainstem, where the tract was now controlling the movement of these fingers.
branches into the spinal cord. The lateral Most likely, plasticity is promoted in the formation of new connections and the strength-
tract crosses the brainstem’s midline, ening of existing connections among different parts of the motor homunculus. Humans who
descending into the right side of the spinal have had a stroke to the motor cortex also display plasticity-mediated recovery. They may at
cord to move limb and digit muscles on first be completely unable to use their contralateral forelimb, but with time and practice they
the body’s right side. The anterior tract
may recover a great deal of movement.
remains on the left side to move muscles at
the body’s midline. As Nudo’s monkey experiment illustrates, one way to enhance
recovery is to restrain the good limb. Constraint-induced ther-
Left-hemisphere
apy, which forces use of the affected limb, is a major therapy for
motor cortex
stroke-induced limb paralysis. Its effectiveness depends on frus-
tration of the good limb, which promotes a concerted effort to use
the bad limb and promotes neural plasticity.
Corticospinal Tracts
Posterior
Br The main efferent pathways from the motor cortex to the brain-
ain
ste Left-hemisphere stem to the spinal cord are the corticospinal tracts. The axons
m
corticospinal tract from these tracts originate mainly in motor cortex layer V
pyramidal cells but also extend from the premotor cortex and the
sensory cortex (see Layering in the Neocortex on page 359). The
Pyramidal axons descend into the brainstem, sending collaterals to numer-
Sp
lc protrusion
in
ous brainstem nuclei, and eventually emerge on the brainstem’s
a
or
d ventral surface, where they form a large bump on each side. These
bumps, or pyramids, give the corticospinal tracts their alternative
name, the pyramidal tracts.
Lateral corticospinal tract Anterior corticospinal At this point, some axons descending from the left hemisphere
Anterior
moves limbs and digits tract moves muscles at the cross over to the right side of the brainstem. Likewise, some axons
on the body’s right side. body’s midline. descending from the right hemisphere cross over to the left side
of the brainstem. The remaining axons stay on their original side.
This division produces two corticospinal tracts, one crossed and the
other uncrossed, entering each side of the spinal cord. Figure 11-9
illustrates the division of tracts originating in the left-hemisphere
cortex. The dual tracts on each side of the brainstem descend into
the spinal cord, forming the two spinal cord tracts.
The cross section of a spinal cord in Figure 11-10 shows the
location of the two tracts, on the left and right sides. The fibers that
11-2 • Motor System Organization 371
cross to the opposite side of the brainstem descend the spinal cord
Lateral corticospinal tract
in a lateral (side) position to form the lateral corticospinal tract. The synapses with interneurons and
fibers that remain on their original side continue from the brain- motor neurons that innervate
Anterior horn muscles of the limbs and digits.
stem down the spinal cord in an anterior (front) position, to form of spinal
the anterior corticospinal tract. cord
Interneurons project to motor
Retracing the pathway, the corticospinal tracts originate in
neurons.
the neocortex and terminate in the spinal cord. Within the spinal
cord, corticospinal fibers make synaptic connections with both Motor neurons project to
interneurons and motor neurons, but the motor neurons carry all muscles of the body.
nervous system commands out to the muscles.
Anterior corticospinal tract
synapses with interneurons
Motor Neurons and motor neurons that
innervate the trunk (midline of
Spinal cord motor neurons are located in the anterior part of the the body).
spinal cord, the anterior horns, which jut out from the anterior part Fingers
of the spinal cord. The anterior horns contain two kinds of neu- Arms Trunk The interneurons and motor
rons. Interneurons lie just medial to the motor neurons and proj- Shoulders
neurons of the spinal cord are
envisioned as a homunculus
ect onto them. The motor neurons send their axons to the body representing the muscles that
muscles. The fibers from the corticospinal tracts make synaptic they innervate.
connections with both the interneurons and the motor neurons,
but the motor neurons carry all nervous system commands to the muscles. Motor Tract
Figure 11-10
Figure 11-10 shows that a homunculus of the body is represented again in the spinal
Organization Interneurons and motor
neurons in the left and right anterior spinal
cord. The more lateral motor neurons project to muscles that control the fingers and hands, cord tracts are topographically arranged:
whereas intermediate motor neurons project to muscles that control the shoulders and arms. the more lateral neurons innervate more
The most medial motor neurons project to muscles that control the body’s trunk. Axons of distal parts of the limbs (those farther from
the lateral corticospinal tract connect mainly with the lateral interneurons and motor neu- the midline), and the more medial neurons
rons, and axons of the anterior corticospinal tract connect mainly to the medial interneurons innervate more proximal body muscles
(those closer to the midline).
and motor neurons.
To visualize how the cortical regions responsible for different movements relate to the
motor neuron homunculus in the spinal cord, look again at Figure 11-9. Place your finger on
the index finger region of the motor homunculus on the left side of the brain. If you trace
the axons of the cortical neurons downward, your route takes you through the brainstem,
across its midline, and down the right lateral corticospinal tract.
The journey ends at the interneurons and motor neurons in the most lateral region of the
spinal cord’s right anterior horn—the horn on the opposite (contralateral) side of the nervous If you are right-handed, the neurons your
system from which you began. Following the axons of these motor neurons, you find that brain is using to carry out this task are the
they synapse on muscles that move the right index finger. same neurons that you are tracing.
If you repeat the procedure by tracing the pathway from the trunk area of the motor
homunculus, near the top on the left side of the brain, you follow the same route through
the upper part of the brainstem. You do not cross over to the opposite side, however.
Instead, you descend into the spinal cord on the left side, the same (ipsilateral) side of
the nervous system on which you began, eventually ending up in the most medial inter-
neurons and motor neurons of the left side’s anterior horn. (At this point, some of these
constraint-induced therapy Procedure
axons also cross over to the other side of the spinal cord.) Thus, if you follow these motor
in which restraint of a healthy limb forces a
neuron axons, you end up at their synapses with the muscles that move the trunk on
patient to use an impaired limb to enhance
both sides of the body. recovery of function.
This visualization can help you remember the routes taken by motor system axons. The
corticospinal tract Bundle of nerve fibers
limb regions of the motor homunculus contribute most of their fibers to the lateral cortico-
directly connecting the cerebral cortex to the
spinal tract, the fibers that cross over to the opposite side of the spinal cord. They activate
spinal cord, branching at the brainstem into
motor circuits that move the arm, hand, leg, and foot on the opposite side of the body. In an opposite-side lateral tract that informs
contrast, the trunk regions of the motor homunculus contribute their fibers to the anterior movement of limbs and digits and a same-
corticospinal tract. Only a few of these fibers cross, close to their termination in the spinal side anterior tract that informs movement of
cord; most control the trunk and limbs on the same side of the body. the trunk; also called pyramidal tract.
372 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Remember that the motor cortex is organized in terms
of functional movement categories, such as reaching or
climbing (see Figure 11-8). A similar template in the spi-
nal cord ensures that instructions from the motor cortex
are reproduced faithfully. Presumably, lateral interneu-
rons produce acts of reaching or bringing the hand to the
Triceps (extensor muscle) mouth, and the medial interneurons and motor neurons
extends the lower arm produce whole-body movements, including walking. Re-
away from the body.
call that a spinal cord isolated from the brain by a cut is
Spinal cord
Biceps (flexor muscle)
capable of many kinds of movements, and it is able to do so
moves the lower arm because the movements are organized by its interneurons
toward the body. and motor neurons.
In addition to the corticospinal pathways, about 24
Acetylcholine is the
other pathways from the brainstem to the spinal cord
neurotransmitter at the
neuromuscular junction. carry instructions, such as information related to posture
and balance (see Section 11-4), and they control the enteric
Extensor motor neurons The spinal cord anterior nervous system as well as portions of the sympathetic divi-
and flexor motor neurons horn contains interneurons sion of the ANS. Remember that for all these functions,
project to muscles. and motor neurons.
the motor neurons are the final common path.
Coordinating Muscle
Figure 11-11
Movement
Control of Muscles
Spinal cord motor neurons synapse on the muscles that control body movements. For
example, the biceps and triceps of the upper arm control movement of the lower arm.
Limb muscles are arranged in pairs, as shown in Figure 11-11. One member of a pair, the
extensor, moves (extends) the limb away from the trunk. The other member of the pair, the
flexor, moves (flexes) the limb in toward the trunk. Experiment 11-2 on page 368 demon-
strates the on–off responses of cortical motor neurons, depending on whether the flexor
or extensor muscle is being used.
Connections between spinal cord interneurons and motor neurons ensure that the mus-
cles work together so that when one muscle contracts, the other relaxes. Thus, the spinal
cord interneurons and motor neurons not only relay instructions from the brain but also,
Figure 4-26 illustrates ACh action at a motor through their connections, cooperatively organize the movement of many muscles. As you
neuron–muscle junction. know, the neurotransmitter at the motor neuron–muscle junction is acetylcholine.
11-2 review
Motor System Organization
Before you continue, check your understanding.
1. The organization of the motor cortex is represented by a ,
in which parts of the body that are capable of the most skilled movements (especially the
mouth, fingers, and thumbs) are regulated by cortical regions.
2. Change can take place in the cortical to aid in recovery of function after
motor cortex injury.
3. Instructions regarding movement travel out from the motor cortex through the
tracts to terminate on interneurons that project to motor neurons in the
anterior horn of the spinal cord. Many corticospinal-tract fibers cross to the opposite side
of the spinal cord to form the tracts; some stay on the same side to form
the tracts.
4. The anterior corticospinal tracts carry instructions for movements,
whereas the lateral corticospinal tracts carry instructions for and
movements.
11-3 • Basal Ganglia, Cerebellum, and Movement 373
5. Motor neuron axons in the spinal cord carry instructions to that are
arranged in pairs. One a limb; the other the limb.
6. What does the plan of movements in the motor cortex as revealed by electrical stimulation
tell us about the brain’s representation of movement?
Answers appear at the back of the book.
For additional study tools, visit : Caudate Tail of
putamen caudate nucleus
www.macmillanhighered.com/launchpad/kolb5e
11-3 Basal Ganglia, Cerebellum,
and Movement
The main evidence that the basal ganglia and the cerebellum perform motor functions Amygdala
is that damage to either structure impairs movement. Both have extensive connec- Substantia
tions with the motor cortex, which further suggests their participation in movement. nigra
After an overview of each structure’s anatomy, we look at some symptoms that arise
after damage to the basal ganglia or the cerebellum. Then we consider the roles each Thalamus Corpus callosum
structure plays in controlling movement.
Lateral ventricle
Basal Ganglia and the Force Caudate
nucleus
of Movement Putamen
Basal
ganglia
The neocortex connects extensively with the basal ganglia, a collection of nuclei
Globus
lying just beneath the cortex, as illustrated in Figure 11-12. The basal ganglia do pallidus
not produce movement directly, but rather modulate the activity of cortical motor
systems. The nuclei participate in a wide range of functions, including association Subthalamic
nucleus
or habit learning, motivation, and emotion, as well as motor control.
Anatomy of the Basal Ganglia Substantia nigra
Among the nuclei forming the basal ganglia are the caudate nucleus and the Figure 11-12 Basal Ganglia Connections The
putamen, which together form the striatum (meaning striped body and named for caudate putamen in the basal ganglia connects to
the fibers, including corticospinal fibers, running through it), and the subthalamic the amygdala through the tail of the caudate nucleus.
nucleus and globus pallidus. As shown in Figure 11-12, the prominent striatum The lateral see-through view shows the basal ganglia
relative to surrounding structures, including the
extends as a tail (caudate means having a tail) into the temporal lobe, ending in the
substantia nigra, with which it shares reciprocal
amygdala. There are three main basal ganglia connections: connections. The basal ganglia receive input from
1. All areas of the neocortex and more primitive allocortex project to the basal most regions of the cortex and send input into the
ganglia. frontal lobes through the subthalamic nucleus.
2. The basal ganglia project to the motor cortex via relays in the thalamus.
3. The basal ganglia receive connections from the dopamine cells of the midbrain
substantia nigra over the nigrostriatal pathway and also project to the substantia nigra. Figure 5-17 traces the nigrostriatal pathways
in the dopaminergic activating system and
Through these connections, the basal ganglia form reciprocal circuits, or loops, connecting
highlights their importance for maintaining
all neocortical and allocortical regions to the motor cortex. Other loops connect the basal
healthy motor behavior.
ganglia and substantia nigra, allowing the substantia nigra to modulate the subcortical–motor
cortex loops. Separate loops likely participate in selecting and producing skilled movements
for learned actions and emotional expression. Some of these loops’ functions are revealed in
behavioral deficits that follow damage to the basal ganglia.
How the Basal Ganglia Control Movement Force
Two types of movement disorders—in many ways opposites—result from basal ganglia
damage. If cells of the caudate putamen are damaged, unwanted writhing and twitching
movements called dyskinesias result. In Huntington disease, for example, characterized
374 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Focus 3-4 describes the genetic basis of by involuntary, exaggerated, and disjointed movements, striatal cells are destroyed. Other
Huntington disease. involuntary movements related to striatal damage are the unwanted tics and vocalizations
peculiar to the topic of Clinical Focus 11-4, Tourette Syndrome.
In addition to causing involuntary movements, or hyperkinetic symptoms, as just
described, basal ganglia damage can result in a loss of motor ability, or hypokinetic symptoms
Detailed coverage of Parkinson disease and that feature rigidity and difficulty initiating and producing movements. Parkinson disease
its treatment appears in Chapters 5, 7, and 16. is marked by hypokinetic symptoms caused by the loss of dopamine cells in the substantia
nigra that project into the basal ganglia.
The fact that both hyperkinetic and hypokinetic symptoms arise subsequent to basal
ganglia damage suggests that one function of these nuclei is regulating movement force. The
idea is that hyperkinetic disorders such as Huntington disease result from errors of too much
hyperkinetic symptom Excessive force and so result in excessive movement. Hypokinetic disorders such as Parkinson disease
involuntary movement, as seen in Tourette result from errors of too little force and so result in insufficient movement.
syndrome. In support of these ideas, in a reaching task, Huntington subjects reached using too
hypokinetic symptom Paucity of much force, thus seemingly flinging a limb. Parkinson subject reached with too little force,
movement, as seen in Parkinson disease. thus producing slowed movement (Moisello et al., 2011). An MRI study of basal ganglia
CliniCAl F cus 11-4
Tourette Syndrome
The neurological disorder Tourette syndrome (TS) was first described in connect the posterior sensory regions of the cortex to its anterior motor
1885 by Georges Gilles de la Tourette, a French neurologist, who described regions.
the symptoms as they appeared in Madame de D., one of his patients: The urge to make involuntary movements and vocalizations may be
Madame de D., presently age 26, at the age of 7 was afflicted by convulsive similar to behaviors that have an urge-to-action feature, such as yawning
movements of the hands and arms. These abnormal movements occurred and stretching (Tinaz et al., 2015). Using fMRI, the investigators suggest
above all when the child tried to write, causing her to crudely reproduce that an urge-to-action system in the brain involves the right dorsal insula,
the letters she was trying to trace. After each spasm, the movements of the a multifunctional cortical area that integrates sensory and emotional
hand became more regular and better controlled until another convulsive awareness and is important for interoception (self-awareness). Why
movement would again interrupt her work. She was felt to be suffering particular movements and vocalizations that characterize individuals
from over-excitement and mischief, and because the movements became with Tourette syndrome should be caught up by this urge-to-act system
more and more frequent, she was subject to reprimand and punishment.
remains a mystery.
Soon it became clear that these movements were indeed involuntary and
convulsive in nature. The movements involved the shoulders, the neck, Parietal cortex
Frontal cortex
and the face, and resulted in contortions and extraordinary grimaces. As
the disease progressed, and the spasms spread to involve her voice and
m
speech, the young lady made strange screams and said words that made ea
l str
no sense. (Friedhoff & Chase, 1982 ) a
rs
Do
The statistical incidence of Tourette syndrome is about 1 in 1000
people. TS affects all racial groups and seems to be hereditary. The age
range of onset is 2 to 25 years.
The most frequent symptoms of Tourette syndrome are involuntary
tics and complex movements, such as hitting, lunging, or jumping. People
with TS may also emit sudden cries and other vocalizations or inex-
plicably utter words that do not make sense in the context, including
coprolalia and swearing.
Tourette syndrome is thought to reflect an abnormality of the basal Visual
cortex
ganglia, especially in the right hemisphere, because its symptoms can be Temporal cortex
controlled with haloperidol, an antipsychotic drug that blocks dopamine Cerebellum
synapses in the basal ganglia. Using fMRI to correlate resting activity In fMRI analyses of young adults with Tourette syndrome, brain areas
with brain regions, Church and colleagues (2009) documented corti- that show enhanced (green) or decreased (red) connectivity suggest
cal changes associated with TS. These include increased connectivity, abnormalities in dorsal stream structures linking the parietal cortex to
mainly in the parietal cortex of Tourette patients, and decreased con- the frontal cortex. Information from J. A. Church, D. A. Fair, N. U. Dosenbach, et
nectivity between parietal and frontal cortex. This finding, diagrammed al. (2009). Control networks in paediatric Tourette syndrome show immature and
in the illustration, suggests altered functioning in neural circuits that anomalous patterns of functional connectivity. Brain, 32, pp. 225–238.
11-3 • Basal Ganglia, Cerebellum, and Movement 375
activity in healthy participants who, for a small monetary reward, consid- Cortex
ered how much force to apply in a gripping task, showed more basal ganglia
activity when they contemplated using a more forceful grip and less activity
Indirect Direct
when contemplating a less forceful grip (Kurniawan et al., 2010). Together, pathway pathway
Putamen
these studies suggest that the basal ganglia play a role not just in producing
force but also in computing the effortful costs of making movements.
What features of the reciprocal basal ganglia loops allow for selecting Globus pallidus
movements or modulating movement force? One theory holds that the external
basal ganglia can influence whether movement occurs (Friend & Kravitz, Thalamus
2014). As illustrated in Figure 11-13, a pathway (green) from the thalamus Subthalamic
to the cortex to the spinal cord produces movement. The globus pallidus nucleus
(red) can inhibit this pathway at the level of the thalamus.
The globus pallidus is controlled by two basal ganglia pathways, one in- Brainstem, Globus pallidus
direct and one direct. If the globus pallidus is excited, it in turn inhibits the spinal cord internal
thalamus and blocks movement. If it is inhibited, motor cortex circuits that
Figure 11-13 Regulating Movement Force Two
include the thalamus are able to produce movement. The globus pallidus
pathways in the basal ganglia modulate movements produced
thus acts like a volume control. If it is turned down, movement can occur; if in the cortex. Green pathways are excitatory; red are
it is turned up, movement is blocked. This model proposes that diseases of inhibitory. The indirect pathway excites the globus pallidus
the basal ganglia affecting its “volume control” function impair movement internal, whereas the direct pathway has an inhibitory effect.
so that it is either excessive or slowed. If activity in the indirect pathway dominates, the thalamus
The idea that the globus pallidus acts like a volume control is the basis shuts down, and the cortex is unable to produce movement. If
direct-pathway activity dominates, the thalamus can become
for several treatments for Parkinson disease. Consistent with the volume hy-
overactive, amplifying movement. Information from R. E. Alexander &
pothesis, recordings made from globus pallidus cells show excessive activity, M. D. Crutcher (1990). Functional architecture of basal ganglia circuits: Neural
which inhibits movement in people with Parkinson disease. If the globus pal- Substrates of parallel processing. Trends in Neuroscience, 13, p. 269.
lidus or the subthalamic nucleus (a relay in the indirect pathway) is partially
surgically destroyed in Parkinson patients, muscular rigidity is reduced and
normal movement is improved. Similarly, deep brain stimulation (DBS) of the Figure 1-6 shows electrodes implanted in the
globus pallidus inactivates it, freeing movement. brain for DBS.
Interestingly, impairments in the application of force may underlie motor disorders of
skilled movements such as writer’s cramp, one of a number of impairments called selective
dystonias. One such impairment, the yips, is distorted execution of skilled movements by
professional athletes. For example, the yips have ended the career of many professional golf-
ers by ruining the player’s swing (Belton et al., 2014).
Another structure in the basal ganglia, the nucleus accumbens, is also called the ventral Frontal
cortex
striatum, because it is the most ventral basal ganglia nucleus. The nucleus accumbens re-
ceives projections from dopamine cells of the ventral tegmental area, a nucleus just medial
to the substantia nigra in the midbrain. Called the mesolimbic dopamine pathway, it is a part
of a loop that aids our perception of cues signaling reward.
Cerebellum and Movement Skill Nucleus
accumbens
Musicians have a saying: “Miss a day of practice and you’re OK, miss two days and you of basal ganglia
notice, miss three days and the world notices.” Apparently, changes take place in the brain
Hippocampus Ventral
when we practice or neglect to practice a motor skill. The cerebellum may be the affected (part of limbic tegmental
component of the motor system. Whether the skill is playing a musical instrument, pitching system) area of midbrain
a baseball, or texting, the cerebellum is critical for acquiring and maintaining motor skills. The mesolimbic DA pathway (purple
projections from ventral tegmentum)
Anatomy of the Cerebellum is a substrate not only of reward but of
addictive behavior as well. See Section 6-4.
The cerebellum, a large and conspicuous part of the motor system, sits atop the brainstem,
clearly visible just behind the cerebrum, and like the cerebrum, is divided into two hemi-
spheres (Figure 11-14). A small lobe, the flocculus, projects from its ventral, or inferior,
surface. Although smaller than the cerebrum, the cerebellum has many more gyri and sulci, The elephant’s cerebellum, by contrast, contains
and for all us primates, contains about four times as many neurons as does the cortex. 98.5% of its neurons. Details in Focus 1-3.
376 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Cerebellum
Face and Medial part of cerebellar
trunk hemispheres (movement of
Lateral parts of cerebellar DigitsLimbs body midline)
hemispheres (movement of body
appendages)
Homunculus
Figure 11-14 Cerebellar Homunculus
The cerebellar hemispheres control body
movements, and the flocculus controls
eye movements and balance. In the
cerebellum’s topographical organization,
relatively medial parts represent the
body’s midline and relatively lateral parts Floccular lobe
represent the limbs and digits. (eye movements and balance)
As Figure 11-14 shows, the cerebellum can be divided into several regions, each special-
ized for an aspect of motor control. At its base, the flocculus receives projections from the
middle ear vestibular system, described in Section 11-4, and takes part in controlling bal-
ance. Many projections from the flocculus go to the spinal cord and to the motor nuclei that
control eye movements.
Just as the motor cortex has a homuncular organization and multiple homunculi, the cer-
ebellar hemispheres have at least two, as shown in Figure 11-14. The medial part of each ho-
munculus controls the face and the body’s midline. The more lateral parts connect to motor
cortex areas associated with movements of the limbs, hands, feet, and digits. Pathways from
the cerebellar hemispheres project to nuclei at the interface of the cerebellum and spinal
cord. These in turn project to other brain regions, including the motor cortex.
To summarize the cerebellum’s topographic organization, the midline of the homun-
culus is represented in its central part; the limbs and digits are represented in the lateral
parts. Tumors or damage to midline areas of the cerebellum disrupt balance, eye movement,
upright posture, and walking but do not substantially disrupt other movements such as reach-
ing, grasping, and using the fingers. A person with medial damage to the cerebellum may,
when lying down, show few symptoms. Damage to lateral parts of the cerebellum disrupts
arm, hand, and finger movements much more than movements of the body’s trunk.
The arrangement and connections of the cerebellum are built to a common plan. The
cerebellar cortex consists of three layers of cells, with the distinctive Purkinje cells forming
the second layer. Purkinje cells are the output cells of the cerebellum. This plan suggests
Ramón y Cajal’s drawing of a Purkinje cell, that the cerebellum has a common function with respect to its control over other motor
circa 1900. system regions.
How the Cerebellum Improves Movement Control
Attempts to understand how the cerebellum controls movement have centered on two major
ideas. Damage to the cerebellum (1) does not abolish any movement but (2) does disrupt the
timing and execution of movement. Thus, the cerebellum must regulate the timing and flow
of movement as required for the situation.
11-3 • Basal Ganglia, Cerebellum, and Movement 377
Tom Thach (2007), in an intriguing experiment, illustrates how the cerebellum helps
make the adjustments needed to keep movements accurate. Control participants and
subjects with cerebellar damage threw darts at a target, as shown in the Procedure section
of Experiment 11-4. After a number of throws that allowed them to become reasonably
accurate, both groups donned glasses containing wedge-shaped prisms that displaced the
apparent location of the target to the left. Now when they threw a dart, it landed to the
left of the intended target.
Both groups showed this initial distortion in aim. But then came an important differ-
ence, graphed in the Results section of Experiment 11-4. When controls saw the dart miss
the mark, they adjusted each successive throw until reasonable accuracy was restored. In
contrast, subjects with cerebellar damage could not correct for this error. Time after time,
they missed the target far to the left.
Next, the controls removed the prism glasses and threw a few more darts. Again, a
significant difference emerged. The first dart thrown by each participant was much too far
to the right (owing to the previous adjustment they had learned to make), but soon each one
adjusted once again until his or her former accuracy was regained.
ExpErimEnt 11-4
Question: Does the cerebellum help to make adjustments required to keep movements accurate?
Procedure
No prism Prism No prism
Prism
glasses
Subject or healthy Subject or control Prisms removed, healthy
control throws participant wears control adapts; subject
dart at target prisms that divert gaze shows no change
Results
Control participant Subject with damage to cerebellum
40 40
(to the right)
Initial throws With prisms Prisms removed Initial throws With prisms Prisms removed
20 20
Distance from target
0 0
–20 –20
A subject with damage
(to the left)
to the cerebellum fails
–40 A control participant –40
to correct throws while
adapts when wearing wearing the prisms and
–60 the prisms and shows –60
shows no aftereffects
aftereffects when the when the prisms are
–80 prisms are removed. –80
Trials Trials removed.
Conclusion: Many movements we make depend on moment-to-moment learning and adjustments made by the cerebellum.
Information from W. T. Thach, H. P. Goodkin, & J. G. Keating (1992). The Cerebellum and the Adaptive Coordination of Movement. Annual Review of Neuroscience, 15, p. 429.
378 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
In contrast, subjects with damage to the cerebellum showed no aftereffects of wearing the
prisms; they had never compensated for the glasses to begin with. This experiment suggests
that many movements we make—whether throwing a dart or organizing a movement
sequence to shoot a basketball—depend on moment-to-moment learning and adjustments
made by the cerebellum.
To examine the role of learning in this task, monkeys were trained on a similar task to
point a finger to a target on a computer screen. Once they had mastered the task, they were
Cortex required to perform it with prism glasses. The monkeys displayed a displacement of pointing
and an aftereffect when the prism glasses were removed.
Error After 30 days of training with and without prisms, displacement and aftereffect dis-
correction appeared, and the monkeys were immediately accurate when wearing the prisms and after
Corticospinal tracts
Inferior olive they were removed. When the arm region of the cerebellar homunculus was then anesthe-
sends copy Cerebellum tized with lidocaine, a local anesthetic agent, pointing without prisms was normal, but the
of instructions
learned adaptation to prisms was abolished. This experiment illustrates that the cerebellum
Spinocerebellar
is responsible not only for online adjustments of movement but also for learning relatively
permanent movement skills (Norris et al., 2011). Using a somewhat similar task, Hashimoto
and associates (2015) obtained similar results using humans who have cerebellar damage.
tract
To better understand how the cerebellum improves motor skills by adjusting movements,
Movement Feedback consider the model charted in Figure 11-15. Imagine throwing a dart. You aim at the bull’s-
instructions from actual eye, throw the dart, and find that it misses the board completely. You aim again, this time
reach spinal cord movement adjusting your throw to correct for the original error. The model illustrates that there are ac-
tually two versions of your action: (1) the movement you intended to make and (2) the actual
Figure 11-15 Intention, Action, and
Feedback By comparing the message movement as recorded by sensory receptors in your arm and shoulder. If you carry out the
for the intended movement with the intended movement successfully, you need make no correction on your next try. But if you
movement that was actually performed, miss, and you frequently will, an adjustment is called for.
the cerebellum sends an error message The model illustrates that the cortex sends instructions to the spinal cord to throw a dart
to the cortex to improve the accuracy of a at the target. A copy of the same instructions is sent to the cerebellum through the inferior
subsequent movement.
olive, a nucleus in the brainstem that projects to the cerebellum. Then, when you throw the
dart, the sensory receptors in your arm and shoulder code the actual movement you make
and send a message about it back to the cerebellum through the spinocerebellar tract. The
cerebellum now has information about both versions of the movement—what you intended
to do and what you actually did—and can calculate the error and inform the cortex how to
correct the movement. When you next throw a dart, you incorporate the correction into your
throw. If the cerebellum is damaged, the ability to correct errors by comparing intended and
actual movements is impaired (Therrien & Bastian, 2015).
11-3 review
Basal Ganglia, Cerebellum, and Movement
Before you continue, check your understanding.
1. The contribute to motor control by adjusting the associated
with each movement.
2. Damage to the basal ganglia results either in unwanted involuntary
movements (too much force exerted) or in such rigidity that movements
are difficult to perform (too little force exerted).
3. The cerebellum contributes to motor control by improving movement and
the learning of motor .
4. Describe how the cerebellum improves execution of motor skills.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
11-4 • Somatosensory System Receptors and Pathways 379
11-4 Somatosensory System
Receptors and Pathways
The motor system produces movement, but without sensation, movement would lack direc-
tion and quickly become impaired. The somatosensory system is indispensable for move-
ment. The body senses tell us about the physical contact we make with the world as well as
how successful our physical interactions with the world are.
Somatic sensation is unique among sensory systems. For the most part, it is distributed
throughout the body, not localized in the head, as are vision, hearing, taste, and smell.
Somatosensory receptors found in the skin, muscles, and internal organs, including the circu-
latory system, feature specialized dendritic attachments on sensory neurons, or the dendrites
themselves are the sensory receptors. Somatosensory neurons convey information to the
spinal cord and brain. One part of the system, however, is confined to a single organ. The
inner ear houses the vestibular system, which contributes to our sensations of balance and
head movement.
In considering the motor system, we started at the cortex and followed the motor path-
ways out to the spinal cord (review Figures 11-9 and 11-10). This efferent route follows the
outward flow of neural instructions regarding movement. As we explore the somatosen-
sory system, we proceed in the opposite direction, because afferent sensory information
flows inward, from the body’s sensory receptors through sensory pathways in the spinal
cord to the cortex.
Somatosensory Receptors and Perception
Our body is covered with somatosensory receptors. Receptors include body hair, which is
attached to the dendrites of sensory neurons. Many receptor types are embedded in surface
skin, in deeper layers of the skin, and in muscles, tendons, and joints. Some receptors consist
simply of a sensory neuron dendrite. Others are specialized capsules or connective tissue
surrounding a dendrite, and still others include a dendrite attached to the base of a hair.
The density of somatosensory receptors, which varies greatly throughout the body,
determines sensitivity to stimulation. Body parts that are highly sensitive to touch—including
the hands, feet, lips, and tongue—have far more sensory receptors than less sensitive body
parts—the arms, back, and legs.
Humans have two kinds of skin, hairy skin and glabrous skin, which includes the palms
of the hands and feet, lips, and tongue. Glabrous skin is hairless and exquisitely sensitive to
a wide range of stimuli. It covers the body parts that we use to explore objects—hence its
heightened sensitivity.
The skin’s touch sensitivity is often measured with a two-point sensitivity test. By
touching the skin with two sharp points simultaneously, we can observe how close
together the points can be placed while still being detected by the participant as two
points rather than one. On glabrous skin, we can detect the two points when they are as
close as 3 millimeters apart. Two-point sensitivity test
On hairy skin, two-point sensitivity is weaker by a factor of about 10. The two points seem
to merge into one below a separation distance ranging from 2 to 5 cm, depending on the
exact body part tested. You can confirm these differences in sensitivity on your own body
by touching two sharp pencil points to a palm and to a forearm, varying the distances that
you hold the points apart. Be sure not to look as you touch each surface.
Classifying Somatosensory Receptors
The varied types of somatosensory receptors in the human body may total as many as 20 glabrous skin Skin that does not have
or more, but they can all be classified into the three functional groupings illustrated in hair follicles but contains larger numbers of
Figure 11-16 as perceptions of irritation, pressure, or movement. sensory receptors than do hairy skin areas.
380 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Damage or irritation to the
Nociception (pain, temperature, itch) Adaptation dendrite or to surrounding
cells releases chemicals that
Free nerve endings for pain
Slow stimulate the dendrite to
(sharp pain and dull pain) produce action potentials.
Free nerve endings for temperature
Slow
(heat or coldness)
Pressure on the various
Hapsis (fine touch and pressure) Adaptation types of tissue capsules
Meissner’s corpuscle (touch) Rapid mechanically stimulates the
dendrites within them to
Pacinian corpuscle (flutter) Rapid produce action potentials.
Ruffini corpuscle (indentation) Slow
Hair
Merkel's receptor
Slow
(steady skin indentation)
Hair receptors (flutter or steady
Slow
skin indentation)
Movements stretch the
Proprioception (body awareness) Adaptation receptors to mechanically
Muscle spindles (muscle stretch) Rapid stimulate the dendrites
within them to produce
Golgi tendon organs (tendon stretch) Rapid action potentials.
Joint receptors (joint movement) Rapid
Figure 11-16 Somatosensory
Receptors Perceptions derived from
the body senses of nociception, hapsis,
and proprioception depend on various irritation Nociception is the perception of pain, temperature, or itch. Most nociceptors
receptors in various parts of the skin, are free nerve endings, the tips of sensory neuron dendrites, as diagrammed at the top of
muscles, joints, and tendons. Figure 11-16. When damaged or irritated, these endings secrete chemicals, usually peptides,
that stimulate the nerve to produce an action potential. The action potential then conveys a
message about pain, temperature, or itch to the central nervous system.
pressure Hapsis (from the Greek for touch) is the ability to discriminate objects on the
basis of touch. Haptic receptors enable us to perceive fine touch and pressure and to identify
objects that we touch and grasp. Haptic receptors occupy both superficial and deep skin lay-
ers and are attached to body hairs as well.
As diagrammed in the center of Figure 11-16, haptic receptors consist of a dendrite at-
tached to a hair, to connective tissue, or to a dendrite encased in a capsule of tissue. Mechani-
Figure 4-25 illustrates the cellular processes cal stimulation of the hair, tissue, or capsule activates special ion channels on the dendrite,
at work in a sensory neuron dendrite when a which in turn initiate an action potential. Differences in the tissue forming the capsule
touch receptor is activated. determine the kinds of mechanical energy transduced by the haptic receptor to the nerve.
For example, pressure that squeezes the capsule of a Pacinian corpuscle is the necessary
stimulus for initiating an action potential conveying pressure information. Displacement of
a hair is a necessary stimulus for initiating action potentials conveying some other types of
touch information.
movement Proprioception, or body awareness, is the perception of body location and
movement. Proprioceptors are encapsulated nerve endings sensitive to the stretch of muscles
and tendons and the movement of joints. In the Golgi tendon organ shown at the bottom of
Figure 11-16, for instance, an action potential is triggered when the tendon moves, stretching
the receptor attached to it.
Duration of Receptor Response
Somatosensory receptors are specialized to tell us when a sensory event occurs and/or
whether it is still occurring. Information about when a stimulus occurs is handled mainly
11-4 • Somatosensory System Receptors and Pathways 381
by rapidly adapting receptors, which activate neurons when stimulation begins and when it
nociception Perception of pain, temperature,
ends. As shown in Figure 11-16, haptic receptors that respond to touch (Meissner corpuscles),
and itch.
to fluttering sensations (Pacinian corpuscles), and to vibration (Ruffini corpuscles) all are
rapidly adapting receptors. hapsis Perceptual ability to discriminate
objects on the basis of touch.
In contrast, slowly adapting receptors activate neurons as long as a sensory event is pres-
ent: they detect whether a stimulus is still occurring. For instance, after you have put on proprioception Perception of the position
an article of clothing and become accustomed to how it feels, only slowly adapting haptic and movement of the body, limbs, and head.
receptors (such as Merkel receptors and hair receptors) remain active. rapidly adapting receptor Body sensory
The difference between a rapidly adapting and a slowly adapting receptor rests on two receptor that responds briefly to the onset of
factors: how the receptor is stimulated and how the ion channels in the membrane of its a stimulus on the body.
dendrite respond to mechanical stimulation. The stimulation may be sharp or cold, fluttery slowly adapting receptor Body sensory
or deep, a stretch or a swerve. receptor that responds as long as a sensory
stimulus is on the body.
Posterior Root Ganglion Neurons
The dendrites that carry somatosensory information into the CNS belong to neurons whose
cell body is just outside the spinal cord in posterior root ganglia. Their axons enter the spinal
cord. As illustrated in Figure 11-17, such a posterior root ganglion neuron contains a single
long dendrite. Only the tip is responsive to sensory stimulation. This dendrite is continuous Dendrite
with the somatosensory neuron’s axon, which enters the spinal cord. The somatosensory cell
Axon Cell body
body sits to one side of this long pathway.
Every spinal cord segment is flanked by a posterior root ganglion that contains many
types of neurons. Each type responds to a particular kind of somatosensory information.
Within the spinal cord, the axons of posterior root ganglion neurons may synapse with other
neurons or continue to the brain or do both.
The axons of posterior root ganglion neurons vary in diameter and myelination. These
structural features are related to the kind of information the neurons carry. Proprioceptive Somatosensory neuron
information (location and movement) and haptic information (touch and pressure) are car-
ried by posterior root ganglion neurons that have large, well-myelinated axons. Nociceptive
information (pain, temperature, itch) is mainly carried by posterior root ganglion neurons
that have smaller axons with little or no myelin.
Because of their size and myelination, the larger neurons carry information faster than Myelin is the fatty coating around
the smaller neurons do. One possible reason proprioceptive and haptic neurons are designed axons, formed by glial cells, that speeds
to carry messages quickly is that their information requires rapid response. Imagine that neurotransmission. See Section 3-1.
Somatosensory
cortex
Somatosensory
homunculus
Thalamus
Brainstem Figure 11-17 Haptic Neuron of the
1 Posterior-root Posterior Root Ganglion The
ganglion neurons that 3 The cell body is located dendrite and axon of this neuron of
carry fine-touch and in a posterior-root 4 Fine-touch and pressure the posterior root ganglion, which are
pressure information… ganglion. axons ascend in the ipsilateral contiguous, carry sensory information
spinal cord, forming the from the skin to the CNS. These large,
posterior spinothalamic tract. myelinated ganglionic axons travel up the
spinal cord to the brain in the posterior
column, whereas the small axons synapse
2 …have large, myelinated axons Spinal cord
with neurons whose axons cross the spinal
whose receptors are located in cord and ascend on the other side (shown
the skin, muscles, and tendons.
in Figure 11-19).
382 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
you’ve touched a hot stove. A myelinated pain fiber activates and instructs the hand to
withdraw quickly. A nonmyelinated pain fiber, less hurried, will let you know for some time
afterward that your finger has been burned.
Disruption of Posterior Root Ganglion Function
We can support the claim that sensory information is essential for movement by describing
what happens when posterior root ganglion cells do not function. A clue comes from a visit
to the dentist. If you have ever had a tooth frozen for dental work, you have felt the strange
effect of losing sensation on one side of your face. Not only do you lose pain perception but
you also seem to lose the ability to move your facial muscles properly, making it awkward to
talk and smile and downright dangerous to chew. Similarly, if your hands or mouth become
terribly cold, disrupting receptor function, talking or making hand movements becomes
difficult. So even though only the sensory nerves are blocked, movement is affected as well.
In much the same way, sensory nerve damage affects both sensory perceptions and
motor abilities. John Rothwell and his coworkers (1982) described a patient, G. O., who was
deafferentated (had lost afferent sensory fibers) by a disease that destroyed somatosensory
posterior root ganglion neurons. G. O. received no sensory input from his hands. He could
not, for example, feel when his hand was holding something.
However, G. O. could still accurately produce a range of finger movements, and he could
outline figures in the air even with his eyes closed. He could also move his thumb accurately
through different distances and at different speeds, judge weights, and match movement
force. Nevertheless, his hands were relatively useless to him in daily life. Although G. O.
could drive his old car, he was unable to learn to drive a new one. He was also unable to write,
to fasten shirt buttons, and to hold a cup.
G. O. began movements quite normally, but as he proceeded, the movement patterns grad-
ually fell apart, ending in failure. Part of G. O.’s difficulties lay in maintaining muscle force
for any time. When he tried to carry a suitcase, he would quickly drop it unless he continually
looked down to confirm that he was carrying it. Clearly, although only G. O.’s sensory neurons
were damaged, he also had severe motor disability, including inability to learn new motor skills.
Disruption of Body Awareness
Movement abnormalities also result from more selective damage to neurons that carry pro-
Oliver Sacks’s research informed scientific prioceptive information about body location and movement. Neurologist Oliver Sacks (1998)
understanding of conditions as diverse as gives a dramatic example in his description of a patient, Christina, whose proprioceptive
Parkinson disease (Focus 5-3 and Section sensory fibers throughout her body were damaged after she took megadoses of vitamin B6.
16-3), ventral visual stream injury (Section 9-4), Christina was left with little ability to control her movements and spent most of each day
and thinking (Section 15-1). lying prone. Here is how she describes what a loss of proprioception means:
“What I must do then,” she said slowly, “is use vision, use my eyes, in every situation where
I used—what do you call it?—proprioception before. I’ve already noticed,” she added, musingly,
“that I may lose my arms. I think they are in one place, and I find they’re in another. This
proprioception is like the eyes of the body, the way the body sees itself. And if it goes, as it’s gone
with me, it’s like the body’s blind. My body can’t see itself if it’s lost its eyes, right? So I have to
watch it—be its eyes.” (Sacks, 1998, p. 46)
Clearly, Christina’s motor system is intact, but with no sense of where in space her body
is and what it is doing, she is almost completely immobilized. Jonathan Cole (1995) described
the case of Ian Waterman, who lost proprioception after a presumed viral infection at age 19.
He is the only person reported to have learned how to move again, and this relearning took
years. He was even able to drive. All his regained movement was mediated by vision, however,
without which he was as helpless as Christina.
Somatosensory Pathways to the Brain
As the axons of somatosensory neurons enter the CNS in the spinal cord, they divide,
forming two pathways to the brain. The haptic-proprioceptive axons for touch and body
awareness ascend the spinal cord ipsilaterally, whereas nociceptive (pain, temperature, itch)
11-4 • Somatosensory System Receptors and Pathways 383
Primary somatosensory cortex 6 Afferent somatosensory
information arrives in the
primary somatosensory cortex
(areas 3-1-2).
5 The ventrolateral area of the
thalamus relays sensory information
to the primary somatosensory cortex. Thalamus
4 In the brainstem, posterior spinothalamic neurons
cross to the contralateral pathway, where axons of
the medial lemniscus carry information from posterior Medial
and anterior tracts to the ventrolateral thalamus. lemniscus
3 Posterior column nuclei that Brainstem
relay haptic–proprioceptive
sensations ascend the dorsal 2 After crossing to the contralateral side
spinothalamic tract ipsilaterally. of the spinal cord, nociceptive nuclei form
the anterior spinothalamic tract, which
joins the medial lemniscus pathway.
1 Posterior root ganglion neurons respond to Posterior
fine touch and pressure; joint, tendon, and root Dual Somatosensory
Figure 11-18
Spinal cord
muscle change; pain, temperature, and itch. ganglion Pathways to the Brain As neurons
from the posterior root ganglia enter
the spinal cord, the two somatosensory
pathways to the brain diverge.
nerve fibers synapse with neurons whose axons cross to the contralateral side of the spinal
cord before ascending to the brain. Figure 11-18 shows these two routes through the spinal Ipsilateral connections lie on the side of
cord. The posterior haptic-proprioceptive pathway is shown as a solid red line, the anterior the body on which they enter; contralateral
nociceptive pathway as a dashed red line. connections lie on the side opposite.
The Posterior Spinothalamic Tract
Haptic-proprioceptive axons, which lie in the posterior portion of the spinal cord, form
the posterior spinothalamic tract. These axons for fine touch and pressure synapse in the
posterior column nuclei at the base of the brain. As shown in Figure 11-18, axons of neurons
in the posterior column nuclei cross to the other side of the brainstem and ascend as part of
a pathway called the medial lemniscus.
These posterior column axons synapse in the ventrolateral thalamus, the part of the
thalamus that sends afferent information about body senses on to the somatosensory cortex.
Although ventrolateral thalamic neurons send most of their axons to the somatosensory
cortex, some do go to the motor cortex. Thus, three relay neurons are required to carry haptic-
proprioceptive information to the cortex: posterior root ganglia neurons, posterior column nu-
clei neurons, and thalamic neurons. Because posterior column neurons cross to the opposite deafferentation Loss of incoming sensory
input, usually due to damage to sensory
hemisphere, each hemisphere perceives the opposite side of the somatosensory world.
fibers; also loss of any afferent input to a
The Anterior Spinothalamic Tract structure.
Most nociceptive axons take a different route to the brain. As shown in Figure 11-18, they first posterior spinothalamic tract Pathway that
synapse with neurons in the anterior part of the spinal cord’s gray matter, and in turn, these carries fine-touch and pressure fibers.
neurons send their axons across to the other side of the spinal cord. There they form the ventrolateral thalamus Part of the thalamus
anterior spinothalamic tract, which carries afferent information about pain, temperature, that carries information about body senses to
and itch to the thalamus. This tract joins the medial lemniscus in the brainstem to continue the somatosensory cortex.
on to the ventrolateral thalamus. The thalamic neurons project to the somatosensory cor- anterior spinothalamic tract Pathway from
tex. So again, conveying information to the cortex requires three groups of relay neurons: the spinal cord to the thalamus that carries
posterior root neurons, spinal cord gray matter neurons, and ventrolateral thalamic neurons. information about pain and temperature.
384 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Effects of Unilateral Somatosensory
System Damage
Unilateral damage dissociates the functions of the two somatosensory pathways—
haptic-proprioceptive and nociceptive. Because they enter the spinal cord together,
separate in the spinal cord, and finally join up again in the brainstem, unilateral dam-
Unilateral age to the system results in distinctive sensory losses, depending upon the site of injury.
damage to Damage to the posterior roots produces global somatosensory deficits in a particu-
Cut
spinal cord
lar part of the body. In contrast, as illustrated in Figure 11-19, after unilateral spinal
cord injury, loss of hapsis and proprioception occurs unilaterally, to the side of the
body below where the damage occurred. Loss of nociception occurs contralaterally.
This occurs because hapsis and proprioception take different routes through the spi-
nal cord. Unilateral damage at the points where the pathways merge in the brainstem,
Unilateral damage
thalamus, and cortex again affects hapsis, proprioception, and nociception together,
causes loss of …and loss of pain
fine-touch and and temperature because these parts of the pathways again lie in close proximity.
pressure sensation sensation on the
on the same side
of the body below
opposite side of
the body below Spinal Reflexes
the cut… the cut. Not only do somatosensory nerve fibers convey information to the cortex, they also
participate in behaviors mediated by the spinal cord and brainstem. Spinal cord so-
Effects of Unilateral
Figure 11-19 matosensory axons, even those ascending the posterior columns, give off axon collaterals
Damage to the Somatosensory that synapse with interneurons and motor neurons on both sides of the spinal cord. The
System
circuits made between sensory neurons and muscles through these connections mediate
spinal reflexes.
The simplest spinal reflex is formed by a single synapse between a sensory neuron and a
motor neuron. Figure 11-20 illustrates such a monosynaptic reflex, the knee jerk. It affects
the quadriceps muscle of the thigh, which is anchored to the leg bone by the patellar tendon.
When the lower leg hangs free and this tendon is tapped with a small hammer, the quadri-
ceps muscle is stretched, activating the stretch-sensitive sensory receptors embedded in it.
The sensory receptors then send a signal to the spinal cord through sensory neurons
that synapse with motor neurons projecting to the same thigh muscle. The discharge
from the motor neurons stimulates the muscle, causing it to contract to resist the stretch.
1 A tap on the patellar 2 The sensory nerve 3 …by sending a signal to the spinal
tendon stretches the responds to the cord, where it connects to a motor
quadriceps muscle. muscle stretch… neuron through a single synapse.
Spinal cord
Quadriceps
muscle
4 The motor neuron
stimulates the quadriceps
muscle to contract and
reduce the stretch.
5 The quadriceps contracts,
extending the lower leg.
Extension
Figure 11-20 Monosynaptic Reflex
11-4 • Somatosensory System Receptors and Pathways 385
Because the tap is brief, the stimulation is over before the motor message arrives, and the
muscle contracts even though it is no longer stretched. This contraction pulls the leg up,
producing the knee jerk reflex.
This simplest of reflexes entails monosynaptic connections between single sensory neu-
rons and single motor neurons. Somatosensory neurons receiving information from the
skin make much more complex connections with both interneurons and motor neurons.
These multisynaptic connections are responsible for more complex spinal movements,
such as those involved in standing and walking, actions that include many muscles on
both sides of the body.
Feeling and Treating Pain
As many as 30 percent of physician visits involve pain symptoms, as do 50 percent of emergency
room visits. People have pain as a result of acute injuries such as broken bones, chronic condi-
tions such as cancer and arthritis, and everyday conditions such as stiff muscles from exercis-
ing. Women have pain during menstruation, pregnancy, and childbirth. The incidence of
living with pain increases as people age, and for many people, pain is a constant companion.
Perceiving Pain
People can experience central pain in a part of the body that is not obviously injured. One type
of central pain is phantom limb pain. As described in Research Focus 11-5, Phantom Limb Pain
on page 386, phantom sensations are felt in a limb that has been lost, hence the term.
People in pain would happily dispense with it. But pain is necessary: the rare person born
without pain receptors has body deformities because of failure to adjust posture and acute
injuries because of failure to avoid harm.
Pain perception results from synthesizing a plethora of sensory information. There
may be as many as eight kinds of pain fibers, judging from the peptides and other chemi-
cals released by these nerves when irritated or damaged. Some of these chemicals irritate
surrounding tissue, stimulating it to release other chemicals to stimulate blood flow and
to stimulate the pain fibers themselves. These reactions contribute to pain, redness, and
swelling at the site of an injury.
Consider itch. We may feel itchy and consequently scratch a foreign object on our
body. We also frequently feel itch in the absence of an obvious stimulus. Some drugs,
including opioids, enhance itch sensations in the absence of a physical stimulus at the
itchy body part.
Haptic information also contributes to pain perception. For example, people can accu-
rately report the location and characteristics of various kinds of pain, but in the absence of
fine-touch and pressure information, pain is more difficult to identify and localize.
The anterior spinothalamic tract, illustrated in Figure 11-18, is the main pain pathway to
the brain, but as many as four other pathways may carry pain information from the spinal
cord to the brain. These pathways are both crossed and uncrossed and project to the reticular
formation of the midbrain, where they produce arousal; to the amygdala, where they produce
emotional responses typically associated with pain; and to the hypothalamus, where they
activate hormonal and cardiovascular responses.
The existence of multiple pain pathways in the spinal cord makes it difficult to treat
chronic pain, even by selectively cutting the anterior spinothalamic tract—one radical pro-
cedure used to control chronic pain. It is likely that each pain pathway has its own function,
whether for sensation, arousal, emotional responses, or other physiological responses.
Responding to Pain
Neuronal circuits in the spinal cord allow haptic-proprioceptive and nociceptive pathways to
interact. Such interactions may be responsible for our puzzling and variable responses to pain. monosynaptic reflex Reflex requiring
For example, people who are engaged in combat or intense athletic competition may receive one synapse between sensory input and
a serious physical injury but start to feel the pain only much later. movement.
386 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
RESEARCH F cus 11-5
Phantom Limb Pain
Up to 80 percent of people who have had a limb amputated also endure REM, sleep and asked them to recount their dreams. In none of the
phantom limb phenomena, including pain and other sensations and dreams did the participants remember having an amputated limb or
motor phantoms, such as phantom movement and cramps (Kern et al., phantom limb sensations.
2009). Phantom sensations and movements are illusions that originate This finding suggests that the integrity of brain regions associated
in the brain. with a limb is preserved even though the limb is absent. When awake,
Various techniques used to minimize phantom limb pain include the loss of moment-to-moment sensory activity from the limb results in
drug-based pain management with opioids and the injection of pain the opportunity for phantom perceptions.
medications into the spinal cord. An innovative method devised by
V. S. Ramachandran (1996) assists the patient in setting up a counter-
illusion that the limb is intact and is providing normal sensory input
to the brain.
Ramachandran devised a mirror box into which a person who has
lost an arm inserts the intact arm and then observes its reflection in the
mirror. The reflection suggests that the missing arm is present and can
be controlled, as shown in the illustration. The perception of the limb as
intact counteracts phantom pain and cramps.
Inspired by Ramachandran’s mirror box, researchers have developed
other illusions to suggest that a missing limb is present and can be con-
trolled. One method uses virtual reality goggles. Another uses the so-
called rubber limb phenomenon to produce the illusion that a missing
limb is present. To induce this phenomenon, the stump of the amputated
limb is stimulated tactually while the subject observes a prosthetic limb
being touched.
All of the illusions lessen phantom limb pain and cramps by sug-
gesting that a normal limb is present. Using similar logic, Hellman and
associates (2015) suggest the possibility of developing neuroprosthetic
limbs that provide their users sensory information to alleviate phantoms.
Alessandria and colleagues (2011) asked whether phantom limbs and
their associated sensations also occur during dreaming. They awoke
sleeping participants with amputations during rapid eye movement, or
A friend of ours was attacked by a grizzly bear while hiking and received 200 stitches to
bind his wounds. When friends asked if it hurt to be bitten by a grizzly bear, he surprisingly
answered no, explaining, “I had read the week before about someone who was killed and
eaten by a grizzly bear. So I was thinking that this bear was going to eat me unless I got
away. I did not have time for pain. I was fighting for my life. It was not until the next day
that I started feeling pain.”
The primacy of our friend’s fear over his pain is related to the stress he was under. Not
feeling pain in a fight-or-flight situation is obviously adaptive, as this story illustrates, and may
Section 6-2 notes similarities between be related to the activation of endogenous opioid peptides. Treatments for pain include opioid
the brain’s endogenous opioids and opioid drugs (such as morphine), acupuncture (which entails the rapid vibration of needles embedded
analgesic drugs. in the skin), and simply rubbing the area surrounding the injury. Psychological factors interact
with pain treatments, and most studies on pain management find that placebos can be as ef-
fective as actual treatments. Pain is puzzling in the variety of ways that lessen it.
To explain both the perception of pain and how it can be suppressed in so many ways,
Ronald Melzack and Patrick Wall (1965) proposed a gate theory of pain. Its essence as applied
to pain perception is that activities in different sensory pathways play off against each other
and so determine whether and how much pain is perceived as a result of an injury. Melzack
and Wall propose that haptic-proprioceptive stimulation can reduce pain perception,
whereas the absence of such stimulation can increase pain perception through interactions
at a pain gate.
11-4 • Somatosensory System Receptors and Pathways 387
Fine-touch and pressure Pain and temperature
pathway to the brain pathway to the brain Figure 11-21 Pain Gate A spinal cord interneuron receives excitatory
input (plus signs) from the fine-touch and pressure pathway; and
inhibitory input (minus signs) from the pain and temperature pathway.
Fine-touch The interneuron’s relative activity then determines whether pain and
and pressure pathway temperature information ascends to the brain. Information from R. Melzack (1973).
from body receptors Large The Puzzle of Pain (p. 154). New York: Basic Books.
(myelinated)
+
– Interneuron
Pain and –
temperature pathway
from body receptors Small +
(unmyelinated)
A model of the pain gate, illustrated in Figure 11-21, consists of a haptic-proprioceptive
fiber that conveys fine touch and pressure information and a nociceptive fiber that conducts
pain information. Each fiber synapses with the same interneuron. Collaterals from the hap-
tic-proprioceptive pathway excite the interneuron, whereas collaterals from the nociceptive
pathway inhibit it. The interneuron, in turn, inhibits a neuron that relays pain information
from the spinal cord to the brain. Consequently, when the haptic-proprioceptive pathway is
active, the interneuron is stimulated, inhibiting the secondary pain neuron, and the inter-
neuron acts as a gate, reducing the pain sensation.
Treating Pain
Gate theory helps to explain how so many pain treatments work (Foster et al., 2015). When
you stub your toe, for instance, you feel pain because the pain pathway to the brain is open.
Rubbing the toe activates the haptic-proprioceptive pathway and reduces the information
flow in the pain pathway because the pain gate partly closes, relieving the pain by crowding
it out.
Similarly, a variety of pain treatments, including massage, warm water immersion, and
acupuncture, may produce pain-relieving effects by selectively activating haptic and proprio-
ceptive fibers relative to pain fibers, thus closing the pain gate. For acupuncture, vibrating
needles on different body points presumably activate fine-touch and pressure fibers. The
pain gate model may also explain why opioid drugs influence pain. The interneuron that is
the gate uses an endogenous opioid as an inhibitory neurotransmitter. Thus, opioids have
one of their effects in relieving pain by mimicking the actions of the endogenous opioid
neurotransmitter of the interneuron.
One of the most successful pain treatments is injecting small amounts of morphine under
the dura mater, the outer layer of the meninges. This epidural anesthesia is mediated by Figure 2-4 diagrams the triple-layered
the action of morphine on interneurons in the spinal cord. Although morphine is a highly meninges encasing the brain and spinal cord.
useful pain treatment, its effects lessen with continued use. This form of habituation may
be related to changes that take place on the postsynaptic receptors of pain neurons in the
spinal cord and brain.
Gate theory also suggests an explanation for the pins and needles we feel after sitting
too long in one position. Loss of oxygen from reduced blood flow first deactivates the large
myelinated axons that carry touch and pressure information, leaving the small unmyelinated
fibers that carry pain and temperature messages unaffected. As a result, ungated sensory
information flows in the pain and temperature pathway, leading to the pins and needles.
Neural circuits resembling pain gates may be located in the brainstem and cortex as well
as the spinal cord. These gates help to explain how cognition and emotion influence pain and
how other approaches to pain relief work. For example, researchers have found that feelings pain gate Hypothetical neural circuit in
of severe pain can be lessened when people can shift their attention from the pain to other which activity in fine-touch and pressure
stimuli. Dentists have long used this technique by giving their patients something soothing pathways diminishes the activity in pain and
to watch or listen to during procedures. temperature pathways.
Substantia Periaqueductal
nigra gray matter
Ante
rior Cerebral The brain can also influence the pain signal it receives from the spinal cord. The cell
aqueduct
bodies of periaqueductal gray matter (PAG) neurons surround the cerebral aqueduct con-
necting the third and fourth ventricles. Electrical stimulation of the PAG is effective in
Pos
terio suppressing pain. Neurons in the PAG produce their pain-suppressing effect by exciting
r
pathways (including serotonergic and noradrenergic pathways) in the brainstem that proj-
Red Reticular Superior
nucleus formation colliculus ect to the spinal cord. There they inhibit neurons that form the ascending pain pathways.
The PAG is one nucleus in the midbrain’s Activation in these inhibitory circuits in part explains why pain sensation and perception
tegmentum (floor), shown here in cross ease during sleep. Deep brain stimulation of the PAG by implanted microelectrodes is one
section. DBS is pictured in Figure 1-6. way of treating pain that proves resistant to all other therapies, including treatment with
opioid drugs.
Many internal organs, including the heart, kidneys, and blood vessels, have pain recep-
tors, but the ganglion neurons carrying information from these receptors do not have their
own pathway to the brain. Instead, they synapse with spinal cord neurons that receive no-
Area of ciceptive information from the body’s surface. Consequently, the spinal cord neurons that
referred pain
relay pain and temperature messages to the brain receive two sets of signals: one from the
body’s surface and the other from the internal organs.
These spinal cord neurons cannot distinguish the two sets of signals—nor can we. As
a result, pain in body organs is felt as referred pain coming from the body surface. For
example, pain in the heart associated with a heart attack is felt as pain in the left shoulder
and upper arm (Figure 11-22). Pain in the stomach is felt as pain in the midline of the trunk;
pain in the kidneys is felt as pain in the lower back. Pain in blood vessels in the head is felt as
diffuse pain that we call a headache. (Remember, the brain has no pain receptors.)
Vestibular System and Balance
The only localized part of the somatosensory system, the vestibular system, consists of two
organs, one in each inner ear. As Figure 11-23A shows, each vestibular organ consists of
Figure 11-22 Referred Pain During a
two groups of receptors: the three semicircular canals and the otolith organs, the utricle and
heart attack, pain from receptors in the
the saccule. These vestibular receptors do two jobs: (1) they tell us the position of the body
heart is commonly felt in the left shoulder
and upper arm, especially in men. in relation to gravity and (2) they signal changes in direction and speed of head movement.
In Figure 11-23A the semicircular canals are oriented in three planes that correspond to
Vestibular hair cells work on the same the three dimensions in which we move through space. Each canal furnishes information
principles as cochlear hair cells, which about movement in its particular plane. The semicircular canals are filled with a fluid called
mediate hearing. See Section 10-2. endolymph. Immersed in the endolymph is a set of hair cells.
When the head moves, the endolymph also moves, pushing against the hair cells and
bending the cilia at their tips. The force of the bending is converted into receptor potentials
in the hair cells that send action potentials over auditory vestibular nerve axons to the brain.
Cranial nerve 8 conveys both hearing These axons are normally quite active: bending the cilia in one direction increases receptor
and balance information to the brain. potentials, consequently increasing vestibular nerve axon activity; bending them in the other
See Figure 2-27. direction decreases vestibular afferent axon activity. These responses are diagrammed in
Figure 11-23B. Typically, when the head turns in one direction, the receptor message on that
side of the body increases neuronal firing. The message on the body’s opposite side leads to
decreased firing.
The utricle and saccule lie stacked just beneath the semicircular canals, as shown at the
right in Figure 11-23A. These organs also contain hair cells, but the receptors are embedded
in a gelatinous substance that contains otoconia (sing. otoconium), small crystals of the salt
calcium carbonate. When you tilt your head, the gelatin and otoconia press against the hair
cells, bending them. The mechanical action of the hair bending modulates the rate of ac-
tion potentials in vestibular afferent axons that convey messages about the head’s position
in three-dimensional space.
The receptors in the vestibular system tell us about our location relative to gravity, about
acceleration and deceleration of our movements, and about changes in movement direction.
They also allow us to ignore the otherwise destabilizing influence that our movements might
388
11-4 • Somatosensory System Receptors and Pathways 389
(A) The
Figure 11-23
Semicircular Vestibular System
Vestibular canals (A) The vestibular organs
system in each inner ear contain
hair cells sensitive to
head movement and to
gravity. (B) A vestibular
neuron is normally
Utricle active. Its activity
Otolith increases if the cilia at
Saccule
organs
the tips of its hair cell
Nerve fibers exiting receptors bend in one
a semicircular canal direction but decreases if
the receptors bend in the
(B) Move right Move left opposite direction.
Receptor
Receptor potential Depolarization Hyperpolarization
Resting Increased impulse Decreased impulse
Nerve impulses discharge frequency frequency
have on us. When you are standing on a moving bus, for example, even slight movements
periaqueductal gray matter (pAG) Nuclei
of the vehicle could potentially throw you off balance, but they do not. Similarly, when you
in the midbrain that surround the cerebral
move, you easily avoid tipping over, despite the constant shifting of your body weight. Your
aqueduct joining the third and fourth
vestibular system enables your stability. ventricles; PAG neurons contain circuits for
To demonstrate vestibular receptors’ role in helping you to compensate for your own species-typical behaviors (e.g., female sexual
movements, try this experiment. Hold your hand in front of you and shake it. Your hand behavior) and play an important role in the
appears blurry. Now shake your head instead of your hand, and the hand remains in focus. modulation of pain.
Compensatory signals from your vestibular system allow you to see the hand as stable even referred pain Pain that arises in one of the
though you are moving around. internal organs but is felt on the surface of
Vertigo (from the Latin for spinning), a sensation of spinning when one is not moving, a the body.
dysfunction of the inner ear, can be accompanied by nausea as well as difficulty maintain-
vestibular system Somatosensory system
ing balance while walking. A common way to induce vertigo is to spin, as children do when comprising a set of receptors in each inner
playing. Vertigo can also occur from looking down from a height or looking up at a tall object ear that respond to body position and to
and as one is simply standing up or sitting down. One intoxicating effect of alcohol is vertigo. movement of the head.
Ménière disease, named after a French physician, is a disorder of the inner ear resulting in
ménière disease Disorder of the middle ear
vertigo and loss of balance (Lopez-Escamez et al., 2015). resulting in vertigo and loss of balance.
11-4 review
Somatosensory System Receptors and Pathways
Before you continue, check your understanding.
1. Body senses contribute to the perception of (touch and pressure),
(location and movement), and (temperature, pain, itch).
2. Haptic-proprioceptive information is carried into the CNS by the
spinothalamic tract; nociceptive information is carried in by the
spinothalamic tract.
3. The two tracts interact in the spinal cord to regulate pain perception via a .
4. In the midbrain, the suppresses pain by activating neuromodulatory circuits
that inhibit pain pathways.
390 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
5. The only localized somatosensory system is the system, which helps us
to maintain by signaling information about the head’s position and our
movement through space.
6. Explain how proprioception acts as the “eyes of the body.”
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
11-5 Exploring the Somatosensory
Cortex
Somatosensory neurons do more than convey sensation to the brain: they enable us to per-
ceive things that we describe as pleasant or unpleasant, the shape and texture of objects, the
effort required to complete tasks, and even our spatial environment. They also play a central
role in movement. Figure 11-24 illustrates the two main somatosensory areas in the cortex.
The primary somatosensory cortex (S1), which receives projections from the thalamus,
Korbinian Brodmann numbered these areas consists of Brodmann areas 3-1-2 (all appear red in Figure 11-24). The primary somatosensory
more than a century ago on his map of the cortex begins to construct perceptions from somatosensory information. It mainly consists of
cortex (see Figure 2-23). the postcentral gyrus in the parietal lobe, just behind the central fissure. Thus, S1 lies adja-
cent to the primary motor cortex, on the other side of the central fissure in the frontal lobe.
The secondary somatosensory cortex (Brodmann areas 5 and 7, shaded orange and yellow
in Figure 11-24) is located in the parietal lobe just behind S1. The secondary somatosensory
cortex (S2) refines perceptual constructions in relation to potential movement and sends
information to the frontal cortex.
Somatosensory
Figure 11-24
Primary somatosensory Secondary somatosensory
Cortex Stimulation of the primary cortex receives sensory
5
cortex receives sensory
3–1–2
somatosensory cortex in the parietal lobe information from the 7 information from the
produces sensations that are referred to body. primary somatosensory
appropriate body parts. Information from cortex.
the primary somatosensory cortex travels
to the secondary somatosensory cortex for
further perceptual analysis.
Somatosensory Homunculus
In his studies of human patients undergoing brain surgery, Wilder Penfield electrically stimu-
lated the somatosensory cortex and recorded patients’ responses. Stimulation at some sites
elicited sensations in the foot; stimulation of other sites produced sensations in a hand, the
trunk, or the face. By mapping these responses, Penfield was able to construct a somatosen-
sory homunculus in the cortex, shown in Figure 11-25A. The sensory homunculus looks
nearly identical to the motor homunculus shown in Figure 11-6 in that the most sensitive
areas of the body are accorded relatively large cortical areas.
Using smaller electrodes and more precise recording techniques in monkeys, Jon Kaas
(1987) found that Penfield’s homunculus could be subdivided into a series of smaller homun-
culi. When Kaas stimulated sensory receptors on the body and recorded the activity of cells
in the sensory cortex, he found that the somatosensory cortex comprises four representations
of the body. Each is associated with a class of sensory receptors.
The progression of these representations across S1 from front to back is shown in
Figure 11-25B. Area 3a cells are responsive to muscle receptors; area 3b cells are responsive
11-5 • Exploring the Somatosensory Cortex 391
(A) Penfield’s single-homunculus model (B) Four-homunculus model
Primary somatosensory Primary somatosensory
cortex cortex S1 is organized into four
separate homunculi
S1 is organized as a single consisting of areas 3a, 3b, 1,
homunculus with large and 2. Information is passed
areas representing body from other areas into area
parts that are very sensitive 2, which is responsive to
to sensory stimulation. combined somatosensory
information.
3b 1
Two Models of the
Figure 11-25 3a 2
Primary Somatosensory Cortex
to slow-responding skin receptors. Area 1 cells are responsive to rapidly
adapting skin receptors, and area 2 cells are responsive to deep tis- Muscles Skin (slow) Skin (fast) Joints, pressure
sue pressure and joint receptors. In another study, Hiroshi Asanuma
(1989) and his coworkers found still another sensory representation in
the motor cortex (area 4) in which cells respond to muscle and joint
receptors.
Perceptions constructed from elementary sensations depend on
combining the sensations. This combining takes place as areas 3a and
3b project onto area 1, which in turn projects onto area 2. Whereas a
cell in area 3a or 3b may respond to activity in only a certain area on
a certain finger, for example, cells in area 1 may respond to similar
information from a number of fingers.
At the next level of synthesis, cells in area 2 respond to stimulation in a number of loca-
tions on a number of fingers as well as to stimulation from different kinds of somatosensory
receptors. Thus, area 2 contains multimodal neurons responsive to force, orientation, and
direction of movement. We perceive all these properties when we hold an object in our hands
and manipulate it.
With each successive information relay, both the size of the pertinent receptive fields and See Section 9-1 for details on receptive fields.
the synthesis of somatosensory modalities increase. The segregation of sensory neuron types
at the level of the cortex is likely the basis for our ability to distinguish among different kinds
of sensory stimuli coming from different sources. For example, we distinguish between tac-
tile stimulation on the surface of the skin, which is usually produced by some external agent,
and stimulation coming from muscles, tendons, and joints, which is usually produced by our
own movements.
At the same time, we perceive the combined sensory properties of a stimulus. For in-
stance, when we manipulate an object, we know the object both by its sensory properties,
such as temperature and texture, and by the movements we make as we handle it. Thus,
the cortex provides for somatosensory synthesis too. The tickle sensation seems rooted in
an other-versus-us somatosensory distinction, as described in Research Focus 11-6, Tickling,
on page 392.
Research by Vernon Mountcastle (1978) shows that cells in the somatosensory cortex are
arranged in functional columns running from layer I to layer VI, similar to the functional Figure 9-33 shows functional column
columns found in the visual cortex. Every cell in a functional somatosensory cortical column organization in V1.
responds to a single class of receptors. Some columns are activated by rapidly adapting skin
receptors, others by slowly adapting skin receptors, still others by pressure receptors, and so
forth. All neurons in a functional column receive information from the same local skin area.
In this way, neurons lying within a column seem to be an elementary functional unit of the
somatosensory cortex.
392 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
RESEARCH F cus 11-6
Tickling
Everyone knows the effects and consequences of tickling. The percep- Intrigued by findings that all apes appear to laugh during tickling,
tion is a curious mixture of pleasant and unpleasant sensations. The two Ross and coworkers (2009) compared tickle-related laughter in apes
kinds of tickling are kinismesis, the sensation from a light caress, and and found that human laughter is more similar to chimpanzee laughter
gargalesis, the pleasurable effect of hard rhythmic probing. than to the laughter of gorillas and other apes. We humans thus have
The tickle sensation is felt not only by humans but also by other inherited from our common ape ancestors both a susceptibility to tickling
primates and by cats, rats, and probably most mammals. Play in rats is and laughter as well.
associated with 50-kilohertz vocalizations, and tickling body regions that
are targets of the rats’ own play also elicits 50-kilohertz vocalizations
(Panksepp, 2007).
Tickling is rewarding because people and animals solicit tickles from
others. They even enjoy observing others being tickled. Using a robot
and brain imaging techniques, Sarah Blakemore and her colleagues
(1998) explained why we cannot tickle ourselves.
Blakemore had participants deliver two kinds of identical tactile
stimuli to the palms of their hand. In one condition, the stimulus was
predictable and in the other a robot introduced an unpredictable delay in
the stimulus. Only the unpredictable stimulus was perceived as a tickle.
Thus, it is not the stimulation itself but its unpredictability that accounts
for the tickle perception. This is why we cannot tickle ourselves. Yet
Windt and associates (2015), using a self-report method, find that during
lWa-dann tardif/corbiS
lucid dreams, the self–other distinction is absent: people do dream that
they tickle themselves.
One interesting feature of tickling is the distinctive laughter it evokes.
This laughter can be identified by sonograms (sound analysis), and peo-
ple can distinguish tickle-related laughter from other forms of laughter.
Effects of Somatosensory Cortex Damage
Damage to S1 impairs the ability to make even simple sensory discriminations and move-
ments. Suzanne Corkin and her coworkers (1970) demonstrated this effect by examining
patients with cortical lesions that included most of areas 3-1-2 in one hemisphere. The re-
searchers mapped the primary sensory cortex of these patients before they underwent elec-
tive surgery for removal of a carefully defined piece of that cortex, including the hand area.
The patients’ sensory and motor skills in both hands were tested on three occasions: before
the surgery, shortly after the surgery, and almost a year afterward.
The tests included pressure sensitivity, two-point touch discrimination, position sense
(reporting the direction in which a finger was being moved), and haptic sense (using touch to
identify objects, such as a pencil, a coin, eyeglasses, and so forth). For all the sensory abilities
tested, the surgical lesions produced a severe and seemingly permanent deficit in the con-
tralateral hand. Sensory thresholds, proprioception, and hapsis—all were greatly impaired.
The results of other studies of both humans and other animals have shown that damage to
the somatosensory cortex also impairs simple movements. For example, limb use in reaching for
an object is impaired, as is the ability to shape the hand to hold an object (Leonard et al., 1991).
Nevertheless, like the motor cortex, the somatosensory cortex is plastic. Plasticity is
illustrated by the reorganization of somatosensory cortex after deafferentation. In 1991, Tim
Pons and his coworkers reported a dramatic change in the somatosensory maps of monkeys
in which the ganglion cells for one arm had been cut, deafferentating the limb, a number of
years earlier. The researchers had wanted to develop an animal model of damage to sensory
Section 7-7 considers debates over using nerves that could offer insight into human injuries, but they were interrupted by a legal
laboratory animals in brain–behavior dispute with an animal advocacy group. Years later, as the health of the animals declined, a
research. court injunction allowed the mapping experiment to be conducted.
11-5 • Exploring the Somatosensory Cortex 393
(A) Control monkey Figure 11-26 Somatosensory
Plasticity Information from T. P. Pons, P. E.
This area of the somatosensory cortex This normal pattern is illustrated by a
Garraghty, A. K. Ommaya, J. H. Kaas, & M. Mishkin
represents the arm and face. normal face.
(1991). Massive cortical reorganization after sensory
Leg deafferentation in adult macaques. Science, 252, p. 1858.
Trunk
Arm
Face
(B) Deafferentated monkey
The area of the somatosensory cortex This expansion is illustrated by an
that formerly represented the arm has elongated face.
been taken over by expansion of the
face area.
Leg
Trunk
Face
Pons and his coworkers discovered that the area of somatosensory cortex that had formerly
represented the arm no longer did so. Light touches on a monkey’s lower face now activated
cells in what had formerly been the cortical arm region. As illustrated in Figure 11-26, the
cortical facial area had expanded by as much as 10 to 14 millimeters, virtually doubling its
original size by entering the arm area.
This massive change was completely unexpected. The stimulus–response patterns as-
sociated with the expanded facial area of the cortex appeared indistinguishable from those
associated with the original facial area. Furthermore, the trunk area, which bounded the
other side of the cortical arm area, did not expand into the vacated arm area.
What could account for this expansion of the face area into the arm area? There is
evidence for preexisting axon collaterals that are not normally active, but these collaterals
would probably not be able to extend far enough to account for all of the cortical reorga-
nization. Another possibility is that within the thalamic and brainstem relay pathways,
facial-area neurons project collaterals to arm-area neurons. These neurons are close to-
gether, so the collaterals need travel only a millimeter or so (Kambi et al., 2014). Whatever
the mechanism, the dramatic cortical reorganizations observed in the Pons study are
helpful in understanding other remarkable phenomena, including phantom limb sensa-
tions. In humans who have lost a forelimb, touches to the face can be felt as touches to
the missing forearm. Figure 14-23 diagrams this phenomenon.
Somatosensory Cortex and Complex
Movement
How are our abilities to move and to interpret stimulation on the body related? Our
somatosensory cortex actually makes an important contribution to movement. Damage
to the secondary somatosensory cortex does not disrupt the plans for making movements,
394 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
but it does disrupt how the movements are performed, leaving their execution fragmented
and confused. This inability to complete a plan of action accurately—to make a voluntary
Apraxia derives from the Greek words for no movement—is called apraxia. The following case highlights its symptoms.
and action.
A woman with a biparietal lesion [damage on the left- and right-hemisphere secondary
somatosensory cortex] had worked for years as a fish-filleter. With the development of her
symptoms, she began to experience difficulty in carrying on with her job. She did not seem to
know what to do with her knife. She would stick the point in the head of a fish, start the first
stroke, and then come to a stop. In her own mind she knew how to fillet fish, but yet she could not
execute the maneuver. The foreman accused her of being drunk and sent her home for
mutilating fish.
Information from the secondary somatosensory cortex The same patient also showed another unusual phenomenon that might possibly
contributes to the dorsal stream by specifying the be apraxic in nature. She could never finish an undertaking. She would begin a job,
movement used for grasping a target. drop it, start another, abandon that one, and within a short while would have four or
five uncompleted tasks on her hands. This would cause her to do such inappropriate
Secondary actions as putting the sugar bowl in the refrigerator, and the coffeepot inside the
somatosensory oven. (Critchley, 1953, pp. 158–159)
cortex
Do
The somatosensory cortex contributes to movement by participating in both
rsa Visual the dorsal and the ventral visual streams. The dorsal (how) stream, working
l
str
ea cortex
m without conscious awareness, provides vision for action, as when we automati-
cally shape a hand as we reach to grasp a cup (recall Figure 11-1). Within this
stream a number of channels specify the movements—reaching, manipulat-
Ventral stream ing, bringing a hand to the mouth, walking—that we should make in response
not only to somatosensory information but also to visual and auditory informa-
tion. The ventral (what) stream, in contrast, works with conscious awareness for
perception—that an object is a cup.
As Figure 11-27 illustrates, the dorsal visual stream projects to the second-
ary somatosensory cortex and then to the frontal cortex (Kaas et al., 2012).
Information from the secondary somatosensory cortex In this way, visual information is integrated with somatosensory information
contributes to the ventral stream by providing information to produce unconscious movements appropriately shaped and directed to
about objects’ size, shape, and texture.
their targets, as in reaching for a cup. The secondary somatosensory area
contributes perceptual information to the ventral stream by providing con-
Figure 11-27 Visual Aid Section 9-4
explains how visual information from the scious haptic information about object identity and completed movements. From this
dorsal and ventral streams contributes to information the frontal cortex can imagine the consequence of a movement and select
movement. the actions that appropriately follow from those already completed.
11-5 review
Exploring the Somatosensory Cortex
Before you continue, check your understanding.
1. The somatosensory cortex, arranged as a series of homunculi, feeds
information to the somatosensory cortex, which produces somatosensory
perception.
2. Damage to the secondary somatosensory cortex produces , an inability to
complete a series of movements.
3. The somatosensory cortex provides information to the stream to produce
apraxia Inability to make voluntary unconscious movements and also provides information to the stream for
movements in the absence of paralysis conscious recognition of objects.
or other motor or sensory impairment, 4. Explain briefly what phantom limb pain tells us about the brain.
especially an inability to make proper use of Answers appear at the back of the book.
an object.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
Summary 395
summary
In the nervous system, the somatosensory and motor systems are modulating the movements initiated by the cortex. The basal ganglia
interrelated at all levels. At the level of the spinal cord, sensory regulate force; the cerebellum maintains accuracy and participates in
information contributes to motor reflexes; in the brainstem, sensory learning.
information contributes to complex regulatory movements. At the level
of the neocortex, sensory information represents the sizes, shapes, Somatosensory System Receptors
11-4
and positions of objects and records just-completed movements. and Pathways
Distributed throughout the body, the somatosensory system consists
11-1 Hierarchy of Movement Control of more than 20 types of specialized sensory neurons and receptors,
Movement is organized hierarchically, using the entire nervous system
each sensitive to a particular form of mechanical energy. Located in
(review Figure 11-1). The forebrain plans, organizes, and initiates
posterior dorsal root ganglia, each of these neurons carries sensory
movements, whereas the brainstem coordinates regulatory functions,
information into the spinal cord and the brain.
such as eating and drinking, and controls neural mechanisms
Neurons carrying proprioceptive (location and movement)
that maintain posture and produce locomotion. Many reflexes are
information and haptic (touch and pressure) information have axons
organized at the level of the spinal cord and occur without the brain’s
that ascend the spinal cord as the posterior spinothalamic tract.
involvement.
These fibers synapse in the posterior column nuclei at the base of
11-2 Motor System Organization the brain. From there axons cross to the other side of the brainstem
Maps produced by stimulating the primary motor cortex show that it to form the medial lemniscus, which ascends to the ventrolateral
is organized topographically as a homunculus with different cortical thalamus. Most of the ventrolateral thalamus cells project to the
areas capable of producing different movements. Motor cortex neurons somatosensory cortex.
initiate movement, produce movement, control movement force, and Nociceptive (pain, temperature, and itch) posterior root ganglion
indicate movement direction. Disuse of a limb, as might result from neurons synapse on entering the spinal cord. Their relay neurons cross
a motor cortex injury, results in shrinkage of the limb’s cortical the spinal cord to ascend to the thalamus as the anterior spinothalamic
representation. This shrinkage can be prevented, however, if the limb tract.
can be somehow forced into use, as in constraint-induced therapy. Because the two somatosensory pathways take somewhat different
Two corticospinal pathways emerge from the motor cortex to the routes, unilateral spinal cord damage impairs proprioception and hapsis
spinal cord. Lateral corticospinal axons project from cortical areas ipsilaterally below the site of injury and nociception contralaterally
that control arm and hand movements. The lateral tract crosses from below the site.
the contralateral brain hemisphere to form synapses with spinal
interneurons and motor neurons located laterally in the spinal cord, 11-5 Exploring the Somatosensory Cortex
and on the side opposite the brain hemisphere where the lateral tract The somatosensory system is represented topographically in parietal
formed. Anterior corticospinal tract axons project from the cortical areas 3-1-2. The most sensitive body parts are accorded the largest
motor regions that produce whole-body movements. The anterior tract somatosensory regions, as befits the body parts most capable of fine
synapses with interneurons and motor neurons located medially and movements.
ipsilaterally in the spinal cord. A number of sensory homunculi represent various sensory
Spinal cord interneurons and motor neurons also are topographically modalities, and these regions are hierarchically organized. If sensory
organized: lateral motor neurons project to digit, hand, and arm input from anywhere in the body is cut off from the cortex by damage
muscles to produce arm and hand movements, and medial motor to sensory fibers, adjacent functional sensory cortex can expand into
neurons project to trunk muscles and mediate whole-body movements, the now-unoccupied region.
including locomotion. Through the dorsal visual stream, the somatosensory cortex
contributes to directing hand and body movements to visual targets.
11-3 Basal Ganglia, Cerebellum, and Movement The somatosensory cortex also contributes to the ventral visual
Movement abnormalities result from damage to the basal ganglia or stream to produce perception of external objects, through which we
to the cerebellum. Both structures participate in movement control by can imagine the consequences of our movements.
396 Chapter 11 • HOW DOES THE NERVOUS SYSTEM RESPOND TO STIMULATION AND PRODUCE MOVEMENT?
Key terms
anterior spinothalamic tract, glabrous skin, p. 379 neuroprosthetics, p. 357 quadriplegia, p. 364
p. 383 hapsis, p. 381 nociception, p. 381 rapidly adapting receptor, p. 381
apraxia, p. 394 homunculus, p. 367 pain gate, p. 387 referred pain, p. 389
cerebral palsy, p. 363 hyperkinetic symptom, p. 374 paraplegia, p. 364 scratch reflex, p. 364
connectome, p. 363 hypokinetic symptom, p. 374 periaqueductal gray matter slowly adapting receptor, p. 381
constraint-induced therapy, locked-in syndrome, p. 363 (PAG), p. 389 topographic organization, p. 367
p. 371 posterior spinothalamic tract,
Ménière disease, p. 389 ventrolateral thalamus, p. 383
corticospinal tract, p. 371 p. 383
monosynaptic reflex, p. 385 vestibular system, p. 389
deafferentation, p. 383 proprioception, p. 381
motor sequence, p. 359
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
12 What Causes Emotional RESEARCH FOCUS 12-1 The Pain of RejecTion
12-1 IdEntIFyIng tHE CAUSES OF BEHAvIOR
and Motivated BehavioR foR BRain MainTenance
neuRal ciRcuiTS and BehavioR
Behavior? 12-2 tHE CHEmICAl SEnSES
olfacTion
GuSTaTion
12-3 EvOlUtIOn, EnvIROnmEnt, And BEHAvIOR
evoluTionaRy influenceS on BehavioR
enviRonMenTal influenceS on BehavioR
infeRRinG PuRPoSe in BehavioR: To Know a Fly
12-4 nEUROAnAtOmy OF mOtIvAtEd And EmOtIOnAl BEHAvIOR
ReGulaToRy and nonReGulaToRy BehavioR
ReGulaToRy funcTion of The hyPoThalaMic ciRcuiT
oRGanizinG funcTion of The liMBic ciRcuiT
execuTive funcTion of The fRonTal loBeS
ClInICAl FOCUS 12-2 aGeneSiS of The fRonTal loBeS
STiMulaTinG and exPReSSinG eMoTion
aMyGdala and eMoTional BehavioR
PRefRonTal coRTex and eMoTional BehavioR
eMoTional diSoRdeRS
ClInICAl FOCUS 12-3 anxieTy diSoRdeRS
12-5 COntROl OF REgUlAtORy And nOnREgUlAtORy BEHAvIOR
conTRollinG eaTinG
ClInICAl FOCUS 12-4 WeiGhT loSS STRaTeGieS
EXPERImEnt 12-1 QueSTion: doeS The hyPoThalaMuS Play a
Role in eaTinG?
conTRollinG dRinKinG
conTRollinG Sexual BehavioR
ClInICAl FOCUS 12-5 andRoGen inSenSiTiviTy SyndRoMe and The
andRoGeniTal SyndRoMe
Sexual oRienTaTion, Sexual idenTiTy, and BRain oRGanizaTion
coGniTive influenceS on Sexual BehavioR
12-6 REwARd
Katherine Streeter
397
398 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
RESEARCH F cus 12-1
The Pain of Rejection
We use words like sorrow, grief, and heartbreak to describe a loss. Loss emotional reactions to social rejection may have developed by co-opting
evokes painful feelings, and the loss or absence of contact that comes brain circuits that support the affective component of physical pain. We
with social rejection leads to hurt feelings. Several investigators have hasten to point out, however, that the overlapping activity in brain regions
attempted to discover whether physically painful and emotionally hurtful does not rule out unique neural components of emotional experiences.
feelings are manifested in the same neural regions. Certainly our subjective experiences are unique (e.g., Woo et al., 2014).
Physical pain (say, hot or cold stimuli) is easy to inflict, but inducing Another insight from the Kross study is that normalizing the activity of
equivalently severe emotional, or affective, pain is more difficult. Ethan these brain regions probably provides a basis for both physical and men-
Kross and colleagues (2011) performed an experiment that may have suc- tal restorative processes. Seeing the similarity in brain activation during
ceeded in balancing participants’ degree of emotional and physical pain. social pain and physical pain helps us understand why social support can
Using fMRI, they scanned 40 people who had recently gone through reduce physical pain, much as it soothes emotional pain.
an unwanted breakup. To compare brain activation, the participants
viewed two photographs: one of their ex-partner, to evoke negative emo- Insula dACC Thalamus S2
tion, or the photo of a same-gender friend with whom the participant
shared a pleasant time at about the time of the breakup. The picture
order was randomized across participants.
Emotional cue phrases associated with each photograph directed the
participants to focus on a specific experience they shared with each
person. The physical stimulus employed by the researchers, which was dACC Thalamus S2
Insula
administered in a separate session, was either painfully hot or painless
warm stimulation of participants’ forearm.
The research question is, do physical pain and social pain have a
common neuroanatomical basis? The results, shown in the illustration,
reveal that four regions respond to both types of pain: the insula, dorsal
anterior cingulate cortex (dACC), somatosensory thalamus, and second-
ary somatosensory cortex (S2). The conclusion: Social rejection hurts
Overlapping Social Rejection and Physical Pain
These fMRIs result from averaging scans from 40 participants to
in much the same way physical pain hurts.
image the brain’s response to physical or emotional pain. We see
Previous studies, including Eisenberger and colleagues, 2003, 2006, activation in the insula, dorsal anterior cingulate cortex (dACC),
showed anterior cingulate activity during the experience of both physi- somatosensory thalamus, and/or secondary somatosensory cortex
cal and emotional pain. But new results also showed activity in corti- (S2). Research from E. Kross, M.G. Berman, W. Mischel, E.E. Smith, & T.D. Water, “Social
cal somatosensory regions related to physical pain. The results imaged rejection shares somatosensory representations with physical pain,” 2011, Proceedings of
by Kross and colleagues suggest that the brain systems underlying the National Academy of Sciences (USA), 108, 6270–6275.
Knowing that the brain makes emotional experience real—more than mere metaphors
of hurt or pain—how do we incorporate our thoughts and reasons for behaving as we do?
Clearly, our subjective feelings and thoughts influence our actions. The cognitive interpreta-
tions of subjective feelings are emotions—anger, fear, sadness, jealousy, embarrassment, joy.
These feelings can operate outside our immediate awareness.
This chapter begins by exploring the causes of behavior. Sensory stimulation, neural
circuits, hormones, and reward are primary factors in behavior. We focus both on emotion
and on the underlying reasons for motivation—behavior that seems purposeful and goal-
directed. Like emotion, motivated behavior is both inferred and subjective, and it can occur
without awareness or intent. It includes both regulatory behaviors, such as eating, which are
essential for survival, and nonregulatory behaviors, such as curiosity, which are not required
to meet an animal’s basic needs.
Research on the neuroanatomy responsible for emotional and motivated behavior focuses
on a neural circuit formed by the hypothalamus, the limbic system, and the frontal lobes.
But behavior is influenced as much by the interaction of our social and natural environments
and by evolution as it is by biology. To explain how all these interactions affect the brain’s
12-1 • Identifying the Causes of Behavior 399
control of behavior, we concentrate on two specific examples, feeding and sexual activity.
emotion Cognitive interpretation of subjective
Our exploration leads us to revisit the idea of reward, which is key to explaining emotional
feelings.
and motivated behaviors.
motivation Behavior that seems purposeful
and goal-directed.
12-1 Identifying the Causes
of Behavior
We may think that the most obvious explanation for our behavior is simply that that we act
in a state of free will: we do what we want to, and we always have a choice. But free will is
not a likely cause of behavior.
Consider Roger. We first met 25-year-old Roger in the admissions ward of a large mental
hospital when Roger approached us and asked if we had any snacks. We had chewing gum,
which he accepted eagerly. We thought little about this encounter until 10 minutes later,
when we noticed Roger eating the flowers from the stems in a vase on a table. A nurse took
the vase away but said little to Roger.
Later, as we wandered about the ward, we encountered a worker replacing linoleum floor
tiles. Roger was watching the worker, and as he did, he dipped his finger into the pot of gluing
compound and licked the glue from his finger, as if he were sampling honey from a jar. When
we asked Roger what he was doing, he said that he was really hungry and that this stuff was
not too bad. It reminded him of peanut butter.
One of us tasted the glue and concluded that it did not taste like peanut butter. It tasted
awful. Roger was undeterred. We alerted a nurse, who quickly removed him from the glue.
Later, we saw him eating flowers from another bouquet.
Neurological testing revealed that a tumor had invaded Roger’s hypothalamus at the base
of his brain. He was indeed hungry all of the time and in all likelihood could consume more
than 20,000 calories a day if allowed to do so.
Would you say that Roger was exercising free will regarding his appetite and food prefer-
ences? Probably not. Roger seemed compelled to eat whatever he could find, driven by a
ravenous hunger. The nervous system, not an act of free will, produced this behavior and
undoubtedly produces many others.
If free will does not adequately explain why we act as we do, what does? One obvious
answer is that we do things that we find rewarding. Rewarding experiences must activate
brain circuits that make us feel good. Consider the example of prey killing by domestic cats.
One frustrating thing about being a cat owner is that even well-fed cats kill birds—often
lots of birds. Most people are not much bothered when their cats kill mice: they view mice
as a nuisance. But birds are different. People enjoy watching birds in their yard and garden.
Many cat owners wonder why their pets keep killing birds.
To provide an answer, we look to the activities of neural circuits. Cats must have a brain
circuit that controls prey killing. When this circuit is active, a cat makes an “appropriate”
kill. Viewed in an evolutionary context, it makes sense for cats to have such a circuit: in the
days when doting humans did not keep cats as pets, cats did not have food dishes that were
regularly filled.
Why does this prey-killing circuit become active when a cat does not need food? One
explanation is that, to secure survival, the activity of circuits like the prey-killing circuit are Many people find watching and sharing cute
in some way rewarding—they make the cat feel good. As a result, the cat will engage often in cat videos rewarding: it makes them feel
the pleasure-producing behavior. This helps to guarantee that it will usually not go hungry. good, and they do it often.
In the wild, after all, a cat that did not like killing would probably be dead. In the early
1960s, Steve Glickman and Bernard Schiff (1967) first proposed the idea that behaviors such
as prey killing are rewarding. We return to reward in Section 12-6 because it is important in
understanding the causes of behavior.
400 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Air conditioner
FIGUre 12-1 Sensory Deprivation EEG wires
Microphone Fan
Experimenters record the EEG of a
participant lying on a bed in a dimly lit
environmental cubicle 24 hours a day,
with time out only for meals and bathroom
breaks. A translucent plastic visor restricts
the participant’s vision; a U-shaped pillow
and the noise of a fan and air conditioner Tape
limit hearing. Cotton gloves and long recorder
cardboard cuffs restrict the sense of
touch. Information from W. Heron (1957). The Pathology
of Boredom. Scientific American, 197(4), p. 52.
Behavior for Brain Maintenance
Some experiences are rewarding; others are aversive, again because brain circuits are acti-
vated to produce behaviors that reduce the aversive experience. One example is the brain’s
inherent need for stimulation.
Donald Hebb and his coworkers (Heron, 1957) studied the effects of sensory deprivation,
depriving people of nearly all sensory input. They wanted to see how well-fed, physically
comfortable college students who were paid handsomely for their time would react if they
did nothing, saw nothing, and heard or touched very little 24 hours a day. Figure 12-1 shows
the experimental setup.
Each student lay on a bed in a small, soundproofed room with ears enveloped by a
FIGUre 12-2 Brain Maintenance hollowed-out pillow that muffled the monotonous hums of a nearby fan and air conditioner.
Monkeys quickly learn to solve puzzles
or perform other tricks to gain access to Cardboard tubes covered the hands and arms, cutting off the sense of touch, and a trans-
a door that looks out from their dimly lit lucent visor covered the eyes, blurring the visual world. The participants were given food
quarters into an adjacent room. A toy train and access to bathroom facilities on request. Otherwise, they were asked simply to enjoy
is a strong visual incentive for the monkey the peace and quiet. For doing so, they would receive $20 per day—about four times what a
peeking through the door; a bowl of fruit is student could earn 60 years ago, even for a day’s hard labor.
less rewarding. From R. A. Butler and H. F. Harlow
Wouldn’t you think the participants would be ecstatic to contribute to scientific knowl-
(1954). Persistence of Visual Exploration in Monkeys.
Journal of Comparative and Physiological Psychology, 47, edge in such a painless way? In fact, they were far from happy. Most were content for perhaps
p. 260. 4 to 8 hours; then they became increasingly distressed. They craved stimulation of almost
any kind. In one version of the experiment, the participants
could listen, on request, to a talk for 6-year-old children on the
dangers of alcohol. Some of them asked to hear it 20 times a day.
Few lasted more than 24 hours in these conditions.
What caused their distress? Why did they find sensory depri-
vation so aversive? The answer, Hebb and colleagues concluded,
must be that the brain has an inherent need for stimulation.
Psychologists Robert Butler and Harry Harlow (1954) came
to a similar conclusion through a series of experiments they
conducted at about the same time Hebb conducted his sensory
deprivation studies. Butler placed rhesus monkeys in a dimly lit
room with a small door that could be opened to view an adjoining
room. As shown in Figure 12-2, the researchers could vary the
stimuli in the adjoining room so that the monkeys could view dif-
university of Wisconsin
ferent objects or animals each time they opened the door.
Monkeys in these conditions spent a lot of time opening the
door and viewing whatever was on display, such as toy trains cir-
cling a track. The monkeys were even willing to perform various
12-2 • The Chemical Senses 401
tasks just for an opportunity to look through the door. The longer they were deprived of a
sensory deprivation Experimental setup in
chance to look, the more time they spent looking when finally given the opportunity.
which a participant is allowed only restricted
The Butler and Harlow experiments, together with Hebb and colleagues’ research on
sensory input; participants generally have a
sensory deprivation, show that in the absence of stimulation, the brain will seek it out. low tolerance for deprivation and may even
hallucinate.
Neural Circuits and Behavior androgen Male hormone related to level of
Researchers have identified brain circuits for “reward” and discovered that these circuits can sexual interest.
modulate to increase or decrease activity. Researchers studying the rewarding properties of
sexual activity in males, for example, found that a man’s frequency of copulation correlates with
his levels of androgens (male hormones). Unusually high androgen levels are related to ultrahigh
sexual interest; abnormally low androgen levels are linked to low sexual interest or perhaps no
interest at all. The brain circuits are more difficult to activate in the absence of androgens.
Another way to modulate reward circuits comes via our chemical senses, smell and taste.
The odor of a mouse can stimulate hunting in cats, whereas the odor of a cat will drive mice
into hiding. Similarly, the smell from a bakery can make us hungry, whereas foul odors can
reduce the rewarding value of our favorite foods. Although we tend to view the chemical
senses as relatively minor in our daily lives, they are central to motivated and emotional
behavior, as discussed next, in Section 12-2.
Understanding the neural basis for motivated behavior has wide application. For instance,
we can say that Roger had a voracious and indiscriminate appetite either because the brain
circuits that initiate eating were excessively active or because the circuits that terminate
eating were inactive. Similarly, we can say that Hebb’s participants were highly upset by
sensory deprivation because the neural circuits that respond to sensory inputs were forced
into abnormal underactivity. So the main reason for a particular thought, feeling, or action
lies in what is going on in brain circuits.
12-1 reVIeW
Identifying the Causes of Behavior
Before you continue, check your understanding.
1. One reason cats kill when they may not be hungry is that the killing behavior is
.
2. A reason animals get bored and seek new things to do is to maintain a(n) .
3. Which senses strongly modulate neural circuits?
4. Why is free will inadequate to explain why we do the things we do?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
12-2 The Chemical Senses
Chemical reactions are central to nervous system activity, and chemosignals (chemical
signals) play a central role in motivated and emotional behavior. Mammals identify group
members by odor, mark their territory with urine and other odorants, identify favorite and
forbidden foods by taste, and form associations among odors, tastes, and emotional events.
Olfaction
Olfaction is the most puzzling sensory system. We can discriminate thousands of odors,
yet we have great difficulty finding words to describe what we smell. We may like or dislike
smells or compare one smell to another, but we lack a vocabulary for olfactory perceptions.
402 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Wine experts rely on olfaction to tell them about wines, but they must learn to use smell
to do so. Training courses in wine sniffing typically run one full day per week for a year, and
most participants still have great difficulty passing the final test. This degree of difficulty
contrasts with that of vision and audition, senses designed to analyze the specific qualities
of sensory input, such as pitch in audition or color in vision. In contrast, olfaction seems
designed to discriminate whether information is safe or familiar—is the smell from an ed-
ible food? from a friend or a stranger?—or identifies a signal, perhaps from a receptive mate.
Receptors for Smell
Conceptually, identifying chemosignals is similar to identifying other sensory stimuli (light,
sound, touch). But rather than converting physical energy such as light or sound waves into
receptor potentials, scent interacts with chemical receptors. This constant chemical interac-
tion must be tough on the receptors: in contrast with receptors for light, sound, and touch,
chemical receptors are constantly being replaced. The life of an olfactory receptor neuron
is about 60 days.
The receptor surface for olfaction, illustrated in Figure 12-3, is the olfactory epithelium
in the nasal cavity. The epithelium is composed of receptor cells and support cells. Each re-
ceptor cell sends a process ending in 10 to 20 cilia into a mucous layer, the olfactory mucosa.
Chemicals in the air we breathe dissolve in the mucosa to interact with the cilia. If an olfac-
Figure 5-15A illustrates activity in such a tory chemosignal affects the receptors, metabotropic activation of a specific G protein leads
metabotropic receptor. to an opening of sodium channels and a change in membrane potential.
The epithelial receptor surface varies widely across species. In humans, this area is esti-
mated to range from 2 to 4 square centimeters; in dogs, about 18 square centimeters; and in
cats, about 21 square centimeters. No wonder our sensitivity to odors is less acute than that of
dogs and cats: they have 10 times as much receptor area as humans have! Roughly analogous
to the tuning characteristics of cells in the auditory system, olfactory receptor neurons in
vertebrates do not respond to specific odors but rather to a range of odors.
How does a limited number of receptor types allow us to smell many different odors?
The simplest explanation is that any given odorant stimulates a unique pattern of recep-
tors, and the summed activity or pattern of activity produces our perception of a particular
odor. Analogously, the visual system enables us to identify several million colors with only
three receptor types in the retina: the summed activity of the three cones leads to our
richly colored life.
FIGUre 12-3 Olfactory Epithelium
Olfactory bulb Mitral cells
To pyriform cortex
Glomeruli
Bone
Olfactory Odorant receptor
receptors
Nasal Support
epithelium cells
Cilia
Olfactory mucosa Air with odorant molecules
12-2 • The Chemical Senses 403
A fundamental difference, however, is that the olfactory system is estimated to contain To thalamus and To hypothalamus
orbitofrontal cortex
about 400 kinds of receptors compared with 4 (rods plus the cones) in the visual system. Some
researchers propose that humans can discriminate up to 1 trillion smells. At present the true
number is unknown but likely more than commonly believed (Gerkin & Castro, 2015).
Olfactory Pathways
Olfactory receptor cells project to the olfactory bulb, ending in ball-like tufts of dendrites—
the glomeruli shown in Figure 12-3—where they form synapses with the dendrites of mitral Olfactory bulb
cells. Mitral cells send their axons from the olfactory bulb to the broad range of forebrain To amygdala Pyriform and
areas summarized in Figure 12-4. Many olfactory targets, such as the amygdala and pyriform entorhinal cortex
cortex, have no connection through the thalamus, as do other sensory systems. However, a
thalamic connection (to the dorsomedial nucleus) does project to the orbitofrontal cortex
(OFC), the prefrontal area behind the eye sockets (the orbits) that receives projections from
this thalamic nucleus. In Section 12-4 we explain the OFC’s central role in emotional and
social behaviors as well as in eating.
Accessory Olfactory System
A unique class of odorants is pheromones, biochemicals released by one animal that act
as chemosignals and can affect the physiology or behavior of another animal of the same
species. For example, Karen Stern and Martha McClintock (1998) found that when women
reside together, their estrous cycles begin to synchronize. Furthermore, the researchers
found that the synchronization of menstrual cycles, a phenomenon called the Whitten effect,
is stimulated by the odor of male urine. FIGUre 12-4 Olfactory Pathways
Pheromones appear able to affect more than sex-related behavior. A human chemosig-
nal, androstadienone, has been shown to alter glucose utilization in the neocortex—that
is, how the brain uses energy (Jacob et al., 2001). Thus, a chemosignal appears to affect
cortical processes even though that signal was not consciously detected. The puzzle is why
we would evolve such a mechanism and how it might actually affect cerebral functioning.
Pheromones are unique odors because they are detected by a special olfactory receptor
system, the vomeronasal organ, which is made up of a small group of sensory receptors con-
nected by a duct to the nasal passage. The receptor cells in the vomeronasal organ send their
axons to the accessory olfactory bulb, which lies adjacent to the main olfactory bulb. The
vomeronasal organ connects primarily with the amygdala and hypothalamus, via which it
probably plays a role in reproductive and social behavior.
It is likely that the vomeronasal organ participates not in general olfactory behavior but
rather in the analysis of pheromones, such as those in urine. You may have seen bulls or
cats engage in a behavior known as flehmen, illustrated in Figure 12-5. When exposed to
novel urine from a cat or human, cats raise their upper lip to close off the nasal passages
and suck air into the mouth. The air flows through the duct on the roof of the mouth en
route to the vomeronasal organ.
courtesy of arthur nonneman and
orbitofrontal cortex (OFc) Prefrontal cortex
behind the eye sockets (the orbits); receives
projections from the dorsomedial nucleus of
the thalamus; central to a variety of emotional
Bryan Kolb
and social behaviors, including eating; also
called orbital frontal cortex.
FIGUre 12-5 Response to Pheromones Left: A cat sniffs a urine-soaked cotton ball. pheromone Odorant biochemical released
Center: It raises its upper lip to close off the nasal passages. Right: It follows with the full by one animal that acts as a chemosignal
gape response characteristic of flehmen, a behavior mediated by the accessory olfactory and can affect the physiology or behavior of
system. another animal.
404 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Human Olfactory Processing
Our ability to distinguish a surprisingly large number of odors upends the common misper-
ception that people have a miserable sense of smell relative to other mammals. Still, our
threshold for detecting many smells is certainly inferior to that of our pet dogs, cats, and
horses. Yet humans have a surprisingly acute sensitivity to behaviorally significant smells.
Several studies show convincingly that people can identify their own odor, the odor of kin
versus not-kin, and the odor of friends versus strangers with an accuracy well above chance
(e.g., Olsson et al., 2006). Johan Lundstrom and colleagues (2008) used PET scans to identify
the neural networks that process human body odors. They made two surprising findings.
First, the brain analyzes common odors and body odors differently. Although both acti-
vate primary olfactory regions, body odors also activate structures not previously believed to
participate in olfactory processing, including the posterior cingulate cortex, occipital cortex,
and anterior cingulate cortex—regions also activated by visually emotional stimuli. Consid-
ered in an evolutionary perspective, the ability to identify human odors probably is uniquely
important to safety.
Second, smelling a stranger’s odor activates the amygdala and insular cortex, similar to
The insula contains regions related to activation observed for fearsome visual stimuli such as masked or fearsome faces. The inves-
language, taste perception, and social tigators also asked participants to rate the intensity and pleasantness of odors; they found
cognition. that strangers’ odors were rated as stronger and less pleasant than those of familiar persons.
Lundstrom and colleagues conclude that processing body odors is mostly unconscious.
It represents an automatic process that matches odors to a learned library of smells. Similar
unconscious processes seem to occur during visual and auditory information processing and
to play an important role in our emotional reactions.
Gustation
Research reveals significant differences in taste preferences both between and within spe-
cies. Humans and rats like sucrose and saccharin solutions, but dogs reject saccharin and
cats are indifferent to both, inasmuch as they do not detect sweetness at all. The failure of
cats to taste sweet may not be surprising: they are pure carnivores, and nothing that they
normally eat is sweet.
Within the human species, clear differences in taste thresholds and preferences are obvi-
ous. An example is the preference for or dislike of bitter tastes—the flavor of brussels sprouts,
for instance. People tend to love them or hate them. Linda Bartoshuk (2000) showed absolute
differences among adults: some perceive certain tastes as very bitter, whereas others are in-
different to them. Presumably, the latter group is more tolerant of brussels sprouts.
Sensitivity to bitterness is related to genetic differences in the ability to detect a specific
bitter chemical (6-n-propylthiouracil, or PROP). PROP bitterness associates with allelic varia-
tion in the taste receptor gene TAS2R38. People able to detect minute quantities of PROP
find the taste extremely bitter; they are sometimes called supertasters. Those who do not
taste PROP as very bitter are nontasters. The advantage of being a supertaster is that many
bitter “foods” are poisonous. The disadvantage is that supertasters avoid many nutritious
fruits and vegetables that they find bitter.
Valerie Duffy and her colleagues (2010) investigated sensitivity to quinine (usually per-
ceived as bitter) in participants who were assessed for the TAS2R38 genotype. They esti-
mated participants’ taste bud density by counting the number of papillae (the little bumps on
the tongue). Quinine was reported as more bitter to those who tasted PROP as very bitter or
to those who had more taste buds. Thus, detection of bitterness is related both to TAS2R38
and to tongue anatomy.
Nontasters, either by genotype or phenotype (for few taste buds), reported greater con-
sumption of vegetables, both bitter and not. Nontasters with higher numbers of taste buds
reported eating about 25% more vegetables than the other groups. These data suggest
that genetic variation in taste can explain differences in overall consumption of all types
12-2 • The Chemical Senses 405
of vegetables. It also suggests that persuading supertasters to eat more healthy
foods—that is, vegetables—may prove difficult.
Differences in taste thresholds also emerge as we age. Children are much more Tongue Taste pore
Microvilli
responsive to taste than adults and are often intolerant of spicy foods because Bitter
they have more taste receptors than adults have. It is estimated that by age 20, Sweet
humans have lost at least 50 percent of their taste receptors. No wonder children Sour
Salt
and adults have different food preferences.
Receptors for Taste
Taste receptors are found in taste buds on the tongue, under the tongue, on the
soft palate on the roof of the mouth, on the sides of the mouth, and at the back
of the mouth on the nasopharynx. Each of the five taste receptor types responds
to a different chemical component in food. The four most familiar are sweet,
sour, salty, and bitter. The fifth type, called the umami receptor, is especially Processes of cranial
nerves 7, 9, 10
sensitive to glutamate, a neurotransmitter molecule, and perhaps to nucleotides.
(Nucleotide bases are the structural units of nucleic acids such as DNA and RNA.)
FIGUre 12-6 Anatomy of a Taste Bud
Taste receptors are grouped into taste buds, each containing several receptor types, as
Information from D. V. Smith & G. M. Shepherd (2003).
illustrated in Figure 12-6. Gustatory stimuli interact with the receptor tips, the microvilli,
Chemical senses: Taste and olfaction. In L. R. Squire,
to open ion channels, leading to changes in membrane potential. At its base, the taste bud F. E. Bloom, S. K. McConnell, J. L. Roberts, N. C. Spitzer, &
contacts the branches of afferent cranial nerve 7 (facial), 9 (glossopharyngeal), or 10 (vagus). M. J. Zigmond (Eds.), Fundamental Neuroscience (2nd ed.,
pp. 631–667), New York: Academic Press.
Gustatory Pathways
Cranial nerves 7, 9, and 10 form the main gustatory nerve, the solitary tract. On entering
the brainstem, the tract splits, as illustrated in Figure 12-7. One route (traced in red) travels
through the posterior medulla to the ventroposterior medial nucleus of the thalamus. This
nucleus in turn sends out two pathways, one to the primary somatosensory cortex (S1) and
the other to the primary gustatory cortex of the insula, a region just rostral to the secondary
somatosensory cortex (S2). FIGUre 12-7 Gustatory Pathways
The gustatory region in the insula is dedicated to taste, whereas S1 is also responsive to Ventral Primary Primary
tactile information and is probably responsible both for localizing tastes on the tongue and posteromedial gustatory
nucleus of somatosensory
for our reactions to a food’s texture. The gustatory cortex sends a projection to the orbital cortex (insula) cortex
thalamus
cortex in a region near the input from the olfactory cortex. Neuroimaging studies suggest
that the mixture of olfactory and gustatory input in the orbital cortex gives rise to our percep-
tion of flavor. Ambience, including music and light, also affects this region of orbital cortex,
increasing blood flow and so enhancing our experience of flavor.
A meta-analysis of noninvasive imaging studies that demonstrate taste-responsive brain
regions, conducted by Maria Veldhuizen and colleagues (2011), also shows a brain asymmetry.
The investigators conclude that areas in the right orbital cortex mediate the pleasantness
of tastes, whereas the same region in the left hemisphere mediates the unpleasantness of
tastes. Whereas the insula identifies the nature and intensity of flavors, the OFC evaluates
the affective properties of tastes. Lateral
Amygdala
The second pathway from the gustatory nerve (shown in blue in Figure 12-7) projects via hypothalamus
Nucleus of
the nucleus of the solitary tract in the brainstem to the hypothalamus and amygdala. Re- solitary tract
searchers hypothesize that these inputs somehow participate in feeding behavior, possibly Cranial nerves
7, 9, 10
evaluating the pleasantness and strength of flavors.
12-2 reVIeW
The Chemical Senses
Before you continue, check your understanding.
1. The receptor surface for olfaction is the .
2. Olfactory and gustatory pathways eventually merge in the orbitofrontal cortex, leading to
the perception of .
406 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
3. Chemosignals that convey information about the sender are called .
4. The perception of bitterness is related to both the and the .
5. How do a relatively limited number of receptor types allow us to smell a trillion different
odors?
Answers appear at the back of the book.
For additional study tools, visit
www.macmillanhighered.com/launchpad/kolb5e
12-3 Evolution, Environment, and
Behavior
Odor and taste play a fundamental role in the biology of emotional and motivated behavior.
innate releasing mechanism (IRM) Why does the sight or smell of a bird or a mouse trigger stalking and killing in a cat? Why does
Hypothetical mechanism that detects specific the human body stimulate sexual interest? We can address such questions by investigating the
sensory stimuli and directs an organism to
evolutionary and environmental influences on brain circuit activity that contribute to behavior.
take a particular action.
evolutionary psychology Discipline that
seeks to apply principles of natural selection Evolutionary Influences on Behavior
to understand the causes of human behavior. One evolutionary explanation hinges on the concept of innate releasing mechanisms (IRMs),
activators for inborn adaptive responses that aid an animal’s survival. IRMs help an animal to
feed, reproduce, and escape predators. The concept is best understood by analyzing its parts.
IRMs are present from birth rather than acquired through experience, as the term innate
implies. These mechanisms have proved adaptive and therefore have been maintained in the
genome of the species. The term releasing indicates that IRMs act as triggers for behaviors
set in motion by internal programs.
Let us return to prey killing by cats. The cat’s brain must have a built-in mechanism that
triggers stalking and killing in response to such a stimulus as a bird or a mouse. A cat must
(A) also have a built-in mechanism that triggers mating behavior in the presence of a suitable
cat of the opposite sex. Not all cat behaviors are due to IRMs, but you probably can think of
other innate releasing mechanisms that cats possess—arching and hissing on encountering a
threat, for example. For all these IRMs, the animal’s brain must have a set of norms against
which it can match stimuli to trigger an appropriate response.
The following experiment suggests the existence of such innate, internalized norms.
Bryan Kolb and Arthur Nonneman allowed a litter of 6-week-old kittens to play in a room and
courtesy of arthur nonneman and Bryan Kolb
become familiar with it. After this adjustment period, they introduced a two-dimensional
(B) image of an adult cat in a Halloween posture, as shown in Figure 12-8A.
The kittens responded with raised fur, arched backs, and bared teeth, all signs of being
threatened by the image of the adult. Some even hissed at the model. These kittens had
no experience with any adult cat except their mother, and there was no reason to believe
that she had ever shown them this behavior. Some sort of template of this posture must be
prewired in the kitten brain. Seeing the model that matched this preexisting template auto-
matically triggered a threat response. This innate trigger is an IRM.
FIGUre 12-8 Innate Releasing The IRM concept also applies to humans. In one study, Tiffany Field and her colleagues
Mechanism in Cats (A) Displaying (1982) had an adult display to young infants various exaggerated facial expressions, such as
the Halloween cat image stimulates happiness, sadness, and surprise. As Figure 12-9 shows, the babies responded with very much
defensive responses in cats—raised the same expressions the adults displayed. These newborns were too young to be imitating
fur, arched backs, and bared teeth. This
the adult faces intentionally. Rather, babies must innately match these facial expressions to
behavior appears at about 6 weeks of
age in kittens who have never seen such internal templates, in turn triggering some prewired program to reproduce the expressions
a posture before. (B) The scrambled in their own faces. Such an IRM would have adaptive value if these facial expressions serve
“Picasso cat” evokes no response at all. as important social signals for humans.
12-3 • Evolution, Environment, and Behavior 407
Evidence for a prewired motor program related to facial expressions also comes from
study of congenitally blind children, who spontaneously produce the very same facial
expressions that sighted people do, even though they have never seen them in others.
IRMs are prewired into the brain, but experience can modify them. Our cat Hunter’s
stalking skills were not inherited fully developed at birth but rather matured functionally
as she grew older. The same is true of many human IRMs, such as those for responding
to sexually arousing stimuli.
Different cultures may emphasize different stimuli as arousing. Even within a sin-
gle culture, what different people find sexually stimulating varies. Nonetheless, some
human attributes are universally sexually arousing. For most human males, an example
is the hip-to-waist ratio of human females. This ratio is probably part of an IRM.
The IRM concept can be related to the Darwinian view of nervous system evolution.
Natural selection favors behaviors that prove adaptive for an organism, and these behav-
iors are passed on to future generations. Because behavior patterns are produced by the Section 1-2 reviews Darwin’s theory,
activity of neurons in the brain, the natural selection of specific behaviors is really the materialism, and contemporary perspectives
selection of particular brain circuits. on brain and behavior.
Animals that survive long enough to reproduce and have healthy offspring are more
likely to pass on their brain circuit genes than are animals with traits that make them
less likely to survive and successfully reproduce. Thus, feral cats adept at stalking prey
or responding fiercely to threats are more likely to survive and produce many offspring,
passing on their adaptive brain circuits and behaviors to their young. In this way, the
behaviors become widespread in the species over time.
The Darwinian view seems straightforward when we consider how cats evolved
brain circuits for stalking prey or responding to threats. It is less obvious when ap-
plied to complex human behaviors, however. Why, for instance, have humans evolved
the behavior of killing other humans? At first glance, it seems counterproductive to
the survival of the human species. Why has it endured? For an answer, we turn to
evolutionary psychology, the field that applies principles of natural selection to expla-
doctor Tiffany M. field
nations of human behavior.
Evolutionary psychologists assume that any behavior, including homicide, occurs be-
cause natural selection has favored the neural circuits that produce it. When two men
fight a duel, one commonsense explanation might be that they are fighting over griev-
ances. But evolutionary psychologists would instead ask, why is a behavior pattern that
FIGUre 12-9 Innate Releasing
risks people’s lives sustained in a population? Their answer: fights are about social status.
Mechanism in Humans Facial
Men who fought and won duels passed on their genes to future generations. Through expressions made by young infants in
time, therefore, the traits associated with successful dueling—strength, aggression, agility— response to expressions made by the
became more prevalent among humans, as did dueling. Martin Daly and Margot Wilson experimenter. From M. Field, R. Woodson,
(1988) extended this evolutionary analysis to further account for homicide. In their view, R. Greenberg, D. Cohen, “Discrimination and imitation
of facial expression by neonates,” Science 8 October
homicide may endure in our society despite its severe punishment because it is related to
1982: Vol. 218 no. 4568 pp. 179–181, Figure 1, permission
behaviors that were adaptive in the human past.
conveyed through Copyright Clearance Center, Inc.
Suppose that natural selection favored sexually jealous males who, to guarantee that
they had fathered all offspring born of their mates, intimidated their rivals and bullied their
mates. Male jealousy would be a prevalent motive for interpersonal violence, including ho-
micide. Homicide itself does not help a man produce more children. But men who are apt
to commit homicide are more likely to engage in other behaviors (bullying and intimidation)
that improve their social status and therefore their reproductive fitness. Homicide therefore
is related to adaptive traits that have been selected through millennia.
David Buss (2014) has examined patterns of mate selection across thousands of partici-
pants from 37 cultures, seeking to identify factors beyond culture that influence mate selec-
tion. His conclusions after nearly 30 years of study are that women around the world value Section 15-5 posits a genetic explanation
dependability, stability, education, and intelligence in a long-term mate. Men, however, value for the evolution of sex-related cognitive
good looks, health, and a desire for home and children more than women do. differences.
408 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Older men and younger women are most likely to exhibit the mutually desired set of traits,
which leads to a universal tendency for age differences between mates. Although the idea is
controversial, Buss argues that these preferences are a product of natural selection in a Stone
Age environment, when women and men would have faced different daily problems and thus
would have developed separate adaptations related to mating.
Section 1-2 reviews Darwin’s theory, Evolutionary theory cannot account for all human behavior, perhaps not even homicide
materialism, and contemporary perspectives or mate selection. By casting an evolutionary perspective on the neurological bases of be-
on brain and behavior. havior, though, evolutionary psychologists can generate intriguing hypotheses about how
natural selection might have shaped the brain and behavior.
Environmental Influences on Behavior
Many psychologists have emphasized learning as a cause of behavior. No one would question
that we modify our behavior as we learn, but the noted behaviorist B. F. Skinner (1938) went
much further. He believed that behaviors are selected by environmental factors.
Skinner’s argument is simple. Certain events function as rewards, or reinforcers. When
a reinforcing event follows a particular response, similar responses are more likely to occur.
Skinner argued that reinforcement can be manipulated to encourage the display of complex
behaviors.
The power of experience to shape behavior by pairing stimuli and rewards is typified by
one of Skinner’s experiments. A pigeon is placed in a box that has a small disc on one wall
(the stimulus). If the pigeon pecks at the disc (the response), a food tray opens, and the pigeon
can feed (the reinforcement or reward). The pigeon quickly learns the association between
the stimulus and the response, especially if the disc has a small spot on it. It pecks at the spot
Skinner box and within minutes it has mastered the response needed to receive a reward.
Now the response requirement can be made more complex. The pigeon might be re-
quired to turn 360 degrees before pecking the disc to gain the reward. The pigeon can learn
this response too. Other contingencies might then be added, making the response require-
ments even more complex. For instance, the pigeon might be trained to turn in a clockwise
circle if the disc is green, to turn in a counterclockwise circle if the disc is red, and to scratch
at the floor if the disc is yellow.
If you suddenly came across this complex behavior in a pigeon, you would probably be
astounded. But if you understood the experience that had shaped the bird’s behavior, you
would understand its cause. The rewards offered to the pigeon altered its behavior: its re-
sponses were controlled by the color of the disc on the wall.
Skinner extended behavioral analysis to include actions of all sorts—behaviors that at
first do not appear easily explained. For instance, he argued that understanding a person’s
reinforcement history could account for various phobias. Someone who once was terrified
by a turbulent plane ride thereafter avoids air travel and manifests a phobia of flying. The
avoidance of flying is rewarding because it lowers the person’s anxiety level, maintaining the
phobic behavior.
Skinner also argued against the commonly held view that much of human behavior is
under our own control. From Skinner’s perspective, free will is an illusion, because behavior
is controlled not by the organism but rather by the environment, through experience. But
what is the experience actually doing? Increasing evidence suggests that epigenetic changes
regulate changes in memory circuits. Skinner was not studying the brain directly, but it is
Epigenetic mechanisms mediate synaptic becoming clear that epigenetics supports his perspective. We learn many complex behaviors
plasticity, especially in learning and memory. through changes in memory-related genes that act to modify neural circuits (see the review
See Section 14-4. by Day and Sweatt, 2011).
The environment does not always change the brain. A case in point can be seen again in
pigeons. A pigeon in a Skinner box can quickly learn to peck a disc to receive a bit of food,
but it cannot learn to peck a disc to escape from a mild electric shock to its feet. Why not?
Although the same simple pecking behavior is being rewarded, apparently the pigeon’s brain
12-3 • Evolution, Environment, and Behavior 409
is not prewired for this second kind of association. The bird is prepared genetically to make
reinforcer In operant conditioning, any event
the first association, for food, but not prepared for the second. This makes adaptive sense:
that strengthens the behavior it follows.
typically, it flies away from noxious situations.
John Garcia and R. A. Koelling (1966) were the first psychologists to demonstrate the learned taste aversion Acquired association
specific nature of this range of behavior–consequence associations that animals are able to between a specific taste or odor and illness;
leads to an aversion to foods that have the
learn. Garcia observed that farmers in the western United States are constantly shooting at
taste or odor.
coyotes for attacking lambs, yet despite the painful consequences, the coyotes never seem
to learn to stop killing lambs in favor of safer prey. The reason, Garcia speculated, is that a preparedness Predisposition to respond to
coyote’s brain is not prewired to make this kind of association. certain stimuli differently from other stimuli.
So Garcia proposed an alternative to deter coyotes from killing lambs—an association that
a coyote’s brain is prepared to make: the connection between eating something that makes
one sick and avoiding that food in the future. Garcia gave the coyotes a poisoned lamb car-
cass, which sickened but did not kill them. With only one pairing of lamb and illness, most
coyotes learned not to eat sheep for the rest of their lives.
Many humans have similarly acquired food aversions because a certain food’s taste—es-
pecially a novel taste—was subsequently paired with illness. This learned taste aversion is
acquired even when the food eaten is in fact unrelated to the later illness. As long as the taste
and the nausea are paired in time, the brain is prewired to connect them.
One of us ate his first Caesar salad the night before coming down with a stomach flu. A
year later, he was offered another Caesar salad and, to his amazement, felt ill just at the smell
of it. Even though he knew that the salad had not caused his earlier illness, he nonetheless
had formed an association between the novel flavor and the illness. This strong and rapid
associative learning makes adaptive sense. Having a brain that is prepared to make a connec-
tion between a novel taste and subsequent illness helps an animal avoid poisonous foods and
so aids in its survival. A curious aspect of taste aversion learning is that we are unaware of Section 14-4 has more on how our brains are
having formed the association until we encounter the taste and/or smell again. wired to link unrelated stimuli.
The fact that the nervous system is often prewired to make certain associations but
not to make others has led to the concept of preparedness in learning theories. Prepared-
ness can help account for some complex behaviors. For example, if two rats are paired
in a small box and exposed to a mild electric shock, they will immediately fight with one
another, even though neither was responsible for the shock. Apparently, the rat brain is
predisposed to associate injury with nearby objects or other animals. The extent to which
we might extend this idea to explain such human behaviors as bigotry and racism is an
interesting topic to ponder.
Inferring Purpose in Behavior: To Know a Fly Stretch Foregut
We may tend to assume that behavior is intentional. A wonderful little book, To Know a Fly, receptors
Brain
by Vincent Dethier (1962), disabuses this assumption by illustrating the problems in inferring
Recurrent
purpose from an organism’s actions. nerve
When a fly lands on a kitchen table, it wanders about, occasionally stomping its feet. Even- Esophagus
tually, it finds a bit of food and sticks its proboscis (an extension like an elephant’s trunk) into
Proboscis Midgut Crop
the food and eats. The fly may then walk to a nearby place and begin to groom by rubbing
its legs together quickly. Finally, it spends a long period motionless. Taste receptors
If you observed a fly engaged in these behaviors, it might appear to have been searching on feet
for food because it was hungry. When it found food, you might assume that it gorged itself FIGUre 12-10Feeding System of the
until it was satisfied, then it cleaned up and rested. In short, the fly’s behavior might seem Fly After the fly samples the surface
to you to be motivated—to have some purpose or intention. using taste buds on its feet, it takes in
Dethier studied flies for years to understand what a fly is actually doing when it engages food through the proboscis and passes it
through the esophagus to the gut. Stretch
in these behaviors. His findings have little to do with purpose or intention. When a fly
receptors at the gut entrance determine
wanders about a table, it is not deliberately searching. Rather, it is tasting what it walks on. when the esophagus is full. The recurrent
As Figure 12-10 shows, a fly’s taste receptors are on its feet. Tasting is automatic when nerve alerts the brain to signal cessation
a fly walks. An adult fly’s nervous system has a built-in preference for sweet tastes and of eating.
410 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
an aversion to sour, salty, and bitter tastes. Therefore, when a fly encounters something
sweet, it automatically lowers its proboscis and eats—or drinks if the sweet is liquid. The
sweeter the food, the more a fly will consume. (Sweet foods attract us humans too, as
Clinical Focus 12–4, Weight Loss Strategies, reports.)
Why does a fly stop eating? A logical possibility is that its blood sugar level rises to some
threshold. If this were correct, injecting glucose into the circulatory system of a fly would
prevent the fly from eating. But that does not happen. Blood glucose level has no effect on
a fly’s feeding. Furthermore, injecting food into the animal’s stomach or intestine has no
effect either. So what is left?
Flies have a nerve (the recurrent nerve) that extends from the neck to the brain and car-
ries information about whether any food is present in the esophagus. If the recurrent nerve
is cut, the fly is chronically hungry and never stops eating. Such flies become so full and fat
that their feet no longer reach the ground, and they become so heavy that they cannot fly.
Even though a fly appears to act with a purpose in mind, a series of very simple mecha-
nisms actually control its behavior—mechanisms not remotely related to our concept of
thought or intent. Hunger is simply the activity of the nerve. Clearly, we should not assume
simply from appearances that a behavior carries intent. Behavior can have very subtle causes
that do not include conscious purpose. How do we know that any behavior is purposeful?
That question turns out to be difficult to answer.
12-3 reVIeW
Evolution, Environment, and Behavior
Before you continue, check your understanding.
1. B. F. Skinner argued that behaviors could be shaped by in the environment.
2. John Garcia used the phenomenon of to discourage coyotes from killing
lambs.
3. The brain of a species is prewired to produce to specific sensory stimuli
selected by evolution to prompt certain associations between events.
4. When a fly wanders around on a table, it is not exploring so much as .
5. Explain briefly how the concept of preparedness accounts for puzzling human
behaviors.
Answers appear at the back of the book.
For additional study tools, visit
www.macmillanhighered.com/launchpad/kolb5e
12-4 Neuroanatomy of Motivated
and Emotional Behavior
The neural circuits that control behavior encompass regions at all levels of the brain, but the
critical neural structures in emotional and motivated behavior are the hypothalamus and as-
sociated pituitary gland, the limbic system, and the frontal lobes. The expression of emotions
includes physiological changes: in heart rate, blood pressure, and hormone secretions. It also
includes motor responses, especially movements of the muscles that produce facial expres-
sions (see Figure 12-9). So much of human life revolves around emotions that understanding
them is central to understanding our humanness.
But emotions are not restricted to people. A horse that is expecting alfalfa for dinner will
turn its nose up at grass hay and may stomp its front feet and toss its head. Two dogs that are
in competition for attention may snap at one another. Charles Darwin interpreted such be-
haviors as emotions in his classic book The Expression of the Emotions in Man and Animals,
12-4 • Neuroanatomy of Motivated and Emotional Behavior 411
published in 1872. We now know that emotional expression in all mammals is related to
activity in the limbic system and frontal lobes.
Although the hypothalamus plays a central role in controlling motivated behavior, it takes
its instructions from the limbic system and the frontal lobes. The limbic and frontal regions
project to the hypothalamus, which houses many basic neural circuits for controlling behav-
ior and for autonomic processes that maintain critical body functions within a narrow, fixed Section 6-5 explores hormonal regulation of
range—that is, homeostatic mechanisms. homeostatic mechanisms.
In Figure 12-11, the neck of a funnel represents the hypothalamus, and the limbic system
and frontal lobes form the funnel’s rim. To produce behavior, the hypothalamus sends axons
to other brainstem circuits. But not all behavior is controlled via the funnel to the hypothala-
mus. Many other routes to the brainstem and spinal cord bypass the hypothalamus, among
them projections from the motor cortex to the brainstem and spinal cord. Thus it is primarily FIGUre 12-11 Funneling Signals
motivated behaviors that require hypothalamic involvement. In this model, many inputs from the frontal
lobes and limbic system funnel through
the hypothalamus, which sends its axons
Regulatory and Nonregulatory Behavior to control brainstem circuits that produce
We seek mates, food, or sensory stimulation because of brain activity, but we talk about such motivated behaviors.
behavior as being motivated. Motivated behaviors are not something in the brain that we can
ystem Frontal lobe
point to, however. Rather, motivations are inferences we make about why someone, ourselves Limbic s s
included, engages in a particular behavior. The two general classes of motivated behaviors
are regulatory and nonregulatory. In this section we explore both categories before exploring
the neuroanatomy of motivation and emotion.
Regulatory Behaviors
Regulatory behaviors—behaviors motivated by an organism’s survival—are controlled by Hypothalamus
homeostatic mechanisms. By analogy, consider a house whose thermostat is set at 18 degrees
Celsius (°C). When the temperature falls below a certain tolerable range (say, to 16°C), the
Motivated
thermostat turns the furnace on. When the temperature rises above a certain tolerable level behavior
(say, 20°C), the thermostat turns on the air conditioner.
Human body temperature is controlled in a somewhat similar manner by a thermostat
in the hypothalamus that holds internal temperature at about 37°C, a temperature referred
to as a set point. Even slight variations cause us to engage in various behaviors to regain the
set point. For example, when body temperature drops slightly, neural circuits that increase
body temperature turn on. These neural circuits might induce an involuntary response such
as shivering or a seemingly voluntary behavior such as moving closer to a heat source. Con-
versely, if body temperature rises slightly, we sweat or move to a cooler place.
Similar mechanisms control many other homeostatic processes, including the amount
of water in the body, the balance of dietary nutrients, and the blood sugar level. Control
of many such homeostatic systems is quite complex, requiring both neural and hormonal
mechanisms. In some way, however, all of the body’s homeostatic systems involve hypotha-
lamic activity.
Imagine that specific cells are especially sensitive to temperature. When they are cool,
they become very active; when they are warm, they become less active. These cells could
function as a thermostat, telling the body when it is too cool or too warm. A similar set of cells
could serve as a glucostat, controlling the level of sugar in the blood, or as a hydrostat, control-
ling the amount of water in the body. In fact, the body’s real homeostatic mechanisms are
slightly more complex than this imagined one, but they work on the same general principle.
Mechanisms to hold conditions such as temperature constant have evolved because the
body, including the brain, is a chemical soup in which thousands of reactions are taking place homeostatic mechanism Process that
all the time. Maintaining constant temperature is critical. When temperature changes, even maintains critical body functions within a
by 2°C, the rates at which chemical reactions take place change. narrow, fixed range.
Such changes might be tolerable, within certain limits, if all the reaction times changed regulatory behavior Behavior motivated to
to the same extent. But they do not. Consequently, an increase of 2°C might increase one meet the animal’s survival needs.
412 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
reaction by 10 percent and another by only 2 percent. Such uneven changes would wreak
havoc with finely tuned body processes such as metabolism and the workings of neurons.
A similar logic applies to maintaining homeostasis in other body systems. For instance,
cells require certain concentrations of water, salt, and glucose to function properly. Wild
fluctuations in the concentrations cause a gross disturbance of metabolic balance and even-
tually biological disaster.
Nonregulatory Behaviors
categories of Motivated Behavior Unlike regulatory behaviors, such as eating or drinking, nonregulatory behaviors are neither
some Regulatory Behaviors required to meet the basic survival needs of an animal nor controlled by homeostatic mecha-
nisms. Thus, nonregulatory behaviors include everything else we do—from sexual inter-
Internal body temperature
course to parenting to such curiosity-driven activities as conducting psychology experiments.
Eating and drinking
Some nonregulatory behaviors, such as sexual intercourse, entail the hypothalamus, but
Salt consumption
most of them probably do not. Rather, such behaviors entail a variety of forebrain structures,
Waste elimination especially the frontal lobes. Presumably, as the forebrain evolved and enlarged, so did our
some Nonregulatory Behaviors range of nonregulatory behaviors.
Sex Most nonregulatory behaviors are strongly influenced by external stimuli. As a result,
Parenting sensory systems must play some role in controlling them. For example, the sexual behav-
Aggression ior of most male mammals is strongly influenced by the pheromone emitted by receptive
females. If the olfactory system is not functioning properly, we can expect abnormalities in
Food preference
sexual behavior. We will return to sexual behavior in Section 12-5, as we investigate how a
Curiosity
nonregulatory behavior is controlled. But first we explore the brain structures that take part
Reading
in motivated behaviors—nonregulatory and regulatory.
Regulatory Function of the
Hypothalamic Circuit
The hypothalamus maintains homeostasis by acting on both the endocrine system and the
Figure 2-30 diagrams ANS pathways and autonomic nervous system (ANS) to regulate our internal environment. The hypothalamus
connections. also influences the behaviors selected by the rest of the brain, especially by the limbic sys-
tem. Although it constitutes less than 1 percent of the human brain’s volume, the hypothala-
mus controls an amazing variety of motivated behaviors, ranging from heart rate to feeding
and sexual activity.
Hypothalamic Involvement in Hormone Secretions
A principal function of the hypothalamus is to control the pituitary gland, which is at-
tached to it by a stalk (Figure 12-12A). Figure 12-12B diagrams the anatomic location of the
hypothalamus in each hemisphere, with the thalamus above and the optic tracts just lateral.
We can divide the hypothalamus into three regions, lateral, medial, and periventricular,
illustrated in frontal view in Figure 12-12B. The lateral hypothalamus, composed both of nu-
clei and of nerve tracts running up and down the brain, connects the lower brainstem to the
forebrain. The principal tract, shown in Figure 12-13, is the medial forebrain bundle (MFB).
The MFB connects brainstem structures with various parts of the limbic system and
forms the activating projections that run from the brainstem to the basal ganglia and frontal
Section 6-4 elaborates on dopamine’s cortex. Fibers that ascend from the dopamine- and noradrenaline-containing cells of the
importance in experiences related to drug use. lower brainstem form a significant part of the MFB. The dopamine-containing MFB fibers
contribute to the control of many motivated behaviors, including eating and sex. They also
contribute to pathological behaviors, such as addiction and impulsivity.
Section 5-2 reviews the structures and Each hypothalamic nucleus is anatomically distinct, and most have multiple functions, in
functions of peptide neurotransmitters. part because the cells in each nucleus contain a different mix of peptide neurotransmitters.
Each peptide participates in different behaviors. For instance, transmitters in the cells in
the paraventricular nucleus may be vasopressin, oxytocin, or various combinations of other
peptides (such as enkephalin and neurotensin). When peptide neurotransmitters act, we may
12-4 • Neuroanatomy of Motivated and Emotional Behavior 413
(A) Preoptic Paraventricular Dorsomedial FIGUre 12-12 Nuclei and Regions
nucleus nucleus hypothalamic nucleus
of the Hypothalamus (A) Medial
view shows the relation between the
hypothalamic nuclei and the rest of the
brain. (B) Frontal view shows the relative
Posterior nucleus positions of the hypothalamus, thalamus,
and—in the midline between the left and
right hemispheres—the third ventricle.
Note the three principal hypothalamic
regions: periventricular, lateral, and medial.
Ventromedial
Hypothalamus hypothalamic nucleus
(B) Pituitary Pituitary
gland stalk
Third ventricle
Periventricular region
Lateral
hypothalamic region
Medial
hypothalamic region
Ventromedial
hypothalamic nucleus
Optic tract
experience a range of feelings such as well-being (endorphins) or attachment (oxytocin and nonregulatory behavior Behavior
vasopressin). For example, oxytocin is released during intimate moments such as nurturing unnecessary to the animal’s basic survival
behavior, hugging, or sex, and thus is sometimes known as the bonding hormone. needs.
The production of various neuropeptides hints at the special relation between the hypo- pituitary gland Endocrine gland attached to
thalamus and the pituitary. The pituitary consists of distinct anterior and posterior glands, as the bottom of the hypothalamus; its secretions
shown in Figure 12-14. The posterior pituitary is composed of neural tissue and is essentially control the activities of many other endocrine
a continuation of the hypothalamus. glands; associated with biological rhythms.
Neurons in the hypothalamus make peptides (e.g., oxytocin and vasopressin) that are medial forebrain bundle (MFB) Tract
transported down their axons to terminals lying in the posterior pituitary. If these neurons that connects brainstem structures with
become active, they send action potentials to the terminals to release the peptides stored various parts of the limbic system; forms
there. But rather than affecting another neuron, as occurs at most synapses, capillaries (tiny the activating projections that run from the
blood vessels) in the posterior pituitary’s rich vascular bed pick up these peptides. brainstem to basal ganglia and frontal cortex.
The peptides then enter the bloodstream,
which carries them to distant targets where they Basal ganglia Allocortex
exert their effects. Vasopressin, for example, af- Frontal Hypothalamus
fects water resorption by the kidneys, and oxytocin cortex
controls both uterine contractions and the ejec-
tion of milk by mammary glands in the breasts.
Peptides can have multiple functions, depending Medial Forebrain
FIGUre 12-13
on where their receptors are. Thus, oxytocin not Bundle The activating projections
only controls milk ejection in females but also per- that run from the brainstem to the
basal ganglia and frontal cortex
forms a more general role in several forms of affili- Temporal
lobe are major components of the
ative behavior, including parental care, grooming, MFB, a primary pathway for fibers
Medial
and sexual behavior in both men and women (Insel forebrain bundle connecting various parts of the
& Fernald, 2004). limbic system with the brainstem.
414 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
FIGUre 12-14 Hypothalamus 1 Hormones are synthesized 3 Releasing hormones are
and Pituitary Gland The here and sent to axon synthesized here and
Hypothalamus
anterior pituitary is connected terminals in the posterior secreted into capillaries that
to the hypothalamus by a system pituitary. carry them to the anterior
of blood vessels that carry pituitary.
hormones from the hypothalamus
to the pituitary. The posterior
pituitary receives input from
axons of hypothalamic neurons.
Both regions respond to
hypothalamic input by producing
Capillaries
hormones that travel in the Blood in
Pituitary
bloodstream to stimulate target gland
organs.
Blood in
Axon 2 Hormones released by
4 Releasing hormones then terminals
axon terminals in the
leave the capillaries and act posterior pituitary are picked
on hormone-secreting up by capillaries and carried
anterior pituitary cells. Anterior Posterior
pituitary pituitary into the bloodstream.
Blood out Blood out
(carrying posterior
pituitary hormones)
The glandular tissue of the anterior pituitary, by contrast, synthesizes various hormones.
The major hormones and their functions are listed in Table 12-1. The hypothalamus controls
the release of these anterior pituitary hormones by producing releasing hormones, peptides
that act to increase or decrease hormone release. Produced by hypothalamic cell bodies,
releasing hormones are secreted into capillaries that transport them to the anterior pituitary,
as Figure 12-14 shows.
taBLe 12-1 Major hormones Produced by the anterior Pituitary
hormone Function
Adrenocorticotrophic hormone (ACTH) Controls secretions of the adrenal cortex
Thyroid-stimulating hormone (TSH) Controls secretions of the thyroid gland
Follicle-stimulating hormone (FSH) Controls secretions of the gonads
Luteinizing hormone (LH) Controls secretions of the gonads
Prolactin Controls secretions of the mammary glands
Growth hormone (GH) Promotes growth throughout the body
A releasing hormone can either stimulate or inhibit the release of an anterior pituitary
hormone. For example, the anterior pituitary produces the hormone prolactin, but its release
is controlled by a prolactin-releasing factor and a prolactin release–inhibiting factor, both
synthesized in the hypothalamus. Hormone release by the anterior pituitary in turn provides
the brain a means for controlling what is taking place in many other parts of the body. Three
factors control hypothalamic hormone-related activity: feedback loops, neural regulation,
and experience-based responses.
FeeDBaCK LOOpS When the level of, say, thyroid hormone is low, the hypothalamus re-
releasing hormone Peptide released by the leases thyroid-stimulating hormone–releasing hormone (TSH-releasing hormone), which
hypothalamus that increases or decreases stimulates the anterior pituitary to release TSH. TSH then acts on the thyroid gland to
hormone release from the anterior pituitary. secrete more thyroid hormone.
12-4 • Neuroanatomy of Motivated and Emotional Behavior 415
(A) Feedback loop (B) Neural regulation FIGUre 12-15 Hypothalamic
(–) Controls (A) Releasing hormones
Hypothalamus Infant-related (+) (–)
from the hypothalamus stimulate the
Hypothalamus Anxiety
stimuli
Releasing anterior pituitary to release hormones. The
hormones (+) Oxytocin (–) pituitary hormones stimulate target organs,
release such as the thyroid and adrenal glands, to
(+)
release their hormones. In the feedback
Anterior Mammary glands
pituitary
loop, those hormones in turn influence the
Feedback
hypothalamus to decrease its secretion
Pituitary of the releasing hormones. (B) In the milk
hormones letdown response, oxytocin released from
(+) the hypothalamus stimulates the mammary
Milk letdown
Target glands to release milk. Milk letdown is
organs enhanced by infant-related stimuli and
inhibited by maternal anxiety.
Hormones
Receptors in the hypothalamus detect the thyroid hormone level. When that level rises,
the hypothalamus lessens its secretion of TSH-releasing hormone. This type of system is
essentially a form of homeostatic control that works as a feedback mechanism, a system
in which a neural or hormonal loop regulates the initiation of neural activity or hormone
release, as illustrated in Figure 12-15A.
The hypothalamus initiates a cascade of events that culminates in hormone secretion,
Thyroid
but it pays attention to how much hormone is released. When a certain level is reached, it gland
stops its hormone-stimulating signals. Thus, the feedback mechanism in the hypothalamus
maintains a fairly constant circulating level of certain hormones.
NeUraL CONtrOL Hormonal activities of the hypothalamus necessitate regulation by other
brain structures, such as the limbic system and the frontal lobes. Figure 12-15B diagrams this
neural control in relation to the effects of oxytocin released from the hypothalamus by the
paraventricular nucleus, which lies within the periventricular region illustrated in Figure 12-12.
As stated earlier, one function of oxytocin is to stimulate cells of the mammary glands to
release milk. As shown in Figure 12-15B, when an infant suckles the breast, the tactile stimu-
lation causes hypothalamic cells to release oxytocin, which stimulates milk letdown. In this
way, the oxytocin cells participate in a fairly simple reflex that is both neural and hormonal.
Other stimuli can influence oxytocin release, however, which is where control by other
brain structures comes in. For example, the sight, sound, or even thought of her baby can
trigger a lactating mother to eject milk. Conversely, as diagrammed in Figure 12-15B, feelings
of anxiety in a lactating woman can inhibit milk ejection. These excitatory and inhibitory
influences exerted by cognitive activity imply that the cortex can influence neurons in the
periventricular region. It is likely that projections from the frontal lobes to the hypothalamus
perform this role.
eXperIeNtIaL reSpONSeS A third control on the hormonal activities of the hypothala-
mus is the brain’s responses to experience: neurons in the hypothalamus undergo structural Recall the principle of neuroplasticity from
and biochemical changes just as cells in other brain regions do. In other words, hypothalamic Section 2-6.
neurons are like neurons elsewhere in the brain in that they can be changed by heavy de-
mands on them.
Such changes in hypothalamic neurons can affect hormone output. For instance, when
a woman is lactating, the cells producing oxytocin increase in size to promote oxytocin
release and meet the increasing demands of a growing infant for more milk. Through
this control, which is mediated by experience, a mother provides her baby with sufficient
milk over time.
416 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
In the absence of Stimulation
stimulation, the animal wire When stimulated, the The animal stops digging
sits quietly. animal digs vigorously. when stimulation stops.
FIGUre 12-16 Generating Behavior When rats receive electrical stimulation to the
hypothalamus, they produce goal-directed behaviors. This rat is stimulated to dig when and
only when the electricity is on. If the sawdust is removed (not shown), there is no digging.
hippocampus From the Greek word for
Hypothalamic Involvement in Generating Behavior
seahorse; distinctive allocortical structure Not only does the hypothalamus control hormone systems, it is also central in generating be-
lying in the medial temporal lobe; participates havior. This function was first demonstrated by studies in which stimulating electrodes were
in species-specific behaviors, memory, and placed in the hypothalamus of various animals, ranging from chickens to rats and cats. When
spatial navigation and is vulnerable to the a small electric current was delivered through a wire electrode, an animal suddenly engaged
effects of stress. in some complex behavior—eating, drinking, or digging; displaying fear, attack, predatory,
or reproductive behavior. Which behavior depended on which site was stimulated. All the
behaviors were smooth, well integrated, and indistinguishable from typically occurring ones.
Furthermore, all were goal directed.
The onset and termination of these behaviors depended entirely on hypothalamic stimu-
lation. For example, if an electrode in a certain location elicited feeding behavior, the animal
ate as soon as the stimulation was turned on and continued to eat until the stimulation was
turned off. If the food was removed, however, the animal would not eat but might engage
in other behaviors, such as drinking. Recall that Roger, profiled in Section 12-1, ate con-
tinuously if foodlike materials were present, corresponding to the continuous hypothalamic
activity caused by a tumor.
Figure 12-16 illustrates the effect of stimulation at a site that elicits digging. When no
current is delivered, the animal sits quietly. When the current is turned on, the animal vig-
orously digs in the sawdust; when the current is turned off, the animal stops digging. If the
sawdust is removed, it does not dig.
Two more important characteristics of behaviors generated by hypothalamic stimulation are
related to (1) survival and (2) reward. Animals apparently find the stimulation of these behaviors
pleasant, as suggested by the fact that they willingly expend effort, such as pressing a bar, to
trigger the stimulation. Recall that cats kill birds and mice because the act of stalking and kill-
ing prey is rewarding to them. Similarly, we can hypothesize that animals eat because eating is
rewarding, drink because drinking is rewarding, and mate because mating is rewarding.
Organizing Function of the Limbic Circuit
We now turn our attention to parts of the brain that interact with the hypothalamus in gen-
erating motivated and emotional behaviors. These brain structures evolved as a ring around
The limbic circuit derives its name from the the brainstem in early amphibians and reptiles. Nearly 150 years ago, Paul Broca, impressed
Latin limbus, meaning border. by this evolutionary development, called these structures the limbic lobe.
Known collectively as the limbic system today, these structures are formed from a primi-
tive three-layered cortex known as allocortex, which lies adjacent to the six-layered neocortex.
Allocortex is found in the brain of mammals In mammals, the allocortex encompasses the cingulate (meaning girdle) gyrus and the hip-
and other chordates, especially birds and pocampal formation, as shown in Figure 12-17. The hippocampal formation includes the hip-
reptiles. pocampus—a cortical structure important in species-specific behaviors, memory, and spatial
navigation and vulnerable to the effects of stress—and the parahippocampal cortex adjacent to it.
12-4 • Neuroanatomy of Motivated and Emotional Behavior 417
FIGUre 12-17 Limbic Lobe Encircling the
Cingulate gyrus brainstem, the limbic lobe as described by
Broca consists of the cingulate gyrus and
Corpus callosum hippocampal formation (the hippocampus
Anterior
Fornix and parahippocampal cortex), the
nucleus of
dorsal amygdala, the mammillothalamic tract, and
thalamus the anterior thalamus.
Mammillo-
Prefrontal Basal thalamic
cortex forebrain
nuclei tract
Mammillary
Temporal body
Olfactory
lobe
bulb
Amygdala Hippocampus Hippocampal
Parahippocampal cortex formation
Organization of the Limbic Circuit
As anatomists began to study the limbic structures, connections to the hypothalamus became
evident. It also became apparent that the limbic system has a role in emotion. For instance, in
the 1930s, James Papez observed that people with rabies display radically abnormal emotional be-
havior, and postmortem examinations showed that the rabies (C)
(A)
had selectively attacked the hippocampus. (Definitive proof of Sensory association Limbic Frontal
Cingulate cortex system lobes
rabies remains postmortem hippocampal examination.) cortex Anterior
Papez concluded from his observations that the limbic thalamus
lobe and associated subcortical structures provide the neu- Hypothalamus
ral basis of emotion. He proposed a neural circuit, traced
in Figure 12-18A, now known as the Papez circuit, whereby
emotion could reach consciousness, presumed at that time Hypothalamus
to reside in the cerebral cortex. In 1949, Paul MacLean ex- Prefrontal
cortex
panded Papez’s concept of the limbic circuit to include the Mammillary Emotional and
amygdala and prefrontal cortex. Figures 12-17 and 12-18A Amygdala Hippocampal nucleus motivated behavior
formation
show the amygdala lying adjacent to the hippocampus in the
temporal lobe, with the prefrontal cortex lying just anterior. (B)
Figure 12-18B charts the limbic circuit schematically.
Prefrontal Sensory
The hippocampus, amygdala, and prefrontal cortex all association
cortex
connect with the hypothalamus. The mammillary nucleus cortex
of the hypothalamus connects to the anterior thalamus,
which in turn connects with the cingulate cortex. The cin-
gulate cortex completes the circuit by connecting with the Cingulate
cortex FIGUre 12-18 Limbic
hippocampal formation, amygdala, and prefrontal cortex. Amygdala System (A) In this
This anatomical arrangement can be compared to the fun- contemporary conception
nel in Figure 12-18C, which shows the hypothalamus as the
Hippocampal of the limbic system, an
spout leading to motivated and emotional behavior. formation interconnected network of
Anterior
There is now little doubt that most limbic system thalamus structures—the Papez circuit—
controls emotional expression.
structures, especially the amygdala and hypothalamus,
(B) A schematic representation,
take part in emotional behaviors, as detailed later in this Mammillary coded to brain areas shown in
section. But most limbic structures perform important nucleus part A by color, charts the limbic
roles in various motivated behaviors as well, especially in system’s major connections.
Hypothalamus
motivating species-typical behaviors such as feeding and (c) A reminder that parts A
sexual activity. The critical structures for such motivated and B can be conceptualized as
part of a funnel rim of outputs
behaviors, as well as for emotion, are the hypothalamus, Behavior that, through the hypothalamus,
which we have already considered, and the amygdala, to produce emotional and
which we turn now. motivated behavior.
418 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Amygdala
Named for the Greek word for almond because of its shape, the amygdala consists of three
principal subdivisions, the corticomedial area, the basolateral area, and the central area.
Like the hypothalamus, the amygdala receives inputs from all sensory systems. But in con-
trast with the hypothalamic neurons, more complex stimuli are necessary to excite amyg-
dalar neurons. Indeed, many amygdalar neurons are multimodal: they respond to more
than one sensory modality. In fact, some respond to the entire sensory array: sight, sound,
Section 15-3 elaborates on multisensory touch, taste, and smell. These amygdalar cells must shape a rather complex image of the
integration and the binding problem. sensory world.
The amygdala sends connections primarily to the hypothalamus and the brainstem,
where it influences neural activity associated with emotions and species-typical behavior. For
example, when the amygdala of a person with epilepsy is electrically stimulated before brain
surgery, the person becomes fearful and anxious. We observed a woman who responded with
increased respiration and heart rate, saying that she felt as if something bad was going to
happen, although she could not specify what.
Amygdala stimulation can also induce eating and drinking. We observed a man who drank
amygdala Almond-shaped collection of water every time the stimulation was turned on. (There happened to be a pitcher of water on
nuclei in the limbic system; plays a role in the table next to him.) Within 20 minutes, he had consumed about 2 liters of water. When
emotional and species-typical behaviors. asked if he was thirsty, he said, “No, not really. I just feel like drinking.”
prefrontal cortex (PFc) Extensive frontal The amygdala’s role in eating can be seen in patients with amygdalar lesions. Like Roger
lobe area anterior to the motor and premotor as a result of his tumor, many of these patients lose discrimination in their food choices,
cortex; key to controlling executive functions eating foods that were formerly unpalatable to them. Lesions of the amygdala may also give
such as planning. rise to hypersexuality.
Executive Function of the Frontal Lobes
The amygdala is intimately connected to the functioning of the frontal lobes that constitute
Figure 11-2 charts the hierarchy of frontal all cortical tissue anterior to the central sulcus. This large area is made up of several function-
lobe regions with regard to movement. ally distinct regions mapped in Figure 12-19A.
The motor cortex controls fine movements, especially of the fingers, hands, toes, feet,
tongue, and face. The premotor cortex participates in selecting appropriate movement se-
quences. For instance, a resting dog may get up in response to its owner’s call, which serves
as an environmental cue for a series of movements processed by one region of the premotor
cortex. Or a dog may get up for no apparent reason and wander about the yard, a sequence
of actions in response to an internal cue processed by a different premotor region.
FIGUre 12-19 Gross Subdivisions of
the Frontal Lobe and Prefrontal
Cortex
(A) Lateral view (B) Ventral view (C) Medial view
Dorsolateral Premotor Motor Central Ventromedial Orbitofrontal
prefrontal cortex cortex sulcus prefrontal cortex cortex
cortex
Dorsomedial
prefrontal
cortex
Prefrontal
cortex Anterior
cingulate
cortex
Ventromedial
prefrontal cortex
Orbitofrontal
cortex
12-4 • Neuroanatomy of Motivated and Emotional Behavior 419
Prefrontal Anatomy and Connections
As shown in Figure 12-19A, the prefrontal cortex (PFC) is anterior to the premotor cor- Prefrontal literally means in front of the front.
tex. The PFC is key to controlling executive functions such as planning movements. Its
three primary areas are the dorsolateral region; the orbitofrontal cortex (OFC), also shown
from a ventral aspect in Figure 12-19B; and the ventromedial PFC. The anterior cingulate
cortex (ACC), shown in Figure 12-19C, is closely associated with the PFC, although not
strictly part of it.
The prefrontal cortex contributes to specifying the goals toward which movement should
be directed. It controls the processes by which we select movements appropriate to the We focus here on the PFC and motivation and
particular time and context. This selection may be cued by internal information, such as emotion. In Section 15-2 we turn to the PFC
memory and emotion, or it may be made in response to context (environmental information). and cognition.
Like the amygdala, the frontal lobes receive highly processed information from all sensory
areas, and many neurons in the prefrontal cortex, like those in the amygdala, are multimodal.
As shown in Figure 12-20, the prefrontal cortex receives input via connections from the
amygdala, dorsomedial thalamus, sensory association cortex, posterior parietal cortex, and
the dopaminergic cells of the ventral tegmental area.
Dopaminergic input is important for regulating how prefrontal neurons react to stimuli,
including emotional ones. Abnormalities in this dopaminergic projection may account for
some disorders, including schizophrenia, in which people evince little emotional reaction to Section 16-4 elaborates on the causes of and
typically arousing stimuli. treatments for schizophrenia.
Figure 12-20 also shows the areas to which the prefrontal cortex sends connections—its
output. The inferior prefrontal region projects axons to the amygdala and the hypothalamus
in particular. These PFC axons provide a route for influencing the ANS and ENS, which
control changes in blood pressure, respiration, and other internal processes. The dorsolateral PFC output influences movement
prefrontal region sends its connections primarily to the sensory association cortex, posterior (Section 11-1), memory (Section 14-3), and
parietal cortex, cingulate cortex, basal ganglia, and premotor cortex. cognition (Section 15-2).
Prefrontal Functions
The prefrontal cortex takes part in selecting behaviors appropriate to the particular time and
place. Selection may be cued by internal information or made in response to the environmental
context. Disruption to this selection function can be seen in people with injury to the dorsolat-
eral frontal lobe (see Figure 12-19A). They become overly dependent on environmental cues to
determine their behavior. Like small children, they can be easily distracted by what they see or
hear. We have all experienced a loss of concentration to some extent, but for a patient with fron-
tal lobe damage, the problem is exaggerated and persistent. Because the person becomes so ab-
sorbed in irrelevant stimuli, he or she cannot act on internalized information most of the time.
Dorsomedial Sensory association Ventral tegmental
thalamus cortex area (dopamine)
Inputs to Outputs from
prefrontal cortex prefrontal cortex
Prefrontal
cortex
Posterior
Amygdala Premotor Basal parietal
cortex ganglia cortex
FIGUre 12-20 Prefrontal Connections At left, the PFC receives
inputs (red arrows) and sends outputs (blue arrows) to the areas Hypothalamus Cingulate
cortex
charted on the right.
420 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
A good example is J. C., in whom bilateral damage to the dorsolateral prefrontal cortex
resulted from having a tumor removed. J. C. would lie in bed most of the day fixated on
television programs. He was aware of his wife’s opinion of this behavior, but only the sound
of the garage door opening when she returned home from work in the evening would stimu-
late him into action. Getting out of bed was controlled by this specific environmental cue;
without it, he seemed to lack motivation. Television completely distracted him from acting
on internal knowledge of things that he could or should do.
Adapting behavior appropriately to the environmental context also is a PFC function.
Most people readily change their behavior to match the situation at hand. We behave one
way with our parents, another with our friends, another with our children, and yet another
with our coworkers. Each set of people constitutes a different context, and we shift our be-
haviors accordingly. Our tone of voice, our use of slang or profanity, and the content of our
conversations are quite different in different contexts.
Even among our peers we act differently, depending on who is present. We may be relaxed
in the presence of some people and ill at ease with others. It is therefore no accident that the
size of the frontal lobes is related to species’ sociability. Social behavior is extremely rich in
contextual information, and humans are highly social animals.
Controlling behavior in context requires detailed sensory information, which is conveyed from
Focus 1-1 and Section 1-2 recount behavioral all sensory regions to the frontal lobes. This sensory input includes not only information from the
effects of TBI; Section 14-5 details recovery; external world but also internal information from the ANS. People with damage to the orbital pre-
Section 16-3 explores TBI symptoms and frontal cortex, as is common in traumatic brain injuries, have difficulty adapting their behavior to
treatments. the context, especially the social context. Consequently, they often make social gaffes.
In summary, the role of the frontal lobes in selecting behaviors is important for con-
sidering what causes behavior. The frontal lobes act much like a composer, but instead of
selecting notes and instruments, they select our actions. Not surprisingly, the frontal lobes
Section 15-2 considers the frontal lobes and are sometimes described as housing the brain’s executive functions. To grasp the full extent
the executive function of planning. of frontal lobe control of behavior, see Clinical Focus 12-2, Agenesis of the Frontal Lobe.
CliniCAl F cus 12-2
Agenesis of the Frontal Lobes
The role of the frontal lobes in motivated behavior is perhaps best under- Perhaps as a result, not until he was 19 years old was J. P.’s
stood by looking at J. P.’s case, described in detail by Stafford Ackerly true condition detected. To prevent him from serving a prison term
(1964). Born in December 1914, J. P. was a problem child. Early on, he for repeated automobile theft, a lawyer suggested that J. P. undergo
became a wanderer. Policemen would find him miles from home, as he psychiatric evaluation. The psychiatrist who examined him ordered an
had no fear of being lost. Severe whippings by his father did not deter him. X-ray (the only brain scan available at the time). The image revealed
J. P.’s behavioral problems continued and expanded as he grew older, that J. P. lacked a right frontal lobe, and his left frontal lobe was about
and by adolescence, he was constantly in trouble. Yet J. P. also had 50 percent of normal size. It is almost certain that his frontal lobes
a good side. When he started school, his first-grade teacher was so simply failed to develop.
impressed with his polite manners that she began writing a letter to his Failure of a structure to develop is known as agenesis; J. P.’s condition
parents to compliment them on having such a well-mannered child who was agenesis of the frontal lobes. His case offers an unusual opportunity
was such a good influence in the class. to study the role of the frontal lobes in motivated behavior.
As she was composing the letter, she looked up to find J. P. exposing Clearly, J. P. lacked the bag of mental tricks that most people use
himself to the class and masturbating. This juxtaposition of polite man- to come to terms with the world. Normally behavior is affected both by
ners and odd behavior characterized J. P.’s conduct throughout his life. its past consequences and by current environmental input. J. P. did not
At one moment he was charming; at the next he was engaged in socially seem much influenced by either factor. As a result, the world was simply
unacceptable behavior. too much for him. He always acted childlike and was unable to formulate
J. P. developed no close friendships with people of either sex, in large plans or to inhibit many of his behaviors. He acted on impulse. At home,
part because of his repeated incidents of public masturbation, steal- he was prone to aggressive outbursts about small matters, especially
ing, excessive boastfulness, and wandering. He was a person of aver- with regard to his mother.
age intelligence who seemed unaffected by the consequences of his Curiously, J. P. seemed completely unaware of his life situation. Even
behavior. Police officers, teachers, and neighbors all ascribed intention to though the rest of his brain was working fairly well—his IQ score was
J. P.’s behavior: all believed that he was willfully misbehaving and blamed in the normal range, and his language skills were very good—the rest
his parents for not enforcing sufficiently strict discipline. of his brain was unable to compensate for the absence of frontal lobes.
12-4 • Neuroanatomy of Motivated and Emotional Behavior 421
Stimulating and Expressing Emotion
Emotion, like motivation, is intangible: it is an inferred state. But the importance of
emotion to our everyday lives is hard to exaggerate. Emotion can motivate us. It in- Spinal cord
spires artistic expression, for example, from poetry to filmmaking to painting. Many
people enjoy the arts simply because they evoke emotions. And while people find
certain emotions pleasant, severe and prolonged negative emotions, especially anxiety Increase
0.6
and depression, can cause clinical disorders.
To explore neural control of emotions, we must first specify the types of behav- 0.4
Change in emotionality subsequent to spinal cord lesion
ior we want to explain. Think of any significant emotional experience you’ve had 0.2
recently. Perhaps you had a serious disagreement with a close friend. Maybe you
0
just got engaged to be married.
A common characteristic of such experiences includes autonomic responses such –0.2
as rapid breathing, sweating, and dry mouth. Emotions may also entail strong sub- –0.4
jective feelings that we label as anger, fear, or love, among others. Finally, emotions
–0.6
typically entail thoughts or plans related to the experience itself and may take the
form of replaying conversations and events in your mind, anticipating what you might –0.8
say or do under similar circumstances in the future or in planning your married life. –1.0
These three forms of emotional experience suggest the influence of different neural –1.2
systems. The autonomic component must include the hypothalamus and associated
–1.4
structures, as well as the enteric nervous system. The components of subjective feelings Anger
are more difficult to localize but clearly include the amygdala and probably parts of the –1.6
frontal lobes. And thoughts and plans are likely to be cortical. What is the relation be- –1.8
tween our cognitive experience of an emotion and the associated physiological changes? Fear
–2.0
One view is that physiological changes (such as trembling and rapid heartbeat)
come first, and the brain then interprets these changes as an emotion. This perspec- Decrease
Sacral Lumbar Low High Cervical
tive implies that the brain (most likely the cortex) produces a cognitive response to (low) thoracic thoracic (high)
autonomic information. That response varies with the context in which the autonomic Location of lesion in spinal cord
arousal occurs, including the effects on the gut via the ENS. In cases of extreme auto-
FIGUre 12-21 Losing Emotion Spinal
nomic activity, serotonin release surges in the gut, which can lead to diarrhea and cramp- cord injury blunts the emotional
ing. If we are frightened by a movie, we feel a weaker, shorter-lived emotion than if we are experience. Loss of emotionality is
frightened by a real-life encounter with a gang of muggers. Variations of this perspective greatest when the lesion is high on the
have gone by many terms, beginning with the James–Lange theory, named for its origina- spine. Information from J. Beatty (1995). Principles of
Behavioral Neuroscience (p. 339). Dubuque, IA: Brown &
tors, but all assume that the brain concocts a story to explain bodily reactions.
Benchmark.
Two lines of evidence support the James–Lange theory and similar points of view. One is
that the same autonomic responses can accompany different emotions. That is, particular
emotions are not tied to unique autonomic changes. This line of evidence leaves room for
interpreting what a particular pattern of arousal means, even though particular physiologi-
cal changes may suggest only a limited range of possibilities. The physiological changes
experienced during fear and happiness are unlikely to be confused.
The second line of evidence supporting the view that physiological changes are the start-
ing point for emotions comes from people with reduced information about their own auto-
nomic arousal, for example, owing to spinal cord injury. Spinal injury results in a decrease in After Christopher Reeve’s spinal cord was
perceived emotion, and its severity depends on how much sensory input is lost. Figure 12-21 severed at the cervical level (high), his
illustrates this relation. People with the greatest loss of sensory input, which occurs with emotions may have been blunted, but his
injuries at the uppermost end of the spinal cord, also have the greatest loss of emotional motivation clearly remained intact. See
intensity. In contrast, people with low spinal injuries retain most of their visceral input and Section 11-1.
have essentially typical emotional reactions.
Antonio Damasio (1999) emphasized an important additional aspect of the link between
emotional and cognitive factors in his somatic marker hypothesis. When Damasio studied somatic marker hypothesis Proposal that
patients with frontal lobe injuries, he was struck by how they could be highly rational in marker signals arising from emotions and
analyzing the world yet still make decidedly irrational social and personal decisions. The feelings act to guide behavior and decision
explanation, he argued, is that the neural machinery underlying emotion no longer affects making, usually in an unconscious process.
422 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
the reasoning of people with frontal lobe injury, either consciously or unconsciously. Cut off
from critical emotional input, many social and personal decisions suffer.
To account for these observations, Damasio proposed that emotions are responses in-
duced by either internal or external stimuli not normally attended to consciously. For exam-
The grizzly bear attack recounted in ple, if you encounter a bear as you walk down the street (presuming that you live in a place
Section 11-4 confirms the primacy of where this event could take place), the stimulus is processed rapidly without conscious ap-
emotion—fear—over other factors, praisal. In other words, a sensory representation of the bear in the visual cortex is transmit-
including pain. ted directly to brain structures, such as the amygdala, that initiate an emotional response.
This emotional response includes actions on structures in the forebrain and brainstem
and ultimately on the ANS. The amygdala has connections to the frontal lobes, so the emo-
tional response can influence the frontal lobes’ appraisal. But if the frontal lobes are injured,
emotional information is excluded from cognitive processing, so the quality of emotion-
related appraisals suffers, and the response to the bear might be inappropriate.
To summarize, Damasio’s somatic marker hypothesis proposes how emotions are nor-
mally linked to a person’s thoughts, decisions, and actions. In a typical emotional state,
certain brain regions send messages to many other brain areas and to most of the rest of the
body through hormones and the ANS. These messages produce a global change in the organ-
ism’s state, and the altered state influences behavior, often unconsciously.
Amygdala and Emotional Behavior
In addition to controlling certain species-typical behaviors, described earlier, the amygdala
influences emotion (Davis et al., 2003). Its role can be seen most clearly in monkeys whose
amygdala has been removed. In 1939, Heinrich Klüver and Paul Bucy reported an extraordi-
nary result, now known as Klüver–Bucy syndrome, that followed removal of the amygdala
and anterior temporal cortex of monkeys. The principal symptoms included the following:
1. Tameness and loss of fear
2. Indiscriminate dietary behavior (eating many types of formerly rejected foods)
3. Greatly increased autoerotic, homosexual, and heterosexual activity with inappropriate
object choice (e.g., the sexual mounting of chairs)
4. Tendency to attend to and react to every visual stimulus
5. Tendency to examine all objects by mouth
Section 9-4 describes varieties of visual form 6. Visual agnosia, an inability to recognize objects or drawings of objects
agnosia in a range of case studies.
Visual agnosia results from damage to the ventral visual stream in the temporal lobe, but
the other symptoms are related to the amygdalectomy. Tameness and loss of fear are espe-
cially striking. Monkeys that normally show a strong aversion to stimuli such as snakes show
no fear of them whatsoever. In fact, amygdalectomized monkeys may pick up live snakes and
even put them in their mouth.
Although Klüver–Bucy syndrome is not common in humans—because bilateral temporal
Focus 2-2 examines some causes and lobectomies are rare—its symptoms can be seen in people with certain forms of encephalitis,
symptoms of encephalitis. a brain infection. In some cases, encephalitis centered on the base of the brain can damage
both temporal lobes and produce many Klüver–Bucy symptoms, including especially indis-
criminate sexual behavior and the tendency to examine objects by mouth.
The amygdala’s role in Klüver–Bucy syndrome points to its central role in emotion. So
does its electrical stimulation, which produces an autonomic response (such as increased
blood pressure and arousal) as well as a feeling of fear. Fear produced by the brain in the
Throughout human history, exploiting fear absence of an obvious threat may seem odd, but fear is basic to species’ survival. To improve
has proved especially effective in controlling their chances of surviving, most organisms using fear as a stimulus minimize their contact
group behavior. with dangerous animals, objects, and places and maximize their contact with safe things.
Awareness of danger and of safety has both an innate and a learned component, as Joe
LeDoux (1996) emphasized. The innate component, much as in the IRMs described in
12-4 • Neuroanatomy of Motivated and Emotional Behavior 423
Section 12-3, is the automatic processing of species-relevant sensory information—inputs from
Klüver–Bucy syndrome Behavioral
the visual, auditory, and olfactory systems. The importance of olfactory inputs is not obvious
syndrome, characterized especially by
to us humans. Our senses are dominated by vision. But olfactory information connects directly
hypersexuality, that results from bilateral
to the amygdala in the human brain (see Figure 12-17). For many other animals, olfactory cues
injury to the temporal lobe.
predominate.
psychosurgery Any neurosurgical technique
A rat that has never encountered a ferret thus shows an immediate fear response to the
intended to alter behavior.
odor of ferret. Other novel odors (such as peppermint or coffee) do not produce an innate
fear reaction. The innate response triggers in the rat an autonomic activation that stimulates
conscious awareness of danger.
In contrast, the learned component of fear consists of the avoidance of specific animals,
places, and objects that the organism has come to associate with danger. The organism is
not born with this avoidance behavior prewired. In a similar way, animals learn to increase
contact with environmental stimuli that they associate with positive outcomes, such as food
or sexual activity or, in the laboratory, drugs. Damage to the amygdala interferes with all
these behaviors. The animal loses not only its innate fears but also its acquired fears of and
preferences for certain environmental stimuli.
To summarize, a species’ survival requires a functioning amygdala. It influences auto-
nomic and hormonal responses through its connections to the hypothalamus. It influences
our conscious awareness of the positive and negative consequences of events and objects
through its connections to the prefrontal cortex.
Prefrontal Cortex and Emotional Behavior
At about the same time that Klüver and Bucy began studying their monkeys, Carlyle Jacob-
sen was studying the effects of frontal lobotomy on the cognitive capacities of two chimpan-
zees. A frontal lobotomy destroys substantial brain tissue as the result of inserting a sharp
instrument into the frontal lobes and moving it back and forth.
In 1936, Jacobsen reported that one of the chimps was particularly neurotic before being
subjected to this procedure. It became more relaxed afterward. Incredibly, a leading Por-
tuguese neurologist of the time, Egas Moniz, seized on this observation as a treatment for
behavioral disorders in humans, and the frontal lobotomy, illustrated in Figure 12-22, was
initiated as the first technique of psychosurgery, or neurosurgery intended to alter behavior.
The use of psychosurgery grew rapidly in the 1950s. In North America alone, nearly
40,000 people received frontal lobotomies as a treatment for psychiatric disorders. Not until
the 1960s was any systematic research conducted into the effects of frontal lesions on social
and emotional behavior. By this time, the frontal lobotomy had virtually vanished as a “treat-
ment.” We now know that prefrontal lesions in various species, including humans, severely
affect social and emotional behavior.
Agnes is a case in point. We met Agnes at the psychiatric hospital where we met Roger
(whose indiscriminate eating we described in Section 12-1). At the time, Agnes, a 57-year-old
woman, was visiting one of the nurses. She had, however, once been a patient.
The first thing we noticed about Agnes was that she exhibited no outward sign of emotion.
She showed virtually no facial expression. Agnes had been subjected to a procedure known
as a frontal leukotomy because her husband, an oil tycoon, felt that she was too gregarious.
Evidently, he felt that her “loose lips” were a detriment to his business dealings. He convinced
two psychiatrists that she would benefit from psychosurgery, and her life was changed forever.
To perform a leukotomy, as illustrated in Figure 12-22, a surgeon uses a special knife
called a leukotome to sever the connections of a region of the orbitofrontal cortex (see Figure Transorbital
FIGUre 12-22
12-19). In our conversations with Agnes, we quickly discovered her considerable insight into
Leukotomy In this procedure, a
leukotome is inserted through the bone
the changes brought about by the leukotomy. In particular, she indicated that she no longer of the eye socket to disconnect the
had any feelings about things or most people, although, curiously, she was attached to her orbitofrontal cortex from the rest of
dog. She said that she often just felt empty and much like a zombie. the brain.
424 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Agnes’s only moment of real happiness in the 30 years since her operation was the sud-
den death of her husband, whom she blamed for ruining her life. Unfortunately, Agnes had
squandered her dead husband’s considerable wealth as a consequence of her inability to plan
or organize. This inability, we have seen, is another symptom of prefrontal injury.
The orbitofrontal area has direct connections with the amygdala and hypothalamus. Its
stimulation can produce autonomic responses, and as we saw in Agnes, damage to the orbital
region can produce severe personality change characterized by apathy and loss of initiative
or drive. The orbital cortex is probably responsible for the conscious awareness of emotional
states produced by the rest of the limbic system, especially the amygdala.
Agnes’s loss of facial expression is also typical of frontal lobe damage. In fact, people with
ASD is the topic of Focus 8-2; schizophrenia, frontal lobe injuries and people who have schizophrenia or autism spectrum disorder are
of Focus 8-5. usually impaired at both producing and perceiving facial expressions, including a wide range
of expressions found in all human cultures—happiness, sadness, fear, anger, disgust, and
surprise. As with J. P.’s frontal lobe agenesis, described in Clinical Focus 12-2, it is difficult to
imagine how such people can function effectively in our highly social world without being
able to express their own emotions or to recognize others’.
Although facial expression is a key to recognizing emotion, so is tone of voice, or prosody.
Patients with damage to the frontal lobe are devoid of prosody, both in their own conversa-
tions and in understanding the prosody of others. The lost ability to comprehend or produce
emotional expression in both faces and language partly explains those patients’ apathy. In
some ways, they are similar to spinal cord patients who have lost autonomic feedback and so
can no longer feel the arousal associated with emotion. These patients can no longer either
read emotion in other people’s faces and voices or express it in their own.
Some psychologists have proposed that our own facial expressions provide us with impor-
tant clues to what we are feeling. This idea has been demonstrated in experiments reviewed
by Pamela Adelmann and Robert Zajonc (1989). In one such study, people were required to
contract their facial muscles by following instructions about which parts of the face to move.
Unbeknown to the participants, the movements produced happy and angry expressions.
Afterward, they viewed a series of slides and reported how the slides made them feel.
They said that they felt happier when they were inadvertently making a happy face and
angrier when making the angry face. Patients with frontal lobe damage presumably have no
such feedback from their own facial expressions, which could contribute to their emotional
experiences being dampened.
Emotional Disorders
Major depression, a highly disruptive emotional disorder, is characterized by some or all the
Major depression, detailed in Focus 6-3,
is among the most treatable psychological following: prolonged feelings of worthlessness and guilt, the disruption of normal eating
disorders. Cognitive and intrapersonal habits, sleep disturbances, a general slowing of behavior, and frequent thoughts of suicide. A
therapies are as effective as drugs. See depressed person feels severely despondent for a long time. Major depression is common in
Section 16-4. our modern world, with a prevalence of about 6 percent of the population at any given time.
Depression has a genetic component. It not only runs in families but also frequently tends
to occur in both members of a pair of identical twins. The genetic component in depression
generalized anxiety disorder Persistently implies a biological abnormality, but the cause remains unknown. However, neuroscience
high levels of anxiety often accompanied by researchers’ interest in the role of epigenetic changes in depression is increasing. One hy-
maladaptive behaviors to reduce anxiety; pothesis is that early life stress may produce epigenetic changes in the prefrontal cortex (see
thought to be caused by chronic stress. the review by Schroeder et al., 2010).
phobia Fear of a clearly defined object or Excessive anxiety is an even more common emotional problem than depression. Anxiety
situation. disorders, including posttraumatic stress disorder (PTSD), phobias, generalized anxiety disorder,
panic disorder Recurrent attacks of intense panic disorder, and obsessive-compulsive disorder (OCD), are estimated to affect 15 percent to
terror that come on without warning and 35 percent of the population. As described in Clinical Focus 12-3, Anxiety Disorders, symptoms
without any apparent relation to external include persistent fears and worries in the absence of any direct threat, usually accompanied by
circumstances. various physiological stress reactions, such as rapid heartbeat, nausea, and breathing difficulty.
12-4 • Neuroanatomy of Motivated and Emotional Behavior 425
CliniCAl F cus 12-3
Anxiety Disorders
Animals typically become anxious at times, especially when they are in Freud believed that anxiety disorders are psychological in origin and
obvious danger. But anxiety disorders are different. They are characterized treatable with talking therapies in which people confront their fears. Today,
by intense feelings of fear or anxiety inappropriate for the circumstances. cognitive-behavioral therapies serve this purpose, as shown in the accom-
People with an anxiety disorder have persistent and unrealistic worries panying photo. More recently, a behavioral therapy called mindfulness, a form
about impending misfortune. They also tend to have multiple physical of meditation is proving effective in treating anxiety disorders. Its effective-
symptoms attributable to hyperactivity of the sympathetic nervous system. ness is correlated with suppressed activity in the anterior cingulate region
G. B.’s case is a good example. He was a 36-year-old man with two (Garrison et al., 2015). The effect is greater in trained as opposed to novice
college degrees who began to have severe spells initially diagnosed as a meditators, which supports the value of mindfulness training programs.
heart condition. He would begin to breathe heavily, sweat, develop heart Pharmacologically, anxiety disorders are most effectively treated with
palpitations, and sometimes feel pains in his chest and arms. During these benzodiazepines such as diazepam (Valium), the best known. Alprazolam
attacks, he was unable to communicate coherently and would lie helpless (Xanax) is the most commonly prescribed drug for panic attacks. Benzo-
on the floor until an ambulance arrived to take him to an emergency room. diazepines act by augmenting GABA’s inhibitory effect and are believed
Extensive medical testing and multiple attacks over about 2 years to exert a major influence on neurons in the amygdala.
eventually led to the diagnosis of generalized anxiety disorder. Like Whether treatments are behavioral, pharmacological, or both, the
most of the 5 percent of the U.S. population who have an anxiety dis- general goal is normalizing brain activity in the limbic system.
order at some point in their life, G. B. was unaware that he was overly
anxious. The cause of generalized anxiety is difficult to pinpoint, but one
likely explanation is related to the cumulative effect of general stress.
Although G. B. appeared outwardly calm most of the time, he had
been a prodemocracy activist in communist Poland, a dangerous position.
Because of the dangers, he and his family eventually escaped from Poland
to Turkey, and from there they went to Canada. G. B. may have had con-
tinuing worries about the repercussions of his political activities—worries
(and stress) that eventually found expression in generalized anxiety attacks.
The most common and least disabling type of anxiety disorders are
phobias. A phobia pertains to a clearly defined, dreaded object (such
as spiders or snakes) or situation (such as enclosed spaces or crowds).
Most people have a mild aversion to some types of stimuli. Such aver-
sion becomes a phobia only when a person’s feelings about a disliked
stimulus lead to overwhelming fear and anxiety.
The incidence of disabling, that is, serious enough to interfere with
living well, phobias is surprisingly high—estimated to affect at least 1 in
10 people. Most people with a phobia control the emotional reaction by
avoiding what they dread. Others face their fears in controlled settings,
with the goal of overcoming them.
Panic disorder has an estimated incidence on the order of 3 percent
of the population. Symptoms include recurrent attacks of intense terror
that begin without warning and without any apparent relation to external
circumstances. Panic attacks usually last only a few minutes, but the
experience is always terrifying. Sudden activation of the sympathetic
nervous system leads to sweating, a wildly beating heart, and trembling. lea Paterson/Science Source
Although panic attacks may occur only occasionally, the victim’s
dread of another episode may be continual. Consequently, many people
with panic disorder also have agoraphobia, a fear of public places or
situations in which help might not be available. This phobia makes some
sense, because a person with a panic disorder may feel particularly vul- Up to 90 percent of people with an animal phobia overcome their
nerable about the possibility of having an attack in a public place. fears in a single exposure therapy session that lasts 2 or 3 hours.
As with depression, the root cause of anxiety disorders is unknown, but the effectiveness
of the drug treatments described in Clinical Focus 12-3 implies a biological basis. The most
widely prescribed anxiolytic (antianxiety) drugs are the benzodiazepines, such as Valium,
Librium, and Xanax. Why would the brain have a mechanism for benzodiazepine action?
426 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
It certainly did not evolve to allow us to take Valium. Probably this mechanism is part of a
system that both increases and reduces anxiety levels. The mechanism for raising anxiety
Figure 6-7 illustrates antianxiety agents’ seems to entail a compound known as diazepam-binding inhibitor, which appears to bind
action at the GABA A receptor. antagonistically with the GABA A receptor, increasing anxiety.
Increased anxiety can be beneficial, especially if we are drowsy and need to be alert to
Section 16-4 further explores anxiety deal with a crisis. Impairment of this survival mechanism or the one that reduces anxiety
disorders and reviews treatments. can cause serious emotional problems, even anxiety disorders.
12-4 reVIeW
Neuroanatomy of Motivated and Emotional Behavior
Before you continue, check your understanding.
1. The two types of motivated behaviors are behaviors, which maintain
homeostasis, and behaviors, encompassing basically all other
behaviors.
2. The brain’s homeostat for many functions is found in the .
3. The three brain structures housing the major behavioral circuitry involved in motivation
and emotion are , , and .
4. The prefrontal cortex has three main subdivisions: , , and
.
5. Damage to the is the primary cause of Klüver–Bucy syndrome.
6. The anterior pituitary gland produces .
7. Contrast the functions of the limbic system and the frontal lobes.
Answers appear at the back of the book.
For additional study tools, visit
www.macmillanhighered.com/launchpad/kolb5e
12-5 Control of Regulatory and
Nonregulatory Behavior
The two distinctly different types of motivated behaviors described in Section 12-4 are
regulatory behaviors, which maintain vital body system balance, or homeostasis; and non-
regulatory behaviors, those not controlled by a homeostatic mechanism—basically all other
behaviors. In this section, we focus first on the control of two regulatory behaviors in hu-
mans—eating and fluid intake. Then we explore the control of human sexual behavior.
While sexual behavior is nonregulatory; that is, not essential for an individual organism’s
survival, it is of enormous psychological significance to humans.
Controlling Eating
Feeding behavior entails far more than sustenance alone. We must eat and drink to live, but
we also derive great pleasure from these acts. For many people, eating is a focus of daily life,
if not for survival, for its centrality to social activities, from get-togethers with family and
friends to business meetings and even to group identification. Are you a gourmet, a vegetar-
ian, or a snack food junkie? Do you diet?
Control over eating is a source of frustration and even grief for many people in the
developed world. In 2000, the World Health Organization identified obesity, the excessive
accumulation of body fat, as a worldwide epidemic. The United States is a case in point.
From 1990 to 2010, the proportion of overweight people increased from about 50 percent
12-5 • Control of Regulatory and Nonregulatory Behavior 427
to 65 percent of the population. The proportion of people considered obese increased from
obesity Excessive accumulation of body fat.
about 12 percent in 1990 to 33 percent in 2014.
The increasing numbers of overweight and obese children and adults persist despite anorexia nervosa Exaggerated concern with
a substantial decrease in fat intake in American diets. What behaviors might cause per- being overweight that leads to inadequate
food intake and often excessive exercising;
sistent weight gain? One key to understanding weight gain in the developed world is
can lead to severe weight loss and even
evolutionary. Even 40 years ago, much of our food was only seasonally available. In a
starvation.
world with uncertain food availability, it makes sense to store excess body calories in the
form of fat to be used later when food is scarce. Down through history and in many cul-
tures today, plumpness was and is desirable as a standard of beauty and a sign of health
and wealth.
In postindustrial societies, where food is continuously and easily available, overweight
may not be the healthiest condition. People eat as though food will be scarce and fail to
burn off the extra calories by exercising, and the result is apparent. About half of the U.S.
population has dieted at some point in their life. At any given time, at least 25 percent report
that they are currently on a diet. For a comparison of how some well-known dieting programs
perform, see Clinical Focus 12-4, Weight Loss Strategies, on page 428.
Most Americans are overweight despite living in a culture obsessed with slimness. The
human control system for feeding has multiple neurobiological inputs, including cognitive
factors such as thinking about food and the association between environmental cues (e.g.,
watching television or studying) and the act of eating. The constant pairing of such cues with
eating can result in the cues alone becoming a motivation—an incentive to eat. We return to
this phenomenon in the discussion of reward and addiction in Section 12-6.
Eating disorders entail being either overweight or underweight. Anorexia nervosa is an
eating disorder with a huge cognitive component: self-image. A person’s body image is highly
distorted in anorexia. This misperception leads to an exaggerated concern with being over-
weight. That concern spirals to excessive dieting, compulsive exercising, and severe, poten-
tially life-threatening weight loss. Anorexia is especially prevalent among adolescent girls.
The neurobiological control of feeding behavior in humans is not as simple as it is in the
fly described in Section 12-3. The multiple inputs to the human control system for feeding
come from three major sources: the cognitive factors already introduced, the hypothalamus,
and the digestive system.
Digestive System and Control of Eating
As illustrated in Figure 12-23, the digestive tract begins in the mouth and ends at the anus.
Digestion is controlled by the enteric nervous system. As food travels through the tract, Figure 2-31 diagrams the inner workings
the digestive system extracts three types of nutrients: lipids (fats), amino acids (the building of the ENS and Section 5-3 the main
blocks of proteins), and glucose (sugar). Each nutrient is a specialized energy reserve. Because neurotransmitters it employs.
we require varying amounts of these reserves depending on what we are doing, the body has
detector cells to keep track of the level of each nutrient in the bloodstream.
Glucose is the body’s primary fuel and virtually the only energy source for the brain.
Because the brain requires glucose even when the digestive tract is empty, the liver acts as a
short-term reservoir of glycogen, a starch that acts as an inert form of glucose. When blood
sugar levels fall, as when we are sleeping, detector cells tell the liver to convert glycogen into
glucose for release into the bloodstream.
Thus the digestive system functions mainly to break down food, and the body needs
to be apprised of how this breakdown is proceeding. Feedback mechanisms provide such
information. When food reaches the intestines, it interacts with receptors in the ENS to
trigger the release of at least 10 different peptide hormones, including cholecystokinin
(CCK), glucagonlike peptide 1 (GLP-1), and peptide YY (PYY). Each, by virtue of its
release as food, is absorbed and acts as a satiation or satiety signal that inhibits food
intake. For example, when CCK is infused into an animal’s hypothalamus, the animal’s
appetite diminishes.
428 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
CliniCAl F cus 12-4
Weight Loss Strategies
Among the wide range of diets and weight loss strategies on the market, whole grains, fruits, nuts, and yogurt. Other lifestyle factors related to
none has stopped the obesity epidemic facing the developed world. Diets weight change included the amount of television watching (gain) and
range widely in their recommended allowed proportions and types of physical activity (loss).
fats, carbohydrates, and proteins. Teresa Fung and her colleagues (2010) conducted a prospective
A study by Iris Shai and colleagues (2008) compared a low-fat diet, study of mortality over a 26-year period in 85,000 women and 45,000
a low-carbohydrate diet, and the Mediterranean diet high in fruits, veg- men. They found that a low-carbohydrate diet based on animal food
etables, legumes, and whole grains and including fish, nuts, and low-fat sources was associated with higher mortality from all causes, whereas
dairy products (Panagiotakos et al., 2004). The Shai study lasted 2 years a vegetable-based, low-carbohydrate diet was associated with lower
and had relatively low dropout rates: 95.4 percent remained on their diet mortality from all causes.
at 1 year and 84.6 percent at 2 years. Shai and her colleagues concluded that health care professionals
Figure A shows that all three diets led to weight loss. The low- might suggest more than one dietary approach based on individual
carbohydrate diet produced the largest acute weight loss. Over the preferences and metabolic needs, as long as the effort is sustained.
2-year period subjects gained back some weight, and in the second At present, the only certain formula for weight loss appears to include
year the low-carbohydrate and Mediterranean dieters achieved similar (1) a permanent switch to a diet reduced in calories and fat and
weight loss. (2) increased ingestion of high-fiber foods (e.g., beans, whole grains,
The low-carbohydrate diet had more favorable effects on lipid levels, greens) combined with (3) increased physical activity. The results of the
whereas the Mediterranean diet provided better control of glucose and Mozaffarian study suggest cutting back on foods and beverages with
insulin levels. Those who followed the low-fat diet lost weight but fared high sugar content as well.
less well than those on the other regimens.
The question of which foods are most likely to lead to weight gain
was studied in a 20-year prospective study of three cohorts totaling
about 120,000 U.S. women and men (Mozaffarian et al., 2011). None
Potato chips
were obese when the study began. Participants gained an average of
3.4 pounds during every 4-year period. Potatoes or fries
Shown graphically in Figure B, weight gain was most strongly Red meats
related to the intake of potato chips, potatoes, sugar-sweetened bever- Sugar-sweetened beverages
ages, and red meat. Weight loss was related to the intake of vegetables,
Butter
Sweets and desserts
0
Refined grains
–1 Cheese
Mean weight change (kg)
Vegetables
–2
Low-fat diet Nuts
–3
Whole grains
Mediterranean diet
–4 Fruits
Yogurt
–5
Low-carbohydrate diet
–6 21.0 20.5 0.0 0.5 1.0 1.5 2.0
–7 Average weight increase or decrease, in pounds per 4-year
0 2 4 6 8 10 12 14 16 18 20 22 24 period, with each increase in daily serving
Months on diet
Foods Most Likely to Lead to Weight Gain or
FIGUre B
FIGUre a Benefits of Dieting Changes in body weight over a Loss Weight changes recorded for each increase in daily serving
2-year period on three diets. Low-carbohydrate and Mediterranean of a food per 4-year period, based on the diets and weights of
diets were equivalent after 1 year, and both led to more weight loss nearly 125,000 people who were followed over 20 years. Information
than did the low-fat diet. Information from I. Shai, D. Schwarzfuchs, Y. Henkin, from D. Mozaffarian, M. P. H. Tao Hao, E. B. Rimm, W. C. Willett, & F. B. Hu (2011). Changes
et al. (2008). Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. New in diet and lifestyle and long-term weight gain in women and men. New England Journal of
England Journal of Medicine, 13, pp. 229–241. Medicine, 3654, pp. 2392–2404.
12-5 • Control of Regulatory and Nonregulatory Behavior 429
Oral cavity
Food travels from the oral cavity to the
stomach through the esophagus. Tongue
Esophagus
The large intestine
In the stomach, hydrochloric acid breaks absorbs most of the
food into smaller particles, and the water and electrolytes
enzyme pepsin breaks proteins down Liver
remaining in food.
into amino acids. Gallbladder
Duodenum
Pancreas
Partly digested food moves through the
Stomach
duodenum to the upper small intestine,
Large intestine
where enzymes produced in the
gallbladder and pancreas break the
Small intestine
food down further, allowing the Waste passes out of
bloodstream to absorb amino acids, Rectum the body through the
fats, and simple sugars. The
FIGUre 12-23
anus.
Anal canal Digestive System
Hypothalamus and Control of Eating
Feeding behavior is influenced by hormones, including insulin, growth hormone, and sex Section 6-5 reviews the general categories of
steroids, that stimulate and inhibit feeding and aid in converting nutrients into fat and fat hormones and how they work.
into glucose. The hypothalamus, which controls hormone systems, is the key brain structure
in feeding as well as in satiety.
Investigation into how the hypothalamus controls feeding began in the early 1950s, when
researchers discovered that damage to the lateral hypothalamus in rats caused the animals to
stop eating, a symptom known as aphagia (in Greek, phagein means to eat). In contrast, dam-
age to the ventromedial hypothalamus (VMH) caused the animals to overeat—display hyper-
phagia. A VMH-lesioned rat that overate to the point of obesity is shown in the Procedure
section of Experiment 12-1 on page 430. The Results section reveals that the VMH-lesioned
rat weighed more than 1 kilogram, three times the weight of her healthy sister, at 340 grams.
The researchers also found that electrical stimulation of the lateral hypothalamus elicits
feeding, whereas stimulation of the ventromedial hypothalamus inhibits feeding. The op-
posing effects of injury and stimulation to these two regions led to the idea that the lateral
hypothalamus signals turn eating on, whereas the VMH signals turn eating off. This model
quickly proved too simple.
Not only does the lateral hypothalamus contain cell bodies; fiber bundles also pass through
it. Damage to either the cell bodies or the fibers can produce aphagia. Similarly, damage to
fibers passing through the VMH often causes injury as well to the paraventricular nucleus
of the hypothalamus (review Figure 12-12A). But the role of the hypothalamus in controlling
feeding involves more than the activities of its lateral and ventromedial structures alone.
In fact, another hypothalamic region, the arcuate nucleus, contains two major classes of aphagia Failure to eat; may be due to an
neurons, one that initiates eating (e.g., neurons expressing genes for neuropeptide Y) and one unwillingness to eat or to motor difficulties,
that reduces eating behavior, the principal transmitter being a-melanocyte–stimulating hor- especially with swallowing.
mone (a-MSH). Changes in hormone levels reflecting glucose (insulin) and lipid (leptin) levels hyperphagia Overeating that leads to
in the blood act to stimulate either the first class, which initiates eating, or the second class, significant weight gain.
430 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
ExPERIMENt 12-1 which acts to inhibit eating. Neurons of the arcuate nucleus also connect to
the paraventricular nucleus. Damage to this region produces hyperphagia.
Question: Does the hypothalamus play a role in eating?
The summed activity of all such hypothalamic neurons constitutes
Procedure a complex homeostat that controls feeding. Figure 12-24 shows that this
The ventromedial homeostat receives inputs from three sources: the enteric nervous system
hypothalamus (VMH) (such as information about blood glucose levels), hormone systems (such as
of the rat on the information about the level of appetite-diminishing CCK), and parts of the
right was damaged,
and her body weight
brain that process cognitive factors. We turn to these cognitive factors next.
was monitored for a
year. Her sister on the Cognitive Control of Eating
left is normal.
Pleasure and its absence are cognitive factors in controlling eating. Just
Intact brain of sister rat Rat brain with lesion thinking about a favorite food can make many of us feel hungry. The cogni-
tive aspect to feeding includes not only images of food that we pull from
memory but also external sensations, especially food-related sights and
smells. Learned associations, such as the taste aversions discussed in Section
12-3, are also related to feeding.
Neural control of the cognitive factors important for controlling eating
in humans probably originates in multiple brain regions. Two structures are
Photos courtesy of Bryan Kolb and ian Whishaw
clearly important: the amygdala and the orbital prefrontal cortex. Damage
Results
The VMH-lesioned rat showed a dramatic to the amygdala alters food preferences and abolishes taste aversion learning.
increase in food intake and body weight. These effects are probably related to the amygdala’s efferent connections to
the hypothalamus.
1500
The amygdala’s role in regulating species-typical behaviors is well
established, but the role of the orbital PFC is more difficult to pin down.
Rats and monkeys with damage to the orbital cortex lose weight, in part
Lesioned rat
Body weight (g)
1000 because they eat less. Humans with orbital injuries are invariably slim, but
we know of no formal studies on their eating habits. The orbital prefrontal
cortex receives projections from the olfactory bulb, and cells in this region
500 respond to smells. Because odors influence the taste of foods, it is likely that
Control rat
damage to the orbital cortex decreases eating, owing to diminished sensory
responses to food odor and perhaps to taste.
100
An additional cognitive factor in control of eating is the pleasure we derive
0 1 2 3 4 5 6 7 8 9 10 11 12
from it, especially from eating foods with certain tastes. Think chocolate.
Time (months)
What pleasure is and how the brain produces it are discussed in Section 12-6
Conclusion: The VMH plays a role in controlling the in the context of reward.
cessation of eating. Damage to the VMH results in Randy Seeley and Stephen Woods (2003) noted that in spite of contem-
prolonged and dramatic weight gain. porary problems with weight gain, adult mammals do a masterful job of
matching their caloric intake to caloric expenditure. Consider that a typical
man eats 900,000 calories per year. To gain just one extra pound requires
him to eat 4000 calories more than he burned in that year. This increase
FIGUre 12-24 Modeling Control of amounts to only 11 calories per day, equivalent to a single potato chip. But
Feeding Behavior people rarely eat just one chip. As Figure B in Clinical Focus
12-4 illustrates, potato chips top the list of major food sources
ENS linked to weight gain over time.
Hormones Hypothalamus Eating Controlling Drinking
Dissolved in the water that is 70 percent of the human body
Cognitive are chemicals that participate in the hundreds of reactions nec-
factors essary to bodily functions. Essential homeostatic mechanisms
control water levels (and hence chemical concentrations) within
Amygdala Sensory Prefrontal rather narrow limits. The rate of a chemical reaction is partly
systems cortex
determined by the concentration of the participating chemicals.
12-5 • Control of Regulatory and Nonregulatory Behavior 431
As with eating, we drink for many reasons. We consume some beverages, such as cof-
osmotic thirst Thirst that results from a
fee, wine, beer, and juice, for an energy boost or to relax, as part of social activities, or just
high concentration of dissolved chemicals, or
because they taste good. We drink water for its health benefits, to help wash down a meal
solutes, in body fluids.
or to intensify the flavor of dry foods. On a hot day, we drink water because we are thirsty,
presumably because we become dehydrated through sweating and evaporation. hypovolemic thirst Thirst produced by a
loss of overall fluid volume from the body.
These examples illustrate the two kinds of thirst. Osmotic thirst results from increased
concentrations of dissolved chemicals, known as solutes, in the body fluids. Hypovolemic
thirst results from a loss of overall fluid volume from the body.
Osmotic Thirst
Solutes found inside and outside cells are ideally concentrated for the body’s chemical reac-
tions. Maintaining this concentration requires a kind of homeostat, much like the mecha-
nism that controls body temperature. Deviations from the ideal solute concentration activate
systems to reestablish it.
When we eat salty foods, such as potato chips, the salt (NaCl) spreads through the blood
and enters the extracellular fluid between our cells. This shifts the solute concentration away
from the ideal. Receptors in the hypothalamus along the third ventricle detect the altered Turning to sugar-sweetened beverages
solute concentration and relay the message too salty to various hypothalamic areas that in to quench thirst from eating salty foods
turn stimulate us to drink. Other messages are sent to the kidneys to reduce water excretion. increases the likelihood of weight gain.
Water Intoxication
Eating too much leads to obesity. What happens when we drink too much water? Our kid-
neys are efficient at processing water, but if we drink a large volume all at once, the kidneys
cannot keep up.
The result is a condition called water intoxication. Body tissues swell with the excess
fluid, essentially drowning the cells in freshwater. At the same time, the relative concentra-
tion of sodium drops, leading to an electrolyte imbalance.
Water intoxication can produce widely ranging symptoms, from irregular heartbeat to
headache. In severe cases, people may act as though they are drunk. The most likely way
for an adult to develop water intoxication is to sweat heavily, by running a marathon in hot
weather, for example, then drink too much water without added electrolytes.
Hypovolemic Thirst
Unlike osmotic thirst, hypovolemic thirst arises when the total volume of body fluids de-
clines, motivating us to drink more and replenish them. In contrast with osmotic thirst,
however, hypovolemic thirst encourages us to choose something other than water, because
water would dilute the solute concentration in the blood. Rather, we prefer to drink flavored
beverages that contain salts and other nutrients.
Hypovolemic thirst and its satiation are controlled by a hypothalamic circuit different
from the one that controls osmotic thirst. When fluid volume drops, the kidneys send a hor-
mone signal (angiotensin) that stimulates midline hypothalamic neurons. These neurons, in
turn, stimulate drinking.
Controlling Sexual Behavior
Individuals must feed and drink continually to survive. This is the essence of regulatory
behavior. But notwithstanding procreation, which is essential to the survival of the species,
sexual behavior is nonregulatory: it is not essential for the individual organism’s survival.
That fact does nothing to convince most of us that sex is unimportant.
In Sigmund Freud’s psychodynamic theory, sexual drives are central to human
behavior. Sexual themes repeatedly appear in our art, literature, and films. They
bombard us via advertising and other sales pitches. Such significance makes it all the
more important to understand the control of human sexual behavior in terms of both
gonadal hormones and brain circuits.
432 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Effects of Sex Hormones on the Brain
During the fetal stage of prenatal development, a male’s Y chromosome controls the dif-
ferentiation of embryonic gonad tissue into testes, which in turn secrete testosterone. This
process is an organizing effect of gonadal hormones. Testosterone masculinizes both the sex
organs and the brain during development. A major organizing effect of gonadal hormones on
the brain is in the hypothalamus, especially the preoptic area of the medial hypothalamus.
Organizing effects also operate in other nervous system regions, notably the amygdala, the
prefrontal cortex, and the spinal cord.
Gonadal hormones produce enzymes necessary for epigenetic changes such as gene
methylation. One action of steroid hormones is to methylate brain regions. For example, es-
trogen methylates the preoptic area of females, leading to the suppression of male character-
istics. Growing evidence indicates that increased environmental levels of compounds, such
as agricultural pesticides, can interfere with hormone activity, resulting in multigenerational
The case study in Section 3-3 describes such epigenetic effects (e.g., McCarthy et al., 2009). These effects may be linked to anxiety levels
epigentic inheritance. and obesity and possibly to the organizational effects of gonadal hormones.
Sex-related differences in the nervous system make sense behaviorally. After all, animal
courtship rituals differ between the sexes, as do copulatory behaviors, with females typically
engaging in sexually receptive responses and males in mounting ones. Producing these sex
differences in behaviors depends on the action of gonadal hormones on the brain during
development and in adulthood.
Hormonal actions on the adult brain are referred to as activating effects, in contrast with
developmental organizing effects. Next we consider both, separately.
OrGaNIZING eFFeCtS OF SeX hOrMONeS During fetal development, a male’s testes
produce male hormones, the androgens. In the developing rat, androgens are produced dur-
ing the last week of fetal development and the first week after birth. The androgens pro-
Section 8-4 explains organizing influences duced at this time greatly alter both neural structures and later behavior. For example, a male
of gonadal hormones and critical periods in rat’s hypothalamus and prefrontal cortex differ structurally from those of both female rats
brain development. and of males that were not exposed to androgens during development.
Males with little exposure to the androgen testosterone during development behave like
genetically female rats in adulthood. If given estrogen and progesterone, they become sexu-
ally receptive and display typical female behaviors when mounted by males. Male rats cas-
OH
CH3 trated in adulthood do not act in this way.
Sexual dimorphism, the differential development of brain areas in the two sexes, arises
CH3 from a complex series of steps. Cells in the brain produce aromatase, an enzyme that con-
verts testosterone into estradiol, one of the class of female sex hormones called estrogens.
OH
CH3 That is, when males produce testosterone, the brain converts it to an estrogen. Thus a female
O
Testosterone hormone, estradiol, actually masculinizes the male brain.
Females are not masculinized by the presence of estrogens because fetuses of both sexes
produce a liver enzyme (alpha fetoprotein) that binds to estrogen, rendering it incapable of
entering neurons. Testosterone is unaffected by alpha fetoprotein: it enters neurons and is
HO
converted into estradiol.
Estradiol
The organizing effects of testosterone are clearly illustrated in the preoptic area of the hypo-
thalamus (see Figure 12-12A), which plays a critical role in male rats’ copulatory behavior. Com-
paring this area in males and females, Roger Gorski (1984) and his colleagues found a nucleus
about five times as large in the males as in the females. Significantly, manipulating gonadal hor-
mones during development can alter the sexual dimorphism of the preoptic area. Castrating male
rats at birth leads to a smaller preoptic area; treating infant females with testosterone enlarges it.
The organizing effects of gonadal hormones are more difficult to study in humans. How-
ever, John Money and Anke Ehrhardt (1972) revealed an important role of these hormones
in human development. Clinical Focus 12-5, Androgen Insensitivity Syndrome and Andro-
genital Syndrome, describes this role.
12-5 • Control of Regulatory and Nonregulatory Behavior 433
CliniCAl F cus 12-5
Androgen Insensitivity Syndrome and the Androgenital Syndrome
After the testes have formed in a male fetus, sexual development
depends on the actions of testicular hormones. Studying people with
androgen insensitivity syndrome makes this dependence crystal clear. In
this syndrome, an XY (genetic male) fetus produces androgens, but the
body cannot to respond to them.
Because androgen insensitivity syndrome does not affect estro-
gen receptors, these people are still responsive to estrogen produced
by both the adrenal glands and the testes. As a result, they develop
female secondary sexual characteristics during puberty, even with-
john Money and anke a. ehrhardt/john’s hopkins university Press
out additional hormone treatment. A person with androgen insensi-
tivity syndrome is therefore a genetic male who develops a female
phenotype, that is, appears to be female, as shown in the photograph
on the left.
If no Y chromosome is present to induce the growth of tes-
tes, an XX (genetic female) fetus develops ovaries and becomes a
female. If the adrenal glands of either the mother or the infant pro-
duces an excessive amount of androgens, however, exposure of the
female fetus to them produces the androgenital syndrome (congenital
adrenal hyperplasia).
The effects vary, depending on when the androgens are produced
and on the level of exposure. In extreme cases, the clitoris enlarges
until it can be mistaken for a small penis, as shown in the photograph
Left: In androgen insensitivity syndrome, a genetic male (XY)
on the right.
is insensitive to gonadal androgens but remains sensitive to
In less severe cases, no gross change in genital structure develops, estrogens, which leads to the development of a female phenotype.
but there is a behavioral effect: these girls show a high degree of tom- Right: In congenital adrenal hyperplasia, a genetic female (XX) is
boyishness. In early childhood, they identify with boys and prefer boys’ exposed to androgens produced by the adrenal gland embryonically,
clothes, toys, and games. One explanation for this behavioral effect is which leads to the partial development of male external genitalia.
that the developing brain is masculinized, which changes later behavior. Reprinted from J. Money & A. A. Ehrhardt (1972). Man and Woman, Boy and Girl (p. 116).
Baltimore: Johns Hopkins University Press.
aCtIVatING eFFeCtS OF SeX hOrMONeS The sexual behavior of both males and fe- Section 6-5 details broader activating
males also depends on the actions of gonadal hormones on the adult brain. In most verte- effects of sex hormones on male and female
brate species, female sexual behavior varies in the course of an estrous cycle, during which behavior.
the levels of ovarian hormones fluctuate. The rat’s estrous cycle is about 4 days long, with
sexual receptivity occurring only in the few hours during which the production of the ovar-
ian hormones estrogen and progesterone peaks. These ovarian hormones alter brain activity,
which in turn alters behavior. In female rats, various chemicals released after mating inhibit
further mating behavior.
The activating effect of ovarian hormones can be seen clearly in hippocampal cells.
Figure 12-25 compares hippocampal pyramidal neurons taken from female rats at two
points in the estrous cycle: one when estrogen levels are high and the other when they are
low. When estrogen levels are high, more dendritic spines and presumably more synapses
emerge. These neural differences during the estrous cycle are all the more remarkable when
we consider that cells in the female hippocampus are continually changing their connec-
tions to other cells every 4 days throughout the animal’s adulthood.
In males, testosterone activates sexual behavior in two distinct ways. First, testosterone’s
actions on the amygdala are related to the motivation to seek sexual activity. Second, the
actions of testosterone on the hypothalamus are needed to produce copulatory behavior. We sexual dimorphism Differential development
look at both processes next. of brain areas in the two sexes.
434 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
FIGUre 12-25 Hormonal Effects Rat brain
A comparison of the dendrites of
Estrogen Estrogen
hippocampal pyramidal neurons at high levels levels
and low levels of estrogen in the rat’s high low
Hippocampus
(4-day) estrous cycle reveals far fewer
dendritic spines in the low period. Information Pyramidal
neuron
from C. S. Woolley, E. Gould, M. Frankfurt, & B. McEwen
(1990). Naturally occurring fluctuation in dendritic spine
density on adult hippocampal pyramidal neurons. Journal
of Neuroscience, 10, p. 1289.
Hypothalamus, Amygdala, and Sexual Behavior
The hypothalamus is the critical structure controlling copulatory behaviors in both male
and female mammals. The ventromedial hypothalamus controls the female mating posture,
which in quadrupedal animals is called lordosis: arching the back and elevating the rump
while the female otherwise remains quite still. Damage to the VMH abolishes lordosis. The
Typical posture
role of the VMH is probably twofold: it controls the neural circuit that produces lordosis, and
it influences hormonal changes in the female during coitus.
In males, neural control of sexual behavior is somewhat more complex. The medial pre-
optic area, which is larger in males than in females, controls copulation. Damage to this area
Lordosis greatly disrupts mating performance, whereas its electrical stimulation activates mating,
provided that testosterone is circulating in the bloodstream. Curiously, although destruc-
tion of the medial preoptic area stops male mammals from mating, they continue to show
interest in receptive females. For instance, monkeys with lesions in the medial preoptic area
will not mate with receptive females, but they will masturbate while watching them from
across the room.
Barry Everitt (1990) designed an ingenious apparatus that allows male rats to press a
bar to deliver receptive females. After males were trained to use this apparatus, shown in
Figure 12-26, lesions were made in their medial preoptic areas. Immediately, their sexual
behavior changed. They would still press the bar to obtain access to females but would no
longer mate with them.
Apparently, the medial preoptic area controls mating but not sexual motivation. The brain
structure responsible for motivation appears to be the amygdala. When Everitt trained male
rats in the apparatus and then lesioned their amygdala, they would no longer press the bar to
gain access to receptive females, but they would mate with receptive females provided to them.
It is not practical to discriminate small hypothalamic nuclei in fMRI studies of humans.
Studies have shown a bilateral increase in hypothalamic activity when men view erotic video
clips but not when they view sports video clips (Figure 12-27). The degree of sexual arousal
is related to the increase in hypothalamic activity (e.g., Brunetti et al., 2008).
Barry j. everitt
In summary, the hypothalamus controls copulatory behavior in both male and female
mammals. In males, the amygdala influences sexual motivation and probably plays a key role
in female sexual motivation as well, especially among females of species, such as humans,
FIGUre 12-26 Studying Sexual
whose sexual activity is not tied to fluctuations in ovarian hormones.
Motivation and Mating In this
experiment, a male rat must press the
bar 10 times to gain access to a receptive
female who drops in through a trapdoor.
Sexual Orientation, Sexual Identity, and
The copulatory behavior of the male rat Brain Organization
illustrates mating behavior, whereas the Does sexual orientation—a person’s sexual attraction to the opposite sex or to the same
bar pressing for access to a female rat
sex or to both sexes—have a neural basis? Sexual orientation appears to be determined
illustrates sexual motivation. Barry J. Everitt,
Department of Experimental Psychology and the MRC-
during early development, influenced by genetics and by epigenetic factors during pre-
Wellcome Behavioural and Clinical Neuroscience Institute, natal brain development. No solid evidence points to any postnatal experience directing
University of Cambridge. sexual orientation.
12-5 • Control of Regulatory and Nonregulatory Behavior 435
Indeed, it appears virtually impossible to change a person’s sexual orientation. Lesbian
couples commonly rear heterosexual children, and no evidence supports the notion that
homosexuality is a lifestyle choice or that it is an effect of social learning (Bao & Swaab, 2011).
The place to look for differences, therefore, is in the brain of people who identify themselves
as heterosexual and homosexual.
Like rats, humans have sex-related differences in the structure of the hypothalamus and
amygdala. Several hypothalamic nuclei are two to three times larger in males (for a review,
see Becker and colleagues, 2008). Sexual differentiation of the brain results from the effect
of testosterone and is complete by birth.
But sex differences in the brain are not simply a matter of hormones. Epigenetics plays
a role too, beginning early in development. In females, for example, one of the two X chro-
mosomes is largely silenced, but not all its genes are silenced, which provides a basis for sex
differences. Furthermore, emerging evidence suggests that sex differences in the hypothala-
mus result from differences in gene methylation (for a review, see McCarthy and coworkers,
2009). FIGUre 12-27 Hypothalamus and
Among homosexuals, variations in epigenetic effects could lead to differences in the
Sex in Males Red regions on the left
and right represent bilateral activity in
architecture and function of the hypothalamus. Differences in the hypothalamus of het- the hypothalamus of men viewing erotic
erosexual and homosexual men suggest that homosexual men form, in effect, a third sex film clips. This activity was absent as the
because their hypothalamus differs from that of both females and heterosexual males. men watched sports clips. Republished from
Architectural and functional differences in the hypothalamus may form a basis for the ”The Hypothalamus, Sexual Arousal and Psychosexual
Identity in Human Males: A functional Magnetic Resonance
spectrum of gender identity—a person’s degree of feeling male or female. People who
Imaging Study,” by M. Brunetti, C. Babiloni, A. Ferretti,
view themselves as transgender, whose personal characteristics transcend traditional gen-
C. Del Gratta, A. Merla, and M. Olivetti Belardino, 2008,
der boundaries and corresponding sexual norms, believe they were born the wrong sex. European Journal of Neuroscience, 27, 2922–2927, Figure
Their desire to live as a member of the other sex can be so strong that they undergo sex 2, permission conveyed through Copyright Clearance
change surgery. Center, Inc.
Several biological factors appear to influence the likelihood of transgender identity—
chromosomal abnormalities, polymorphisms of the genes for the estrogen and androgen
receptors, atypical gonadal hormone levels, prenatal exposure to certain anticonvulsants,
and immune system activity directed toward the Y chromosome. These factors are hypoth-
esized to lead to changes in the architecture and function of brain structures, especially the More evidence favoring a neural basis for
hypothalamus, which match transgender peoples’ identities even while their sex organs do gender identity, including transgender identity,
not (Bao & Swaab, 2011). in Section 15-5.
In summary, differences in sexual orientation and gender identity appear to result from
prenatal events that influence the organization and function of the brain, not from postnatal
social or environmental experiences.
Peter Brooker/Rex features/alamy
sexual orientation A person’s pattern of
sexual attraction—to the opposite sex or to
ncP/Star Max/Getty images
the same sex or to both sexes.
© neal Preston/corbis
gender identity The degree to which a
person feels male or female.
transgender Possessing personal
Before accepting the Arthur Ashe Courage Award at the 2015 ESPY ceremony, Caitlyn characteristics that transcend traditional
Jenner was known worldwide as Bruce Jenner. Bruce won Olympic Gold in the 1976 gender boundaries and corresponding sexual
decathlon competition. Caitlyn began her physical transition nearly four decades later. norms; a person’s belief that he or she was
At left, Bruce in 1984 and at center in 2003; at right, Caitlyn in 2015. born the wrong sex.
436 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Cognitive Influences on Sexual Behavior
People think about sex, dream about sex, make plans about sex. These behaviors may
include activity in the amygdala or the hypothalamus, but they must certainly also in-
clude the cortex. This is not to say that the cortex is essential for sexual motivation and
copulation.
In studies of rats whose entire cortex has been removed, both males and females still
engage in sexual activity, although the males are somewhat clumsy. Nevertheless, the cortex
must play a role in certain aspects of sexual behavior. For instance, imagery about sexual ac-
tivity must include activity in the cortical ventral visual pathway. And thinking about sexual
activity and planning for it must require frontal lobe participation.
As you might expect, these aspects of sexual behavior are not easily studied in rats, and
they remain uncharted waters in research on humans. However, changes in the sexual behav-
ior of people with frontal lobe injury are well documented. And recall J. P.’s case, described
in Clinical Focus 12-2. Although J. P. was uninhibited in his sexual behavior, frontal lobe
damage is just as likely to produce a loss of libido (sexual interest). The wife of a man who 5
years earlier had a small tumor removed from the medial frontal region complained that she
and her husband had since had no sexual contact whatever. He was simply not interested,
even though they were both still in their twenties.
The husband said that he no longer had sexual fantasies or sexual dreams, and although
he still loved his wife, he did not have any sexual urges toward her or anyone else. Such cases
clearly indicate that the human cortex is important in controlling sexual behaviors. The
exact nature of its role remains poorly understood.
12-5 reVIeW
Control of Regulatory and Nonregulatory Behavior
Before you continue, check your understanding.
1. The three main hypothalamic regions that control feeding are ,
, and .
2. The key structures in the control of sexual behavior are the and the
.
3. The two types of effects that hormones exert on the brain are and
.
4. thirst results from an increase in the concentration of dissolved chemicals;
thirst results from a decline in the total volume of body fluids.
5. Describe why sex differences in the brain are not simply a matter of hormones.
Answers appear at the back of the book.
For additional study tools, visit
www.macmillanhighered.com/launchpad/kolb5e
12-6 Reward
Throughout this chapter we have concluded repeatedly that animals engage in a wide range
of voluntary behaviors because those behaviors are rewarding. That is, they increase the
activity in neural circuits that function to maintain an animal’s contact with certain envi-
ronmental stimuli, either in the present or in the future. Presumably, the animal perceives
the activity of these circuits as pleasant. This would explain why reward can help maintain
not only adaptive behaviors such as feeding and sexual activity but also potentially nonadap-
12-6 • Reward 437
tive behaviors such as drug addiction. After all, evolution would not have prepared the brain
specifically for the eventual development of psychoactive drugs.
The first clue to the presence of a reward system in the brain came with an accidental dis-
covery by James Olds and Peter Milner in 1954. They found that rats would perform behaviors Section 7-1 describes how electrical
such as pressing a bar to administer a brief burst of electrical stimulation to specific sites in stimulation works both as a treatment and as
their brain. This phenomenon is called intracranial self-stimulation or brain stimulation reward. a research tool.
Typically, rats will press a lever hundreds or even thousands of times per hour to obtain this
brain stimulation, stopping only when they are exhausted. Why would animals engage in such
behavior when it has absolutely no survival value to them or to their species? The simplest ex-
planation is that the brain stimulation is activating the system underlying reward (Wise, 1996).
After more than a half-century of research on brain stimulation reward, investigators Prefrontal
cortex
now know that dozens of brain sites maintain self-stimulation. Some especially effective
regions are the lateral hypothalamus and medial forebrain bundle (see Figures 12-12 and
12-13). Stimulation along the MFB tract activates fibers that form the ascending pathways
from dopamine-producing cells of the midbrain tegmentum, shown in Figure 12-28.
This mesolimbic dopamine pathway sends terminals to sites that include especially the
nucleus accumbens in the basal ganglia and the prefrontal cortex. Nucleus
accumbens in
Neuroscientists have several reasons to believe that the mesolimbic dopamine system
basal ganglia
is central to circuits mediating reward: Ventral
tegmenum Cerebellum
1. Dopamine release shows a marked increase when animals are engaged in intracranial
self-stimulation.
FIGUre 12-28 Mesolimbic Dopamine
2. Drugs that enhance dopamine release increase self-stimulation, whereas drugs that
System Axons emanating from the
decrease dopamine release also decrease self-stimulation. It seems that the amount of ventral tegmentum (blue arrows) project
dopamine released somehow determines how rewarding an event is. diffusely through the brain. Dopamine
release in these mesolimbic pathways has
3. When animals engage in behaviors such as feeding or sexual activity, dopamine release
a role in feelings of reward and pleasure.
rapidly increases in locations such as the nucleus accumbens. The nucleus accumbens is a critical
4. Highly addictive drugs such as nicotine and cocaine increase the dopamine level in the structure in this reward system.
nucleus accumbens.
Even opioids appear to affect at least some of an animal’s actions through the dopamine
system. Animals quickly learn to press a bar to obtain an opioid injection directly into the
midbrain tegmentum or the nucleus accumbens. The same animals do not work to obtain
the opioid if the dopaminergic neurons of the mesolimbic system are inactivated. Apparently,
then, animals engage in behaviors that increase dopamine release.
Nor is dopamine the only rewarding compound in the brain. For example, opioid trans-
mitters such as encephalin and dynorphin are also rewarding, as are benzodiazepines.
Robinson and Berridge (2008) propose that reward contains separable psychological com-
ponents corresponding roughly to wanting, which is often called incentive, and liking, which Robinson and Berridge’s wanting-and-liking
is equivalent to an evaluation of pleasure. This idea can be applied to discovering why we theory of addiction includes a multipart
increase contact with a stimulus such as chocolate. reward system; see Section 6-4.
Two independent factors are at work: our desire to eat the chocolate (wanting) and the
pleasurable effect of eating the chocolate (liking). This distinction is important. If we main-
tain contact with a certain stimulus because dopamine is released, the question becomes
whether the dopamine plays a role in the wanting or the liking aspect of the behavior. Robin-
son and Berridge propose that wanting and liking processes are mediated by separable neural
systems and that dopamine is the transmitter for the wanting. Liking, they hypothesize,
entails opioid and benzodiazepine–GABA systems.
According to Robinson and Berridge, wanting and liking are normally two aspects of the
same process, so rewards are usually wanted and liked to the same degree. However, it is pos-
sible, under certain circumstances, for wanting and liking to change independently.
Consider rats with lesions of the ascending dopaminergic pathway to the forebrain.
These rats do not eat. Is it simply that they do not desire to eat (a loss of wanting), or has
438 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
Positive reactions Negative reactions
Human Reactions to
FIGUre 12-29
Taste Sucrose and other palatable tastes elicit
positive (hedonic) reactions, including licking the
fingers and the lips. Quinine and other unpleasant tastes
elicit negative (aversive) reactions, including spitting,
expressing distaste, and wiping the mouth with the back
of the hand. Information from K. C. Berridge (1996). Food reward:
Brain substrates of wanting and liking. Neuroscience and Biobehavioral
Reviews, 20, p. 6.
food become aversive to them (a loss of liking)? To find out which factor is at work, the
animals’ facial expressions and body movements in response to food can be observed to
see how liking is affected. After all, when animals are given various foods to taste, they
produce different facial and body reactions, depending on whether they perceive the food
as pleasant or aversive.
Among humans, typically when a person tastes something sweet, he or she responds by
licking the fingers or the lips, as shown at the left of Figure 12-29. If the taste is unpleasantly
salty, say, as shown in the right panel, the reaction is often spitting, grimacing, or wiping the
mouth with the back of the hand. Rats, too, show distinctive positive and negative responses
to pleasant and unpleasant tastes.
By watching the responses when food is squirted into the mouth of a rat that otherwise
refuses to eat, we can tell to what extent a loss of liking is a factor in the animal’s food rejec-
tion. Interestingly, rats that do not eat after receiving lesions to the dopamine pathway act
as though they still like food.
Now consider a rat with a self-stimulation electrode in the lateral hypothalamus. This
rat will often eat heartily while the stimulation is on. The obvious inference is that the food
must taste good—presumably even better than usual. But what happens if we squirt food
into the rat’s mouth and observe its behavior when the stimulation is on versus when it is off?
If the brain stimulation primes eating by evoking pleasurable sensations, we would expect
the animal to be more positive in its facial and body reactions to foods when the stimulation
is turned on. In fact, the opposite occurs. During stimulation, rats react more aversively
to tastes such as sugar and salt than when stimulation is off. Apparently, the stimulation
increases wanting but not liking.
Such experiments show that what appears to be a single event—reward—is actually
composed of at least two independent processes. Just as our visual system independently
processes what and how information in separate streams, our reward system appears to pro-
cess wanting and liking independently. Reward is not a single phenomenon any more than
perception or memory is.
Like the networks underlying perception and memory, the prefrontal and limbic net-
works underlying reward are diffuse. Amy Janes and her colleagues (2012) used resting-state
fMRI to identify a prefrontal–anterior cingulate network believed to support reward, illus-
trating the breadth of the reward system. They then compared these networks in nicotine
Summary 439
FIGUre 12-30 Craving
Increases OMPFC Network
Coupling Participants craving nicotine
show an increase in the coupling of
the orbital and medial prefrontal cortex
(OMPFC, shown in green) with other
regions including anterior cingulate cortex,
other prefrontal regions, the striatum,
right hippocampal region, ventral occipital
cortex, and cerebellum (shown in shades
of orange). An Increase in Tobacco Craving Is
Associated with Enhanced Medial Prefrontal Cortex
Network Coupling Amy C. Janes, Stacey Farmer, Blaise
Medial view Frontal view Dorsal view
deB. Frederick, Lisa D. Nickerson, Scott E. Lukas, PLoS
One. 2014 Feb 5;9(2):e88228. doi: 10.1371/journal.
pone.0088228.eCollection 2014.
addicts and nonaddicts finding greater connectivity in the prefrontal–striatal connections
in nicotine addicts. In a follow-up study the investigators also showed that craving in nico-
tine addicts is related to enhanced connectivity in this prefrontal network (Figure 12-30).
(Janes et al., 2014).
The general conclusions from these studies and from related studies of gamblers are that
neural reward pathways are diffuse and that the pathways’ size and activity are related to
the reward’s intensity. The hope is that rs-fMRI can be used as a biomarker for both severity
of addiction and efficacy of treatment. But the extent of addiction-related changes suggests
that eliminating nicotine addiction is not easy—a conclusion many nicotine addicts would
agree with.
12-6 reVIeW
Reward
Before you continue, check your understanding.
1. Animals engage in voluntary behaviors because the behaviors are .
2. Neural circuits maintain contact with rewarding environmental stimuli in the present or in
the future through and subsystems.
3. The neurotransmitter systems hypothesized to be basic to reward are ,
, and systems.
4. What is intracranial self-stimulation, and why is it rewarding?
Answers appear at the back of the book.
For additional study tools, visit
www.macmillanhighered.com/launchpad/kolb5e
SUMMary
12-1 Identifying the Causes of Behavior The brain inherently needs stimulation. In its absence, the brain will
Our inner subjective feelings (emotions) and goal-directed thoughts seek it out.
(motivations) influence how we behave and adapt as individuals and as Sensory stimulation leads to hormone activity and to dopamine
a species. Emotion and motivation are inferred states that can escape activity in the brainstem. Neural circuits organized in the brainstem
conscious awareness or intent and make the case for free will difficult control species-typical behaviors, such as mouse killing by cats and
to argue. singing by birds. These brainstem circuits manifest their evolutionary
Biologically, reward motivates animals to engage in behavior. advantage: they are rewarding. Rewarding behavior motivates living
Aversive circumstances prompt brain circuits to produce behaviors beings. When animals disengage from behaviors that motivate their
that will reduce them. Such are the effects of sensory deprivation. species, they go extinct.
440 Chapter 12 • WHAT CAUSES EMOTIONAL AND MOTIVATED BEHAVIOR?
12-2 The Chemical Senses Control of Regulatory and Nonregulatory
12-5
In the olfactory and gustatory senses, chemical neuroreceptors in Behavior
the nose and tongue interact with chemosignals, leading to neural The two distinctly different types of motivated behaviors are
activity in cranial nerve 1 for olfaction and cranial nerves 7, 9, and 10 (1) regulatory (homeostatic) behaviors that maintain vital body system
for taste. The cranial nerves enter the brainstem, and through a series balance and (2) nonregulatory behaviors, basically all nonreflexive
of synapses, pass into the forebrain. Smell and taste inputs merge in behaviors and behaviors not controlled by a homeostatic mechanism.
the orbitofrontal cortex to produce our perception of flavor. Feeding is a regulatory behavior controlled by the interaction of
the digestive and hormonal systems, the enteric nervous system,
12-3 Evolution, Environment, and Behavior and the hypothalamic and cortical circuits. Sexual activity is a
Behavior is controlled by its consequences as well as by its biology.
nonregulatory behavior motivated by the amygdala. Copulatory
Consequences may affect a species’ evolution or an individual’s
behavior is controlled by the hypothalamus (ventromedial
behavior. Behaviors selected by evolution are often triggered by innate
hypothalamus in females and the preoptic area in males). Sexual
releasing mechanisms. Behaviors selected only in an individual animal
orientation (a person’s attraction to the opposite or same sex)
are shaped by that animal’s environment and are learned.
and gender identity (a person’s feeling of being male or female)
Neuroanatomy of Motivated and Emotional
12-4 are related to the organization of the hypothalamus. Differences in
Behavior hypothalamic organization are likely related to epigenetic effects in
The neural structures that initiate emotional and motivated behaviors early development.
are the hypothalamus, pituitary gland, amygdala, the dopaminergic and
noradrenergic activating pathways from nuclei in the lower brainstem, 12-6 Reward
and the frontal lobes. Survival depends on maximizing contact with some environmental
The experience of both emotion and motivation is controlled by stimuli and minimizing contact with others. The reward mechanism
activity in the ANS, hypothalamus, and forebrain, especially the controls this differential. Two independent features of reward
amygdala and frontal cortex. Emotional and motivated behavior may are wanting and liking. The wanting component is thought to
be unconscious responses to internal or external stimuli controlled be controlled by dopaminergic activating systems, whereas the
either by the activity of innate releasing mechanisms or by cognitive liking component is thought to be controlled by opioid and GABA–
responses to events or thoughts. benzodiazepine systems.
Key terMS
amygdala, p. 418 homeostatic mechanism, p. 411 nonregulatory behavior, p. 413 psychosurgery, p. 423
androgen, p. 401 hyperphagia, p. 429 obesity, p. 427 regulatory behavior, p. 411
anorexia nervosa, p. 427 hypovolemic thirst, p. 431 orbitofrontal cortex (OFC), p. 403 reinforcer, p. 409
aphagia, p. 429 innate releasing mechanism osmotic thirst, p. 431 releasing hormone, p. 414
emotion, p. 399 (IRM), p. 406 panic disorder, p. 424 sensory deprivation, p. 401
evolutionary psychology, p. 406 Klüver–Bucy syndrome, p. 423 pheromone, p. 403 sexual dimorphism, p. 433
gender identity, p. 435 learned taste aversion, p. 409 phobia, p. 424 sexual orientation, p. 435
generalized anxiety disorder, medial forebrain bundle (MFB), pituitary gland, p. 413 somatic marker hypothesis,
p. 424 p. 413 p. 421
prefrontal cortex (PFC), p. 418
hippocampus, p. 416 motivation, p. 399 transgender, p. 435
preparedness, p. 409
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
13 Why Do We Sleep
CliniCal FoCus 13-1 Doing the Right thing at the Right time
13-1 a CloCk For all seasons
and Dream?
oRigins of Biological Rhythms
Biological clocks
experiment 13-1 Question: is plant movement exogenous
oR enDogenous?
measuRing Biological Rhythms
fRee-Running Rhythms
ZeitgeBeRs
CliniCal FoCus 13-2 seasonal affective DisoRDeR
13-2 neural Basis oF the BiologiCal CloCk
supRachiasmatic Rhythms
keeping time
pacemaking ciRcaDian Rhythms
researCh FoCus 13-3 synchRoniZing BioRhythms at the
moleculaR level
pacemaking ciRcannual Rhythms
cognitive anD emotional Rhythms
13-3 sleep stages and dreaming
measuRing how long we sleep
measuRing sleep in the laBoRatoRy
stages of waking anD sleeping
a typical night’s sleep
contRasting nRem sleep anD Rem sleep
CliniCal FoCus 13-4 Restless legs synDRome
DReaming
what we DReam aBout
13-4 What does sleep aCComplish?
sleep as a Biological aDaptation
sleep as a RestoRative pRocess
sleep anD memoRy stoRage
13-5 neural Bases oF sleep
ReticulaR activating system anD sleep
neuRal Basis of the eeg changes associateD with waking
neuRal Basis of Rem sleep
13-6 sleep disorders
DisoRDeRs of nRem sleep
CliniCal FoCus 13-5 sleep apnea
Katherine Streeter
DisoRDeRs of Rem sleep
13-7 What does sleep tell us aBout ConsCiousness?
441
442 Chapter 13 • WHY DO WE SLEEP AND DREAM?
CliniCal F cus 13-1
Doing the Right Thing at the Right Time
We have all heard this advice: Maintaining regular sleeping and eating clock that controls feeding responds to eating. Their activity is reciprocal:
habits contributes to good health. Scientific evidence supports this good disrupting one disrupts the other.
advice. Irregular sleep and meal schedules thus change the synchrony of
We humans are diurnal animals (from the Latin dies, meaning biological clocks. Metabolic rate, plasma glucose, and pancreatic insulin
day): we are active during daylight and we sleep when it is dark. This secretion can slow down or speed up at inappropriate times, contribut-
circadian rhythm is the day–night rhythm found in most animals. It ing to obesity and diabetes. Prevention and treatment for obesity and
evolved to maximize food acquisition during the day, when we see best, diabetes can include doing the right thing at the right time when it comes
and to minimize expending our energy stores by sleeping during the to sleep schedules and mealtimes.
night hours, when do not see well.
Today our environment allows us to intrude on our
circadian rhythm in two ways. Artificial lighting allows
us to extend our waking hours well into the night and
into sleep time. Handy food sources—often easily me-
tabolized high-calorie foods—allow us to eat whenever
we want.
Together these intrusions into our natural circa-
dian rhythm contribute to a combination of medical
disorders known as metabolic syndrome that col-
lectively increase the risk of developing sleep disor-
ders, cardiovascular disease, and diabetes (Lajoie
et al., 2015).
The roots of metabolic syndrome lie in disruptions
© antonvengo/superstock
of our biological clock, the neural system that times
behavior. One clock controls sleep–waking. Another
controls the functioning of body organs related to feed-
ing, such as the liver, pancreas, and gut. The clock that
controls sleep–waking responds to light, whereas the
humans and other animals perform a remarkable array of behaviors to adapt to daily
and seasonal cycles. Our daily rhythms of sleeping and waking, feeding, exercising, and social
interaction are rhythmical over days and years. Other animals share these daily activities
and also migrate, hibernate, and shed or grow feathers or fur as the seasons change. In this
chapter we answer questions related to these daily and seasonal rhythms, including how the
brain produces biological rhythms, why sleep evolved, and what neural mechanisms regulate
sleeping, waking, and sleep-related disorders.
13-1 A Clock for All Seasons
We first consider evidence that proved the existence of a biological clock: how the clock
keeps time and how it regulates our behavior. Because environmental cues are not always
consistent, we examine how biological clocks help us interpret environmental cues in an
adaptive way.
Origins of Biological Rhythms
Biorhythms, the inherent timing mechanisms that control or initiate various biological pro-
cesses, are linked to the cycles of days and seasons produced by Earth’s rotation on its axis
and by its progression in orbit around the sun (Figure 13-1). Earth rotates on its axis once
13-1 • A Clock for All Seasons 443
Figure 13-1 Origins of
Biorhythms Each point on
Earth between the Arctic and
Seasons change as Earth Antarctic circles faces the sun
revolves around the for part of its daily rotation
sun. Each revolution cycle (daytime) and faces away
Northern winter takes 1 year. from the sun for the other part
Northern summer
(nighttime). Seasonal changes in
temperature and in the amount
of daylight result from the tilt of
Earth’s axis during its annual
revolution around the sun.
Sun
The tilt of Earth on its Day and night result from rotation of
axis determines seasons. Earth on its axis every 24 hours.
every 24 hours, producing a 24-hour cycle of day and night. The day–night cycle changes
across the seasons, however.
Earth’s axis is tilted slightly, so as it orbits the sun once each year, the North and South
Poles incline slightly toward the sun for part of the year and slightly away from it for the rest
of the year. As the Southern Hemisphere inclines toward the sun, its inhabitants experience
summer: more direct sunshine for more hours each day, and the weather is warmer. At the
same time inhabitants of the Northern Hemisphere, inclined away from the sun, experience
winter: less direct sunlight, making the days shorter and the weather colder. Over the year
the polar inclinations reverse, as do the seasons. Tropical regions near the equator undergo
little seasonal or day length change as Earth progresses around the sun.
Daily and seasonal changes have combined effects on organisms, inasmuch as the onset
and duration of daily change depend on the season and latitude. Animals living in polar
regions have to cope with greater seasonal fluctuations in daily temperature, light, and food
availability than do animals living near the equator.
We humans largely evolved as equatorial animals, and our behavior is dominated by a
circadian rhythm of daylight activity and nocturnal sleep. Nevertheless our daily cycles
adapt to extreme latitudes. Not only does human waking and sleep behavior cycle daily;
so also do pulse rate, blood pressure, body temperature, rate of cell division, blood cell
count, alertness, urine composition, metabolic rate, sexual drive, feeding behavior, and
responsiveness to medications. The activity of nearly every cell in our bodies shares a
daily rhythm.
Biorhythms are not unique to animals. Plants display rhythmic behavior exemplified by diurnal animal Organism that is active
species whose leaves or flowers open during the day and close at night. Even unicellular chiefly during daylight.
algae and fungi display rhythmic behaviors related to the passage of the day. Some animals, circadian rhythm Day–night rhythm.
including lizards and crabs, change color in a rhythmic pattern. The Florida chameleon, for
metabolic syndrome Combinations of
example, turns green at night, whereas its coloration matches its environment during the
medical disorders, including obesity and
day. In short, almost every living organism and every living cell displays rhythms related to insulin abnormalities, that collectively increase
daily changes (Bosler et al., 2015). the risk of developing cardiovascular disease
and diabetes.
Biological Clocks biological clock Neural system that times
If animal behavior were affected only by daily changes in external cues, the neural mecha- behavior.
nisms that account for changes in behavior would be simple to study. An external cue—say, biorhythm Inherent timing mechanism that
sunrise—could be isolated and the neural processes that respond to the cue identified. controls or initiates biological processes.
444 Chapter 13 • WHY DO WE SLEEP AND DREAM?
ExpErimEnt 13-1 That behavior is not driven simply by external cues was first recog-
nized in 1729 by the French geologist Jean Jacques d’Ortous de Mairan
Question: Is plant movement exogenous or endogenous?
(see Raven et al., 1992). In an experiment similar to the one illustrated
in the Procedure section of Experiment 13-1, de Mairan isolated a plant
Procedure
from daily light, dark, and temperature cues. He noted that the rhythmic
The movements of the A pen attached to a movements of its leaves seen over a light–dark cycle continued when it was
plant’s leaves are recorded leaf is moved when isolated as graphed in the Results section of the experiment.
in constant dim light. the leaf moves,… What concerned investigators who came after de Mairan was the pos-
sibility that some undetected external cue stimulates the plant’s rhythmic
Revolving drum
behavior. Such cues could include changes in temperature, in electromag-
netic fields, and even in the intensity of cosmic rays from outer space. But
further experiments showed that daily fluctuations are endogenous—they
Pen come from within the plant. Thus, the plant must have a biological clock.
The contributions of endogenous rhythms to plants is important both to
agriculture and to food storage (Bendix et al., 2015).
Results
Similar experiments show that almost all organisms, including humans,
…producing a record
of the movement. have biological clocks that synchronize behavior to the temporal passage
Leaf of a real day and make predictions about tomorrow. A biological clock sig-
down
nals that if daylight lasts for a given time today, it will last for about the
same time tomorrow. A biological clock allows us to anticipate events and
prepare for them both physiologically and cognitively. And unless external
Leaf up factors get in the way, a biological clock regulates feeding times, sleeping
1 2 3 4 times, and metabolic activity as appropriate to day–night cycles. Biological
Days in continuous dim light clocks also produce epigenetic effects: they regulate gene expression in
Leaf up
every cell in the body (Zhang et al., 2014).
Measuring Biological Rhythms
Although the existence of endogenous biological clocks was demon-
strated nearly 300 years ago, detailed study of biorhythms had to await the
development of electrical and computer-based timing devices. Behavioral
analysis requires a method for counting behavioral events and a method
for displaying those events in a meaningful way. For example, rodent
behavior was first measured by giving the animal access to a running wheel
Leaf down
for exercise (Figure 13-2A).
A computer records each turn of the wheel and displays the result
(Figure 13-2B). Because most rodents are nocturnal, sleeping during light
hours and becoming active during dark hours, their wheel running takes place
in the dark. If each day’s activity is plotted under the preceding day’s activity
Bryan kolb/ian whishaw
in a column, we observe a pattern—a cycle of activity over time. A glance at
the pattern reveals when and how active the animal is (Figure 13-2C).
The animal’s activity cycle has a period, the time required to complete
one cycle of activity. Most animals’ activity period is about 24 hours in an
environment in which the lights go on and off regularly. Our own sleep–
Conclusion: Movement of the plant is endogenous. It is wake period also is about 24 hours. The measurement of periods and the
caused by an internal clock that matches the temporal
events that control them are central to understanding circadian rhythms.
passage of a real day.
Many behaviors have periods longer or shorter than this 24-hour circa-
dian rhythm. Circannual rhythms last about a year. Many animals’ migra-
tory and mating cycles are circannual. Other biorhythms have monthly or seasonal periods
greater than a day but less than a year. These are infradian rhythms. The menstrual cycle and
associated hormonal changes of human females, with an average period of about 28 days,
In Latin circa means about, annum means is an infradian biorhythm linked to the cycle of the moon and thus also referred to as a
year, and dies means day. circalunar cycle (Amariei et al., 2014).
13-1 • A Clock for All Seasons 445
(A) (B) (C)
Animal’s activity
12 noon 6 P.M. Dark 6 A.M. 12 noon
Each wheel rotation is When activity was plotted for a month under
Rat has access to recorded as a tick on a conditions of no light between 6:00 P.M. and
a running wheel. chart. Each line represents 6:00 A.M., the rat was shown to be active
one day’s activity. during dark hours of the day–night cycle.
Figure 13-2 Recording the Daily
Activity Cycle of a Rat Data from
Ultradian rhythms have a period of less than one day. Our eating behavior, which takes C. P. Richter (1965). Biological clocks in medicine and
psychiatry (pp. 12–15). Springfield, IL: Charles C Thomas.
place about every 90 minutes to 2 hours, including snacks, is one ultradian rhythm. Rodents,
although active throughout the night, display an ultradian rhythm in being most active at
the beginning and end of the dark period.
Biological rhythm time frame example
Circannual Yearly Migratory cycles of birds
Circadian Daily Human sleep–wake cycle
Infradian More than a day Human menstrual cycle
Ultradian Less than a day Human eating cycles
The fact that a behavior appears to be rhythmic does not mean that it is ruled only by a
biological clock. Animals may postpone migrations as long as food supplies last. They adjust
their circadian activities in response to the availability of food, the presence of predators,
and competition from other members of their own species. We humans obviously change
our daily activities in response to seasonal changes, work schedules, and play opportunities.
Therefore, whether a rhythmic behavior is produced by a biological clock and the extent to
which it is controlled by a clock must be demonstrated experimentally.
Free-Running Rhythms
To determine whether a rhythm is produced by a biological clock, researchers design three
types of tests in which they manipulate relevant cues, especially light cues. A test is given
(1) in continuous light, (2) in continuous darkness, or (3) by choice of the participant. Each
treatment yields a slightly different insight into the periods of biological clocks.
Jurgen Aschoff and Rutger Weber first demonstrated that the human sleep–waking
rhythm is governed by a biological clock. They allowed participants to select their light–dark
cycle and studied them in an underground bunker, where no cues signaled when day began
or ended. The participants selected the periods when they were active and when they slept,
and they turned the lights on and off at will. In short they selected the length of their own
day and night.
Measures of ongoing behavior and recording of sleep periods with sensors on the beds
revealed that the participants continued to show daily sleep–activity rhythms. This finding
demonstrates that humans have an endogenous biological clock that governs sleep–waking
behavior. Figure 13-3 shows, however, that the biorhythm is different when compared with
biorhythms before and after isolation. Although the period of the participants’ sleep–wake
cycles approximated 24 hours before and after the test, during the test they lengthened to period Time required to complete an activity
about 25 to 27 hours, depending on the person. cycle.
446 Chapter 13 • WHY DO WE SLEEP AND DREAM?
Free-Running Rhythm in
Figure 13-3 Waking periods of participant placed in
a Human The record for days 1 through the bunker began to change because there
3 shows the daily sleep period under Dark Light were no cues to light and dark periods. The
typical day–night conditions. The record for period period purple lines represent daily activity rhythm.
days 4 through 20 shows the free-running Before
1
rhythm that developed while this participant bunker
was isolated in a bunker and allowed to
control day and night lengths. The daily 5 Over time, the participant in
activity period shifts from 24 hours to the bunker was getting up at
25.9 hours. On days 21 through 25 about the time experimenters
the period returns to 24 hours as the 10 outside the bunker were
going to bed. In
participant is again exposed to a natural bunker
Days
light–dark cycle. Data from J. A. Hobson (1989).
Sleep (p. 33). New York: Scientific American Library. 15
20
After
bunker
25
0 8 16 24 8 16 24 8 16 24 8
Hour of day
The participants chose to go to bed 1 to 2 hours later every “night.” Soon they were getting
up at about the time the experimenters outside the bunker were going to bed. Clearly. the
participants were displaying their own personal cycles. Such a free-running rhythm runs at
a frequency of the body’s own devising when environmental cues are absent. Humans’ self-
selected free-running rhythm is slightly longer than 24 hours.
The period of free-running rhythms also depends on the light-related biology of the spe-
cies. When hamsters, a nocturnal species, are tested in constant darkness, their free-running
periods are a little shorter than 24 hours; when they are tested in constant light, their free-
running periods are a little longer than 24 hours. This test dependency is typical of noctur-
nal animals. As Figure 13-4 shows, the opposite free-running periods are typical of diurnal
animals (Binkley, 1990). When sparrows, diurnal birds, are tested in constant darkness, their
free-running periods are a little longer than 24 hours; when they are tested in constant light,
their free-running periods are a little shorter than 24 hours.
A rule of thumb to explain the period of free-running rhythms in light or dark is that ani-
mals expand and contract their sleep periods as the sleep-related period—light for hamsters
and dark for sparrows—expands or contracts. Understanding this point enables us to predict
how excess artificial lighting, which expands the light portion of our days, influences our
circadian periods. Because we are diurnal, our sleep periods contract and we get less sleep
each night.
Zeitgebers
Endogenous rhythmicity is not the only factor that contributes to circadian periods. A mech-
free-running rhythm Rhythm of the body’s anism exists for setting rhythms to correspond to environmental events as well. To be useful,
own devising in the absence of all external the biological clock must keep to a time that predicts actual changes in the day–night cycle.
cues.
If a biological clock is like a slightly defective wristwatch, it will eventually provide times that
Zeitgeber Environmental event that entrains are inaccurate by hours and so be useless.
biological rhythms: German for time giver. If we reset an errant wristwatch each day, however—say, when we awaken—it provides
entrain Determine or modify the period of a useful information even though it is not perfectly accurate. Equivalent ways of resetting a
biorhythm. free-running biological clock include sunrise and sunset, eating times, and many other activi-
light pollution Exposure to artificial light ties that influence the period of the circadian clock.
that changes activity patterns and so disrupts Aschoff and Weber called a clock-setting cue a Zeitgeber (time giver in German). When
circadian rhythms. a Zeitgeber resets a biorhythm, the rhythm is said to be entrained. Light is the most potent
13-1 • A Clock for All Seasons 447
House sparrow Figure 13-4 Free-Running Rhythms
of a Diurnal Animal Data from S. Binkley
(1990). The Clockwork Sparrow (p. 16). Englewood Cliffs
Each line Blips represent
NJ: Prentice Hall.
represents a day. hops on a perch.
Constant darkness for 18 days
When tested in constant
darkness, sparrows (which
are diurnal birds) extend
their free-running periods
to a little more than 24
hours.
Constant light for 16 days
When tested in constant
light, sparrows contract
their free-running
periods to a little less
than 24 hours and are
much more active
throughout the
testing period.
entraining stimulus. Clinical Focus 13-2, Seasonal Affective Disorder, explains its impor-
tance in entraining circadian rhythms.
The property that allows a biological clock to be entrained explains how circadian
rhythms synchronize with seasonal changes in day–night duration. North and south of the
equator the time of onset and the length of day and night change as the seasons progress. At
extreme latitudes daylight begins very early in the morning in summer and very late in the
morning in winter. An entrained biological clock allows an animal to synchronize its daily
activity across these seasonal changes.
A biological clock that resets each day tells an animal that daylight will begin tomorrow at
approximately the same time that it began today and that tomorrow will last approximately
as long as today did. Current research finds that light Zeitgebers are effective at both sunrise
and sunset: morning light sets the biological clock by advancing it, and evening darkness sets
the clock by retarding it (Schmal et al., 2015).
The potent entraining effect of light Zeitgebers is illustrated by laboratory studies of
Syrian hamsters, perhaps one of the most compulsive animal timekeepers. When given
access to running wheels, hamsters exercise during the night segment of the laboratory
If a hamster happens to blink during this
day–night cycle. A single brief flash of light is an effective Zeitgeber for entraining their Zeitgeber, the light will still penetrate its
biological clocks. closed eyelids and entrain its biological
Considering the less compulsive behavior that most of us display, we should shudder at clock.
the way we entrain our own clocks when we stay up late in artificial light, sleep late some
days, and get up early by using an alarm clock on other days. Light pollution, the extent to
which we are exposed to artificial lighting, disrupts circadian rhythms and accounts for a
great deal of inconsistent behavior associated with accidents, daytime fatigue, alterations in
emotional states, obesity, diabetes, and other disorders characteristic of metabolic syndrome
described in Clinical Focus 13-1, Doing the Right Thing at the Right time (Gerhart-Hines
& Lazar, 2015).
Entrainment works best if the adjustment made to the biological clock is not too large.
People who work night shifts are often subject to huge adjustments, especially when they
448 Chapter 13 • WHY DO WE SLEEP AND DREAM?
CliniCal F cus 13-2
Seasonal Affective Disorder
In seasonal affective disorder (SAD), a form of depression, low levels of A word of caution, however. Decreased exposure to sunlight in winter
sunlight in winter, do not entrain the circadian rhythm. Consequently, a can result in Vitamin D deficiency and is also suggested to contribute to
person’s biorhythm becomes a free-running rhythm. The perception of depression (Kerr et al., 2015).
longer nights by the circadian pacemaker stimulates wanting more sleep.
If the want is not satisfied, cumulative sleep deprivation can result.
Because people vary in the duration of their free-running rhythms,
lack of entrainment affects individuals differently. Some are phase-
retarded, with desired sleep time coming earlier each day; some are
phase-delayed, with desired sleep time coming later each day.
The cumulative changes associated with altered circadian rhythms
can promote depression. The finding that incidence of depressive symp-
Bryan and cherry alexander/science source
toms increases as a function of the latitude at which a person lives
supports this idea.
Because a class of retinal ganglion cells that express a photosensitive
pigment called melanopsin are responsive to blue light (see Section 13-2),
it has been proposed that exposure to bright white light that contains this
blue frequency can reset the circadian clock and ameliorate depression.
In this treatment, called phototherapy, the idea is to increase the short
winter photoperiod by exposing a person to artificial bright light in the
morning or both morning and evening (Mårtensson et al., 2015). Typical During the polar night in northern Norway schoolchildren take
room lighting is not bright enough. light treatment to combat SAD.
work the graveyard shift (11:00 p.m. to 7:00 a.m.), the period when they would normally
sleep. Study results show that adapting to such a change is difficult and stressful, and
it increases susceptibility to disease by altering immune system rhythms (Labrecque &
Cermakian, 2015). Compared with people who have a regular daytime work schedule,
people who work night shifts have a higher incidence of metabolic syndrome. Thus, shift
workers benefit from vigilance in maintaining good sleep habits and diet and in exercising
to minimize other risk factors for metabolic syndrome. Adaptations to shift work fare bet-
ter if people first work the swing shift (3:00 p.m. to 11:00 p.m.) for a time before beginning
the graveyard shift.
Long-distance air travel—say from North America to Europe or Asia—also demands
large and difficult time adjustments. For example, travelers flying east from New York
to Paris begin their first day in Europe just when their biological clock is signaling that
it is time for sleep (Figure 13-5). The difference between a person’s circadian rhythm
and the daylight cycle in a new environment can produce the disorientation and fatigue
of jet lag.
The west-to-east traveler generally has a more difficult adjustment than does the east-to-
west traveler, who needs to stay up only a little longer than usual. The occasional traveler
may cope with jet lag quite well, but frequent travelers such as airline personnel face a sub-
stantial adaptive challenge. The occasional traveler can manage jet lag with sleep on arrival
or shortly after. The brain’s biological clock resets in a day and other body organs follow
after about a week. For frequent travelers and flight crews, resetting is not so easy. Persistent
jet lag Fatigue and disorientation resulting asynchronous rhythms generated by jet lag are associated with altered sleep and tempera-
from rapid travel through time zones and ture rhythms, fatigue, and stress, even reduced success by sports teams traveling more than
exposure to a changed light–dark cycle. 3 hours from west to east (Weingarten and Collop, 2013).
13-1 • A Clock for All Seasons 449
1 Traveler leaves New York at 2 Traveler arrives in Paris at 9:00 A.M., when it’s 3:00 A.M. in New
9:00 P.M., when it’s 3:00 A.M. in York. Because his biological clock is set for New York time, he is
Paris. prepared for sleep, whereas residents of Paris are waking.
Paris (3:00 A.M.) New York (3:00 A.M.) Paris (9:00 A.M.)
West-to-east travel
(6-hour flight)
New York (9:00 P.M.)
Paris (3:00 A.M.)
East-to-west travel
New York (9 PM) (6-hour flight)
Paris (9:00 P.M.) New York (3:00 P.M.)
New York (9:00 P.M.)
4 Traveler arrives in New York at 9:00 P.M. 3 Traveler leaves Paris at 9:00 P.M., when
and needs to stay up only a little longer than it’s 3:00 P.M. in New York.
normal for his biological clock to adjust.
Figure 13-5 Jet Lag Disruption in the entrainment of a person’s biological clock is
undoubtedly more pronounced in west-to-east jet travel because the disruption in the
person’s circadian rhythm is dramatic. On the return journey the traveler’s biological clock
has a much easier adjustment to make.
13-1 reVieW
A Clock for All Seasons
Before you continue, check your understanding.
1. Many behaviors occur in a rhythmic pattern in relation to time. These biorhythms may
display a yearly, or , cycle or a daily, or , cycle.
2. Although biological clocks keep fairly good time, their rhythms may be
slightly shorter or longer than 24 hours unless they are reset each day by .
3. and can disrupt circadian rhythms.
4. Explain why the circadian rhythm is important.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
450 Chapter 13 • WHY DO WE SLEEP AND DREAM?
13-2 Neural Basis of the
Biological Clock
Curt Richter (1965) was the first researcher who attempted to locate biological clocks in the
brain. In the 1930s he captured wild rats and tested them in activity wheels. He found that
the animals ran, ate, and drank when the lights were off and were relatively quiescent when
the lights were on.
By ablating brain tissue with electric current, Richter found that animals lost their
circadian rhythm after damage to the hypothalamus. Subsequently, by making much
more discrete lesions, experimenters have shown that a region of the hypothalamus, the
suprachiasmatic nucleus (SCN), acts as the master biological clock (Webb et al., 2014). The
SCN is named for its location just above (supra-) the optic chiasm, where the optic tracts cross
at the base of the hypothalamus.
ian whishaw
Suprachiasmatic Rhythms
Evidence for the SCN’s role in circadian rhythms now comes from additional lines of
evidence:
Optic Suprachiasmatic Hypothalamus 1. If the suprachiasmatic nuclei are selectively damaged, animals still eat, drink, exercise,
chiasm nucleus
and sleep but at haphazard times.
Suprachiasmatic Nucleus in a 2. If a form of glucose is tagged with a radioactive label, taken up by metabolically active cells,
Rat Brain
and trapped in them but not used by them, cells that are more active will subsequently
emit more radioactivity. When this tracer is injected into rodents, more is found in the
SCN after injections given in the light period of the light–dark cycle than in the dark
period. This experiment demonstrates that suprachiasmatic cells are more active during
the light period.
3. Recording electrodes placed in the SCN confirm that neurons in this region are more
suprachiasmatic nucleus (scn) Master active during the light period of the cycle than during the dark period.
biological clock located in the hypothalamus
just above the optic chiasm. 4. If all the pathways into and out of the suprachiasmatic nucleus are cut, SCN neurons
maintain their rhythmic electrical activity.
retinohypothalamic tract Neural route
formed by axons of photosensitive retinal 5. SCN cells removed from the brain and cultured in a dish retain a periodic rhythm.
ganglion cells from the retina to the Clearly, suprachiasmatic neurons have an intrinsically rhythmic activity pattern. Although
suprachiasmatic nucleus; allows light to
the SCN is the master biological clock, it is not the sole one. Two other neural structures, the
entrain the rhythmic activity of the SCN.
intergeniculate leaflet and the pineal gland, also display clocklike activity. Further, nearly
chronotype Individual differences in every cell in the body has its own clock.
circadian activity. After the SCN is destroyed, some behaviors retain a timed occurrence. One is feeding.
Animals without an SCN can still display anticipatory behavior—becoming active in relation
to scheduled mealtimes—and can organize related behaviors, including memory for food
locations, in relation to mealtimes (Landgraf et al., 2015). How this anticipatory behavior is
timed is not known, but whatever the mechanism, feeding-related activity can act as a Zeit-
geber for the main SCN clock. That is, a regular feeding schedule can entrain the SCN clock
and many other body organs, and cells and an irregular feeding schedule can be disruptive.
Keeping Time
If SCN neurons are isolated from one another, each remains rhythmic, but the period of
some cells differs from that of other cells. Thus rhythmic activity is a property of SCN cells,
but the timing of the rhythm must be set so that the cells can synchronize their activity in
relation to each other. In the brain, SCN cells connect one to another through inhibitory
GABA is main inhibitory neurotransmitter in GABA synapses, and these connections allow them to act in synchrony. Their entrainment
the CNS. depends upon external inputs, however.
13-2 • Neural Basis of the Biological Clock 451
The SCN receives information about light through the retinohypothalamic tract
( Figure 13-6). This pathway begins with specialized retinal ganglion cells (RGCs) that con- Section 9-2 traces three main routes from
tain the photosensitive pigment melanopsin. These melanopsin-containing photosensitive the retina to the visual brain. Figure 9-8
RGCs receive light-related signals from the rods and cones and send that information to diagrams the retina’s cellular structure.
the brain’s visual centers. Melanopsin-containing pRGCs also can be activated directly by
certain wavelengths of blue light in the absence of rods and cones.
Melanopsin-containing photosensitive RGCs are distributed across the retina, and in
humans they make up between 1 percent and 3 percent of all RGCs. Their axons project
to various brain regions, including the SCN, which they innervate bilaterally. Melanopsin-
containing ganglion cells use glutamate as their primary neurotransmitter but also contain Glutamate is the main excitatory
two cotransmitters, substance P and pituitary adenylate cyclase–activating polypeptide neurotransmitter in the CNS.
(PACAP).
When stimulated by light, melanopsin-containing pRGCs are excited, and in turn they
excite cells in the SCN. The existence of light-sensitive retinal ganglion cells that are in-
volved in entraining the circadian rhythm explains the continued presence of an entrained
rhythm in people who are blind as a result of retinal degeneration that destroys the rods and
cones (Zaidi et al., 2007). Even so, melanopsin-containing pRGCs do receive inputs from
cones and rods. Cones can influence their activity in bright daylight, and rods can influence
their activity in dim light.
As illustrated in Figure 13-6, the SCN consists of two parts, a more ventrally located core
and a more dorsally located shell. The retinohypothalamic tract activates the core cells. Core
neurons are not rhythmic, but they entrain the shell neurons, which are rhythmic.
In addition to retinohypothalamic input, the SCN receives projections from other brain
regions, including the intergeniculate leaflet in the thalamus and the raphe nucleus, which
is the nonspecific serotonergic-activating system of the brainstem. The terminal regions of
these inputs to the SCN display variations, suggesting that various portions of the shell and
the core have somewhat different functions.
The SCN’s circadian rhythm is usually entrained by morning and evening light, but it
can also be entrained or disrupted by sudden changes in lighting, by arousal, by moving
about, and by feeding. These influences differ from the light entrainment provided over the
retinohypothalamic tract.
Figure 13-6 The Retinohypothalamic
The intergeniculate leaflet and the raphe nucleus Tract and the SCN
are pathways through which nonphotic events influ-
Suprachiasmic nucleus
ence the SCN rhythm (Cain et al., 2007). The neural
structures mediating these other entraining pathways
SCN drives slave oscillators
explain why being aroused or eating during the sleep Other input (diagrammed in Figure 13-8)
portion of the circadian cycle disrupts the cycle and output and receives signals from
Third
(Mistlberger & Antle, 2011). ventricle other brain and body areas.
It is likely that the regional variation in SCN shell
anatomy provides the substrate for various rhythms of Shell
the circadian cycle. Findings from studies on the genes Signal from SCN core
that control rhythms in fruit flies suggest two separate neurons entrains
Core shell neurons.
groups of circadian neurons. M cells control morning ac-
tivity; they need morning light for entrainment. E cells
Retinohypothalamic
control evening activity; they need onset of darkness tract carries
Optic
for entrainment (Hughes et al., 2015). chaism
information about
Some people are early to bed and early to rise and light changes to core
Retinohypothalamic cells in the SCN.
are energetic in the morning. Other people are late to
tract
rise and late to bed and are energetic in the evening. In-
Photosensitive retinal
dividual differences in circadian activity between these Retina ganglion cells respond
“lark” and “owl” chronotypes are due to differences in to blue light.
SCN shell neurons. The differences may be the equiva-
lent of fruit fly M cells and E cells, When expressed
452 Chapter 13 • WHY DO WE SLEEP AND DREAM?
Healthy differently in people, genes may account for differences in the amplitude of
Normal free-running rhythm
phases in the circadian period. (Pellegrino et al, 2015). Whether students are
in constant darkness
larks or owls does affect their performance on cognitive tasks, possibly by affect-
ing memory for content (Smarr, 2015).
In hamsters and mice, mutant gene variations produce chronotypes with cir-
cadian periods as varied as 24, 20, or 17 hours (Monecke et al., 2011). As genetic
analysis becomes less expensive, the study of the genes underlying human chro-
notypes is providing insights into individual differences in our biological clocks
(Kang et al., 2015).
Suprachiasmatic lesion Absence of circadian rhythm
Immortal Time
in a light–dark environment How do suprachiasmatic cells develop rhythmic activity? Their endogenous
rhythm is not learned. When animals are raised in constant darkness, their be-
havior still becomes rhythmic. In experiments in which animals have been main-
tained without entraining cues for a number of generations, each generation
continues to display rhythmic behavior. Even if the mother has received an SCN
lesion so that her behavior is not rhythmic, her offspring’s behavior is rhythmic.
A line of evidence supporting the idea that suprachiasmatic cells are geneti-
cally programmed for rhythmicity comes from studies performed in Canada
by Martin Ralph and his coworkers with the use of transplantation techniques
(Ralph & Lehman, 1991). Figure 13-7 illustrates the experiment.
Suprachiasmatic transplant Normal free-running rhythm As reflected in the top chart, hamsters are tested in constant dim light or in
in constant darkness
restored by transplant constant darkness to establish their free-running rhythms. They then receive a
suprachiasmatic lesion followed by another test to show that the lesion has abol-
ished their rhythmicity (center chart). Finally, the hamsters receive transplants
of suprachiasmatic cells obtained from hamster embryos. About 60 days later
the hamsters again show rhythmic activity, demonstrating that the transplanted
cells have been integrated into the host brain and have reestablished rhythmic
behavior (bottom chart). Follow-up studies show that the rhythms of many but
not all body organs also show restored rhythmic activity.
0 24
Time (hours)
What Ticks?
Circadian Rhythms Restored by
Figure 13-7
Molecular research is directed toward determining what genes control the tick-
Neural Transplantation Information from M. R. Ralph
ing of the circadian clock. The timing device is in each SCN neuron and in most
& M. N. Lehman (1991). Transplantation: A new tool in the analysis of the
mammalian hypothalamic circadian pacemaker. Trends in Neurosciences, 14, other cells of the body as well.
p. 363. The circadian rhythm involves a feedback loop in which proteins are first
made and then combine. The combined protein, called a dimer, for two pro-
teins, inhibits production of its component proteins. Then the dimer degrades and the
process begins anew. Research Focus 13-3, Synchronizing Biorhythms at the Molecular
Level, describes the main feedback loop in mammals. Just as the back-and-forth swing
of a pendulum makes a grandfather clock tick, the increase and decrease in protein syn-
Figure 3-13 diagrams the process of protein thesis once each day produce the cellular rhythm.
synthesis.
Pacemaking Circadian Rhythms
The SCN itself is not directly responsible for producing behavior. After it has been damaged,
drinking and eating, sleeping and wakefulness still occur. They no longer occur at appropri-
ate times, however.
An explanation for how the SCN controls biological rhythms is illustrated in Figure 13-8.
In this model, light entrains the SCN, and the SCN in turn drives a number of slave oscilla-
tors. Each slave oscillator is responsible for the rhythmic occurrence of one activity. In other
words, drinking, eating, body temperature, and sleeping are each produced by a separate
dimer Two proteins combined into one. slave oscillator.
13-2 • Neural Basis of the Biological Clock 453
researCh F cus 13-3
Synchronizing Biorhythms at the Molecular Level
The retinohypothalamic tract carries information about light changes step 4: deCay After they play their inhibitory role, the PERCRY proteins
from the melanopsin-containing photosensitive retinal ganglion cells decay. Then the CB dimer resumes its activity, the Per and Cry genes
to the core of the SCN, the brain’s main biological timekeeper (see resume expression, and the 24-hour cycle begins anew.
Figure 13-6). Core cells synapse with SCN neurons in the shell and This sequence of gene turn-on followed by gene turn-off occurs in
entrain the SCN shell cells to the light signal’s 24-hour rhythm. an inexorable daily loop.
The timing mechanism in the shell cells is a pair of interlocking Mutations in any circadian gene can lead to circadian alterations,
feedback loops that pace the SCN’s function over a 24-hour period. including absence of a biorhythm or an altered biorhythm. For example,
The complete clockwork in the two feedback loops involves as many alleles of Period 1 and Period 2 genes determine chronotype—whether
as 10 genes and their protein products. The secondary loop regulates an individual will be early to bed and early to rise or late to bed and late
functions for the main clockwork loop. to rise. The search for therapies for clock disorders includes looking for
The main clock mechanism is the transcription-translation-inhibition- small molecules that can act as drugs to reset biorhythms disrupted by
feedback loop. Its sequence, mapped in the illustration, follows: jet lag, shift work, and epigenetic and inherited gene irregularities.
step 1: transCription In the cell nucleus three Period genes (Per1,*
Per2, Per3) and two Cryptochrome genes (Cry1, Cry2) are transcribed
into Per1, Per2, and Per3 messenger RNA and Cry1 and Cry2 mRNA. PER
step 2: translation Ribosomes in the endoplasmic reticulum trans-
late these mRNAs into the proteins PER1,† PER2, PER3, and CRY1, CRY2. PER CRY
C B
In the intracellular fluid the proteins form various dimers, or two-protein Ebox PER
combinations of PERCRY. PER CRY Period Per
mRNA
step 3: inhiBition PERCRY dimers enter the cell nucleus, where they Inhibition Transcription Translation
C B
bind to and inhibit the CB dimer (formed by the CLOCK and BMAL proteins). Cry
Nucleus Ebox
The CB dimer turns on the Enhancer box (Ebox), a part of the DNA that mRNA
Cryptochrome
activates transcription of the Period and Cryptochrome genes, so that when
CRY
the CB dimer is inhibited, the Per and Cry genes are no longer expressed. CRY
Cytoplasm
*
Gene and mRNA names are italicized.
†
PROTEIN names are capitalized. Main SCN Clock Mechanism
The SCN clock entrains slave oscillators through a remarkable array of pathways:
1. SCN neurons send axonal connections to nuclei close by in the hypothalamus and
thalamus. These nuclei in turn connect extensively with other brain and body structures,
to which they pass on the entraining signal.
2. The SCN connects with pituitary endocrine neurons to control hormone release. A wide Figure 12-14 diagrams how the pituitary gland
range of hormones circulates through the body to entrain many body tissues and organs. works.
The pacemaker has a …which in turn control
rhythm that drives functions that exhibit
Light information from …entrains the suprachiasmatic
“slave” oscillators, … circadian activity.
photosensitive RGCs… nucleus pacemaker.
Slave oscillators Circadian functions
Pacemaker
Motor activity
pRGCs
Entrainment Output
pathways pathways
Light
Eating
Retina
1 2 3 Body temperature
Days
Figure 13-8 Circadian Timing System Organization
454 Chapter 13 • WHY DO WE SLEEP AND DREAM?
3. The SCN also sends indirect messages to autonomic neurons in the spinal cord to inhibit
melatonin Hormone secreted by the pineal
the pineal gland from producing the hormone melatonin, which influences daily and
gland during the dark phase of the day–
seasonal biorhythms.
night cycle; influences daily and seasonal
biorhythms. 4. SCN cells themselves release hormones. Silver and colleagues (1996) used a transplantation
technique in which encapsulated SCN cells were transplanted into hamsters that
had received SCN lesions. Even though the transplanted cells did not make axonal
connections, they restored many circadian behaviors, indicating that some SCN signals
must be hormonal and travel through the bloodstream.
An illustration of the SCN’s widespread effects is its control of two hormones, melatonin
and glucocorticoids. The SCN controls melatonin release from the pineal gland so that
melatonin circulates during the dark phase of the circadian cycle. It also controls the release
of glucocorticoids from the adrenal glands so that they circulate during the light phase of
the circadian cycle.
Melatonin promotes sleep and influences the parasympathetic rest-and-digest system
as well as other physiological events in the body. Glucocorticoids mobilize glucose for
Figure 2-30 diagrams the autonomic cellular activity to support arousal responses in the sympathetic system. These two hor-
nervous system. Section 6-5 describes how mones will entrain any body organ that has receptors for them, and most organs do. Thus
glucocorticoids affect the body and brain. melatonin promotes rest activities, and glucocorticoids promote arousal activities during
the dark and the light portions of the circadian cycle, respectively. Their actions explain
in part why it is difficult to sleep during the day and stay awake to work at night. The
role of melatonin as a slave oscillator in part explains its use as a drug for regulating sleep
(Claustrat & Leston, 2015).
Pacemaking Circannual Rhythms
The suprachiasmatic nucleus controls not only daily rhythms but circannual rhythms as
well. Russel Reiter (1980) first illustrated this form of pacemaking in hamsters. Hamsters are
summertime (long-day) breeders. As the days lengthen in springtime, the gonads of male
hamsters grow and release hormones that stimulate sexual behavior. As the days shorten in
the winter, the gonads shrink, the amount of the hormones they produce decreases, and the
males lose interest in sex.
During the dark phase of the day–night cycle the pineal gland secretes melatonin; during
the light phase it does not. Figure 13-9 shows that when a male hamster’s melatonin level
is low, the gonads enlarge, and when the level is high, the gonads shrink. The SCN thus
Spring As daylight lengthens in summer,
melatonin production decreases, allowing
gonads to grow and to increase hormone
production to stimulate sexual behavior.
Gonadal size
Light Dark Gonadal size Light Dark
Melatonin Melatonin
level level
Less
More
testosterone
testosterone
Winter Summer
Figure 13-9 Hamster’s Circannual
As daylight shortens in winter,
increases in melatonin levels cause
Pacemaker Information from R. J. Reiter (1980). gonads to shrink, decreasing hormone
The pineal and its hormones in the control of reproduction Fall
production and sexual interest.
in mammals. Endocrinology Review, 1, p. 120.
13-2 • Neural Basis of the Biological Clock 455
controls the pineal gland’s sway over the gonads. Through connections in the autonomic
nervous system the SCN drives the pineal gland as a slave oscillator.
During the long daylight period of the circadian cycle the SCN inhibits melatonin secretion
by the pineal gland. As the days become shorter, the melatonin inhibition period shortens and
the release period lengthens. When the daylight period is shorter than 12 hours, melatonin
release time becomes sufficient to inhibit the hamster’s gonads, and they shrink. Melatonin
also influences the testes of short-day breeders, such as sheep and deer, that mate in the fall
and early winter. Melatonin’s effect on reproductive behavior in these species is the reverse of
that in the hamster: reproductive activities begin as melatonin release increases.
The SCN’s influence on circadian and circannual cycles is proposed to contribute to obe-
sity in humans (Gangwisch, 2014). The idea is that long daylight hours involve fueling high-
energy demanding activities during summer and thus extra food consumption. If a person is
exposed to light pollution during winter, increased food consumption continues throughout
the year, leading to weight gain. Light exposure can come from surprising sources. Some
street lamps, reading lights, and e-readers emit blue-light wavelengths that activate pRGCs
and through the SCN suppress melatonin (Chang et al., 2015). Thus, incidental light pollu- Figure 13-10 Dysfunctional Clock?
tion can contribute to obesity. Attacks of mental illness displayed by the
English writer Mary Lamb through her
In his classic book Biological Clocks in Medicine and Psychiatry, Curt Richter (1965)
adult life appear to have had a cyclical
hypothesized that many physical and behavioral disorders might be caused by shocks, ei- component. Such observations would be
ther physical or environmental, that upset the timing of biological clocks. For example, the difficult to obtain today because the drugs
record of psychotic episodes of the English writer Mary Lamb illustrated in Figure 13-10 is used to treat psychiatric disorders can
one of many rhythmic records that Richter thought represented the action of an abnormally mask disordered biorhythms. Information from
C. P. Richter (1965). Biological clocks in medicine and
functioning biological clock.
psychiatry (p. 92). Springfield IL: Charles C Thomas.
29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 63 65 67 69 71 73 75 77 79 81 83
Age
Cognitive and Emotional Rhythms
Circadian rhythms are synchronized in many parts of the body. In a phasic manner they
influence cognitive and emotional functions, including emotional experience, learning and
retention, decision making, and motivation. The extent to which a process depends on the
expenditure of metabolic energy dictates optimal times for its activity during the circadian
cycle: time of day can serve as a good index for the time and place at which things should
happen. Studies suggest that as much as 10 percent of the genome is under the epigenetic
control of circadian rhythms.
Many cognitive events require changes in gene expression. Animals remember previous
events better if they are tested at the time of the circadian period when the initial event
occurred. Donald Cain and his colleagues (2008) used a conditional place response to test
rats’ memories for a location at which they had previously received a small foot shock. The
rats receive the noxious stimulation in a test box, then are returned to their home cage.
The following day groups of rats are tested at the time of training or a different time. Rats
trained at time 1 and tested at time 1 show better retention as measured by the time they
spent immobile (freezing) than rats trained at time 1 and tested at time 2, six hours later in
the day. Similarly, rats trained at time 2 and tested at time 2 show better retention than rats
trained at time 2 and tested at time 1, six hours earlier in the day. The results show that the
circadian cycle puts a time stamp on the memory that allows it to be better recalled at the
same time of the period that the initial event occurred.
Cognitive behaviors also synchronize with circadian periods. Animals have a variety of
needs for food, water, and sleep, and it is adaptive for them to know when these resources
become available. If food is available on a schedule, animals display anticipatory behav-
iors, becoming active as the feeding time arrives, for example. Other anticipatory events
456 Chapter 13 • WHY DO WE SLEEP AND DREAM?
include salivation, intestinal activity, and sensations of hunger. Anticipatory activity might
also include recalling events related to the timing of feeding and food location. Many cogni-
tive activities can occur in the absence of the SCN, but it is adaptive for them to occur at
the right time and place. SCN activity enables this. As animals age, their ability to associate
appropriate activity with appropriate time declines, impairing their daily schedule, an effect
that might in part account for poor scheduling and sleep in some older humans (Mulder
et al., 2015).
Studies also find that the circadian period influences emotional behavior. A time of day
effect may account for some of our emotional responses to daily events independent of the
events themselves (Li et al., 2015). Nighttime fear is common, but is it the dark or the nighttime
circadian rhythm that accounts for heightened emotion? By independently varying lighting con-
ditions and test times during the circadian cycle, Li and colleagues found heightened emotional
responses to stimuli at night independent of ambient lighting. Thus the cycle, not just darkness,
contributes to emotional responding. Apparently at least two factors explain why horror movies
watched at night are scarier: the movie’s content and the time of day effect.
13-2 reVieW
Neural Basis of the Biological Clock
Before you continue, check your understanding.
1. Biological rhythms are timed by internal biological clocks. The master clock is
the .
2. Light cues entrain the suprachiasmatic nucleus to control daily rhythms via
the tract, which receives information via cells.
3. Pacemaking produced by the SCN is a product of its cells, which activate
slave oscillators via both signals and connections.
4. Why should studying for an exam and taking the exam occur at the same time of day?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
13-3 Sleep Stages and Dreaming
Waking behavior encompasses periods when we are physically active or inactive, and so
does sleep. Our sleeping behavior consists of periods of rest, napping, long bouts of sleep,
and sleep-related events, including snoring, dreaming, thrashing about, even sleepwalking.
In this section we describe some sleeping and dreaming behaviors and the neural processes
Recommended sleep Duration by age underlying them.
age
Sleep time
(hours) Measuring How Long We Sleep
Newborn up to 3 months 14–17 A crude measure of sleeping and waking behavior is the self-report: people record in a diary
Infant under 1 year 12–15 when they wake and when they retire to sleep. The diaries show both optimal average sleep
durations and considerable variation in sleep–waking behavior. An optimal sleep time of 7 to
Toddler up to 3 years 11–14
8 hours per night is a popular adage, but many exceptions exist. People sleep more when they
Preschool 10–13
are young, after engaging in physical activity, or when pregnant. Some people are long sleep-
Elementary-school age 9–11
ers; some are short sleepers. Numerous genetic mutations have been identified in people
Adolescent 8–10 displaying very short sleep durations—as short as 1 hour.
Adult 7–9 Some people nap for a brief period in the daytime; others never nap. Benjamin Franklin
Adult 65 years and older 7–8 is credited with the aphorism “early to bed and early to rise makes a man healthy wealthy
Source: Information from National Sleep Foundation and wise,” but measures of sleep behavior indicate that the correlation Franklin proposed
13-3 • Sleep Stages and Dreaming 457
(A) Electroencephalogram (EEG)
(B) Electromyogram (EMG)
hank morgan/getty images
(C) Electrooculogram (EOG)
Figure 13-11 Sleep Laboratory Setup Electronic equipment
records readouts from electrodes attached to the sleeper. (A) EEG
made from a point on the skull relative to a neutral point on the ear.
(B) EMG made between two muscles, such as those on the chin and
throat. (c) EOG made between the eye and a neutral point on the ear.
does not actually exist. Variations in sleeping times are normal, and napping normally
is good.
Measuring Sleep in the Laboratory
Laboratory sleep studies allow researchers to measure sleep accurately and to record physi-
ological changes associated with sleep. Miniaturized sleep-measuring technology and data
compression now allow laboratory methods to be extended into the home (Lan et al., 2015).
Measuring sleep requires recording at least three electrical body signals; the brain activity,
muscle activity, and the eye movement. Figure 13-11 illustrates a typical polygraph setup in
a sleep laboratory and these commonly used measures that define sleep.
Electrodes pasted onto standard locations on the skull’s surface yield an electroencepha-
logram (EEG), a record of brain wave activity. Electrodes placed on neck muscles provide an
electromyogram (EMG), a record of muscle activity. Electrodes located near the eyes provide
an electrooculogram (EOG), a record of eye movements. Body temperature, circulating hor-
mones, and blood glucose levels provide additional measures of sleep.
Stages of Waking and Sleeping
Biological measurements show that sleep, like waking, is not a unitary state but encompasses
several stages. For example, the EEG recording shows distinct patterns of brain wave activ-
ity as the neocortex generates distinct rhythmic patterns for states categorized as awake, Figure 7-9 diagrams EEG patterns that reflect
relaxed, drowsy, sleep, deep sleep, and dreaming. a range of conscious states in humans.
Waking State
When a person is awake, the EEG pattern consists of small-amplitude (height) waves with
a fast frequency (repetition period). This pattern, the beta (b) rhythm, is defined by a fre- beta (b) rhythm Fast brain wave activity
quency of 15 to 30 Hz (times per second). The pattern is also called fast-wave activity-activated pattern associated with a waking EEG.
458 Chapter 13 • WHY DO WE SLEEP AND DREAM?
Excited EEG, or waking EEG. Also associated with waking, the EMG is active and the EOG indi-
cates that the eyes move.
Relaxed, eyes closed
Relaxed State
When participants relax and close their eyes, they may produce the alpha (a) rhythm—large,
extremely regular brain waves with a frequency ranging from 7 to 11 Hz. Humans generate
alpha rhythms in the region of the visual cortex at the back of the brain, and the rhythms
abruptly stop if a relaxed person is disturbed or opens his or her eyes. Not everyone displays
Deep sleep alpha rhythms, and some people display them much better than others.
Drowsy State
When a person grows drowsy, the EEG indicates that beta wave activity in the neocortex
1 2 3 gives way to slower EEG wave activity. The amplitude of the EEG waves increases and their
Time (s)
frequency becomes a slower theta (u) rhythm of 4- to 7-Hz waves. Concurrently the EMG re-
mains active, as the muscles have tone, and the EOG indicates that the eyes are not moving.
Sleeping State
As participants enter deeper sleep, they produce yet slower, larger EEG waves called
delta (d) rhythms. Delta rhythm has a frequency of 1 to 3 Hz and is associated with the loss
of consciousness that characterizes sleep. This stage is sometimes called slow-wave sleep.
Still, the EMG indicates muscle activity, signifying that the muscles retain tone, although
the EOG indicates that the eyes do not move.
REM and NREM Sleep Phases
Sleep consists of periods when a sleeper is relatively still and periods when the mouth, fin-
gers, and toes twitch. This behavior is readily observed in household pets and bed partners.
In 1955 Eugene Aserinsky and Nathaniel Kleitman (Lamberg, 2003), working at the Uni-
versity of Chicago, observed that the twitching is periodic and is also associated with rapid
eye movements (REM). Other than twitches and eye movements, the EMG indicates that
muscles are inactive, a condition termed atonia (Greek via Latin, “without tone”).
By accumulating and analyzing REM recorded on EEGs, the Chicago investigators were
the first to identify REM sleep, a fast-wave sleep period whose pattern is reminiscent of a
waking EEG (see Dement, 1972). This discovery led to the contemporary naming of two
sleep states, REM and NREM. The delta rhythm sleep period, during which the EEG pat-
tern is slow and large and the EOG is inactive, is called NREM (for non-REM) sleep to
distinguish it from REM sleep.
Other Sleep- and Waking-Related Activities
Although electrophysiological measures define the sleep stages, many other bodily and physi-
ological events are associated with waking and sleep stages. Measures of metabolic activity,
such as body temperature, generally decline during sleep. Breathing and heart rate provide
further insights into waking and sleeping. The sleeper’s behavior—tossing and turning, moan-
ing and laughing—also occur during specific sleep stages. Taken together, these measures
delta (d) rhythm Slow brain wave activity yield insights into the many causes and symptoms of normal sleep and disturbed sleep.
pattern associated with deep sleep.
slow-wave sleep NREM sleep. A Typical Night’s Sleep
atonia Lacking tone; condition of complete Figure 13-12A displays the EEG patterns associated with waking, NREM sleep, and REM
muscle inactivity produced by motor neuron sleep from a typical night’s sleep. NREM sleep is divided into four stages on the basis of EEG
inhibition. recordings. The main change in the progression from stage 1 sleep through stage 4 sleep is
rEm sleep Fast brain wave pattern displayed the increased size and slowing speed of brain waves.
by the neocortical EEG record during sleep. The designation of these stages assumes that the sleeper moves from relatively shallow
nrEm (non-rEm) sleep Slow-wave sleep sleep in stage 1 to deep sleep in stage 4. Self-reports from participants who are awakened
associated with delta rhythms. from sleep at different times suggest that stage 4 is the deepest sleep: participants act groggy
13-3 • Sleep Stages and Dreaming 459
(A) EEG (B) Sleep Figure 13-12 Sleep Recording and
Revelations (A) EEG patterns
Awake associated with waking with the four
NREM sleep stages and with REM sleep.
1
Stage 1 (B) Over a typical night’s sleep, a person
NREM REM undergoes several sleep state changes in
Stage 2 dominant 2
roughly 90-minute periods. NREM sleep
dominates the early sleep periods, and
Stage 3 3 REM REM sleep dominates later sleep. The
Time duration of each sleep stage is reflected in
(hr) 4 the thickness of each bar, which is color-
Stage 4
REM coded to the corresponding stage in part A.
5 The depth of each stage is graphed as the
REM REM relative length of the bar. Information from D. D.
dominant 6 Kelley (1991). Sleep and Dreaming (p. 794). In E. R. Kandel,
REM
J. H. Schwartz, & T. M. Jessell (Eds.). Principles of
7 REM Neuroscience. New York: Elsevier.
Typical sleep cycles
when awakened from it. As described earlier, REM sleep is distinctive because although a
participant is asleep, EEG activity shows a waking pattern.
Figure 13-12B graphs one participant cycling through these stages in the course of a
night’s sleep. Notice that the depth of sleep changes several times through the four stages of
NREM sleep, then entry into REM sleep. This NREM–REM sequence lasts approximately
90 minutes and occurs five times in the course of the participant’s sleep period.
The labels indicating REM sleep in Figure 13-12B tell us that the sleep stage dura-
tions roughly divide sleep into two parts, the first dominated by NREM sleep, the second 24
dominated by REM sleep. Separate measures of body temperature record that it is lowest
Waking
(about 1.5°C below a normal temperature of 37.7°C) during the earlier NREM-dominated
part of the sleep period and rises during the later REM-dominated part. 16
Findings from sleep laboratory studies confirm that individuals tend to conform to 12
Hours
REM
this sleep pattern with some variability. Studies also confirm that REM sleep takes up 10 sleep
substantial time: adults who typically sleep about 8 hours spend about 2 of those hours 8
in REM. A person’s duration of REM sleep varies at different times of life and changes NREM
dramatically over the life span. Periods of REM sleep are high in infancy; they increase sleep
during growth spurts, in conjunction with physical exertion, and during pregnancy. 0
1 10 30 60 90
Figure 13-13 shows that most people sleep less as they grow older. In the first 2 years of Age (years)
life REM sleep makes up nearly half of sleep time, but it declines proportionately until
Sleeping and Waking
Figure 13-13
in middle age it constitutes little more than 10 percent of sleep time.
over the Life Span The amount of
time humans spend sleeping decreases
Contrasting NREM Sleep and REM Sleep with age. The proportion of REM sleep is
especially high in the first few years of life.
Although it seems an inactive period, a remarkable range of activity takes place during sleep.
Information from H. P. Roffward, J. Muzio, & W. C. Dement
Events associated with NREM sleep and REM sleep, for example, are dramatically different, (1966). Ontogenetic development of the human
not only in physiological measures but also in such behavioral events as cognition, memory sleep–dream cycle. Science, 152, 604–619.
storage, and sleep disorders.
During NREM sleep body temperature declines, heart rate and blood flow decrease,
body weight decreases from water loss in perspiration, and growth hormone levels increase.
NREM sleep is also the time when we toss and turn in bed, pull on the covers, and engage
in other movements. (For an extreme example see Clinical Focus 13-4, Restless Legs Syn-
drome.) If we talk in our sleep or grind our teeth, we do so during NREM sleep. If we flail,
banging an arm or kicking a foot, we usually do so in NREM sleep. Some people even get
up and walk around, and this sleepwalking takes place during NREM sleep. All this activity
during our so-called resting state is remarkable! We maintain muscle tone during NREM
460 Chapter 13 • WHY DO WE SLEEP AND DREAM?
CliniCal F cus 13-4
Restless Legs Syndrome
I’ve always been a fairly untalented sleeper. Even as a child, it would take
me some time to fall asleep, and I would often roll around searching for
a comfortable position before going under. But my real difficulties with
sleeping did not manifest themselves until early adulthood. . . .
Initially, my symptoms consisted of a mild tingling in my legs. It caused
me to be fidgety and made it hard to fall asleep. Eventually, I went through
a number of days without much sleep and reached a point where I simply
could not function. I went to a doctor who prescribed a small course
B. w. hoffmann, u of wi hospital, sleep study program, madison, wi/envision
of sleeping medication (a benzodiazepine). I was able to get good sleep
and my sleep cycle seemed to get back on track. Over the next decade I
had periodic bouts of tingling in my legs which caused me to be fidgety
and interfered with sleep. As time passed, the bouts occurred with
increasing frequency and the symptoms became more noticeable and
uncomfortable. I would simply suffer through these bouts, sleeping poorly
and paying the consequences. . . .
Being a student, I did not have a regular doctor. Unfortunately, most
physicians I met did not know about restless legs syndrome, or RLS,
and thought I was “drug seeking” or merely stressed out. I received a
variety of patronizing responses and found these experiences insulting
and demeaning. . . .
When I took my current position, I started seeing a doctor on a
regular basis, and experimented with better medications. By this time,
my sleep was being seriously affected by RLS. The sensations in my
legs were something like a combination of an ache in my muscles (much
like one gets after exercising) and an electrical, tingling sensation. They
would be briefly relieved with movement, such as stretching, rubbing,
contracting my muscles, or changing position, but would return within Many people who display RLS have a related sleep disorder, periodic
seconds. In fact, my wife says my cycle is about 13 to 15 seconds between limb movement in sleep (PLMS), characterized by involuntary jerking or
movements. I do this either when awake or during sleep. Trying not to
bending leg movements that typically occur every 10 to 60 seconds during
move greatly increases the discomfort—much like trying to not scratch a
sleep. Some people make hundreds of such movements per night; they dis-
very bad itch. The symptoms get worse in the evening and at night. Most
nights, I have trouble falling asleep. Other nights, I wake up after an hour
turb their sleep, can wake themselves, and assuredly annoy bed partners.
or so and then have trouble going back under. . . . RLS may affect as much as 10 percent of the population, more com-
I am very up front about the fact that I have RLS. In fact, whenever monly women than men. In mild cases massage, exercise, stretching,
I teach the topic of sleep and sleep disorders in my brain and behavior and hot baths may be helpful. For more severe cases, patients can re-
classes, I always make some time to talk about my experiences with strict their intake of caffeine and take benzodiazepines to help them get
RLS. Occasionally, students approach me with their own difficulties, and to sleep.
I try to provide them with information and resources. (Stuart Hall, Ph.D., RLS is difficult to treat (Wijemanne & Jankovic, 2015). l-Dopa, a drug
University of Montana) used to treat Parkinson disease, is a frequent treatment, but no evidence
People with the sleep disorder restless legs syndrome (RLS) expe- confirms that RLS occurs more frequently in Parkinson patients, whose
rience unpleasant sensations in the legs—usually in the calf area but condition is related to low dopamine function. RLS has been associated
anywhere from thigh to ankle—described as creeping, crawling, tingling, with poor iron uptake, especially in the substantia nigra, and some people
pulling, or pain. One or both legs may be affected; some people also feel have been helped by iron supplements. One focus of research into RLS
the sensations in their arms. is to improve iron absorption by the brain.
sleep and can sleep in a variety of postures, including standing up, sitting (as might occur in
a lecture), or in any of several reclining positions.
REM sleep is no less eventful than NREM sleep. During REM sleep our eyes move; our
toes, fingers, and mouths twitch; and males have penile erections. Still, we are paralyzed,
as indicated by atonia. This absence of muscle tone stems from motor neuron inhibition by
sleep regions of our brainstem. In the sleep lab atonia is recorded on an electromyogram as
the absence of muscle activity (see Figure 13-11B).
Posture is not completely lost during NREM sleep. You can get an idea of NREM sleep
posture by observing a cat or dog sleeping. During NREM they may be lying down but still
13-3 • Sleep Stages and Dreaming 461
have some posture, with the head partly supported in a partially upright position. At the
onset of REM sleep the animal usually subsides into a sprawled position as muscle paralysis
sets in. Figure 13-14 illustrates the sleep postures of a horse. Horses can sleep while standing
up by locking their knee joints, and they can sleep while lying down with their head held
slightly up. At these times they are in NREM sleep. When they are completely sprawled out,
they are in REM sleep.
During REM sleep mammals’ limbs twitch visibly, and if you look carefully at the face of a
dog or cat, you will also see the skin of the snout twitch and the eyes move behind the eyelids.
It might seem strange that an animal that is paralyzed can make small twitching movements,
but the neural pathways that mediate these twitches obviously are spared the paralysis.
One explanation for the twitching of eyes, face, and distal parts of the limbs is that such
movements help to maintain blood flow in those parts of the body. Another explanation
is that the brain is developing coordinated movements and tuning the neural circuits that
support those movements—an activity especially important to infants, who have not yet
developed full motor control (Blumberg, 2015).
An additional change resulting from atonia during REM sleep is that mechanisms that
regulate body temperature stop working and body temperature moves toward room tem-
perature. You may wake up from REM sleep feeling cold or hot (or because you are cold or
hot), depending on the temperature of the room, because your body has drifted toward room
temperature during a REM period.
Dreaming
The most remarkable aspect of REM sleep—dreaming—was discovered by William Dement
courtesy of ian whishaw
and Nathaniel Kleitman in 1957 (Dement, 1972). When participants were awakened from
REM sleep, they reported that they had been having vivid dreams. In contrast, participants
aroused from NREM sleep were much less likely to report that they had been dreaming, and
the dreams they did report were much less vivid. The technique of electrical recording from
a sleeping participant in a sleep laboratory made it possible to subject dreams and dreaming Figure 13-14 Nap Time Horses usually
to experimental analysis. Such studies provided objective answers to interesting questions seek open, sunny areas for a brief sleep.
concerning dreaming. They also raised many more questions, because the electrical events I. Q. W.’s horse Lady Jones illustrates three
of sleep are complex and difficult to associate with the content of specific dreams (Nir & sleep postures. Top: NREM sleep, standing
Tononi, 2010). with legs locked and head down. Center:
NREM sleep, lying down with head up.
How often do we dream? Reports by people on their dreaming behavior once suggested
Bottom: REM sleep, in which all postural
that dreaming was quite variable: some reported that they dreamed frequently and others and muscle tone is lost.
that they never dreamed. Waking participants up during REM periods showed that everyone
dreams, that they dream several times each night, and that dreams last longer as a sleep ses-
sion progresses. Those who claimed not to dream presumably forgot their dreams. Perhaps
people forget their dreams because they do not wake up during a dream or immediately after-
ward, which allows subsequent NREM sleep activity to erase the memory of the dream. Per-
haps, too, the neural systems that store our daily memories are inactive during NREM sleep.
How long do dreams last? Common wisdom once suggested that dreams last but an
instant. By waking people up at different intervals after the onset of REM sleep and match-
ing the reported dream content to the previous duration of REM sleep, however, researchers
demonstrated that dreams appear to take place in real time. An action that a person performs
in a dream lasts about as long as it would take to perform while awake. It is likely that time
shrinking is a product of remembering a dream, just as time shrinking is a feature of our
recall of other memories.
What We Dream About
Studying dreaming in a sleep laboratory allows researchers to study other questions
that have always intrigued people: Why do we dream? What do we dream about? What do
dreams mean?
462 Chapter 13 • WHY DO WE SLEEP AND DREAM?
Past explanations of dreaming have ranged from messages from the gods to indigestion.
The first modern treatment of dreams was described by the founder of psychoanalysis,
Sigmund Freud, in The Interpretation of Dreams, published in 1900. Freud reviewed the
early literature on dreams, described a methodology for studying them, and provided a
theory to explain their meaning. We briefly consider Freud’s theory because it remains
Figure 16-1 presents a contemporary take on popular in psychoanalysis and in the arts and is representative of other psychoanalytical
Freud’s model of the mind. theories of dreams.
Freud suggested that the function of dreams is the symbolic fulfillment of unconscious
wishes. His theory of personality is that people have both a conscious and an unconscious.
Freud proposed that the unconscious contains unacknowledged desires and wishes that
are sexual. He further proposed that dreams have two levels of meaning. The manifest
content of a dream is a series of often-bizarre, loosely connected images and actions. The
latent content of the dream contains its true meaning. Freud’s images called phallic symbols
reflect sexual events. As interpreted by a psychoanalyst, the symbolic events of a dream
provide a coherent account of the dreamer’s unconscious wishes—for Freud, the wishes
were related to sex.
Freud provided a method for interpreting manifest symbols and reconstructing the latent
content of dreams. For example, he pointed out that a dream usually begins with an incident
from the previous day, incorporates childhood experiences, and includes ongoing unfulfilled
wishes. He also identified several types of dreams, such as those that deal with childhood
events, anxiety, and wish fulfillment. The latent content of the dream was important to
Freud and other psychoanalysts in clinical practice because interpretation of dreams was
proposed to offer insight into a patient’s problems.
Other psychoanalysts, unhappy with Freud’s emphasis on sex, developed their own meth-
ods of interpretation. The psychoanalyst Carl Jung, a contemporary of Freud, proposed that
dream symbolism signifies distant human memories encoded in the brain but long since lost
to conscious awareness. Jung proposed that dreams allow the dreamer to relive the history
of the human race—our “collective unconscious.” As more theories of dream interpretation
developed, their central weakness became apparent: it was impossible to know which inter-
pretation was correct.
The dream research of Freud and his contemporaries was also impeded by their reliance
on a subject’s memory of a dream and by the fact that many subjects were patients. This
situation unquestionably resulted in the selection of the unusual by both the patient and
the analyst. Now researchers study dreams more objectively by waking participants and
questioning them.
Experimental analysis indicates that most dreams are related to events that happened
quite recently and concern ongoing problems. Colors of objects, symbols, and emotional
content most often relate to events taking place in a person’s recent waking period. Calvin
Hall and his colleagues (1982) documented more than 10,000 dreams of healthy people and
found that more than 64 percent are associated with sadness, anxiety, or anger. Only about
18 percent are happy. Hostile acts against the dreamer outnumber friendly acts by more than
two to one. Surprisingly, in regard to Freud’s theory, only about 1 percent of dreams include
sexual feelings or acts.
Contemporary researchers continue to attempt to interpret dream content. The two
approaches that follow are polar: one sees no meaning in dreams, and the other sees the
content of dreams as reflecting biologically adaptive coping mechanisms. The first approach
is bottom-up: the person has a dream, and then either the dreamer or a dream interpreter
analyzes it. The second approach is top-down: the dreamer creates the dream (Foulkes &
Domhoff, 2014).
Dreams as Meaningless Brain Activity
In his bottom-up approach, J. Allan Hobson (2004) proposed the activation–synthesis
hypothesis. During a dream the cortex is bombarded by signals from the brainstem, and
13-3 • Sleep Stages and Dreaming 463
these signals produce the pattern of waking (or activated) EEG. The cortex in response to
this excitation generates images, actions, and emotion from personal memory stores. In the
absence of external verification these dream events are fragmented and bizarre and reveal
nothing more than that the cortex has been activated.
Furthermore, Hobson proposes, on the basis of PET imaging, that part of the frontal
cortex is less active in dreaming than in waking. The frontal cortex controls working memory
for recent events and attention. The dreamer thus cannot remember and link dream events
as they take place, because monitoring by the frontal cortex is required for these functions. Chapter 14 describes the extent of frontal
On waking, the dreamer may attempt to come up with a story line for these fragmented cortex involvement in memory. Attention is
meaningless images. the topic of Section 15-2.
In Hobson’s hypothesis dreams are personal in that memories and experiences are acti-
vated but have no meaning. So the following dream, for example, with its bizarre delusional
and fragmented elements, represents images synthesized to accompany brain activation.
Any apparent meaning is invented after the fact, in this case by the middle-aged dreamer
recounting it.
I found myself walking in a jungle. Everything was green and fresh and I felt refreshed and
content. After some time I encountered a girl whom I did not know. The most remarkable thing
about her was her eyes, which had an almost gold color. I was really struck by her eyes not only
because of their unique color but also because of their expression. I tried to make out other
details of her face and body but her eyes were so dominating that was all I could see. Eventually,
however, I noticed that she was dressed in a white robe and was standing very still with her hands
at her side. I then noticed that she was in a compound with wire around it. I became concerned
that she was a prisoner. Soon, I noticed other people dressed in white robes and they were also
standing still or walking slowly without swinging their arms. It was really apparent that they were
all prisoners. At this time I was standing by the fence that enclosed them, and I was starting to
feel more concerned. Suddenly it dawned on me that I was in the compound and when I looked
down at myself I found that I was dressed in a white robe as well. I remember that I suddenly
became quite frightened and woke up when I realized that I was exactly like everyone else. The
reason that I remembered this dream is the very striking way in which my emotions seemed to
be going from contentment, to concern, to fear as the dream progressed. I think that this dream
reflected my desire in the 1970s to maintain my individuality. (Recounted by A. W.)
Dreams as a Coping Strategy
Anttio Revonsuo of Finland uses content analysis to argue that dreams are biologically
adaptive in that they lead to enhanced coping strategies for threatening life events (Valli &
Revonsuo, 2009). The evolutionary aspect of this top-down approach, or coping hypothesis, is
that enhanced performance is especially important for people whose environment typically
includes dangerous events that constitute extreme threats to reproductive success. Revonsuo
notes that dreams are highly organized and significantly biased toward threatening images,
as was A. W.’s dream. People seldom dream about reading, writing, and calculating even if
these behaviors occupy much of their day.
Dream threats are the same events that are threatening in waking life (Figure 13-15).
For example, animals and strange men who could be characterized as enemies figure
erich lessing/art Resource
Figure 13-15 Dream Content
Terrifying visions that may persist even
after awakening from a frightening dream
as represented in The Night, by Swiss
painter Ferdinand Hodler. The Night, by Ferdinand
Hodler (1853–1918). Oil on canvas 116 3 299 cm.
Kunstmuseum, Bern, Switzerland.
464 Chapter 13 • WHY DO WE SLEEP AND DREAM?
prominently in dreams. Dream content incorporates the current emotional problems of the
dreamer and leads to improvements in and adjustments to life problems.
In contrast with the threat interpretation of dreams and from their own analysis of dream
content, Malcolm-Smith and her coworkers (2012) report that approach behavior occurs more
frequently in dreams than does avoidance behavior. They therefore suggest that reward-
seeking behavior is as likely to represent a dream’s latent content as avoidance behavior is.
An extension of the top-down approach to dream interpretation contends that people are
problem solvers when awake, and problem solving continues during sleep (Edwards et al.,
2013). Have you ever been advised to sleep on it? Did that prove to be good advice?
Part of the challenge in studying dreams is that they occur throughout our sleep–waking
behavior. Dreams occur during NREM sleep but not as vividly as in REM sleep. We can
have dreamlike experiences just as we drop off to sleep, as our ongoing thoughts seem to
disintegrate into hallucinations. Sometimes we are aware of our dreams as we dream, a phe-
nomenon called lucid dreaming. People who have vivid dreamlike experiences when awake
are said to be hallucinating. And of course we daydream when awake. Eric Klinger (1990) sug-
gests that daydreams are ordinary and often fun, with little of the turmoil of REM dreams,
and so seem the true opposite of night dreams.
Much about dreams is not understood. Very young children spend a lot of time in REM
sleep yet do not report complex dreams filled with emotion and conflict. Children may experi-
ence brief frightening dreams called night terrors during NREM sleep. Night terrors can be so
vivid that the child continues to experience the dream and the fear after awaking. A 4-year-old
child suddenly woke up screaming that she was covered in ants. It took hours for her father to
convince her that her experience was not real and that she could go back to bed. Only reassur-
ance from a sleep expert later convinced the father that nothing was amiss with his daughter
and that night terrors are common among young children (Carter et al., 2014).
13-3 reVieW
Sleep Stages and Dreaming
Before you continue, check your understanding.
1. Sleep consists of two phases: , which stands for , and
, which stands for .
2. REM sleep is characterized by eye movement, as recorded by the ; atonia,
recorded by the ; and waking activity, recorded by the .
3. Sleepers experience about REM sleep periods each night, with each period
as sleep progresses.
4. Evidence from sleep lab analysis suggests that dreams and that dreams
take place in .
5. What major factor makes interpreting dreams difficult?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
13-4 What Does Sleep Accomplish?
Sleep is not a passive process that results from a decrease in sensory stimulation. Findings from
basic rest–activity cycle (BrAc) sensory deprivation research reveal that when participants are isolated in quiet bedrooms, they
Recurring cycle of temporal packets, about spend less time asleep, not more. These results do not support the idea that sleep sets in for
90-minute periods in humans, during which lack of anything else to do. Here we consider three contemporary explanations for sleep: as
an animal’s level of arousal waxes and wanes. adaptive, as restorative, and as supportive of memory.
13-4 • What Does Sleep Accomplish? 465
Sleep As a Biological Adaptation
Many lines of evidence argue that sleep is a biologically adaptive behavior influenced by the
ways a species has evolved to interact with its environment:
• Sleep serves as an energy-conserving strategy for coping with times when food is scarce.
Each animal species gathers food at optimal times and conserves energy the rest of the
time. If the food that a species eats has a high nutrient value, the species can spend less
time foraging and more time sleeping.
• Whether a species is predator or prey influences its sleep behavior. A predator can sleep
at its ease; the prey’s sleep time is reduced because it must remain alert and ready to
fight or flee at unpredictable times (Figure 13-16).
• Strictly nocturnal or diurnal animals are likely to sleep when they cannot travel easily.
lynn hoffman/science source
Dement proposed this colloquially: “We sleep to keep from bumping into things in the dark.”
Much about animals’ sleep patterns are consistent with the adaptive explanation.
Figure 13-17 charts the average sleep time of some common mammals. Herbivores, including
donkeys, horses, and cows, spend a long time collecting enough food to sustain themselves.
Relatively short sleep time for them is adaptive. Because they are also prey, not sleeping
much is adaptive, as they watch for predators. Carnivores, including domestic cats and dogs,
Figure 13-16 Do Not Disturb Biological
eat nutrient-rich foods and usually consume most of a day’s or even a week’s food at a single theories of sleep suggest that it is an
meal. Because they do not need to eat constantly and because by resting they can conserve energy-conserving strategy that serves
energy, and because they are not at great risk of predation, a great deal of sleep is adaptive. other functions as well, such as staying
The behavior of some animals does appear odd, so understanding any animal’s sleep safe through the night.
behavior requires understanding its natural history. Opossums, which spend much of their
time asleep, may have specialized in energy conservation as a survival strategy. We humans
are average among species in our sleep time. As we are omnivores, not subject to overwhelm-
ing predation, our sleep is intermediate between that of herbivores and carnivores.
Sleep can contribute to energy conservation. During sleep, energy is not
being expended in moving the body or supporting its posture. The brain
is a major energy user, so switching off the brain during sleep, especially
Donkey
NREM sleep, conserves energy. The decline in body temperature during
sleep is an adaptive energy-conserving mechanism: it decreases the body’s
metabolism, as exemplified by animals that display extreme decreases in Human
body temperature characteristic of hibernation.
A good explanation of sleep must account not only for sleep but also for
Guinea pig
NREM and REM sleep. Before the discovery of REM sleep, Kleitman sug-
gested that animals have a basic rest–activity cycle (BRAC) that for humans
lasts about 90 minutes (see Dement, 1972). Kleitman based his hypothesis on Rat
the observation that human infants have frequent feeding periods between
which they sleep.
As illustrated in Figure 13-18, the behavior of adult humans does suggest Rabbit
that activity and rest are organized into 90-minute temporal packets. School
classes, work periods, exercise sessions, mealtimes, coffee breaks, and snack
Cat
times appear to be divided into intervals of 90 minutes or so. The later dis-
covery that REM sleep occurs at intervals of about 90 minutes suggests that
it too can be considered a continuation into sleep of the 90-minute BRAC Opossum
cycle. This hypothesis assumes that periods of eating are periods of high
brain activity, just as are periods of REM. 0 3 6 9 12 15 18 21 24
Kleitman proposed that the BRAC rhythm is so fundamental that it cannot Average time spent in sleep per day (hours)
be turned off. Accordingly, for a night’s sleep to be uninterrupted by periodic
Figure 13-17 Average Sleep
waking (and perhaps snacking), the body is paralyzed and only the brain is active. An analogy: Time Sleep time is affected both by the
rather than turning off your car’s engine when you’re stopped at a red light, you apply the brakes to amount of time species require to obtain
keep the idling car from moving. For REM sleep the atonia that paralyzes movement is the brake. food and by the risk of predation.
466 Chapter 13 • WHY DO WE SLEEP AND DREAM?
Figure 13-18 Behavioral Rhythms Basic rest–
Our behavior is dominated by a basic activity cycle
rest–activity cycle (red) through which
our activity levels change in the course of
the day and by an NREM–REM sleep cycle Sleep–wake
cycle
(purple) during the night.
Sleep Breakfast Coffee Lunch Snack Dinner Snack Sleep
8:00 A.M. 10:00 A.M. 12:00 P.M. 3:00 P.M. 5:00 P.M. 7:00 P.M.
Sleep as a Restorative Process
In Macbeth’s description of sleep Shakespeare illustrates in words the idea that sleep has
restorative properties:
Sleep that knits up the ravell’d sleave of care,
The death of each day’s life, sore labour’s bath,
Balm of hurt minds, great nature’s second course,
Chief nourisher in life’s feast. —Act II, scene 2
Sleep Deprivation Studies
We can understand the idea of sleep as a restorative from our personal perspective. Toward the
end of the day we grow tired, and when we awaken from sleep, we are refreshed. If we do not get
enough sleep, we become irritable. One hypothesis of sleep as restorative proposes that the chem-
ical events that provide energy to cells are reduced during waking and replenished during sleep.
Even so, fatigue and alertness may simply be aspects of the circadian rhythm and have
nothing at all to do with wear and tear on the body or depletion of its essential resources. To
evaluate whether sleep is essential for bodily processes, investigators have conducted sleep
deprivation studies. These studies have not clearly identified any essential function for sleep
but rather point to multiple physiological and cognitive functions altered by various degrees
of sleep deprivation (Elliott et al., 2014).
Dement participated as an observer in one case study on sleep deprivation that illustrates
this point. In 1965, as part of a science fair project, a high school student named Randy
Gardner planned to break the world record of 260 hours (almost 11 days) of consecutive
wakefulness with the help of two classmates who would keep him awake. Gardner did break
the record, then slept for 14 hours and reported no ill effects. Given concerns about the
deleterious effects that sleep deprivation has on health, Guinness World Records no longer
records wakefulness records.
Dement reported that Gardner hallucinated and had cognitive and memory lapses during
his period of sleep deprivation. These negative effects did not last. Reviews of sleep depriva-
tion research are consistent in concluding that at least limited periods of sleep deprivation
produce no marked physiological alterations.
Sleep deprivation does not seem to have adverse physiological consequences, but it is asso-
ciated with poor cognitive performance. Performance on tasks that require attention declines
as a function of hours of sleep deprivation. Irregular sleep can contribute to metabolic syn-
drome, described in Clinical Focus 13-1. Finally, sleep deprivation figures in accidents at
work and on the road. The sleep deprivation deficit does not manifest itself in an inability to
do a task, because sleep-deprived participants can perform even very complex tasks; rather
the deficit is in maintaining sustained attention.
A confounding factor in evaluating sleep-deprived participants is that they take
microsleeps, brief sleep periods lasting up to a few seconds. During microsleep, participants
may remain sitting or standing, but their eyelids droop briefly and they become less respon-
microsleep Brief sleep period lasting a sive to external stimuli. If you have driven a car while tired, you may have had a microsleep
second or so. and awakened just in time to prevent yourself from driving off the road—or worse.
13-4 • What Does Sleep Accomplish? 467
REM Sleep Deprivation
Some studies have focused on the selective benefits of REM sleep. To deprive a participant
of REM sleep, researchers allow participants to sleep but awaken them as REM sleep begins.
REM-sleep deprivation has two effects:
1. Participants show an increased tendency to enter REM sleep in subsequent sleep sessions,
so awakenings must become more and more frequent.
2. After REM deprivation, participants experience REM rebound, showing more than the
usual amount of REM sleep in the first available sleep session.
Because most sleep studies are of relatively brief duration, capturing potential long-term
physiological changes that may take place during or after sleep deprivation remains elu-
sive. The consequences of sleep deprivation may become apparent only some time after an
experimental manipulation has taken place. Furthermore, gross assessment of behavior may
be less adequate for documenting sleep deprivation’s effects than more focal physiological
and behavioral assessments. For example, some evidence suggests that REM sleep deprivation
weakens the immune system, decreasing resistance to infections and other disease (Lungato
et al., 2015). Other evidence suggests that REM sleep deprivation reduces neurogenesis,
especially in the hippocampus, thus impairing memory processes and weakening resistance
to stress (Kreutzmann et al., 2015).
Two kinds of observations, however, argue against effects of prolonged or even complete
REM sleep deprivation. Virtually all antidepressant drugs, including MAO inhibitors, tricy-
clic antidepressants, and SSRIs, suppress REM sleep either partly or completely. The clinical
effectiveness of these drugs may in fact derive from their REM-suppressant effects (Wilson &
Argyropoulos, 2005). Nevertheless, about 6 percent of people on antidepressants display
REM sleep behavioral disorder, characterized by agitated movements, as if the sleeper were
acting out dreams (see Section 13-6). This disorder argues against the idea that REM sup- Section 6-2 reviews the full spectrum of
pression by antidepressant drugs is complete (Postuma et al., 2013). antidepressant drugs.
In several reported cases lower-brainstem damage has resulted in a complete loss of REM
sleep. For example, patients with brainstem lesions reportedly remained ambulatory and
verbally communicative, but their REM was abolished. They were reported to live quite
satisfactorily without REM sleep (Osorio & Daroff, 1980).
Sleep and Memory Storage
The suggestion that sleep plays a role in memory dates back over a century, and in the inter-
val a lot has changed with respect to our understanding of memory and of sleep. Investiga-
tors now know of two general categories of memory. Episodic memory includes conscious
information such as our autobiographical memories and knowledge of facts. Implicit memory
includes unconscious processes such as motor skills learning. Within these categories specific
types of memory include spatial, emotional, verbal, even immune system memory. Investiga-
tors also know that during the various stages of sleep many EEG and neuronal events, bio-
chemical events, and genetic events take place. Thus the central challenge for sleep-related
memory research lies in associating the complexity of memory with the complexity of brain Section 14-1 expands on the workings of
metabolic and genetic events (Rasch and Born, 2013). explicit and implicit memory systems.
Investigators also know that storing memories takes time. Memory is proposed to have at
least three phases: labile, consolidation (storage), and recall. During the initial labile phase,
as a memory is encoded, it is fragile and must compete with existing memories and the addi-
tion of new memories. The consolidation phase forges a relatively permanent representation
of the memory; it depends upon biochemical and genetic activity that underlie structural
changes in the nervous system. The recall phase puts the memory to work at some future
time and also integrates it into existing memory stores.
Research on the role of sleep in memory focuses on the latter two processes, consolida-
tion and recall, and is conducted within the framework of three theories: multiple process,
468 Chapter 13 • WHY DO WE SLEEP AND DREAM?
sequential process, and storage process. Multiple process theories propose that different
place cell Hippocampal neuron maximally
kinds of memory are stored during different sleep states. Sequential process theories propose
responsive to specific locations in the world.
that memory is manipulated in different ways during different sleep states. For example,
one sleep state erases older competing memories, while another sleep state stores the new
memories. Storage process theories propose that brain regions that handle different kinds of
memory during waking continue to do so during sleep. The advantage is that sleep offers a
state relatively free from the competition of new waking experiences.
Each theory of memory and sleep has generated volumes, but the remainder of this sec-
tion focuses on experimental demonstrations of sleep’s role in the general memory categories
of explicit and implicit memory storage during sleep.
NREM Sleep and Explicit Memory
Gerrard and colleagues (2008) used a method which had found that many hippocampal cells fire
Figure 7-8 shows the classes of place cells when a rat is in a certain location in an environment. These place cells are relatively inactive
and their directional selectivity. until the rat passes through that place again. Recordings from as many as 100 cells at the same
time in three conditions—during NREM sleep, during a food search task, and during NREM
sleep after a food search—show that during the food search the activity of some place cells corre-
lates. During the rats’ subsequent periods of NREM sleep the correlations recur (Figure 13-19).
This result suggests that the memory of the previous food-searching experience is being re-
played and thus stored during NREM sleep. In pursuing the idea that memory for places is
stored during sleep, one research group identified neuronal firing of hippocampal cells in awake
animals in relation to a specific location in a maze. Then during sleep they provided rewarding
brain stimulation whenever that neuronal firing pattern occurred. In a subsequent test in the
maze, the reinforced animals showed a preference for the target location. The experiments had
produced an episodic memory for that place as the animals slept (de Lavilléon et al., 2015).
REM Sleep and Implicit Memory
To determine whether humans’ dreams are related to memory, Pierre Maquet and his
coworkers in Belgium (2000) trained participants on a serial reaction task. The investigators
observed regional blood flow in the brain with PET scans during training and during REM
sleep on the subsequent night. The participants faced a computer screen displaying six posi-
tional markers and were instructed to push one of six keys when a corresponding positional
marker was illuminated. They did not know that the illumination sequence was predeter-
mined. This exemplifies an implicit memory task in which a motor skill is mastered.
Consequently, as training progressed, the participants indicated that they were learning
by the fact that their reaction time improved during trials in which one positional marker
was correlated with a preceding marker. On PET scan measures of brain activation, a similar
pattern of neocortical activation appeared during task acquisition and during REM sleep
(Figure 13-20). On the basis of this result Maquet and coworkers suggest first that the par-
Figure 13-19 Neural Replay? ticipants were dreaming about their learning experience and second that replay during REM
Hippocampal cell activity suggests that
rats dream about their experiences. Dots
on the periphery of the circles represent
Dots represent Red lines connecting dots represent cells that
the activity of 42 hippocampal cells fire at the same time. The thicker the line,
individual
recorded at the same time during (left) hippocampal cells. the higher the correlation of cell activity.
NREM sleep before a food-searching
task, (center) the food-searching task, NREM sleep
and (right) NREM sleep after the task. No before food Search NREM sleep after
search for food food search
strong correlations among cells emerged
during the NREM sleep that preceded the
food search, but correlations were strong The correlation of cell
among cells during the food search and activity during sleep is
similar to that during
during the subsequent slow-wave sleep.
searches for food when
Information from M. A. Wilson & B. L. McNaughton (1994).
previously awake.
Reactivation of hippocampal ensemble memories during
sleep. Science, 165, p. 678.
13-4 • What Does Sleep Accomplish? 469
Reaction-time task REM sleep that night Figure 13-20 Do We Store
Implicit Memories During
REM Sleep? Information from
Participants are Participants P. Maquet, S. Laureys, P. Peigneux,
trained on a display a similar S. Fuchs, C. Petiau, et al. (2000).
reaction-time pattern of Experience-dependent changes in
task, and brain brain activity cerebral activation during human REM
activity is during
sleep. Nature Neuroscience, 3, p. 832.
recorded with subsequent
PET. REM sleep.
strengthened the task memory. Research in which participants are given a language task that
contains hidden rules finds that sleep also strengthens this implicit rule learning (Batterink
et al., 2014). Thus, much rule learning in both motor and cognitive domains likely is strength-
ened during sleep, including REM sleep.
Storing Memories During Sleep
Although evidence shows that memory strengthens during sleep, less clear is whether
the neural and molecular changes that support sleep memory storage are similar or dif-
ferent from those that store memory during wakefulness. Researchers are addressing this
question in innovative animal models of sleep. Nelini and coworkers (2012) studied spatial
memory formation in chicks, a species in which such memories are stored mainly in the right
hemisphere. Chickens, like many bird species, alternate sleep in each hemisphere, and the
researchers showed that after a learning experience, the right hemisphere displayed more
sleep than did the left hemisphere. Birds’ selectivity in hemispheric sleep opens up the pos-
sibility of comparing plastic changes between the hemispheres as a way of understanding
genetic, biochemical, and plastic changes associated with memory formation.
The fruit fly Drosophila also offers insights into the effects of sleep on memory and on
plasticity (Dissel et al., 2015). These researchers identified a variety of mutations that disrupt
memory formation and plasticity and found that the memory disruptions decrease after
sleep. Slight increases in ambient temperature put one mutant strain of fly to sleep, which
greatly aided the research. For this strain a learning task can be followed by various sleep
doses induced by manipulating room temperature. A finding of this research is that the same
group of neurons that enhance memory are those that induce sleep. This finding suggests
a causal link between memory and sleep: Drosophila sleeps to remember! Generalizing this
finding to us humans suggests that learning will make us tired.
13-4 reVieW
What Does Sleep Accomplish?
Before you continue, check your understanding.
1. Sleep is proposed to occur as a(n) adaption, as a(n) process,
or as an aid in storing .
2. memory is associated with NREM sleep, and memory is
associated with REM sleep.
3. In rats performing a spatial task, correlations develop between firing in the
hippocampus that is then replayed in sleep.
4. When you are sleep-deprived, you are more likely to slip into a for a few
seconds.
5. Describe a difficulty in relating memory formation to sleep.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
470 Chapter 13 • WHY DO WE SLEEP AND DREAM?
13-5 Neural Bases of Sleep
The idea that the brain contains a sleep-inducing substance has long been popular and is
reinforced by the fact that a variety of chemical agents induce sleep. Such substances include
sedative-hypnotics and morphine. Our understanding of circadian rhythms suggests, how-
ever, that changes in many neurochemicals and hormones and the metabolic activity of most
of the body’s cells produce our sleep–waking cycles.
The hormone melatonin, secreted from the pineal gland during the dark phase of the
reticular activating system (rAs) Large
light–dark cycle, causes sleepiness. A synthetic form can be taken as a sleep aid, so melatonin
reticulum (mixture of cell nuclei and nerve
might be thought to be the sleep-producing substance. But sleep survives the removal of the
fibers) that runs through the center of the
brainstem; associated with sleep–wake pineal gland. Thus melatonin and many other chemical substances may only contribute to
behavior and behavioral arousal; also called sleep, not cause it (see Research Focus 13-3).
the reticular formation. Some observations suggest that it is not a circulating bloodstream compound that
produces sleep. In dolphins and birds only one brain hemisphere sleeps at a time. This ability
coma Prolonged state of deep
unconsciousness resembling sleep. presumably allows an animal’s other hemisphere to remain behaviorally alert. More impor-
tant, it suggests that sleep is produced by the action of some brain region, and in these spe-
peribrachial area Cholinergic nucleus in the
cies, within each hemisphere.
dorsal brainstem having a role in REM sleep
In this section we consider the neural mechanisms that regulate sleep. First we examine
behaviors; projects to medial pontine reticular
formation. evidence that the activity of a slave oscillator of the suprachiasmatic nucleus produces sleep
(see Figure 13-8). Second we look at evidence that a number of brainstem nuclei control the
medial pontine reticular formation (mprF)
various events associated with sleep, including those associated with REM and NREM sleep.
Nucleus in the pons participating in REM
sleep.
Reticular Activating System and Sleep
A pioneering experiment by Giuseppe Moruzzi and Horace Magoun (1949) began to answer
the question of which brain areas regulate sleep. The experimenters were recording the
cortical EEG from anesthetized cats while electrically stimulating the cats’ brainstem. They
were surprised to find that, in response to the electrical stimulation the large, slow delta EEG
typical of anesthesia is replaced by the low-voltage fast-wave beta EEG typical of waking.
The beta EEG activity outlasted the stimulation period, demonstrating that the effect was
not simply due to the online activity of neurons in the region of the stimulating electrode but
could be maintained by these neurons independent of the stimulation. During the “waking
period” the anesthetized cat did not become behaviorally aroused, but its cortical EEG ap-
peared to indicate that it was awake. In a sleeping cat the same stimulation did lead to waking.
Subsequent experiments show that a waking EEG and waking behavior can be induced
from a large neural area running through the center of the brainstem. Anatomically this area
Cortex
is composed of a mixture of cell nuclei and nerve fibers that form a reticulum. Moruzzi and
Magoun named this brainstem area the reticular activating system (RAS) and proposed that
it is responsible for sleep–waking behavior. Figure 13-21 diagrams the location of the RAS.
If someone disturbs you when you are asleep, you usually wake up. To explain that their
experimentally induced effect did not result simply from sensory stimulation, Moruzzi and
Magoun cut the brainstem just behind the RAS, severing its incoming sensory pathways.
RAS stimulation still produced a desynchronized EEG. Thus, the RAS is the source of wak-
Hypothalamus ing, and sensory stimulation produces waking because it activates RAS neurons.
Reticular activating The idea that the brainstem participates in waking behavior helps to explain why brain-
system (RAS) Sensory stem damage can result in coma, a prolonged state of deep unconsciousness resembling
information
sleep. In one well-publicized case, after taking a minor tranquilizer and having a few drinks
Figure 13-21 Sleep–Wake Controller at a birthday party, a 21-year-old woman named Karen Ann Quinlan sustained RAS damage
The reticular activating system, a region that left her comatose (Quinlan & Quinlan, 1977). She was hospitalized, placed on a respira-
at the center of the brainstem, contains a tor to support breathing, and fed by tubes. Her family fought a protracted legal battle to have
mixture of cell bodies and fiber pathways.
her removed from life support, a battle they finally won before the Supreme Court of New
RAS stimulation produces a waking EEG,
whereas damaging it produces a slow-wave Jersey. Even after she was removed from life support, however, Karen Ann lived for 10 more
sleeplike EEG. years in a perpetual coma.
13-5 • Neural Bases of Sleep 471
Neural Basis of EEG Changes Associated
with Waking
Research built on those pioneering studies of the RAS has since revealed that many neural
systems in the brainstem play a role in sleeping and waking behavior. Case Vanderwolf and Figure 5-17 summarizes the major neural
his coworkers (Vanderwolf, 2002) showed that at least two brainstem systems influence wak- activating systems and their functions.
ing EEG. Figure 13-22 illustrates their locations in the rat brain.
The basal forebrain contains large cholinergic cells. These neurons secrete acetylcholine
(ACh) from their terminals onto cortical neurons to stimulate a waking EEG (beta rhythm).
The midbrain structure the median raphe contains serotonin (5-HT) neurons whose axons
also project diffusely to the cortex, where they also stimulate cortical cells to
produce a waking EEG.
Although the two pathways produce similar patterns of waking EEG activ-
ity, their relations to behavior differ. If the activity of the cholinergic projec-
tion is blocked by drugs or by lesions to the cells of the basal forebrain, the Basal Median
waking EEG normally recorded from an immobile rat is replaced by EEG forebrain (ACh) raphe (5-HT)
activity resembling that of NREM sleep. Only if the rat walks or is otherwise
active is a waking EEG obtained from the cortex. These findings, graphed
in Figure 13-22, suggest that the cholinergic EEG is responsible for waking
associated with being alert yet still, whereas the serotonergic activation is re-
Rest Alert Rest Move
sponsible for the waking EEG associated with movement.
Neither the basal forebrain system nor the median raphe system is respon- Figure 13-22 Brain Activators Basal
sible for behavior. In fact, if both structures are pharmacologically or surgically destroyed, forebrain ACh neurons produce an
a rat can still stand and walk around. Its EEG, however, permanently resembles that of a activated EEG pattern when a rat is alert
but immobile. The 5-HT raphe neurons
sleeping animal.
of the midbrain produce an activated EEG
As long as one activating system is producing a waking EEG, rats can learn simple tasks. pattern when the rat moves.
If both systems are destroyed, an animal, although still able to walk around, is no longer able
to learn or display intelligent behavior. In a sense the cortex is like a house in which the lights
are powered by two separate sources: both must fail for the house to be left in darkness, but
if at least one source is operating, the lights stay on.
These experimental results suggest that the RAS produces its arousal effects by influenc-
ing activity in these two pathways, which then produce EEG events associated with waking.
In humans the basal forebrain and median raphe likely produce the same two desynchro-
nized EEG patterns that they produce in rats. Consequently, when we are alert and still,
cholinergic neurons are active; when we move, serotonin neurons also are active.
Perhaps when you have felt sleepy, say in a class or behind the wheel of a car, you may
have been able to wake yourself up by moving—shaking your head or stretching. Presumably,
while sitting still, your arousal level decreased as your cholinergic neurons became inactive.
When you moved, activating your serotonergic neurons restored your arousal level. When
we enter sleep, both cholinergic and serotonergic neurons become less active, allowing slow
waves to emanate from the cortex.
Neural Basis of REM Sleep
Barbara Jones (1993) and her colleagues described a group of cholinergic neurons known
as the peribrachial area that contributes to REM sleep. This area is located in the dorsal
Peribrachial
brainstem just anterior to the cerebellum (Figure 13-23). Jones selectively destroyed peribra- area Medial pontine
chial cells by spraying them with the neurotoxin kainic acid. She found that REM sleep was reticular formation
drastically reduced. This result suggests that the peribrachial area contributes to REM sleep
Figure 13-23 Brainstem Nuclei
and REM-related behaviors.
Responsible for REM Sleep Damage
The peribrachial area extends into a more ventrally located nucleus called the
to either the peribrachial area or the medial
medial pontine reticular formation (MPRF), shown in Figure 13-23. Lesions of the MPRF pontine formation reduces or abolishes
also abolish REM sleep, and injections of cholinergic agonists (drugs that act like ACh) into REM sleep.
472 Chapter 13 • WHY DO WE SLEEP AND DREAM?
Figure 6-5 shows agonist action at the ACh this region induce REM sleep. If both the peribrachial area and the MPRF take part in pro-
synapse. ducing REM sleep, how do other events related to REM sleep, including a waking EEG, rapid
eye movements (REM), and atonia, take place in the absence of muscle tone? Figure 13-24
charts an explanation showing how other REM-related activities are induced:
• The peribrachial area initiates REM sleep by activating the medial pontine reticular
Peribrachial area initiates formation.
sleep.
Activated EEG in
neocortex produced • The MPRF sends projections to excite basal forebrain cholinergic neurons, resulting
by basal forebrain in an activated EEG recorded from the cortex.
Medial pontine reticular nuclei.
formation produces REM- • The MPRF also excites brainstem motor nuclei to produce rapid eye movements
related activities. Excited brainstem and other twitches.
nuclei produce REM
and other twitching • The atonia of REM sleep is produced by the MPRF through a pathway that sends
movements.
Loss of muscle tone input to the subcoerulear nucleus located just behind it.
produced by the
subcoerulear nucleus • The subcoerulear nucleus excites the magnocellular nucleus of the medulla, which
exciting the magnocellular sends projections to the spinal motor neurons to inhibit them so that paralysis is
nucleus of the medulla . . . achieved during the REM sleep period.
In support of such a neural arrangement French researcher Michel Jouvet (1972)
. . . inhibits spinal motor observed that cats with lesions in the subcoerulear nucleus display a remarkable be-
neurons. havior when they enter REM sleep. Rather than stretching out in the atonia that typi-
cally accompanies REM sleep, the cats he was studying stood up, looked around, and
Figure 13-24 Neural Control of REM made movements of catching an imaginary mouse or running from an imaginary threat.
Sleep
Apparently if cats with damage to this brain region dream about catching mice or escaping
from a threat, they are now acting out their dreams. We revisit Jouvet’s phenomenon in the
next section, describing sleep disorders.
13-5 reVieW
Neural Bases of Sleep
Before you continue, check your understanding.
1. The in the central region of the brainstem is responsible for producing
sleep.
2. Loss of the RAS produces .
3. The peribrachial area and the MPRF, through activating pathways to the neocortex and
spinal cord, are responsible for producing events associated with .
4. Cats with lesions to the nucleus act out their dreams.
5. If you nod off to sleep at an inconvenient time, why does moving awaken you?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
13-6 Sleep Disorders
Occasional sleep disturbances are annoying and may impair performance the following day.
About 15 percent of people complain of ongoing sleep problems; an additional 20 percent
complain of occasional sleep problems. As people age, the incidence of complaints increases.
In the extreme, a rare genetic condition, fatal familial insomnia, causes individuals to stop
sleeping altogether. Their insomnia contributes to death after a number of months without
sleep. Prions (misfolded proteins) are proposed to cause the condition. A proposed treatment
is doxycycline, an antibiotic with antiprion activity (Forloni et al., 2015). In this section we
13-6 • Sleep Disorders 473
consider more common dysfunctions of NREM sleep and REM sleep (for more about prion
disorders, see Chapter 16).
Disorders of NREM Sleep
The two most common sleep disorders occur during NREM sleep are insomnia, prolonged
inability to sleep, and narcolepsy, uncontrollably falling asleep at inappropriate times. Narcolepsy derives from the Greek words for
Insomnia and narcolepsy are related, as anyone who has stayed up late at night can confirm: numbness and to be seized.
a night without sleep is often accompanied by a tendency to fall asleep at inconvenient times
the next day.
Insomnia
Our understanding of insomnia is complicated by the wide variation among people in how
insomnia Disorder of slow-wave sleep
much time they spend asleep. Some short sleepers may think they should sleep more, and
resulting in prolonged inability to sleep.
some long sleepers may think they should sleep less. Yet the sleeping pattern may be ap-
propriate for each. narcolepsy Slow-wave sleep disorder in
People’s sleep is disrupted by lifestyle choices such as those described in Clinical which a person uncontrollably falls asleep at
inappropriate times.
Focus 13-1. Staying up late, for example, may set a person’s circadian rhythm forward, en-
couraging a cascade of late sleep followed by staying up still later. Indoor and outdoor light drug dependence insomnia Condition
pollution contributes to sleep disorders by disrupting circadian rhythms. Some sleep prob- resulting from continuous use of sleeping
lems are brought on by shift work or by jet lag, as described in Section 13-1. Other common pills; drug tolerance also results in deprivation
of either REM or NREM sleep, leading the
causes of sleep disorders are stress, long work hours, and an irregular lifestyle. Just worrying
user to increase the drug dosage.
about insomnia is estimated to play a major role in 15 percent of cases.
Depressed people may sleep too much or too little. Anxiety and depression account for sleep apnea Inability to breathe during sleep,
about 35 percent of insomnias. Quantitative differences also exist in depressed patients’ sleep causing a sleeper to wake up to breathe.
because they enter REM sleep very quickly, as do people who are sleep-deprived.
Insomnia is brought on by sedative-hypnotic drugs, including Seconal, sodium amytal, and
many minor tranquilizers. These sleeping pills do help people get to sleep, but the person
is likely to feel groggy and tired the next day, which defeats the purpose of taking the drug.
Although sleeping pills promote NREM sleep, they deprive the user of REM sleep. In addi-
tion, people develop tolerance to these medications, become dependent on them, and display
rebound insomnia when they stop taking them. A person then may increase the dose each time
the drug fails to produce the desired effect. The syndrome in which patients unsuccessfully Section 6-4 presents theories of drug
attempt to sleep by increasing their drug dosage is called drug dependence insomnia. tolerance and dependence.
Narcolepsy
Like many people, you may suddenly have been overcome by an urge to sleep at an inconve-
nient time, perhaps while attending a lecture. For some people such experiences with narco-
lepsy are common and disruptive. J. S., a junior in college, sat in the front row for his course on
the brain. Within a few minutes after each class began, he dropped off to sleep. The instructor
became concerned and asked J. S. to stay after class to discuss his sleeping behavior.
J. S. reported that sleeping in classes was a chronic problem. Not only did he sleep in class,
he fell asleep whenever he tried to study. He even fell asleep at the dinner table and in other
inappropriate locations. His sleeping problem had made getting through high school a chal-
lenge and was making it difficult for J. S. to pass his college courses.
About 1 percent of people have narcolepsy, which takes surprisingly varied forms. J. S. fell
asleep while sitting still, and his sleeping bouts consisted of brief spurts of NREM sleep last-
ing 5 to 10 minutes. This pattern is similar to napping and to dropping off to sleep in class
after a late night but is distinguishable as narcolepsy by its frequency and disruptive effect.
J. S. eventually discussed his problem with his physician and received a prescription for Focus 6-1 explores amphetamine use for
Ritalin, an amphetaminelike drug that stimulates dopamine transmission. The treatment cognitive enhancement. Focus 7-4 describes
proved helpful. how Ritalin mitigates symptoms of ADHD.
Studies of narcoleptic people in sleep clinics resulted in a surprising discovery concerning
one cause of narcolepsy: sleep apnea, an inability to breathe during sleep. Clinical Focus 13-5, Apnea from Latin a, not, and pnea, breathing.
474 Chapter 13 • WHY DO WE SLEEP AND DREAM?
CliniCal F cus 13-5
Sleep Apnea Four breaths in
The first time I went to a doctor for my insomnia, I was twenty-five— 6 minutes
that was about thirty years ago. I explained to the doctor that I couldn’t
sleep; I had trouble falling asleep, I woke up many, many times during the Breathing
night, and I was tired and sleepy all day long. As I explained my problem
to him, he smiled and nodded. Inwardly, this attitude infuriated me—he Blood
couldn’t possibly understand what I was going through. He asked me oxygen
one or two questions: Had any close friend or relative died recently?
Was I having any trouble in my job or at home? When I answered no, 0 1 2 3 4 5 6
he shrugged his shoulders and reached for his prescription pad. Since Time (min)
that first occasion I have seen I don’t know how many doctors, but none Breathing rate and blood oxygen level recorded during REM
could help me. I’ve been given hundreds of different pills—to put me to sleep from a person with sleep apnea. Blood oxygen increased
sleep at night, to keep me awake in the daytime, to calm me down, to pep after each breath, then continued to fall until another breath
me up—have even been psychoanalyzed. But still I cannot sleep at night. was taken. This person inhaled only 4 times in the 6-minute
(In Dement, 1972, p. 73) period; a healthy sleeper would breathe more than 60 times in
When this patient entered the Stanford University Sleep Disorders the same interval.
Clinic in 1972, recording electrodes monitored his brain, muscle, eye,
and breathing activity while he slept (see Figure 13-11). The attending
researchers were amazed to find that he had to wake up to breathe. even occur in children; it may be related to some cases of sudden infant
They observed that he would go more than a minute without breathing death syndrome (SIDS), or crib death, in which otherwise healthy infants
before he woke up, gasped for breath, and returned to sleep. Then the inexplicably die in their sleep. Sleep apnea is thought to be more com-
sequence began again. mon among overweight people and those who snore, two conditions in
Sleep apnea may be produced by a CNS problem, such as weak neural which airflow is restricted.
command to the respiratory muscles, or it may be obstructive, caused by Treatments for sleep apnea include surgery or an appliance to expand
collapse of the upper airway. When people with sleep apnea stop breath- the upper airway, weight loss, and a face mask to deliver negative pres-
ing, they either wake up completely and have difficulty getting back to sleep sure to open the airway. Untreated sleep apnea can cause high blood
or they partially awaken repeatedly throughout the night to gasp for breath. pressure and other cardiovascular disease, memory problems, weight
Sleep apnea affects people of all ages and both sexes, and 30 per- gain, impotence, headaches, and brain damage due to oxygen insuffi-
cent of those older than 65 may have some form of it. Sleep apnea can ciency (Corrêa Cde et al., 2015).
Sleep Apnea, describes a person who spent all night every night waking up to breathe. This
nighttime behavior left him extremely tired and caused him to nod off in the daytime. Being
overweight contributes to sleep apnea as well as to metabolic syndrome. Clearly the relation-
ship between sleep and health is both complex and interconnected.
Disorders of REM Sleep
Several sleep disorders are associated with the unexpected onset of atonia and dreams, two
main features of REM sleep. We describe three: sleep paralysis, cataplexy, and REM sleep
behavioral disorder.
Sleep Paralysis
In sleep paralysis both atonia and dreaming can occur when a person is awake, usually just
falling asleep or waking up. L. M., a college senior, recounted the following experience.
sleep paralysis Atonia and dreaming She had just gone to sleep when her roommate came into their room. L. M. woke up and
occurring when a person is awake, usually intended to ask her roommate if she wanted to go skating the next morning but found herself
just falling asleep or waking up. unable to speak. She tried to turn her head to follow her roommate’s movements across the
cataplexy State of atonia, as in REM sleep, room but found that she was paralyzed. She had the terrifying feeling that some creature
occurring while a person is awake and active; was hiding in the bathroom waiting for her roommate. She tried to cry out but produced
linked to strong emotional stimulation. only harsh gurgling noises. In response to these peculiar noises the roommate knocked her
hypnogogic hallucination Dreamlike event out of her paralysis by hitting her with a pillow.
as sleep begins or while a person is in a state Sleep paralysis is common. In informal class surveys almost a third of students report
of cataplexy. having had such an experience, as do some war veterans during group therapy sessions.
13-6 • Sleep Disorders 475
The atonia is typically accompanied by dread or fear. It seems likely that in sleep paralysis a
person has entered REM sleep partially. He or she is dreaming, atonia has occurred, but the
sleeper remains “awake.” When sleep paralysis occurs as a person wakes up, the paralysis and
dreaming characteristic of a REM episode continue.
Cataplexy
The atonia of REM sleep can also occur while a person is awake and active, a condition called
cataplexy. The person loses muscle tone and gradually or even quickly falls to the floor, atonic.
The collapse can be so sudden that injury is a real risk. Cataplexy can be triggered by excitement The word cataplexy comes from the Greek
or laughing. While in an atonic condition, the person sees imaginary creatures or hears imagi- word kataplessein, meaning to strike down.
nary voices. People who fall into a state of cataplexy with these hypnogogic hallucinations give Hypnogogic comes from the Greek hypnos,
every appearance of having fallen into REM sleep while remaining “awake.” sleep and agogos, leading into.
Cataplexy can have a genetic basis. In 1970 William Dement was given a litter of Dober-
man pinscher dogs and later a litter of Labrador retrievers. These dogs displayed cataplexy. Figure 3-21 explains inheritance patterns for
The disease is transmitted as a recessive trait: to develop it, a dog must inherit the gene from genetic disorders.
both its mother and its father. The descendants of those dogs continue to provide animal
models for investigating the neural basis of the disease as well as its treatment.
Jerome Siegel (2004) investigated the cause of narcolepsy in dogs. He found that neurons View a researcher working with narcoleptic
in the subcoerulear nucleus become inactive and neurons in the magnocellular nucleus of dogs at https://www.youtube.com/
the medulla become active during attacks of cataplexy, just as they do during REM sleep. watch?v=R6_hwbp97eU.
On the basis of anatomical examinations of the brains of narcoleptic dogs, Siegel suggested
that the death of neurons in the amygdala and adjacent forebrain areas is a one-time event
that occurs just before the onset of the disease early in life.
A remarkable discovery that came from this line of investigation is that a subset of these
affected neurons produces a peptide called orexin (also called hypocretin) that serves as a sig-
naling molecule to maintain wakefulness. Orexin cells, which are located in the hypothala-
mus, send projections to many other brain regions, as do the nonspecific activating systems
using acetylcholine and serotonin. This suggests that orexin plays a role in maintaining
activity during waking.
To test the idea that orexin loss is related to cataplexy, investigators have bred knockout Section 3-3 investigates knockout technology
mice that lack orexin. When these mice become active, such as at feeding time, they col- and other genetic engineering techniques.
lapse into cataplexy, supporting the idea that an orexin system contributes to healthy wak-
ing behavior. Research with mice also suggests that lifestyle may contribute to orexin cell
loss. Mice fed a high-fat diet display a reduction in orexin cells and symptoms of cataplexy View a dancer experiencing narcolepsy with
(Nobunaga et al., 2014). Another proposed cause of narcolepsy in humans is an autoimmune cataplexy at https://www.youtube.com/
reaction: the immune system attacks and kills orexin cells. watch?v=1PuvXpv0yDM.
REM Sleep Behavioral Disorder
In Section 13-4 we described REM sleep behavioral disorder (REM without atonia), a symp-
tom displayed by some people who take antidepressant drugs. They wake up seemingly act-
ing out dream activity. In Section 13-5 we described Jouvet’s experiment: he reported that
cats with lesions to the subcoerulear region of the brainstem entered REM sleep without
accompanying atonia and so apparently acted out their dreams.
A similar condition reported in people may have either a genetic basis or a neurological
cause associated with aging. People who display REM sleep behavioral disorder behave as
though they are acting out their dreams (Mahowald & Schenck, 2015). Following is the
account of a 67-year-old patient (Schenck et al., 1986):
I had a dream where someone was shooting at me with a rifle and it was in a field that had ridges
in it, so I decided to crawl behind a ridge—and I then had a gun too—and I look over the ridge so
when he showed up I would shoot back at him and when I came to [i.e., awakened] I was kneeling
alongside the bed with my arms extended like I was holding the rifle up and ready to shoot.
In the dream the patient saw vivid images but heard nothing and felt afraid. Although
many patients have described such experiences, most are elderly and suffer from brain injury
476 Chapter 13 • WHY DO WE SLEEP AND DREAM?
or other brain-related disorders. REM sleep behavioral disorder can be treated with benzo-
diazepines, antianxiety drugs that block REM sleep.
13-6 reVieW
Sleep Disorders
Before you continue, check your understanding.
1. Disorders of NREM sleep include , in which a person has difficulty falling
asleep at night, and , in which a person falls asleep involuntarily in the
daytime.
2. Treating insomnia with sleeping pills, usually sedative-hypnotics, may cause
: progressively higher doses must be taken to achieve sleep.
3. Disorders of REM sleep include , in which a person awakens but cannot
move and is afraid, and , in which a person may lose all muscle tone and
collapse while awake.
4. The people who act out their dreams, a condition termed , may have
damage to the nucleus.
5. Is orexin the substance that produces waking?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
13-7 What Does Sleep Tell Us about
Consciousness?
René Descartes conceived his idea of a mind through a lucid dream. He dreamed that he was
interpreting the dream as it occurred. Later, when awake, he reasoned that if he could think
and analyze a dream while asleep, his mind must function during both waking and sleep-
Section 1-2 recounts how Descartes chose ing. He proposed therefore that the mind must be independent of the body that undergoes
the pineal gland as the seat of the mind. sleeping and waking transitions. Contemporary fMRI studies suggest that lucid dreaming
is especially common in people who display high levels of prefrontal cortex activity in Brod-
mann’s areas 9 and 10 (Filevich et al., 2015).
As described in preceding sections, what we colloquially refer to as waking comprises at
least three states. First, alert consciousness without accompanying movement is associated
with cholinergic system activity. Second, consciousness with movement is associated with
serotonergic system activity. Third, the peptide orexin also plays a role in maintaining wak-
ing activity.
Similarly, sleep consists of NREM and REM phases. NREM sleep consists of the four
stages indicated by the EEG (see Figure 13-12A). REM sleep periods consist of at least two
stages, one in which small twitching movements occur and one in which such motion twitch-
ing is absent.
REM neurobehavioral events can occur relatively independently. Sleepers may awake to
find themselves in a condition of sleep paralysis, during which they experience the hallucina-
tions and fear common in dreams. People who are awake may fall into a state of cataplexy:
they are conscious of being awake during the atonia and visual and emotional features of
dreams.
Sleep researcher J. Allan Hobson reported his peculiar symptoms after a brainstem stroke
(Hobson, 2002). For the first 10 days after the lesion, he had complete insomnia, neither
REM nor NREM sleep. Whenever he closed his eyes, however, he did have visual hallucina-
tions that had a dreamlike quality. This experience suggested that eye closure is sufficient to
Summary 477
produce the visual components of REM sleep but with neither loss of consciousness nor ato-
nia. Hobson eventually recovered typical sleeping patterns, and the hallucinations stopped.
Beyond teaching us that the neural basis of consciousness is extremely complex, the study
of sleep states and dreaming may help to explain some psychiatric and drug-induced condi-
tions. For example visual and auditory hallucinations are among the symptoms of schizo-
phrenia. Are these hallucinations dream events that occur unexpectedly during waking?
Many people who take hallucinogenic drugs such as LSD report visual hallucinations. Does
the drug initiate the visual features of dreams? People who have panic attacks suffer from
very real fright that has no obvious cause. Are they experiencing the fear attacks that com-
monly occur during sleep paralysis and cataplexy?
What the study of sleep tells us about consciousness is that a remarkable number of varia-
tions of conscious states exist. Some are associated with waking and some with sleeping, and Section 15-7 explores the neural basis of
the two can mix together to produce a variety of odd conditions. When it comes to conscious- consciousness and ideas about why humans
ness, there is far more to sleeping and waking than just sleeping and waking. are conscious.
Summary
13-1 A Clock for All Seasons produce an electromyogram (EMG), and eye movements to produce
Biorhythms are cyclic behavior patterns of varying length displayed by an electrooculogram (EOG).
animals, plants, even single-celled organisms. Biorhythms displayed A typical night’s sleep, as indicated by physiological measures,
by mammals include, among others, circadian (daily) rhythms and consists of stages that take place in cycles over the course of the
circannual (yearly) rhythms. In the absence of environmental cues night. During REM sleep the EEG displays a waking pattern and the
circadian rhythms are free-running, lasting a little more or a little sleeper displays rapid eye movements. Sleep stages in which the EEG
less than their usual period of about 24 hours depending on the has a slower rhythm are called non-REM (NREM) sleep.
individual organism or the environmental conditions. Cues called Intervals of NREM sleep and REM sleep alternate four or five times
Zeitgebers reset biological clocks to a 24-hour rhythm. Circadian each night. The duration of NREM sleep periods is longer earlier in
rhythms allow us to synchronize our behavior with our body’s sleep, whereas the duration of REM sleep periods is longer in the later
metabolic processes—so that we are hungry, and at optimal times. part of sleep. These intervals also vary with age.
Environmental intrusions into our natural circadian rhythm, from A sleeper in NREM has muscle tone, may toss and turn, and has
artificial lighting to jet lag, contribute to metabolic syndrome. dreams that are not especially vivid. A sleeper in REM sleep has vivid
Biological clocks produce epigenetic effects: they regulate gene dreams in real time but has no muscle tone and so is paralyzed. Dream
expression in every cell in the body. duration coincides with the duration of the REM period.
The activation–synthesis hypothesis proposes that dreams are
not meaningful, merely a by-product of the brain’s state of excitation
13-2 Neural Basis of the Biological Clock
during REM. The coping hypothesis suggests that dreaming evolved as
A biological clock is a neural structure responsible for producing
a mechanism to deal with challenges and fears posed by life.
rhythmic behavior. Our master biological clock is the suprachiasmatic
nucleus. The SCN is responsible for circadian rhythms; it has its own 13-4 What Does Sleep Accomplish?
free-running rhythm with a period of a little more or a little less than
Several theories of sleep have been advanced, but the main proposition
24 hours. Stimuli from the environment, such as sunrise and sunset,
is that sleep is a biological adaptation that conserves energy. Sleep
meals, or exercise, entrain the free-running rhythm so that its period
is suggested as a restorative process that fixes wear and tear in the
approximates 24 hours.
brain and body. Sleep also organizes and stores memories.
SCN neurons are active in the daytime and inactive at night. These
neurons retain their rhythmicity when disconnected from other brain 13-5 Neural Bases of Sleep
structures, when removed from the brain and cultured in a dish, and Separate neural regions are responsible for NREM and REM sleep.
after culture in a dish for many generations. When reimplanted in a The reticular activating system, located in the central brainstem,
brain without an SCN, they restore the animal’s circadian rhythms. is responsible for NREM sleep. If the RAS is stimulated, a sleeper
Aspects of neuronal circadian rhythms, including their period, are awakes; if it is damaged, a person may enter a coma.
under genetic and epigenetic control. The peribrachial area and the medial pontine reticular formation in
the brainstem are responsible for REM sleep. If these areas are damaged,
13-3 Sleep Stages and Dreaming REM sleep may no longer occur. Pathways projecting from these areas
Sleep events are measured by recording the brain’s activity to to the cortex produce the cortical activation of REM, and those projecting
produce an electroencephalogram (EEG), muscular activity to to the brainstem produce the muscular paralysis of REM.
478 Chapter 13 • WHY DO WE SLEEP AND DREAM?
13-6 Sleep Disorders the person may have hypnogogic hallucinations similar to dreaming.
Disorders of NREM sleep include insomnia, the inability to sleep at In REM sleep behavioral disorder a sleeping person acts out dreams.
night, and narcolepsy, inconveniently falling asleep in the daytime.
Sedative-hypnotics used to induce sleep may induce drug dependence 13-7What Does Sleep Tell Us
insomnia, a sleep disorder in which progressively larger doses are about Consciousness?
required to produce sleep. Sleep research provides insight into consciousness by revealing many
Disorders of REM sleep include sleep paralysis, in which a person kinds of waking and sleeping. Just as the events of wakefulness intrude
awakens but remains unable to move and sometimes feels fear and into sleep, the events of sleep can intrude into wakefulness. The array
dread. In cataplexy, caused by a loss of orexin cells in the brain, a of conditions thus produced demonstrates that consciousness is not
person collapses into a state of paralysis while awake. At the same time a unitary state.
Key termS
atonia, p. 458 dimer, p. 452 medial pontine reticular reticular activating system
basic rest–activity cycle diurnal animal, p. 443 formation (MPRF), p. 470 (RAS), p. 470
(BRAC), p. 464 drug dependence insomnia, melatonin, p. 454 retinohypothalamic tract, p. 450
beta (b) rhythm, p. 457 p. 473 metabolic syndrome, p. 443 sleep apnea, p. 473
biological clock, p. 443 entrain, p. 446 microsleep, p. 466 sleep paralysis, p. 474
biorhythm, p. 443 free-running rhythm, p. 446 narcolepsy, p. 473 slow-wave sleep, p. 458
cataplexy, p. 474 hypnogogic hallucination, NREM (non-REM) sleep, p. 458 suprachiasmatic nucleus (SCN),
chronotype, p. 450 p. 474 peribrachial area, p. 470 p. 450
circadian rhythm, p. 443 insomnia, p. 473 period, p. 445 Zeitgeber, p. 446
coma, p. 470 jet lag, p. 448 place cell, p. 468
delta (d) rhythm, p. 458 light pollution, p. 446 REM sleep, p. 458
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
14 How Do We Learn CliniCal FoCus 14-1 Remediating dyslexia
14-1 ConneCting learning and MeMory
and Remember? studying leaRning and memoRy in the laboRatoRy
experiMent 14-1 Question: does an animal leaRn
the association between emotional expeRience
and enviRonmental stimuli?
two categoRies of memoRy
what makes explicit and implicit memoRy diffeRent?
what is special about peRsonal memoRies?
14-2 dissoCiating MeMory CirCuits
disconnecting explicit memoRy
disconnecting implicit memoRy
CliniCal FoCus 14-2 patient boswell’s amnesia
14-3 neural systeMs underlying expliCit and
iMpliCit MeMories
neuRal ciRcuit foR explicit memoRies
CliniCal FoCus 14-3 alzheimeR disease
CliniCal FoCus 14-4 koRsakoff syndRome
consolidation of explicit memoRies
neuRal ciRcuit foR implicit memoRies
neuRal ciRcuit foR emotional memoRies
14-4 struCtural Basis oF Brain plastiCity
long-teRm potentiation
measuRing synaptic change
enRiched expeRience and plasticity
sensoRy oR motoR tRaining and plasticity
experiMent 14-2 Question: does the leaRning of a fine
motoR skill alteR the coRtical motoR map?
researCh FoCus 14-5 movement, leaRning, and neuRoplasticity
expeRience-dependent change in the human bRain
epigenetics of memoRy
plasticity, hoRmones, tRophic factoRs, and dRugs
experiMent 14-3 Question: what effect do Repeated doses of
amphetamine, a psychomotoR stimulant, have on neuRons?
some guiding pRinciples of bRain plasticity
14-5 reCovery FroM Brain injury
donna’s expeRience with tRaumatic bRain injuRy
thRee-legged cat solution
new-ciRcuit solution
experiMent 14-4 Question: does neRve gRowth factoR
Katherine Streeter
stimulate RecoveRy fRom stRoke, influence
neuRal stRuctuRe, oR both?
lost neuRon Replacement solution
479
480 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
CliniCal F cus 14-1
Remediating Dyslexia
As children absorb their society’s culture, acquiring language skills When the sounds are spoken slowly, discriminating between them is
seems virtually automatic. Yet some people face lifelong challenges in easy, but as they grow briefer and occur faster, discrimination becomes
mastering language-related tasks. Educators classify these difficulties more difficult. Previous studies using rats and monkeys showed that dis-
under the umbrella of learning disabilities. crimination training stimulates neural plasticity in the auditory system, mak-
Dyslexia, impairment in learning to read, may be the most com- ing it capable of discrimination of sounds that previously was not possible.
mon learning disability. Children with dyslexia (from Greek words sug- The representative fMRIs shown here reveal decreased activation in
gesting bad and reading) have difficulty learning to write as well as many brain regions in untreated dyslexic children compared with typical
to read. children. With training, dyslexic readers can normalize their brain activity
In 1895, James Hinshelwood, an eye surgeon, examined some and presumably its connectivity.
schoolchildren who were having reading problems, but he could find The extent of increased brain activation in the language-related
nothing wrong with their vision. Hinshelwood was the first to suggest regions (circled in the images) correlates to the amount of increased
that children with reading problems were impaired in brain areas associ- brain activation overall. The results suggest that the remedial treatment
ated with language use. Norman Geshwind and Albert Galaburda (1985) both improves brain function in regions associated with phonological pro-
proposed how such impairment might come about. cessing and produces compensatory activation in related brain regions.
Struck by the finding that dyslexia is far more common in boys than
in girls, they reasoned that hormones influence early brain development.
They examined postmortem the brains of a small sample of
people who had dyslexia and found abnormal collections of
neurons, or warts, in and around the brain’s language areas.
This relation between structural abnormalities in the
brain and learning disabilities is further evidence that an in-
tact brain is necessary for healthy human functioning. Gesh-
wind and Galaburda also found abnormalities in the auditory
thalamus, suggesting a deficit in auditory processing. More
recently, brain imaging has determined that, relative to the
brains of healthy participants, activity is reduced in the left
temporoparietal cortex of people with dyslexia.
Michael Merzenich and his colleagues designed a re-
medial treatment program based on the assumption that Typical-reading children while rhyming Dyslexic-reading children while rhyming
(before remediation)
the fundamental problem in learning disabilities lies in au-
Regions of the frontal and temporoparietal cortex that showed decreased
ditory processing, specifically of language sounds (e.g., activation in children with untreated dyslexia. “Neural Deficits in Children with Dyslexia
Temple et al., 2003). Remediation involves learning to make Ameliorated by Behavioral Remediation: Evidence from Functional MRI,” by E. Temple, G. K. Deutsch, R.
increasingly difficult sound discriminations, for example, A. Poldrack, S. L. Miller, P. Tallal, M. M. Merzenich, and J. D. E. Gabrieli, 2003, Proceedings of the National
discriminating ba and da. Academy of Sciences (USA) 100, pp. 2860–2865.
Neuroplasticity is the nervous system’s the brain is plastic. It changes throughout life, allowing us to modify our behavior, to
potential for physical or chemical change that adapt and learn, and to remember. If we reflect on our own lives, we can easily compile a list
enhances adaptability. of experiences that must change the brain:
• Profound changes during development
• Acquisition of culture
• Preferences among foods and beverages, art and music, and other activities and
experiences
• Ability to cope with the neurodegeneration of aging and to accommodate neurological
injury or disease at any age
Learning is common to all these experiences. Understanding how the brain supports
learning is fundamental in neuroscience. At the level of the neuron, synapses change with
experience—learning new information, for example. Such changes can take place anywhere
in the brain.
14-1 • Connecting Learning and Memory 481
We can investigate neuronal changes that support learning specific types of information
by describing changes in cells exposed to specific sensory experiences. Or we can look at
the neural changes that mediate brain plasticity—recovery from brain injury, addiction to
drugs, or conquering a learning disability. This chapter’s goal is to move beyond the general
concept of neuroplasticity toward understanding what stimulates plastic change in the brain.
We inspect changes related to environment and experience, learning and memory, electrical
stimulation, chemical influences, and brain injury.
14-1 Connecting Learning
and Memory
Learning is a relatively permanent change in an organism’s behavior as a result of experi-
ence. Memory is the ability to recall or recognize previous experience. Memory thus implies
a mental representation of a previous experience, sometimes termed a memory trace. Neuro- The memory trace is a psychological
scientists presume that this hypothetical memory trace corresponds to a physical change in construct, an abstract mental process inferred
the brain, most likely involving synapses. only from behavior (see Section 15-1).
At the macro level, we infer what we know about learning and memory formation from Others include learning, language, emotion,
motivation, and thinking.
behavioral changes, not by observing the brain directly. Studying learning and memory
therefore requires behavioral measures that evaluate how these changes come about. We
begin here by reviewing how learning and memory researchers study animals in the labora-
tory. The results suggest, in a general way, how the brain organizes its learning and memory
systems.
Studying Learning and Memory
in the Laboratory
A challenge for psychologists studying memory in laboratory animals (or people) is to get
subjects to reveal what they remember. Because laboratory animals do not speak, investiga-
tors must devise ways for a subject to show its knowledge. Different species “talk” to us in
different ways, so the test choice must match each species’ capabilities.
Mazes or swimming pools are typically used to study rats because rats live in tunnels and
near water. Monkey studies take advantage of their sharp vision and avid curiosity by requir- Figure 7-4 samples swimming pool tests for
ing them to look under objects for food or watch television monitors. With birds, natural rats, Experiment 15-1, monkeys’ perceptual
behaviors such as singing are used. And for humans, investigators tend to use paper-and- threshold, and Focus 15-4, the effects of brain
pencil tests. injuries on humans’ cognitive performance.
Psychologists have devised hundreds of tests over the past century, and the test results
reveal many types of learning and memory. Each appears to have its own neural circuitry.
Two classic traditions for training animals to talk to investigators emerged a century ago.
These diverse approaches are based on the work of Edward Thorndike (1898) in the United
States and on experiments conducted by Ivan Pavlov in Russia. dyslexia Impairment in learning to read and
write; probably the most common learning
Pavlovian Conditioning disability.
Early in the twentieth century, Ivan Pavlov, a Russian physiologist, discovered that when a learning Relatively permanent change in an
food reward accompanies some stimulus, such as a tone, dogs learn to associate the stimulus organism’s behavior as a result of experience.
with the food. Then whenever they hear the tone, they salivate even though no food is pres- memory Ability to recall or recognize
ent. This type of learning has many names, including Pavlovian conditioning, respondent previous experience.
conditioning, and classical conditioning, and many studies document its characteristics.
Pavlovian conditioning Learning achieved
A key feature of Pavlovian conditioning is that animals learn to associate two stimuli (the when neutral stimulus (such as a tone) comes
presentation of the food and the tone) and to communicate to us that they have learned it by to elicit a response after its repeated pairing
giving the same response (salivation) to both stimuli. Pet owners know that to a cat or dog, the with some event (such as delivery of food);
sound of a can being opened is a clear stimulus for food. Two forms of Pavlovian condition- also called classical conditioning or respondent
ing are common in experiments today: eyeblink conditioning and fear conditioning. Each is conditioning.
482 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
Figure 14-1 Eyeblink Conditioning associated with neural circuits in discrete brain
1 Headgear is arranged
Neural circuits in the cerebellum mediate regions; thus both are especially useful.
for eyeblink conditioning.
this form of stimulus–response learning. Eyeblink conditioning has been used to
Electrodes
study Pavlovian learning in rabbits and people
2 Puff of air to
(Figure 14-1). In these studies, a tone (or some
eye causes eye
to blink. other stimulus) is associated with a painless puff
of air to the participant’s eye. The tone is the
Air jet
tube conditioned stimulus (CS) that comes to elicit
a blink produced initially by the air puff. The
Audio air puff is the unconditioned stimulus (UCS),
speaker
because blinking is the normal reaction—the
unconditioned response (UCR)—to a puff
of air. The participant communicates hav-
3 After pairing air puff with tone, ing learned that the signal stimulus predicts
tone alone comes to elicit a blink.
the puff by blinking in response to the signal
(the CS) alone—a conditioned response (CR).
The circuits in the cerebellum that mediate such Pavlovian learning are designed to pair
In the cerebellum, the flocculus controls eye motor responses with environmental events. Eyeblink conditioning experiments take advan-
movements; see Figure 11-14. tage of this biological predisposition.
In fear conditioning, an unpleasant but harmless stimulus is used to elicit an emotional
response: fear. A rat or other animal is placed in a box. A mild but unpleasant electric cur-
rent can be passed through the grid floor. As shown in Experiment 14-1, a tone (the CS) is
presented just before a brief, unexpected mild electric shock. When the tone is presented
later without the shock, the animal acts afraid, becoming motionless and perhaps urinating
in anticipation of the shock. A novel stimulus, say, a light, presented in the same environ-
The shock approximates a spark of static ment has little effect. Thus, the animal communicates that it has learned the association
electricity. between the tone and the shock.
Because the CR is emotional, circuits of the amygdala rather than the cerebellum medi-
ate fear conditioning. Although both eyeblink and fear conditioning are Pavlovian, different
brain areas mediate the learning.
Operant Conditioning
In the United States, Edward Thorndike (1898) began a second tradition for studying learn-
ing and memory. Thorndike was interested in how animals solve problems. In one series of
experiments, he placed cats in a box with a plate of fish outside it (Figure 14-2). The only way
for a hungry cat to get to the fish was to figure out how to get out of the box.
The solution was to press on a lever to activate a system of pulleys that opened the box
door. The cat gradually learned that its actions had consequences: on the initial trial, the cat
ExPErimEnt 14-1
Question: Does an animal learn the association between emotional experience and environmental stimuli?
Procedure and results
Rat receives mild electrical shock If a light is presented alone Rat freezes in fear when tone
in combination with tone. later, rat ignores it. alone sounds.
Tone Light only— Tone only
plus shock no tone
Later Later
Conclusion: The rat has learned an association between the tone and the shock, which
produces a fear response. Circuits that include the amygdala take part in this learning process.
14-1 • Connecting Learning and Memory 483
Pulley
The cat is placed in the box system
with the food reward outside.
The hungry cat
eventually learns that
pressing on the lever will Lever
result in getting out of
the box and getting to
the food.
Food
reward
Figure 14-2 Thorndike’s Puzzle Box
touched the releasing mechanism only by chance as it restlessly paced inside the box. The
eyeblink conditioning Experimental
cat apparently learned that something it had done opened the door, and it tended to repeat
technique in which subjects learn to pair a
its behaviors from just before the door opened. After a few trials, the cat took just seconds
formerly neutral stimulus with a defensive
to get the door open to devour the fish.
blinking response.
Later studies by B. F. Skinner (e.g., 1938) used a similar strategy of reinforcement to train
conditioned stimulus (cs) In Pavlovian
rats to press bars or pigeons to peck keys to obtain food. Just as Thorndike’s cats learned to
conditioning, an originally neutral stimulus
escape his puzzle boxes, many animals learn to press the bar or peck the key simply if they
that after association with an unconditioned
are placed in the apparatus and allowed to discover the response that obtains the reward.
stimulus (UCS) triggers a conditioned
This type of learning is operant conditioning, or instrumental conditioning, as Thorndike response (CR).
called it. The animal demonstrates that it has learned the association between its actions and
unconditioned stimulus (ucs) A
the consequences by performing the task faster.
stimulus that naturally and automatically
The variety of operant associations is staggering: we learn constantly to associate our be-
(unconditionally) triggers an unconditioned
havior with its consequences. No surprise, then, that operant learning is not localized to any response (UCR).
particular brain circuit. The circuits needed vary with the task requirements. For example,
unconditioned response (ucr) Unlearned,
olfactory tasks involve olfactory-related structures like the orbitofrontal cortex and amygdala,
naturally occurring response to the
spatial tasks recruit the hippocampus, and motor tasks require the basal ganglia.
unconditioned stimulus (UCS), such as
salivation when food is in the mouth.
Two Categories of Memory conditioned response (cr) In Pavlovian
Humans present a distinct challenge to researchers studying memory because so much conditioning, the learned response to a
of our learning is verbal. Psychologists have studied human memory since the mid-1800s. formerly neutral conditioned stimulus (CS).
More recently, cognitive psychologists have developed sophisticated measures of learning fear conditioning Conditioned emotional
and memory for neuropsychological investigations. Two such measures help to distinguish response between a neutral stimulus and
between two categories of memory in humans. an unpleasant event, such as a shock, that
In one kind of task, a group of participants reads a list of words, such as spring, winter, car, results in a learned association.
and boat. Another group reads a list consisting of trip, tumble, run, and sun. All the partici- operant conditioning Learning procedure in
pants are then asked to define a series of words. One is fall. which the consequences (such as obtaining
The word fall has multiple meanings, including the season and a tumble. People who a reward) of a particular behavior (such as
have just read the word list containing names of seasons are likely to give the meaning as pressing a bar) increase or decrease the
autumn; those who have read the second list, containing action words, typically give the probability of the behavior occurring again;
meaning as tumble. Some form of unconscious (and unintentional) learning takes place as also called instrumental conditioning.
the participants read the word lists. implicit memory Unconscious memory:
This task measures implicit memory: participants demonstrate knowledge—a skill, con- subjects can demonstrate knowledge, such
ditioned response, or recall of events on prompting—but cannot explicitly retrieve the infor- as a skill, conditioned response, or recall of
mation. People with amnesia, a partial or total loss of memory, perform at normal on tests events on prompting but cannot explicitly
of implicit memory. The amnesic person has no recollection of having read the word list yet retrieve the information.
acts as though some neural circuit has been influenced by it. In amnesia, a dissociation—a amnesia Partial or total loss of memory.
484 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
disconnect—occurs between the memory of the unconscious (or implicit) learning
and explicit memory, conscious recollection of training. Nonamnesic people can
retrieve an explicit memory and indicate that they know the retrieved item is correct.
This implicit–explicit distinction is not restricted to verbal learning; it is true of
visual learning and motor learning as well. For example, when people are shown the
top panel of the Gollin figure test in Figure 14-3 and asked what it shows, they are
unlikely to identify an image. They are then presented with a succession of more
nearly complete sketches until they can identify the picture. When control partici-
pants and amnesics are later shown the same sketch, both groups identify the figure
sooner than they could the first time. Even though the amnesic subjects may not
recall seeing the sketches before, they behave as though they had.
To measure implicit motor skills learning, a person learns a skill, such as the pur-
suit rotor task shown in Figure 14-4. A small metal disc moves in a circular pattern
on a turntable that also is moving. The task is to hold a stylus on the small disc as
it spins. This task is not as easy as it looks, especially when the turntable is moving
quickly. Nonetheless, with an hour’s practice most people become reasonably profi-
cient. Presented with the same task a week later, both controls and amnesics take less
time to perform it. Here, too, the amnesics fail to recall performing the task before.
The distinction between tests of implicit and explicit memory is consistent and
therefore must offer a key to how the brain stores information. Some theorists make
subtle distinctions between the implicit–explicit dichotomy we use and other ter-
minologies for categorizing unconscious and conscious memory. Many researchers
prefer to distinguish between declarative memory, the specific contents of specific
experiences that can be verbally recalled (times, places, or circumstances), and
Figure 14-3 Gollin Figure Test procedural memory, the ability to perform a task. As applied to humans there is little practi-
Participants are shown a series of drawings
cal difference.
in sequence, from least to most clear, and
asked to identify the image. Most people Table 14-1 lists commonly used dichotomies, the general distinction being that one mem-
must see several panels before they can ory category requires recalling specific information, whereas the other refers to knowledge of
identify it. On a retention test some time which we are not consciously aware. We can include Pavlovian conditioning and Thorndike’s
later, however, participants identify the and Skinner’s operant learning in this analysis too: all are forms of implicit learning.
image sooner than they did on the first Nonspeaking animals can display explicit memory. One of us owned a cat that loved to
test, indicating some form of memory for
play with a little ball. One day, as the cat watched, the ball was temporarily put on a high
the image. Amnesic subjects also show
improvement on this test, even though they shelf to keep it away from an inquisitive toddler. For weeks afterward, the cat sat and stared at
do not recall taking it. the shelf where the ball had been placed, even though the ball was not visible—an example
of explicit memory.
Animals also display explicit memory when they learn psychological tasks. Rats can
be trained to find highly palatable food in a new location in a large compound each day.
Rotating
Stylus
target
Figure 14-4 Pursuit-Rotor Task The
participant must keep the stylus in contact
with a metal disc moving in a circular
pattern on a turntable while also rotating
in a circular pattern. Although the task
is difficult, most people show significant
Rotating
improvement after brief training. Given
disk
a second test at some later time, both
participants and amnesics show task
retention, but typically the amnesics do not
recall learning it before.
14-1 • Connecting Learning and Memory 485
The task is to go to the most recent location. This piece of information is explicit and taBLe 14-1 differentiating two memory categories
demonstrably can be forgotten.
terms that describe terms that describe
Suppose a rat trained to find food in a particular location in a small arena is given conscious memory unconscious memory
several trials with the food at a new location and then retested an hour, a day, 3 days,
Explicit Implicit
or a week later. The rat has no difficulty with an hour’s delay or perhaps even a day’s.
Declarative Nondeclarative
Some rats are flawless at 3 days, but most have forgotten the location by the time a
Fact Skill
week has elapsed. Instead, they wander around looking for the food. This behavior il-
lustrates their implicit memory of the learning set, the rules of the game—an implicit Memory Habit
understanding of how a problem can be solved with a rule that can be applied in many Knowing that Knowing how
situations—namely, here, that a desired food can be found with a certain search strategy. Locale Taxon
Conscious recollection Skills
What Makes Explicit and Implicit Elaboration Integration
Memory Different? Memory with record
Autobiographical
Memory without record
Perceptual
One reason explicit and implicit memories differ is that the set of neural structures
Representational Dispositional
that houses each is different. Another reason they differ is that the brain processes
Episodic Procedural
explicit and implicit information differently.
Semantic Nonassociative
Encoding Memories Working Reference
Implicit information is encoded in much the same way it is perceived: it can be de- Note: This paired list of terms differentiates conscious from unconscious forms of
scribed as data-driven, or bottom-up, processing. The idea is that information enters memory. It will help you relate other memory discussions to the one in this book, which
favors the explicit–implicit distinction.
the brain through sensory receptors, then is processed in a series of subcortical and
cortical regions. For example, visual information about an object moves from the photore-
ceptors (the bottom) to the thalamus, occipital cortex, then through the ventral stream to
the temporal lobe (the top), where the object is recognized.
Explicit memory, in contrast, depends on conceptually driven, or top-down, processing:
the person reorganizes the data. If you were searching for a particular object, your keys, for
example, you would ignore other objects. This process is top-down because circuits in the
temporal lobe (the top) form an image (keys) that influences how incoming visual information
(the bottom) is processed and in turn greatly influences information recall later.
Because a person has a relatively passive role in encoding implicit memory, he or she has diffi-
culty recalling the memory spontaneously but recalls it more easily with priming by the original
stimulus or some feature of it. Because a person plays an active role in processing information
explicitly, internal cues used in processing can also be used to initiate spontaneous recall.
Findings from studies of eyewitness testimony demonstrate the active nature of explicit
memory recall—and its fallibility (e.g., Loftus, 1997). In a typical experiment, participants view a explicit memory Conscious memory:
video clip of an accident in which a car collides with another car stopped at an intersection. One subjects can retrieve an item and indicate that
group is asked to estimate how fast the moving car was going when it “smashed” into the other they know the retrieved item is the correct
car. A second group is asked how fast the car was going when it “bumped” into the other car. one.
Later questioning indicates that the memory of how fast the moving car was going is bi- declarative memory Ability to recount
ased by the instruction: participants looking at “smashing” cars estimate faster speeds than what one knows, to detail the time, place,
those estimated by participants looking at “bumping” cars. The instruction actually causes and circumstances of events; often lost in
the information to be processed differently. In both cases, participants were certain their amnesia.
memories were accurate. procedural memory Ability to recall a
Other experiments show that implicit memory also is fallible. For example, participants are movement sequence or how to perform some
read the following list of words: sweet, chocolate, shoe, table, candy, horse, car, cake, coffee, wall, act or behavior.
book, cookie, hat. After a few minutes’ delay, they hear another list of words that includes some learning set Rules of the game; implicit
from the first list and some that are new. Participants are asked to identify which words were understanding of how a problem can be
present on the first list and to indicate how certain they are of the identification. solved with a rule that can be applied in many
One of the words on the second list is sugar. Most participants indicate not just that sugar different situations.
was on the first list but that they are certain it was. Although other sweet things were, sugar priming Using a stimulus to sensitize the
was not. This demonstration is intriguing, because it shows how easily we can form false nervous system to a later presentation of the
memories and defend their veracity with certainty. same or a similar stimulus.
486 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
Processing Memories
Although we can distinguish memories generally as implicit or explicit, the brain does not
process all implicit or all explicit memories in the same way. Memories can be divided ac-
cording to categories that differ from those listed in Table 14-1. For example, we can make a
distinction between memories for different types of sensory information.
Different neural areas process visual and auditory information, so it is reasonable to as-
sume that auditory memories are stored in brain regions different from the regions that
store visual memories. We can also make a distinction between information stored in so-
called short-term memory and information held in long-term memory. In short-term memory,
information—the final score of a playoff game or the combination of your friend’s bike lock,
for instance—is held in memory only briefly, for a few minutes at most, and then discarded.
In long-term memory, information—such as a close friend’s name—is held in memory indefi-
nitely, perhaps for a lifetime.
The frontal lobes are central in short-term memory, whereas the temporal lobe is central
in long-term storage of verbal information. The crucial point is that no single place in the
nervous system can be identified as the location for memory or learning. Virtually the entire
nervous system can be changed by experience, but different parts of an experience change
different parts of the nervous system. One challenge for the experimenter is to devise ways
of manipulating experience to demonstrate change in different parts of the brain.
Storing Memories
Figure 14-5 Memory Distribution Understanding that every part of the brain can learn influences how we view the neural cir-
Blood flow in left-hemisphere regions cuits that mediate memory. We could expect areas that process information to also house the
increases when participants generate color memory of that information. Areas that process visual information, for example, probably
words (red) and action words (blue) to house visual memory. Since the temporal lobe has specialized regions for processing color,
describe static black-and-white drawings shape, and other visual characteristics, we can predict that the memory for various visual
of objects. Purple areas indicate overlap.
attributes of objects is stored separately.
The red region extends into the ventral
temporal lobe, suggesting that object A series of PET studies by Alex Martin and colleagues (1995) at the U.S. National
memory is organized as a distributed Institute of Mental Health confirmed this prediction. In one study, participants were shown
system. Objects’ attributes are stored close black-and-white line drawings of objects and asked to generate words denoting either their
to the cortical regions that mediate their colors or actions. The idea is that processing color and motion are carried out in different
perceptions. Parietal lobe activation likely
temporal lobe locations, and thus the activity linked with the memories of color and motion
is related to movements associated with
action words, and frontal lobe activation, also might be dissociated.
to the spontaneously generated behavior. Just such dissociation was demonstrated. Figure 14-5 shows that color recall activates a
Information from A. Martin, J. V. Haxby, F. M. Lalonde, region in the ventral temporal lobe, just anterior to the area controlling color perception,
C. L. Wiggs, & L. G. Ungerleider (1995). Discrete whereas recall of action words activates a region in the middle temporal gyrus, just anterior
cortical regions associated with knowledge of color
to the area controlling motion perception. This distribution of neural activation shows not
and knowledge of action. Science, 270, p. 104.
only that object memory is at least partly located in the temporal lobes but also
Frontal Parietal that it is found in regions associated with the original perception of the objects.
activation activation
What Is Special about Personal
s
Memories?
yru
por al g One aspect of memory unique to each of us is our personal, or autobiographical,
r tem
Superio memory. This episodic memory includes not only a record of events (episodes)
temporal gyrus
Middle that took place but also a record of our presence and role in the events. Our
personal experiences form the basis of who we are and the rules by which we
oral gyrus
Inferior temp live. That is, we have memories not only for events but also for their context at a
KEY particular time in a particular place. We thus gain a concept of time and a sense
Color words of our personal role in a changing world.
Action words Temporal
Imagine what would happen if we lost our personal memories. We would still
Overlap activation
recall events but we would be unable to see our role in them. People with frontal
14-1 • Connecting Learning and Memory 487
lobe injuries sometimes exhibit such symptoms, as illustrated in a case described by Endel
episodic memory Autobiographical memory
Tulving (2002).
for events pegged to specific place and time
K. C. suffered a serious traumatic brain injury in a motorcycle accident that produced
contexts.
multiple cortical and subcortical lesions. Remarkably, K. C.’s cognitive abilities were intact
and indistinguishable from those of most typical healthy adults. He played chess and the
organ, and his short-term memory was intact. He knew who he was and when his birthday
was, the names of schools he had attended, and the location of the family cottage. Recalling
facts, figures, dates and times posed no difficulty for K. C.
What K. C. could not do was to recall any personally experienced events. This episodic
amnesia covered his entire life, from birth. He knew facts about himself but had no memory
for events that included him personally. For example, K. C. could not describe an event that
took place in school that specifically included him, while at the same time recalling going to
school and the knowledge he had gained there.
Findings from neuroimaging studies of people with episodic amnesia suggest that they
consistently have frontal lobe injuries (Lepage et al., 2001), but exactly why these lesions
produce episodic amnesia remains unclear. Nonetheless, Tulving made the interesting pro-
posal that episodic memory is a marvel of nature: it transforms the brain into a kind of time
machine that allows us to dwell on the past and make plans for the future. He goes further,
suggesting that this ability may be unique to humans and is presumably due to some novel
evolutionary development of the frontal lobe.
Not all people with episodic amnesia have brain injury, however. Many case reports
describe patients with massive memory disturbances resulting from some “psychiatric”
or “psychogenic” disorder. Such cases have been fodder for numerous movie plots. Hans
Markowitsch (2003) noted that the amnesia reported in some of these cases is remark-
ably similar to episodic amnesia seen in neurological patients. Neuroimaging of patients
with psychogenic amnesia shows a massive reduction in brain activity in frontal regions, a
reduction remarkably similar to that seen in neurological patients with episodic amnesia
(Figure 14-6). Therefore, we can assume that patients with psychogenic amnesias have a
dysfunction of frontal brain activity that blocks the retrieval of autobiographical memory.
Just as some people exhibit poor autobiographical memory, a rare group displays highly
superior autobiographical memory (HSAM) (LePort et al., 2012). These people display virtu-
ally complete recall for events in their lives, usually beginning around age 10, and can often
describe any episode, including the day of the week that it occurred and the date. They can
even recall the weather that day, as well as social and public events. Brain imaging of those
who display HSAM shows increased gray matter in the temporal and parietal lobes and in-
creased size in the fiber projection between the temporal and frontal lobes.
Lawrence Pathihis and colleagues (2013) wondered if HSAM individuals might also be
immune to memory distortion, such as the false memories described earlier. The investiga-
tors found that HSAM individuals are as likely to develop false memories as are other par-
ticipants. Whatever the source of their extraordinary autobiographical memory, it does not
prevent the sort of memory distortions the rest of us experience. Possibly that is because the
research paradigms employed are not strictly autobiographical. Figure 14-6 Lost Episodes Left to
right: Horizontal, frontal, and sagittal
sections imaged in a patient with impaired
autobiographical memory. White arrows
point to areas of reduced glucose
metabolism in frontal and temporal
regions as she attempts to retrieve remote
personal memories. Her MRI scan was
normal. Republished with permission of Elsevier
Science and Technology Journals from “The impairment
of recollection in functional amnesic states” Hans J.
Markowitsch and Angelica Staniloiu, Cortex 49 (2013)
1494–1510. Permission conveyed through Copyright
Clearance Center, Inc.
488 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
14-1 reVieW
Connecting Learning and Memory
Before you continue, check your understanding.
1. An organism learns that some stimulus is paired with a reward. This is
conditioning.
2. After learning that consequences follow its behavior, an organism modifies its behavior.
This is conditioning.
3. Information that is unconsciously learned forms memory, whereas specific
factual information forms memory.
4. memory is autobiographical and unique to each person.
5. Where is memory stored in the brain?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
14-2 Dissociating Memory Circuits
Beginning in the 1920s and continuing until the early 1950s, American psychologist Karl
Lashley searched in vain for the neural circuits underlying memories. Lashley’s working
hypothesis was that memories must be represented in the perceptual and motor circuitry
used to learn to solve problems. To find that circuitry, he investigated the ways laboratory
rats and monkeys learn specific tasks for food reward. He believed that if he removed bits of
this circuitry or disconnected it, amnesia should result.
Brain lesions are an ablation technique—the In fact, neither ablation procedure produced amnesia. Lashley found instead that the sever-
first and simplest brain manipulation; see ity of memory disturbance was related to the size of the lesion rather than to its location. After
Section 7-1. searching for 30 years, Lashley concluded that he had failed to find
(A)
the location of a memory trace, although he believed that he knew
where it was not located (Lashley, 1960).
Just two years later, neurosurgeon William Scoville discovered
serendipitously what Lashley’s studies had not predicted. Scoville
was attempting to rid people of seizures by removing the abnor-
mal brain tissue that caused them. In August 1953, Scoville per-
Area of
lesion formed a bilateral medial temporal lobe resection on a young man,
Entorhinal cortex Amygdala Henry Molaison (H. M.), whose severe epilepsy was not controlled
(B) by medication. H. M.’s seizures originated in the medial temporal
lobe region, so Scoville bilaterally removed much of the hippocam-
pal formation, along with some of the amygdala and adjacent neo-
cortical structures. The procedure left the more lateral temporal
lobe tissue intact. As shown in Figure 14-7, removal specifically
included the anterior part of the hippocampus, the amygdala, and
adjacent cortex.
Collateral Entorhinal Hippocampus
sulcus cortex
Figure 14-7 Extent of H. M.’s Surgery H. M.’s right-
(C) hemisphere lesion is highlighted in the brain viewed ventrally. The
lesion runs along the wall of the medial temporal lobe. The left side
of the brain has been left intact to show the relative location of the
medial temporal structures. Parts A, B, and C, based on MRI scans,
depict a series of coronal sections of H. M.’s brain. Research from
S. Corkin, D. G. Amaral, R. G. Gonzalez , K. A. Johnson, & B. T. Hyman (1997).
H. M.’s medial temporal lobe lesion: findings from magnetic resonance imaging.
Hippocampus by Journal of Neuroscience, 17, p. 3966.
14-2 • Dissociating Memory Circuits 489
Disconnecting Explicit Memory
The behavioral symptoms Scoville noted after the surgery were completely unexpected. He
invited Brenda Milner (Milner et al., 1968) to study H. M. Milner had been studying memory
difficulties in patients with unilateral temporal lobe removals for the treatment of epilepsy.
She and her colleagues worked with H. M. for more than 50 years, making his the most
studied case in neuroscience (e.g., Corkin, 2002). H. M. died in 2008.
His most remarkable symptom was severe amnesia: he was unable to recall anything that
had happened since his surgery in 1953. H. M. retained an above-average I.Q. score (118 on
the Wechsler Adult Intelligence Scale; 100 is average), and he performed at normal on per-
ceptual tests. His recall of events from his childhood and school days was intact. Socially,
H. M. was well mannered, and he engaged in sophisticated conversations. However, he had
no recall for recent events. H. M. lacked any explicit memory.
In one study by Suzanne Corkin (2002), H. M. was given a tray of hospital food, which he
ate. A few minutes later, he was given another tray. He did not recall having eaten the first
meal and proceeded to eat another. A third tray was brought, and this time he ate only the
dessert, explaining that he did not seem to be very hungry.
To understand the implications and severity of H. M.’s condition, one need only consider a
few events in his postsurgical life. His father died, but H. M. continued to ask where his father
was, only to experience anew the grief of learning that his father had passed away. (Eventually
H. M. stopped asking about his father, suggesting that some type of learning had taken place.)
Similarly, in the hospital, he typically asked the nurses, with many apologies, to tell him
where he was and how he came to be there. He remarked on one occasion, “Every day is alone in
itself, whatever enjoyment I’ve had and whatever sorrow I’ve had.” He perceived his surroundings
but could not comprehend his situation because he did not remember what had gone before.
Formal tests of H. M.’s memory showed, as you would expect, no recall for specific in-
formation just presented. In contrast, his implicit memory performance was nearly intact.
He performed at normal on tests such as the incomplete figure and pursuit rotor tasks, il-
lustrated in Figures 14-3 and 14-4, respectively. So while his implicit memory system must
have been intact, the systems crucial to explicit memory were missing or dysfunctional. Yet
H. M. recognized faces, including his own, and he recognized that he aged. Face recognition Prosopagnosia, an inability to recognize faces,
depends on the parahippocampal gyrus, which was partly intact on H. M.’s right side. Clini- and other visual form agnosias are topics in
cal Focus 14-2, Patient Boswell’s Amnesia, describes a case similar to H. M.’s. Chapter 9.
Disconnecting Implicit Memory
Among the reasons Lashley’s research did not find a syndrome like that shown by H. M., the two
most important are that Lashley did not damage the medial temporal regions. Nor did he use
tests of explicit memory, so his animal subjects would not have shown H. M.’s deficits. Rather,
Lashley’s tests were mostly measures of implicit memory, with which H. M. had no problems.
The following case illustrates that Lashley probably should have been looking in the
basal ganglia for the deficits that his implicit memory tests revealed. The basal ganglia play
a central role in motor control. Among the compelling examples of implicit memory is motor
learning—driving and playing musical instruments or online games, to name a few.
J. K. was above average in intelligence and worked as a petroleum engineer for 45 years.
In his mid-70s, he began to show symptoms of Parkinson disease, in which the projections Focus features 5-2, 5-3, and 5-4 and
from the dopaminergic cells of the brainstem to the basal ganglia die. At about age 78, J. K.’s Section 7-1 detail aspects of Parkinson
memory difficulties started. disease. Section 16-3 reviews treatments.
Curiously, his memory disturbance was related to tasks J. K. had performed his whole life.
On one occasion, he stood at his bedroom door, frustrated by his inability to recall how to
turn on the lights. “I must be crazy,” he remarked. “I’ve done this all my life and now I can’t
remember how to do it!” On another occasion, he was seen trying to turn the radio off with
the television remote control. This time he explained, “I don’t recall how to turn off the radio
so I thought I would try this thing!”
490 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
CliniCal F cus 14-2
Patient Boswell’s Amnesia
At the age of 48, Boswell developed herpes simplex encephalitis, a brain Lateral view
infection. He had completed 13 years of schooling and had worked for Left hemisphere Right hemisphere
nearly 30 years in newspaper advertising. By all accounts a normal,
well-adjusted person, Boswell was successful in his profession.
Boswell recovered from the acute symptoms, including seizures and
a 3-day coma. His intelligence post disease was low average, probably
owing to neurological damage caused by the infection. Nonetheless, his
speech and language remained typical in every respect, and he showed
Damaged
no perceptual or movement deficits. area
But Boswell was left with a severe amnesic syndrome. If he hears
a short paragraph and is asked to describe its main points, he routinely Medial view
scores zero. He can only guess the day’s date and is unable even to
guess the year. When asked what city he is in, he simply guesses.
Boswell does know his place of birth and can correctly recall his birth
date about half the time. In sum, Boswell has severe amnesia for events
both before and since his encephalitis. Like H. M., he does show implicit
Damaged
memory on tests such as the pursuit rotor task. area
Antonio Damasio and his colleagues (1989) have investigated After recovering from a herpes simplex encephalitis infection, patient
Boswell’s amnesia extensively, and his brain pathology is now well doc- Boswell has great difficulty remembering events before and after his
umented. The critical damage, diagrammed in the adjoining illustration, illness. Areas of damage in the medial temporal region, basal forebrain,
is bilateral destruction of the medial temporal regions and a loss of the and posterior orbitofrontal cortex are highlighted in red. Compare
basal forebrain and the posterior part of the orbitofrontal cortex. In ad- Figure 14-6.
dition, Boswell has lost the insular cortex from the lateral fissure (not
visible in the illustration). old information, probably owing to his insular and prefrontal injuries.
Boswell’s sensory and motor cortices are intact, as are his basal Nonetheless, again like H. M.’s, Boswell’s procedural memory is intact,
ganglia, but his injury is more extensive than H. M.’s. Like H. M., he has illustrating the dissociation between neural circuits underlying explicit
no new memories. Unlike H. M., he also has a severe loss of access to and implicit forms of memory.
J. K.’s clear implicit memory deficit contrasts sharply with his awareness of daily events.
He recalled explicit events as well as most men his age and spoke intelligently on issues of
the day that he had just read about. Once when two of us visited him, one of us entered the
room first and he immediately asked where the other was, even though it had been 2 weeks
since we told him that we would be coming to visit.
This intact long-term memory is vastly different from H. M.’s situation: he would not have
remembered that anybody was coming even 5 minutes after being told. Because Parkinson
disease primarily affects the basal ganglia, J. K.’s deficit in implicit memory was probably
related to his basal ganglia dysfunction.
14-2 reVieW
Dissociating Memory Circuits
Before you continue, check your understanding.
1. Based on the case of H. M., we can conclude that the structures involved in explicit
memory include the , the , and adjacent cortex.
2. Implicit memory deficits in patients with Parkinson disease demonstrate that a major
structure in implicit memory is the .
3. What is the main difference between the Lashley and Milner studies?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
14-3 • Neural Systems Underlying Explicit and Implicit Memories 491
14-3 Neural Systems Underlying entorhinal cortex Located on the medial
Explicit and Implicit
temporal lobe surface; provides a major
route for neocortical input to the hippocampal
Memories
formation; often degenerates in Alzheimer
disease.
Findings from laboratory studies, largely on rats and monkeys, have reproduced the symp- parahippocampal cortex Cortex located
toms of patients such as H. M. and J. K. by injuring the animals’ medial temporal regions along the dorsal medial temporal lobe
and basal ganglia, respectively. Other structures, most notably in the frontal and temporal surface.
lobes, also participate in certain types of explicit memory. We now consider the systems for perirhinal cortex Cortex lying next to the
explicit and implicit memory separately. rhinal fissure on the ventral surface of the
brain.
Neural Circuit for Explicit Memories
The dramatic amnesic syndrome discovered in H. M. in the 1950s led investigators to focus
on the hippocampus, at the time regarded as a large brain structure in search of a function. Turns out, the hippocampus participates in
But H. M. had other damaged structures, too, and the initial focus on the hippocampus as species-specific behaviors, spatial navigation,
the location of explicit memory processing turned out to be misguided. and memory, and it is vulnerable to stress.
After decades of anatomical and behavioral studies sorted out the complexities, consensus
on the anatomy of explicit memory had coalesced by the mid-1990s. The primary structures Consult sources published before 1995, and
for explicit memory include the medial temporal region, the frontal cortex, and structures you may find explanations for memory far
closely related to them. different from this chapter’s (see Gazzaniga,
Before considering the model, we first revisit medial temporal anatomy. Review 2000).
Figure 14-5’s summary of findings, which show that memories for objects’ colors and motion
characteristics reside in separate temporal lobe locations. Thus the medial temporal region
receives multiple sensory inputs.
The macaque monkey’s medial temporal region shares many anatomical similarities
with the region in the human brain. In addition to the hippocampus and amygdala, three
medial temporal areas illustrated in Figure 14-8 take part in explicit memory: lying adja-
cent to the hippocampus are the entorhinal cortex, the parahippocampal cortex, and the
perirhinal cortex. A sequential arrangement of two-way connections, charted in Figure 14-9, In Greek, para means beside; rhino means
projects from the major cortical regions into the perirhinal and parahippocampal cortices, nose. The perirhinal cortex lies beside the
which in turn project to the entorhinal cortex, then to the hippocampus. rhinal sulcus on the bottom of the brain.
The prominent cortical input to the perirhinal region is from the visual ventral stream
coursing through the temporal lobe. The perirhinal region is thus a prime candidate
location for visual object memory. Similarly, the parahippocampal cortex receives strong
input from parietal regions believed to take part in visuospatial processing and likely
Perirhinal Frontal, parietal, temporal,
cortex Amygdala occipital, and cingulate cortices
Figure 14-8 Medial Temporal
Structures Ventral view of
the rhesus macaque monkey Figure 14-9 Reciprocal
brain. Left side: The medial Perirhinal Parahippocampal Medial Temporal
cortex cortex
temporal regions. Each plays Connections Flow of input
a distinct role in processing from the sensory cortices:
sensory information for first to the parahippocampal
memory storage. Right side: and perirhinal regions, then
Entorhinal
The hippocampus and amygdala to the entorhinal cortex, and
cortex
are not directly visible from the finally to the hippocampus. The
brain surface; they lie within the hippocampus feeds back to the
Entorhinal Hippocampus cortical regions illustrated on medial temporal regions and
cortex Parahippocampal the left. All these structures are then to the neocortical sensory
Hippocampus
cortex present on both sides of the brain. regions.
492 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
CliniCal F cus 14-3
Alzheimer Disease
In the 1880s it was noted that the brain may undergo atrophy with aging, age-related neurodegenerative diseases (Walker & Jucker, 2015). Re-
but the reason was not really understood until the German physician searchers are conducting clinical trials on new drugs that act either
Alois Alzheimer published a landmark study in 1906. Alzheimer de- to find and neutralize misfolded proteins or as immunizing agents, to
scribed a set of behavioral symptoms and associated neuropathology in prevent protein misfolding (Wisniewski & Goni, 2015).
a 51-year-old woman who was demented. The cellular structure of her Cortical neurons begin to deteriorate as the cholinergic loss, plaques,
neocortex and allocortex showed various abnormalities. and tangles develop. The first cells to die are in the entorhinal cortex (see
An estimated 5.4 million people in the United States have Alzheimer Figure 14-8). Significant memory disturbance ensues.
disease, although the only certain diagnostic test remains postmortem A controversial idea emerging from stroke neurologists is that
examination of cerebral tissue. The disease progresses slowly, and many dementia may reflect a chronic cerebrovascular condition, marginal
people with Alzheimer disease probably die of other causes before the high blood pressure. Marginal elevations in blood pressure can lead
cognitive symptoms incapacitate them. to cerebral microbleeds, especially in white matter. The cumulative
We knew of a physics professor who continued to work until, when effect of years or even decades of tiny bleeds would eventually lead to
he was nearly 80, he died of a heart attack. Postmortem examination of increasingly disturbed cognition. This may first appear as mild cognitive
his brain revealed significant Alzheimer pathology. His colleagues had impairment (MCI) that slowly progresses with cumulative microbleeds.
attributed the professor’s slipping memory to the old-timer’s disease.
The cause of Alzheimer disease remains unknown, although it has
been variously attributed to genetic predisposition, abnormal levels of
trace elements (e.g., aluminum), immune reactions, slow viruses, and
prions (abnormal, infectious forms of proteins). Two principal neuronal
changes take place in Alzheimer disease:
1. Loss of cholinergic cells in the basal forebrain. One treatment for Al-
zheimer disease, therefore, is medication that increases acetylcholine
levels in the forebrain. An example is Exelon, which is the trade name
for rivastigmine, a cholinergic agonist that appears to provide tempo-
rary relief from the progression of the disease and is available both
thomas deerinck, mcmiR/science source
orally and as a skin patch.
2. Development of neuritic plaques in the cerebral cortex. A neuritic
plaque consists of a central core of homogeneous protein material
(amyloid) surrounded by degenerative cellular fragments. The plaques
are not distributed evenly throughout the cortex but are concentrated
especially in temporal lobe areas related to memory. Neuritic plaques
are often associated with another abnormality, neurofibrillary tangles,
paired helical filaments found in both the cerebral cortex and the The red area near the cell nucleus in this false-color brain cell from a
hippocampus. The prion paradigm holds that misfolded tau proteins, person with Alzheimer disease represents a neurofibrillary tangle of
illustrated here, which have the ability to self-propagate, cause many misfolded tau proteins.
participates in visuospatial memory—using visual information to recall an object’s loca-
Section 9-2 traces visual pathways in detail. tion in space.
Because both the perirhinal and the parahippocampal regions project to the entorhinal
cortex, this region probably participates in more integrative memory functions. The ento-
rhinal cortex is in fact the first area to show cell death in Alzheimer disease, a dementia
Section 16-3 elaborates on Alzheimer and characterized by severe deficits in explicit memory (see Clinical Focus 14-3, Alzheimer
other dementias and on prion theory. Disease).
The Hippocampus and Spatial Memory
We are left with a conundrum. If the hippocampus is not the key structure in explicit
memory even as it receives the entorhinal connections, what does it do? John O’Keefe and
14-3 • Neural Systems Underlying Explicit and Implicit Memories 493
Lynn Nadel were the first to advance the idea, in 1978, that the hippocampus is probably
neuritic plaque Area of incomplete necrosis
engaged in visuospatial memory processes required for places, such as recalling an object’s
(dead tissue) consisting of a central protein
location.
core (amyloid) surrounded by degenerative
Certainly both laboratory animals and human patients with selective hippocampal injury cellular fragments; often seen in the cortex
have severe deficits in various forms of spatial memory. Similarly, monkeys with hippocam- of people with dementias such as Alzheimer
pal lesions have difficulty learning the location of objects (visuospatial learning), as can be disease.
demonstrated in tasks such as the ones illustrated in Figure 14-10.
visuospatial memory Use of visual
Monkeys are trained to displace objects to obtain a food reward (Figure 14-10A), then information to recall an object’s location in
given one of two tasks. In the visual recognition task (Figure 14-10B), the animal displaces space.
a sample object for the food reward. After a short delay, the animal is presented with two
objects. One is novel. The task is to learn to displace the novel object for the food reward.
This task tests explicit visual object memory. Monkeys with perirhinal lesions are impaired
at the task.
In the object position task in Figure 14-10C, the monkey is shown one object to be dis-
placed for a food reward. Then the monkey is shown the same object along with a second
identical one. The task is to learn to displace the object that is in the same position as it was
in the initial presentation. Monkeys with hippocampal lesions are selectively impaired at
this task.
From these results, we would predict that a species with an especially good spatial mem-
ory should have bigger hippocampi than do species with a poorer spatial memory. David Section 1-4 explains the encephalization
Sherry and his colleagues (1992) tested this hypothesis in birds. quotient, an index of ratios of brain to body
Many birds are cachers: they harvest sunflower seeds and other favored foods and hide size. EQs allow comparisons of the relative
brain sizes of different species.
(cache) them to eat later. Some birds can find hundreds of items they have cached. To evalu-
ate whether the hippocampus plays a role in this activity, Sherry and his coworkers measured
hippocampal size in closely related bird species, only one of which is a food cacher. As shown
in Figure 14-11, the hippocampal formation is larger in birds that cache food than in birds
that do not. In fact, the hippocampi of food-storing birds are more than twice as large as
expected for birds of their brain size and body weight.
Figure 14-10 Two Memory Tasks
Sherry found a similar relation when he compared different species of food-storing ro-
for Monkeys (A) In “basic training,”
dents. Merriam’s kangaroo rats, rodents that store food throughout their territory, have larger
a monkey learns to displace an object to
obtain a food reward. In (B) and (c) the
plus and minus signs indicate whether
(A) Basic training (B) Visual-recognition task the object (1) is or (2) is not associated
with food.
+ A monkey is trained to
displace an object to
obtain a food reward...
...then shown two objects.
– + The task is to displace the
new object to obtain the
A monkey is shown reward.
an object,…
(C) Object-position task
The monkey is shown one
object to displace for a
+ food reward.
On the next trial, the
monkey is shown two
identical objects and must
…which it then displaces to choose the one at the same
obtain a food reward. + – location as in the initial
presentation.
494 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
Chickadee hippocampi than bannertail kangaroo rats, which store food only in their burrow. Hippocam-
pal size, both in birds and in mammals, appears to be related to the cognitive demands of two
highly spatial activities, foraging for and storing food.
Relative volumetric ratio of
hippocampus to forebrain
One prediction we might make based on the Sherry experiments is that people who
Common have a job with high spatial demands have large hippocampi. Taxi drivers in London fit this
sparrow category. Successful candidates for a cab driver’s license in London must demonstrate that
they know the location of every street in that huge and ancient city. Using MRI, Eleanor
Maguire and her colleagues (2000) found the posterior region of the hippocampus in London
taxi drivers to be significantly larger than the same region in the control participants. This
finding presumably explains why a select few pass a spatial memory test that most of us
would fail miserably.
Spatial Cells in the Hippocampal Formation
Food-storing Non-food-storing
Given the role of the hippocampus in spatial behavior, we might predict that individual cells
Figure 14-11 Inferring Spatial would code spatial information. They do. Three classes of spatially related cells have been
Memory This graph relates hippocampal identified in the rat and mouse hippocampus (Figure 14-12). Together they form an internal
volume to forebrain volume in food- GPS, a neural global positioning system. That is, neurons vigorously fire when an animal is
storing (left) and non-food-storing (right) in a specific place in the environment. In 2014, John O’Keefe, Edvard Moser, and May-Britt
families of songbirds. Birds that cache
Moser were awarded the Nobel Prize in Physiology or Medicine for this discovery.
food, such as the black-capped chickadee,
have hippocampi about twice as large Place cells, shown in Figure 14-12A and B, discharge when rats are in a spatial location,
as those of birds, such as the sparrow, irrespective of its orientation. Head direction cells (Figure 14-12C) discharge whenever a rat’s
that are not cachers. Data from D. F. Sherry, head points in a particular direction. Grid cells (Figure 14-12D) discharge at many locations,
L. F. Jacobs, & S. J. C. Gaulin (1992). Spatial memory forming a virtual grid invariant to changes in the rat’s direction, movement, or speed.
and adaptive specialization of the hippocampus. Trends
These cells are not localized to the hippocampus but are found within a network that
in Neuroscience, 15, pp. 298–303.
includes the hippocampus as its central structure. Place cells and head direction cells are
located in the hippocampus and closely related structures. Grid cells are found in the ento-
rhinal cortex, a major afferent route into the hippocampus (see Figure 14-9). Taken together,
we can envision the place cell system as indicating where things are in the world, the grid
system indicating how big our present navigating environment is, and the head direction and
grid systems telling us where we ourselves are in the environment.
Reciprocal Connections for Explicit Memory
Explicit memory’s temporal pathway is reciprocal: connections from the neocortex run to
the entorhinal cortex, then back to the neocortex (see Figure 14-9). Reciprocal connections
have two benefits:
1. Signals from the medial temporal regions back to the cortical sensory regions keep the
sensory experience alive in the brain: the neural record of an experience outlasts the
actual experience.
(A) Place cell (B) Place-by-direction cell
Classes of
Figure 14-12
Spatially Related Cells in the
Hippocampal Formation At right
in each part, X–Y coordinates indicate
the directional selectivity of the cell
recorded at left. (A and B) Place cells
discharge when a rat is at a spatial
location, irrespective of its orientation. (C) Head direction cell (D) Grid cell
(c) Head direction cells discharge when
the rat’s head points in a given direction,
courtesy of john o’keefe.
irrespective of its location. (D) Grid cells
discharge at many locations, forming a
virtual grid that is invariant in the face of
changes in the rat’s direction, movement,
or speed. Research from O’Keefe, 2006, Fig. 11-21.
14-3 • Neural Systems Underlying Explicit and Implicit Memories 495
2. The pathway back to the neocortex keeps it appraised of information being processed in The basal ganglia systems that take part
the medial temporal regions. in implicit memory do not feed back to the
cortex, which helps explain its unconscious
Although we have focused on the medial temporal regions, other structures also are
nature.
important in explicit memory. People with frontal lobe injuries are not amnesic like H. M.
or J. K., but they do have difficulties with memory for the temporal (time) order of events.
Imagine being shown a series of photographs and asked to remember them. A few minutes
later, you are asked whether you recognize two photographs and if so, to
indicate which one you saw first. Orange juice
H. M. would not remember the photographs. People with frontal lobe reward
injuries would recall seeing the photographs but would have difficulty re-
calling which one they had seen more recently. The frontal lobe’s role in
In the following tests,
explicit memory clearly is subtler than that of the medial temporal lobe. a monkey is shown a
light, which is the cue,
the Frontal lobe and Short-term memory All sensory systems and then it makes a
in the brain send information to the frontal lobe, as do the medial temporal response after a delay.
regions. This information is not used for direct sensory analysis, so it must
have another purpose. In general, the frontal lobe appears to participate in
many forms of short-term memory.
Cue Delay Choice
Joaquin Fuster (e.g., Fuster, Bodner, & Kroger, 2000) studied single-cell
Off
activity in the frontal lobe during short-term memory tasks. For example, Delayed-response task: The
monkey must choose the
if monkeys are shown an object that they must remember for a short time
light that is in the same
before being allowed to make a response, neurons in the prefrontal cor- location as the cue. On
tex show sustained firing during the delay. Consider the tests illustrated in
Figure 14-13: Delayed-alternation task: The
monkey must choose the
• In the general design for each test, a monkey is shown a light (the cue),
light that is not in the
and after a delay it must make a response to get a reward. same location as the cue.
• In the delayed-response task, the monkey is shown two lights in the choice
test and must choose the one that is in the same location as the cue. Delayed matching-to-sample
task: The monkey must
• In the delayed-alternation task, the monkey is again shown two lights in choose the light that is the
the choice tests but now must choose the light that is not in the same same color as the cue.
location as the cue. Time
• In the delayed matching-to-sample task, the monkey is shown, say, a red light, then, after Testing Short-Term
Figure 14-13
a delay, a red and a green light. The task is to choose the red light regardless of its new Memory A monkey performing a short-
location. term memory task responds by pressing
the disc to get a fruit juice reward (top).
Fuster found that in each task certain cells in the prefrontal cortex fire throughout the
The correct disc varies, depending on the
delay. Animals that have not learned the task show no such cell activity. Curiously, if a task requirements (bottom). (For each task,
trained animal makes an error, its cellular activity corresponds: the cells stop responding an arrowhead shows the correct choice.)
before the error occurs. They have “forgotten” the cue. Information from J. Fuster (1995). Memory in the
cerebral cortex (p. 178). Cambridge, MA: MIT Press.
traCing the expliCit memory CirCuit People who have chronically abused alco-
hol can develop an explicit memory disturbance known as Korsakoff syndrome. In some
cases, severe deficits in explicit memory extend to implicit memory as well. Korsakoff syn-
drome is caused by a thiamine (vitamin B1) deficiency that kills cells in the medial part of
the diencephalon—the between brain at the top of the brainstem—including the medial
thalamus and mammillary bodies in the hypothalamus. In 80 percent of Korsakoff patients,
the frontal lobes show atrophy (loss of cells). The memory disturbance is probably so severe
Korsakoff syndrome Permanent loss of the
because the damage includes not only forebrain but also brainstem structures (see Clinical
ability to learn new information (anterograde
Focus 14-4, Korsakoff Syndrome). amnesia) and to retrieve old information
Mortimer Mishkin and his colleagues (Mishkin, 1982; Murray, 2000) proposed a neural cir- (retrograde amnesia) caused by diencephalic
cuit for explicit memory that incorporates the evidence from both humans and laboratory ani- damage resulting from chronic alcoholism
mals with injuries to the temporal and frontal lobes. Figure 14-14 presents a modified version of or malnutrition that produces a vitamin B1
the Mishkin model. Anatomically (Figure 14-4A), it includes not only the frontal and temporal deficiency.
496 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
CliniCal F cus 14-4
Korsakoff Syndrome
Over the long term, alcoholism, especially when accompanied by mal- (retrograde amnesia) and information learned since the onset of the
nutrition, obliterates memory. When 62-year-old Joe R. was hospital- memory disturbance (anterograde amnesia).
ized, his family complained that his memory had become abysmal. His One unique characteristic of the amnesic syndrome in Korsakoff pa-
intelligence was in the average range, and he had no obvious sensory tients is that they tend to make up stories about past events rather than
or motor difficulties. Nevertheless, he could not say why he was in the admit that they do not remember. These stories are generally plausible,
hospital and usually stated that he was actually in a hotel. like those Joe R. told, because they are based on actual experiences.
When asked what he had done the previous night, Joe R. typically Curiously, Korsakoff patients have little insight into their memory dis-
said that he “went to the Legion for a few beers with the boys.” Although turbance and are generally indifferent to suggestions that they have a
he had, in fact, been in the hospital, it was a sensible response because memory problem. Such patients are generally apathetic to what’s going
going to the Legion is what he had done on most nights in the preceding on around them too. Joe R. was often seen watching television when
30 years. the set was turned off.
Joe R. was not certain what he had done for a living but believed he The cause of Korsakoff syndrome is a thiamine (vitamin B1) defi-
had been a butcher. In fact, he had been a truck driver for a local delivery ciency resulting from poor diet and prolonged intake of large quantities
firm. His son was a butcher, however, so once again his story related to of alcohol. (In addition to a “few beers with the boys,” Joe R. had a long
something in his life. history of drinking a 26-ounce bottle of rum every day.) The thiamine
Joe’s memory for immediate events was little better. On one deficiency results in the death of cells in the midline diencephalon, in-
occasion, we asked him to remember having met us; then we left the cluding especially the medial regions of the thalamus and the mammil-
room. On our return 2 or 3 minutes later, he had no recollection of lary bodies of the hypothalamus.
ever having met us or of having taken psychological tests that we had Most Korsakoff patients also show cortical atrophy, especially in the
administered. frontal lobe. With the appearance of Korsakoff symptoms, which can
Joe R. had Korsakoff syndrome. Sergei Korsakoff was a Russian happen suddenly, prognosis is poor. Only about 20 percent of patients
physician who in the 1880s first called attention to a syndrome that ac- show much recovery after a year on a vitamin B1–enriched diet. Joe R.
companies chronic alcoholism. The most obvious symptom is severe has shown no recovery after several years and will spend the rest of his
memory loss, including amnesia for both information learned in the past life in a hospital setting.
Inability to form new memories.
Future
New memories
dr. peter R. martin from Alcohol Health & Research World,
Anterograde
amnesia Time point of brain injury
Retrograde Inability to access old memories. 9 (spring 1985), cover
amnesia Retrograde amnesia may be
Old memories
incomplete, with older memories
being accessible, whereas more
Preserved recent memories are not.
old
memories PET scans from a healthy patient (larger image) and a Korsakoff patient
(inset) reveal reduced activity in the frontal lobes of the diseased brain. (The
frontal lobes are at the bottom center of each scan.) Red and yellow represent
Past
areas of high metabolic activity; activity is lower in the darker areas.
lobes but also the medial thalamus, implicated in Korsakoff syndrome, and the basal forebrain–
activating systems implicated in Alzheimer disease. Figure 14-4B charts the information flow:
• Sensory and motor neocortical areas send their connections to the medial temporal
regions, which are in turn connected to the medial thalamus and prefrontal cortex.
• Basal forebrain structures are hypothesized to play a role in maintaining appropriate
activity levels in other forebrain structures so that they can process information.
14-3 • Neural Systems Underlying Explicit and Implicit Memories 497
(A) (B)
Basal forebrain Thalamus Sensory
Prefrontal Temporal-lobe Rest of and motor
Neocortex cortex structures neocortex information
Medial
Prefrontal cortex thalamus
Amygdala
Rhinal cortex Hippocampus Brainstem-to-cortex activating systems
Acetylcholine
Serotonin
Noradrenaline
Figure 14-14 Reciprocal Neural
• The temporal lobe structures are hypothesized to be central to long-term explicit
Circuit Proposed for Explicit
memory formation. Memory (A) General neuroanatomical
• The prefrontal cortex is central to maintaining temporary (short-term) explicit memories areas controlling explicit memory.
as well as memory for the recency (chronological order) of explicit events. (B) The information flow begins on the
right with inputs from the sensory and
motor systems, which are not considered
Consolidation of Explicit Memories part of the explicit memory circuit.
Amnesia often appears to be time-dependent. H. M. could not form new explicit memories
but appeared to have good recall of facts and events from periods long before his surgery,
including his childhood. Such findings led to the idea that the medial temporal region could
not be the ultimate storage site for long-term memories; more likely that site was the neocortex
(for a review, see Squire et al., 2015).
This idea led to the hypothesis that the hippocampus consolidates new memories, a pro-
cess that makes them permanent. In consolidation, or stabilizing a memory trace after learn-
ing, memories move from the hippocampus to diffuse neocortical regions. Once they move,
hippocampal involvement is no longer needed.
It is not clear how memories are moved, however, or how long it takes. Robert Sutherland
and his colleagues (2010) propose a model of consolidation, the distributed reinstatement
theory. In their model, a learning episode rapidly produces a stored memory representation
that is strong in the hippocampus but weak elsewhere. The memory is replayed on the time
scale of hours or days after the learning, leading to enhanced representations outside the hip-
pocampus. Each repetition of the learning—that is, each practice—progressively enhances
the nonhippocampal memory representation. Then if the hippocampus is extensively dam-
aged, the memory remains.
Memory is not constant over time. When people get misleading information about
events they have experienced, for example, their later recall of those events often is modi-
fied. Indeed, this contributes to the notorious unreliability of eyewitness testimony. (Do you
remember the “smashing” and “bumping” car collisions from Section 14-1?) The fact that retrograde amnesia Inability to remember
memories appear changeable seems to fly in the face of the consolidation concept, which events that took place before the onset of
presumes that once consolidated, memories are fixed. amnesia.
One solution to this conundrum suggests that whenever a memory is replayed in the anterograde amnesia Inability to remember
mind, it is open to further consolidation, or reconsolidation, the process of restabilizing a events subsequent to a disturbance of the
memory trace after the memory is revisited. Interest in this idea has been intense, and al- brain such as head trauma, electroconvulsive
though the final story is yet to be written, it appears that reconsolidation does occur, at least shock, or neurodegenerative disease.
for some types of memories. consolidation Process of stabilizing a
One way to think of the process is to see memory consolidation as never-ending: new memory trace after learning.
information is constantly being integrated into existing memory networks (for a review, see reconsolidation Process of restabilizing a
McKenzie and Eichenbaum, 2011). After all, we frequently recall memories, rehash them, memory trace after the memory is revisited.
498 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
and integrate them with new events. Our memories are not laid on a tabula rasa but must be
interwoven into a lifetime of memories.
One implication of reconsolidation is that it ought to be possible to erase negative memo-
ries by using amnesic agents when the memory is revisited. This idea has important implica-
Section 5-4 links sensitization to PTSD. tions for reducing or eliminating the effects of strong emotional experiences, such as those
Sections 6-5 and 12-4 document how stress seen in posttraumatic stress disorder (PTSD). One promising agent is the inert gas xenon,
fosters and prolongs its effects, and Focus which has been used in humans as a fast-acting anesthetic and has been shown to erase
16-1 covers treatments. memories during reconsolidation in a rat model of PTSD (Meloni et al., 2014).
Neural Circuit for Implicit Memories
Hypothesizing that the basal ganglia are central to implicit memory, Mishkin and his col-
leagues proposed a neural circuit for implicit memories (Mishkin, 1982; Mishkin et al., 1997).
(A)
Premotor cortex Thalamus As Figure 14-15 shows, the basal ganglia receive input from the entire neocortex and send
Basal ganglia
projections first to the ventral thalamus and then to the premotor cortex. The basal ganglia
also receive widely and densely distributed projections from dopamine-producing cells in the
substantia nigra. Dopamine appears necessary for basal ganglia circuits to function and may
indirectly participate in implicit memory formation.
The connection from the cortex to the basal ganglia in the implicit memory system flows
only in one direction. Most of the neocortex receives no direct information regarding ac-
tivities in the basal ganglia. Mishkin believes that this unidirectional flow accounts for the
Amygdala unconscious nature of implicit memories. For memories to be conscious, the neocortical
regions involved must receive feedback, as they do in the explicit memory system Mishkin
Substantia nigra
and colleagues proposed (see Figure 14-14).
Mishkin’s models show why people with basal ganglia dysfunction, as occurs in Parkinson
(B)
disease, have implicit memory deficits. People with frontal or temporal lobe in-
Rest of Basal Ventral Premotor juries, by contrast, have relatively good implicit memories even as they may have
neocortex ganglia thalamus cortex
profound explicit memory disturbances. Some people with Alzheimer disease
can play games expertly, even with no recollection of having played them before.
Daniel Schacter (1983) wrote of a golfer with Alzheimer disease whose medial temporal
Sensory Substantia
system was severely compromised by the disease, but his basal ganglia were unaffected.
and motor nigra Despite his explicit knowledge impairment, as indexed by his inability to find balls he had
information Dopamine shot or to remember how many strokes he made on each hole, the man retained his ability
to play the game.
Unidirectional Neural
Figure 14-15
Circuit Proposed for Implicit
Memory (A) Anatomical areas Neural Circuit for Emotional Memories
controlling implicit memory. (B) Circuit
Whether emotional memory for the affective properties of stimuli or events is implicit or
diagram showing the one-way flow of
implicit information, beginning with inputs explicit is not altogether clear. It could be both. Certainly people can react with fear to
from the sensory and motor systems not specific stimuli they can identify, and we have seen that they can also fear situations for
considered part of the memory circuit. which they do not seem to have specific memories. Panic disorder is a common pathology
of emotional memory. People show marked anxiety but cannot identify a specific cause.
Emotional memory has a unique anatomical component—the amygdala, which mediates
fear conditioning (see Experiment 14-1) and seems to evoke our feelings of anxiety toward
Section 12-4 details the amygdala’s influence
on emotional behavior. Focus 12-3 describes stimuli that by themselves would not typically produce fear.
panic and other anxiety disorders. Emotional memory has been studied most thoroughly in fear conditioning by pairing
unpleasant stimuli, such as foot shock, with a tone. Michael Davis (1992) and Joseph LeDoux
(1995) used fear conditioning to demonstrate that the amygdala is critical to emotional mem-
ory. Damage to the amygdala abolishes emotional memory but has little effect on implicit
or explicit memory.
The amygdala has close connections with medial temporal cortical structures as well as
with the rest of the cortex. It also sends projections to brainstem structures that control auto-
emotional memory Memory for the affective nomic responses such as blood pressure and heart rate; to the hypothalamus, which controls
properties of stimuli or events. hormonal systems; to the periaqueductal gray matter (PAG), which affects pain perception;
14-3 • Neural Systems Underlying Explicit and Implicit Memories 499
(A) (B)
Frontal, parietal, temporal,
Neural Circuit
Figure 14-16
occipital, and cingulate cortices Proposed for Emotional Memory
(A) The amygdala is the key structure in
emotional memory. (B) Circuit diagram
showing information flow in emotional
memory.
Hypothalamus
and PAG
Hypothalamus
Amygdala Basal Medial temporal
Amygdala
ganglia cortex
and to the enteric nervous system. The amygdala hooks in to the implicit memory system The ANS monitors and controls life support
through its connections with the basal ganglia (Figure 14-16). functions (Figure 2-30); the ENS controls the
Fear is not the only aspect of emotional memory the amygdala codes, as a study of se- gut (Figure 2-31). Section 11-4 reviews the
verely demented patients by Bob Sainsbury and Marjorie Coristine (1986) nicely illustrates. PAG’s role in pain perception.
The patients were believed to have severe cortical abnormalities but intact amygdalar func-
tioning. The researchers first established that the patients’ ability to recognize photographs
of close relatives was severely impaired.
The patients were then shown four photographs, one depicting a relative (either a sibling
or a child) who had visited in the past 2 weeks. The task was to identify the person whom
they liked better than the other three. Although the subjects were unaware they knew any-
one depicted in the photographs, they consistently preferred pictures of their relatives. This
result suggests that although the explicit, and probably the implicit, memory of the relative
was gone, each patient‘s emotional memory guided his or her preference.
We tend to remember emotionally arousing experiences vividly, a fact confirmed by find-
ings from both animal and human studies. James McGaugh (2004) concluded that emo-
tionally significant experiences, pleasant and unpleasant, must activate hormonal and brain
systems that act to stamp in these vivid memories.
McGaugh noted that many neural systems probably take part, but the basolateral part of
the amygdala is critical. The general idea is that emotionally driven hormonal and neuro-
chemical activating systems (probably cholinergic and noradrenergic) stimulate the amygdala. Figure 5-17 traces neural activating system
The amygdala in turn modulates the laying down of emotional memory circuits in the rest of connections. Section 6-5 explains how
the brain, especially in the medial temporal and prefrontal regions and in the basal ganglia. hormones work.
We would not expect people with amygdala damage to have enhanced memory for emotion-
laden events, and they do not (Cahill et al., 1995).
14-3 reVieW
Neural Systems Underlying Explicit and Implicit Memories
Before you continue, check your understanding.
1. The two key structures for explicit memory are and .
2. A system consisting of the basal ganglia and neocortex forms the neural basis of the
memory system.
3. The and associated structures form the neural basis for emotional memory.
4. The progressive stabilization of memories is known as .
5. Why do we remember emotionally arousing experiences so vividly?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
500 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
14-4 Structural Basis
of Brain Plasticity
We have encountered three categories of memory—explicit, implicit, and emotional—and
their underlying brain circuits. Next we consider how the neurons in these circuits change
to allow us to consolidate and store memories. The consensus among neuroscientists is that
the changes take place at the synapse, in part simply because that is where neurons influence
one another. This idea dates to 1928, when the Spanish anatomist Santiago Ramón y Cajal
suggested that learning might produce prolonged morphological (structural) changes in the
efficiency of synapses activated in the learning process. Cajal’s idea turned out to be easier
to propose than to study.
Researchers still encounter a major challenge as they investigate Cajal’s suggestion be-
cause where in the brain to look for synaptic changes that might correlate with memory for a
Cajal’s neuron theory—that it is the nervous specific stimulus is unclear. The task is formidable. Imagine trying to find the exact location
system’s functional unit—is now universally of the neurons responsible for storing your grandmother’s name. You would face a similar
accepted, including the idea that these challenge in trying to pinpoint the neurons responsible for the memory of an object in a mon-
discrete cells’ interactions enable behavior. key’s brain as the monkey performs the visual recognition task illustrated in Figure 14-10B.
One approach to finding memory’s neuronal correlates aims first to determine that syn-
aptic changes do correlate with memory in the mammalian brain; second, to localize the
synaptic changes to specific neural pathways; and third, to analyze the synaptic changes
associative learning Linkage of two or themselves. This section reviews studies that begin to show how experience correlates with
more unrelated stimuli to elicit a behavioral synaptic changes related to memory. We first consider a strategy based on neuronal physiol-
response. ogy and experience. We then look at gross neural changes that correlate with select experi-
long-term potentiation (LtP) Long-lasting ences. These range from potentially good—living in enriched environments and learning
increase in synaptic effectiveness after high- specific tasks—to probably bad—chronic administration of trophic factors, hormones, and
frequency stimulation. addictive drugs. Each diverse experience modifies the brain’s general synaptic organization
long-term depression (LtD) Long-lasting in a strikingly similar manner.
decrease in synaptic effectiveness after low-
frequency electrical stimulation.
Long-Term Potentiation
Findings from studies of behavioral habituation (a weakened response to a stimulus) and
sensitization (a strengthened response) in the sea slug Aplysia show that physical changes
in synapses do underlie learning. Adaptive synapses in the mammalian brain participate in
Experiment 5-2 explains habituation at the associative learning, a response elicited by linking unrelated stimuli together—by learning
neuronal level, Experiment 5-3, sensitization. that A goes with B.
Learned associations are a common type of explicit memory. Associating a face with
a person, an odor with a food, a sound with a musical instrument are everyday examples.
Learning that learning takes place at synapses is another. The phenomenon underlying as-
sociative learning entails an enduring neural change in a postsynaptic cell after an excitatory
signal, or EPSP, from the presynaptic cell crosses the synaptic gap.
Both the relatively simple circuitry of the hippocampus and the ease of recording post-
synaptic potentials there make it ideal for studying the neural basis of associative learning.
In 1973, Timothy Bliss and Terje Lømø demonstrated that repeated electrical stimulation of
Postsynaptic potentials increase (excitatory/ the pathway entering the hippocampus progressively increases EPSP size as recorded from
EPSP) or decrease (inhibitory/IPSP) the hippocampal cells. The enhancement in the size of these graded field potentials lasts several
probability that an action potential will occur. hours to weeks or even longer. Bliss and Lømø called it long-term potentiation (LTP), a long-
See Experiment 4-1. lasting increase in synaptic effectiveness after high-frequency stimulation.
Figure 14-17A illustrates the experimental procedure for obtaining LTP. The presynaptic
neuron is stimulated electrically while the electrical activity the stimulation produces is
recorded from the postsynaptic neuron. The readout in Figure 14-17A shows the EPSP pro-
duced by a single pulse of electrical stimulation. In a typical experiment, many test stimuli are
given to estimate the size of the induced EPSP. Then a strong burst of stimulation, consisting
14-4 • Structural Basis of Brain Plasticity 501
(A) (B)
Stimulate Record 0.4
Each dot represents
EPSP amplitude in
Amplitude of EPSP
response to one weak
test stimulation.
Postsynaptic 0.2
EPSP
Recording Long-Term
Figure 14-17
Presynaptic Postsynaptic Potentiation (A) Experimenters
neuron neuron 0.0 stimulate the presynaptic neuron with
a test pulse and record the EPSP from
–20 –10 0 10 20 30 40 50 60 70 the postsynaptic neuron. (B) After an
Time (min) intense stimulation period, the amplitude
Stimulation
of the EPSP produced by the test pulse
increases: LTP has taken place.
of a few hundred pulses of electrical current per second, is administered (Figure 14-17B). The
test pulse is then given again. The increased amplitude of the EPSP endures for as long as
90 minutes after the high-frequency burst: LTP has taken place. For the EPSP to increase Deep brain stimulation used for severely
in size, more neurotransmitter must be released from the presynaptic membrane, or the depressed subjects induces a change, similar
postsynaptic membrane must become more sensitive to the same amount of transmitter, or to LTP, which appears to increase brain
both changes must take place. plasticity; see Section 16-1.
The discovery of LTP led to a revolution in thinking about how memories are stored. As
investigators varied the stimulation that produced LTP, they discovered its opposite. Instead
of using high-frequency stimulation (e.g., 100 Hz), they used low-frequency stimulation (e.g.,
5 Hz) and recorded a decrease in EPSP size, termed long-term depression (LTD). If LTP
is a mechanism for creating memories, perhaps LTD is a mechanism for clearing out old
memories.
If LTP and LTD form a basis for understanding synaptic changes underlying memory,
two predictions follow. First, when animals learn problems, we should see enhanced LTP in
the recruited pathways. Second, LTP should produce enduring changes in synaptic morphol-
ogy that resemble those seen in memory. Both predictions appear to be true.
The original studies of LTP concentrated on excitatory glutamate synapses. Glutamate
is released from the presynaptic neuron and acts on two different types of receptors on
the postsynaptic membrane, the NMDA and AMPA receptors, as shown in Figure 14-18A.
AMPA receptors ordinarily mediate responses produced when glutamate is released from Figure 14-18 Lasting Effects of
a presynaptic membrane. They allow sodium ions (Na+) to enter, depolarizing and thus Glutamate Enhanced glutamate
prompts a neurochemical cascade that
underlies synaptic change and LTP.
(A) Weak electrical stimulation (B) Strong electrical stimulation (depolarizing EPSP) (C) Weak electrical stimulation
Because the NMDA receptor pore is A strong electrical stimulation can Now glutamate, released by weak
blocked by a magnesium ion, release of depolarize the postsynaptic membrane stimulation, can activate the NMDA
glutamate by a weak electrical sufficiently that the magnesium ion is receptor to allow Ca2+ influx, which,
stimulation activates only the AMPA removed from the NMDA receptor pore. through a second messenger, increases
receptor. the function or number of AMPA
receptors or both.
NMDA receptor
Glutamate Calcium ions
Calcium ions
Magnesium ion
NMDA receptor
NMDA Second
receptor messenger
AMPA receptor AMPA
receptor AMPA
receptor
Presynaptic Postsynaptic
neuron neuron New AMPA receptor
502 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
NMDA is shorthand for N-methyl-d-aspartate; exciting the postsynaptic membrane. The initial amplitude of the EPSP in Figure 14-17A is
AMPA stands for alpha-amino-3-hydroxy-5- produced by this AMPA receptor action.
methylisoazole-4-proprionic acid. NMDA receptors do not usually respond to glutamate, because their pores are blocked
by magnesium ions (Mg2+). NMDA receptors are doubly gated ion channels that can open
to allow the passage of calcium ions if two events take place at approximately the same time:
1. The postsynaptic membrane is depolarized, displacing the magnesium ion from
the NMDA pore (Figure 14-18B). The strong electrical stimulation delivered by the
experimenter serves as a way of displacing magnesium.
2. NMDA receptors are activated by glutamate from the presynaptic membrane
(Figure 14-18C).
With the doubly gated NMDA channels open, calcium ions enter the postsynaptic neuron
and act through second messengers to initiate the cascade of events associated with LTP. These
events include increased responsiveness of AMPA receptors to glutamate, formation of new
AMPA receptors, and even retrograde messages to the presynaptic terminal to enhance gluta-
mate release. One or more of these actions produce the final EPSP amplitude in Figure 14-17B.
Although the studies generated by the Bliss and Lømø discoveries have focused on ex-
citatory synapses, experiments on inhibitory GABA interneurons demonstrate phenomena
similar to LTP and LTD, labeled LTPi and LTDi.This discovery was a surprise. At the time
it was generally believed that inhibitory neurons were not plastic, but they definitely are. It
appears that plasticity of GABAergic (inhibitory) synapses plays some fundamental role in
modulating networks of excitatory neurons.
Studying LTP mechanisms highlights neuroscientists’ uncertainty over where plastic
changes are located. Our discussion emphasizes postsynaptic changes, but a strong case
can be made that key presynaptic changes are at work too (e.g,, MacDougall & Fine, 2014).
In general, plasticity likely requires change on both sides of the synapse. The presynaptic
side, by virtue of being activated first, may prove key in the early phases of synaptic changes.
Measuring Synaptic Change
In principle, experience could change the brain in either of two ways: by modifying existing
circuitry or by creating novel circuitry. In actuality, the plastic brain uses both strategies.
Modifying Existing Circuits
The simplest way to find synaptic change is to look for gross changes in the morphology of
dendrites. Essentially, dendritic spines are extensions of the neuron membrane that allow more
space for synapses. Cells that have few or no dendrites have limited space for inputs, whereas
cells with complex dendritic protrusions may have space for tens of thousands of inputs.
So more dendrites mean more connections. Change in dendritic structure, therefore,
implies change in synaptic organization. In complex neurons, such as pyramidal cells,
Figure 3-5 shows how dendrites branch from 95 percent of synapses are on the dendrites. Measuring the extent of dendritic changes al-
three types of neurons. lows us to infer synaptic change.
Dendritic shape is highly changeable. Dale Purves and his colleagues (Purves & Voyvodic,
1987) labeled cells in the dorsal root ganglia of living mice with a dye that allowed them
to visualize the cells’ dendrites. When they examined the same cells at intervals ranging
from a few days to weeks, they identified obvious qualitative changes in dendritic extent
(Figure 14-19). We can assume that new dendritic branches have new synapses and that lost
branches mean lost synapses.
An obvious lesson from the Purves studies is that neuronal morphology is not static: neurons
change their structure in response to changing experiences. As they search for neural corre-
lates of memory, researchers can take advantage of this changeability by studying variations in
Focus 5-5 diagrams how dendritic spines dendritic morphology that are correlated with specific experiences, such as learning some task.
form and explains why they provide the What do changes in dendritic morphology reveal? Let us consider a given neuron that
structural basis for behavior. generates more synaptic space. The new synapses can provide either additional contacts
14-4 • Structural Basis of Brain Plasticity 503
between neurons that were already connected with that neuron or contacts between neurons
not formerly connected. Figure 14-20 illustrates examples of these distinct synapse types.
New synapses can result either from the growth of new axon terminals or from the forma-
Labeled
tion of synapses along axons as they pass by dendrites (Figure 14-20A and B). In both cases, with dye
new synapses correspond to changes in local or regional circuitry rather than to the devel-
opment of new connections between distant parts of the brain. Forming new connections
between widely separated brain regions would be difficult in a fully grown brain: the dense
plexus of cells, fibers, and blood vessels blocks the way.
Thus, the growth of new synapses indicates modifications to basic circuits already in the
brain. This strategy has an important implication for the location of synaptic changes under- 88–90
days later
lying memory. During development, the brain forms circuits to process sensory information
and to produce movement (behavior). These are the circuits most likely to be modified to
form memories (see Figure 14-5).
Creating Novel Circuits Figure 14-19 Dendritic Plasticity
Reconstructions of parts of the dendrites
Only 25 years ago, the general assumption was that the mammalian brain did not gener- from three mouse spinal ganglion cells
ate new neurons in adulthood. The unexpected discovery in the 1970s that the brains of after 3 months evince changes in both the
songbirds such as canaries grow new neurons to produce songs in the mating season led extension and the retraction of particular
researchers to reconsider this assumption. They found that the adult mammalian brain, too, dendritic branches. Information from D. Purves
& J. T. Voyvodic (1987). Imaging mammalian nerve
is capable of generating new neurons.
cells and their connections over time in living animals.
This discovery emerged from directly injecting animals with a compound—
Trends in Neuroscience, 10, p. 400.
bromodeoxyuridine (BrdU)—taken up by cells when they divide to produce new cells, in-
cluding neurons. When the compound is injected into adult rats, dividing cells incorporate
it into their DNA. In later analysis, a specific stain can identify the new neurons.
The BrdU technique yielded considerable evidence that the mammalian brain, including
the primate brain, can generate neurons destined for the olfactory bulb, the hippocampal
formation, and possibly even the frontal and temporal lobe neocortex (Eriksson et al., 1998;
Gould et al., 1999). The reason is not yet clear, but adult neurogenesis may enhance brain
plasticity, particularly in processes underlying learning and memory. Elizabeth Gould and Experiment 7-1 confirms the hypothesis that
her colleagues (1999) showed, for example, that generation of new neurons in the hippocam- hippocampal neurons contribute to memory
pus is enhanced when animals learn explicit memory tasks. formation.
Experience appears to increase the generation of these new neurons. A fascinating dem-
onstration of experience driving neurogenesis comes from a study by Katherine Woollett and
Eleanor Maguire (2011). We noted in Section 14-3 that London taxi drivers, who must learn
the locations of and pass an exam on central London’s roughly 25,000 irregular streets, have
larger-than-normal volume in their hippocampal posterior region. The investigators asked
whether the increase resulted from taking a 4-year course to pass the exam or was already
present when the candidate drivers started the course.
(A) Before experience (B) After experience (C) Various observed shapes of new dendritic spines
Single synapse New axon
on dendritic Formation of
spine new synapses
Axon 1
New axon from new axon
Axon 1 Axon 2 terminals
Axon 2 New axon
collateral Formation of
Axon 3 Figure 14-20 Effects of Experience on
Axon 3 new synapses Dendrites (A) Three inputs to a pyramidal cell
from original
dendrite. Each axon forms a synapse with a different
terminals
dendritic spine. (B) In forming multiple spine heads,
either the original axons can divide and innervate two
spine heads or new axons or axon collaterals (dotted
outlines) can innervate the new spine heads. (c) Single
dendritic spines may sprout multiple synapses.
504 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
Figure 14-21 Learning Effects on
Hippocampal Volume After a
4-year course devoted to learning London’s Woollett and Maguire recorded structural MRIs from the would-be taxi drivers before
street layout, trainees who qualified as and after training, then compared the trainees who qualified (n = 39) to those who failed
licensed taxi drivers show increased gray (n = 20). The images in Figure 14-21 show that hippocampal volume increased in the quali-
matter volume in the most posterior part fiers. Those who failed showed no changes. The trainees’ average age was about 40 years,
of the hippocampus (orange and yellow
leading Woollett and Maguire to conclude that the capacity for memory improvement and
areas). Republished with permission of Elsevier
Science and Technology Journals, from Woollett, K. correlated structural changes in the hippocampus extends well into adulthood.
and Maguire, E.A. (2011) Acquiring “the knowledge” of
London’s layout drives structural brain changes. Current
Biology, 21, 2109–2114. Permission conveyed through
Enriched Experience and Plasticity
Copyright Clearance Center, Inc. One way to stimulate animals’ brains is to house the animals in environments that provide
sensory or motor experience. Donald Hebb (1947) took laboratory rats home and gave them
Section 8-4 details Hebb’s first enrichment the run of his kitchen. After an interval, Hebb compared these “enriched” rats with a group
exercise—and his wife’s reaction. that had remained caged in his laboratory at McGill University: he trained both groups to
solve various mazes. The enriched animals performed better, and Hebb concluded that one
effect of the enriched experience is to enhance later learning. This important conclusion
laid the foundation for the U.S. Head Start programs, which provide academic experience
for preschool-aged children living in under-resourced environments.
Subsequent investigators have opted for a more constrained enriched enclosure. For ex-
ample, in our own studies, we place groups of about six rats in enclosures. The enclosures
give animals a rich social experience as well as extensive sensory and motor experience. The
most obvious consequence is increased brain weight—on the order of 10 percent relative to
cage-reared animals—even though the “enriched” rats typically weigh less, in part because
they get more exercise.
The key question is: What is responsible for the increased brain weight? A comprehensive
series of studies by Anita Sirevaag and William Greenough (1988) used light- and electron-
microscopic techniques to analyze 36 aspects of cortical synaptic, cellular, and vascular mor-
phology in rats raised either in a cage or in a complex environment. The simple conclusion: in
response to differential experiences a coordinated change occurs not only in dendritic extent
but also in glial, vascular, and metabolic processes (Figure 14-22).
Animals with enriched experience have more synapses per neuron and also more astro-
Enriched Enclosure for Rats cytes, more blood capillaries, and higher mitochondrial volumes. Clearly, when the brain
changes in response to experience, the expected neural changes take place, and adjustments
Mitochondria power the cell. Figure 3-10 in the metabolic requirements of the now larger neurons take place as well.
diagrams these organelles in the context of Gerd Kempermann and his colleagues (1998) sought to determine whether experience
the neuron’s other internal components. actually alters the number of neurons in the brain. To test this idea, they compared neuronal
generation in the hippocampi of mice housed in a complex environment with that of mice
reared in a laboratory cage. They located the number of new neurons by injecting the ani-
mals with BrdU several times while they were living in complex housing.
The new neurons generated in the brain during the experiment incorporated the BrdU.
When the researchers later looked at the hippocampi, they found more new neurons in
14-4 • Structural Basis of Brain Plasticity 505
the complex-housed rats than Figure 14-22 Consequences of
in the caged rats. Although the Dendrite Enrichment Cortical changes that
investigators did not look in length occur in response to experience are
other parts of the brain, such found not only in neurons but also in
Astrocyte
astrocytes and vasculature. Data from A.
as the olfactory bulb, we can processes
Turner & W. T. Greenough (1985). Differential rearing
reasonably expect that similar Vascular effects on rat visual cortex synapses. I. Synaptic and
changes took place in other volume neuronal density and synapses per neuron. Brain
neural structures. This result Research, 329, pp. 195–203 No ref.3; A. M. Sirevaag
Synapses/
is exciting because it implies & W. T. Greenough (1987). Differential rearing effects
neurons
on rat visual cortex synapses. III. Neuronal and glial
that experience not only can
nuclei. Brain Research, 424, pp. 320–332; and B. Kolb,
alter existing circuitry but also 0 10 20 30 40 50
R. Gibb, & G. Gorny (2003). Experience-dependent
Percent increase
can influence neurogenesis and changes in dendritic arbor and spine density in
thus new circuitry. neocortex vary with age and sex Neurobiology of
Learning and Memory, 79, pp. 1–10.
Sensory or Motor Training and Plasticity
Studies showing neuronal change in animals housed in a complex environment demonstrate
that large areas of the brain can change with such experience. This finding leads us to ask
whether specific experiences produce synaptic changes in localized cerebral regions. One
way to approach this question is to give animals specific experiences, then see how their
brain has changed. Another way is to look at the brain of people who have had a lifetime of
some particular experience. We consider each research strategy separately.
Manipulating Experience Experimentally
Fen-Lei Chang and William Greenough (1982) conducted perhaps the most convincing
manipulated-experience study. They took advantage of the fact that the laboratory rat’s
visual pathways are about 90 percent crossed. That is, about 90 percent of connections from
the left eye to the cortex project through the right thalamus to the right hemisphere and In humans, only about half the optic fibers
vice versa for the right eye. cross. Figure 9-10 diagrams the pathways.
Chang and Greenough placed a patch over one eye of each rat, then trained the animals
in a maze. The visual cortex of only one eye received input about the maze, but their two
hemispheres’ auditory, olfactory, tactile, and motor regions were equally active as the animals
explored. A comparison of the neurons in each hemisphere revealed that those in the visual cor-
tex of the trained hemisphere had more extensive dendrites. Because the hemispheres did not
differ in other respects, the researchers concluded that some feature associated with encoding,
processing, or storage of visual input from training was responsible for forming new synapses.
Randy Nudo and his colleagues (1997) conducted complementary studies, mapping the
motor cortex of monkeys. They noted striking individual differences in topography. The in-
vestigators speculated that individual variability might be due to each monkey’s experiences
up to the time at which the cortical map was derived. To test this idea directly, Nudo and
colleagues trained two groups of squirrel monkeys to retrieve banana-flavored food pellets
from either a small or a large food well. A monkey was able to insert its entire hand into the
large well but only one or two fingers into the small well, as illustrated in the Procedures
section of Experiment 14-2.
Monkeys in the two groups were matched for number of finger flexions, which totaled
about 12,000 for the entire study. The monkeys trained on the small well improved with
practice, making fewer finger flexions per food retrieval as training proceeded. Maps of
forelimb movements, shown in the Results section, were produced by microelectrode stimu-
lation of the cortex. The maps show systematic changes in the animals trained on the small
but not on the large well. Presumably, these changes result from the more demanding motor
requirements of the small-well condition. The results demonstrate that learning new motor
skills, not simply repetitive motor use, shapes the functional topography of the motor cortex.
Most studies demonstrating plasticity in the motor cortex have been performed with
laboratory animals whose cortex was mapped by microelectrode stimulation. Today, imaging
506 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
ExPErimEnt 14-2 techniques such as transcranial magnetic stimulation (TMS)
Question: Does the learning of a fine motor skill alter and functional magnetic resonance imaging (fMRI) make it
the cortical motor map? possible to show parallel results in humans who have special
motor skills. For example, right-handed musicians who play
Procedures
stringed instruments show an increased cortical representation
Difficult task Simple task
of the fingers of the left hand and Braille readers an increased
One group of monkeys Another group of monkeys
cortical representation of the reading finger.
was trained to retrieve was trained to retrieve
food from a small well. food from a large well. Thus, the functional organization of the motor cortex is al-
tered by skilled use in humans. It can also be altered by chronic
injury in humans and laboratory animals. Jon Kaas (2000)
showed that when the sensory nerves in one limb are severed
in monkeys, large-scale changes in somatosensory maps ensue.
In particular, in the absence of input, the relevant part of the
cortex no longer responds to limb stimulation, which is not
surprising. But this cortex does not remain inactive. Rather,
the deafferented cortex begins to respond to input from other
Both groups were allowed 12,000 finger flexions. The small-well
body parts. The region that formerly responded to hand stimu-
task was more difficult and required the learning of a fine
motor skill in order to match performance of the simpler task. lation now responds to stimulation on the face, a cortical area
normally adjacent to the hand area.
1200 1200
Similar results can be found in the cortical maps of people
1000 1000
Retrievals per day
Retrievals per day
whose limb has been amputated. For example, Vilayanur
800 800 Ramachandran (1993) found that when a hand amputee’s face
600 600 is brushed lightly with a cotton swab, the person has a sen-
400 400 sation of the amputated hand being touched. Figure 14-23
200 200 illustrates the rough map of the hand that Ramachandran was
0 0
0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 actually able to chart on the face. The likely explanation is
Day of training Day of training that the face area in the motor cortex has expanded to occupy
Results
The motor representation of digit, wrist, and arm was mapped.
(A) (B)
Cotton swab
Thumb
Ball
of thumb
Index finger
r
inge
ie f
Pink
KEY
Figure 14-23 Cortical Reorganization When a hand
Digit Wrist/forearm Digit, wrist, and forearm amputee’s face is stroked lightly with a cotton swab (A), the
person experiences the stroke as a light touch on the missing
Conclusion: The digit representation in the brain of the animal with hand (B) as well as a touch to the face. The deafferented
the more difficult task is larger, corresponding to the neuronal cortex forms a representation of the amputated hand on the
changes necessary for the acquired skill. face. As in the normal somatosensory homunculus, the thumb
is disproportionately large. Information from V. S. Ramachandran (1993).
Information from R. J. Nudo, E. J. Plautz, & G. W. Miliken (1997). Adaptive plasticity in primate
motor cortex as a consequence of behavioral experience and neuronal injury. Seminars in Behavioral and magnetoencephalographic correlates of plasticity in the adult
Neuroscience, 9, p. 20. human brain. Proceedings of the National Academy of Sciences USA, 90, p. 10418.
14-4 • Structural Basis of Brain Plasticity 507
the deafferented limb cortex, but the brain circuitry still responds to the cortical activity as
representing input from the limb. This response may explain the phantom limb pain often Focus 11-5 recounts Ramachandran’s therapy
experienced by amputees. for minimizing phantom limb pain.
The idea that experience can alter cortical maps can be demonstrated with other experi-
ences. For example, if animals are trained to make certain digit movements over and over
again, the cortical representation of those digits expands at the expense of the remaining
motor areas. Similarly, if animals are trained extensively to discriminate among different
sensory stimuli such as tones, the auditory cortical areas responding to those stimuli increase
in size.
As described in Research Focus 14-5, Movement, Learning, and Neuroplasticity, one
effect of musical training is to alter the motor representations of the digits used to play
different instruments. We can speculate that musical training probably alters the auditory Sections 10-4 and 15-4 discuss music’s
representations of specific sound frequencies as well. Both changes are essentially forms of benefits for the brain.
memory, and the underlying synaptic changes likely take place on the appropriate sensory
or motor cortical maps.
researCh F cus 14-5
Movement, Learning, and Neuroplasticity
Many lines of research show that practicing a motor skill—playing a mu- difficulty in coordinating hand and finger movements. Dystonia can be so
sical instrument, for instance—induces changes in the cortical somato- disabling that some musicians must give up their occupation.
sensory and motor maps. The mental maps generally become larger, Typically, dystonia afflicts musicians who practice trying to make
at least the finger and hand representations. perfect finger movements on their instru-
Presumably, musical skill improves with ments. Musicians at high risk include string
practice, but are other abilities enhanced players, who receive vibratory stimulation at
too? Patrick Ragert and colleagues (2003) their fingertips. The constant practice has
showed that professional pianists not only been suggested to lead not only to improved
have better motor skills in their fingers but musical ability but also to distorted or dis-
enhanced somatosensory perception as well. ordered cortical motor maps. Synchronous
When the researchers measured the activation of the digits by the vibration leads
ability to detect subtle sensory stimulation to this unwanted side effect.
of the fingertips, they found that the pianists Victor Candia and colleagues (2003) rea-
were more sensitive than controls. They soned that musicians’ dystonia was probably
also found that the enhanced tactile sensitiv- an example of disordered learning and could
ity was related to the hours per day that the be treated by retuning the motor map. The
© michel garnier/lebrecht music & arts/corbis
musicians spent practicing. investigators used magnetoencephalogra-
The investigators then asked whether phy (MEG) to measure changes in sensory-
the enhanced perceptual ability precluded evoked magnetic fields in the cortex.
further improvement in the musicians. Sur- At the beginning of the study, the musi-
prisingly, when both the musicians and con- cians with dystonia had a disordered motor
trols were given a 3-hour training session map: the finger areas overlapped one an-
designed to improve tactile sensitivity, the other. In training, each subject used a hand
musicians showed more improvement than splint tailored to his or her hand. The splint al-
did the controls. Again the extent of improve- lowed for immobilizing different fingers while
ment correlated with daily practice time. the subjects independently moved the others.
This result implies that well-practiced musicians not only learn to After 8 days of training for about 2 hours per day, the subjects
play music but also develop a greater capacity for learning. Rather showed marked alleviation in the dystonic symptoms, and the neuro-
than using up all the available synapses, they gain the capacity to make imaging showed a normalization of the cortical map, with distinct finger
even more. areas. Thus, training reversed the learned changes in the motor map and
Not all motor learning is good, however. Many musicians develop treated the dystonia. The musicians had actually learned a disorder, and
focal hand dystonia—abnormal finger and hand positions, cramps, and they were able to unlearn it.
508 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
Experience-Dependent Change
in the Human Brain
According to Ramachandran’s amputee study, the human brain appears to change with
altered experience. But this study did not examine neuronal change directly; it inferred
neuronal change from behavior. The only way to examine synaptic change directly is to look
directly at brain tissue. In living humans, this is not an option, but the brain of people who
died of something other than neurological causes can be examined and the structure of their
cortical neurons related to their experiences.
One way to approach this idea is to look for a relation between neuronal structure and
education. Arnold Scheibel and his colleagues conducted many such studies in the 1990s
(e.g., Jacobs and Scheibel, 1993; Jacobs, Scholl, and Scheibel, 1993). In one, they found a rela-
Wernicke’s area contributes to speech and to
tion between dendrite size in Wernicke’s area and level of education. In the brain of deceased
language comprehension; see Figure 10-18.
people with a college education, the cortical neurons from this language area had more den-
dritic branches than did those from people with a high-school education, which in turn, had
more dendritic material than did those from people with less education. People who have
more dendrites may be more likely to go to college, but that hypothesis is not easy to test.
Another way to look at the relation between neurons in Wernicke’s area and behavior is
Figure 15-16 diagrams tasks that consistently to take advantage of the now well-documented observation that on average females’ verbal
show, on average, that females’ verbal fluency abilities are superior to those of males. When Scheibel and his colleagues examined the
surpasses males’ and that males outperform structure of neurons in Wernicke’s area, they found that females do have more extensive
females on spatial reasoning tasks. dendritic branching there than males do.
Finally, these investigators took a slightly different approach to the link between experi-
ence and neuronal morphology. They began with two hypotheses. First, they suggested a
relation between the complexity of dendritic branching and the nature of the computational
Finger Trunk
Somatosensory tasks performed by a brain area.
area area
area To test this hypothesis, they examined the dendritic structure of neurons in different cor-
tical regions that handle different computational tasks. For example, when they compared
the structure of neurons corresponding to the somatosensory representation of the trunk
with those for the fingers, they found the latter to have more complex cells (Figure 14-24).
They reasoned that the somatosensory inputs from receptive fields on the chest wall would
constitute less of a computational challenge to cortical neurons than would those from the
fingers and that the neurons representing the chest would therefore be less complex.
The group’s second hypothesis was that dendritic branching in all regions is subject to
experience-dependent change. The researchers hypothesized that predominant life experi-
ence (e.g., occupation) should, as a result, alter dendritic structure. Although they did not test
Wernicke’s
area this hypothesis directly, they did make an interesting observation. In their study comparing
Language
area cells in the trunk area, in the finger area, and in the supramarginal gyrus—a parietal lobe
region associated with higher cognitive processes (thinking)—they found curious individual
differences.
For example, especially large differences in trunk and finger neurons appeared in the
brain of people who had a high level of finger dexterity maintained over long periods (say,
Experience and
Figure 14-24 career word processors). In contrast, no difference between trunk and finger neurons was
Neuronal Complexity Confirmation found in sales representatives. Remember, Scheibel and colleagues conducted their research
of Scheibel’s hypothesis that cell
before portable electronic devices entered the workplace. We would not expect a good deal
complexity is related to the computational
demands required of the cell. Neurons of specialized finger use among sales reps of that time and thus less complex demands on
that represent the body’s trunk area have their finger neurons.
relatively less computational demand In summary, although the studies showing a relation between experience and neuronal
than do cells representing the finger structure in humans depend on correlations rather than actual experiments, the findings
region. In turn, cells engaged in higher are consistent with those observed in experimental studies of other species. We are thus
cognitive functions (such as language,
led to the general conclusion that specific experiences can produce localized changes in
as in Wernicke’s area) have greater
computational demand than do those the synaptic organization of the brain and that such changes form the structural basis of
engaged in finger functions. memory.
14-4 • Structural Basis of Brain Plasticity 509
Epigenetics of Memory
An enigma in the search for neural mechanisms underlying memory is the fact that whereas
memories remain stable over time, all cells are constantly undergoing molecular turnover.
The simplest explanation for this is epigenetic: specific sites in the DNA of neurons involved
in specific memories might exist in either a methylated or a nonmethylated state.
Courtney Miller and colleagues (2010) tested this idea directly by measuring methylation
in the hippocampi of rats that underwent contextual fear conditioning (see Experiment 14-1).
They showed that fear conditioning is associated with rapid methylation, but if they blocked Figure 3-25 illustrates two aspects of
methylation, there was no memory. The investigators conclude that epigenetic mechanisms methylation: histone and DNA modification.
mediate synaptic plasticity broadly, but especially in learning and memory. One implication
of these results is that cognitive disorders, including memory defects, could result from aber-
rant epigenetic modifications (for a review, see Day et al., 2015).
Plasticity, Hormones, Trophic Factors,
and Drugs
The news media often report that psychoactive drugs can damage your brain. Some drugs
certainly do act as toxins and can selectively kill brain regions, but a more realistic mode of
drug action is to change the brain. Although not many studies have looked at drug-induced
morphological changes, evidence reveals that some compounds can greatly change the
brain’s synaptic organization. These compounds include hormones, neurotrophic factors,
and psychoactive drugs. We briefly consider each category.
Hormones and Plasticity
Levels of circulating hormones are critical both in determining brain structure and in elicit- Section 6-5 explains the classes, functions,
ing certain behaviors in adulthood. Although the structural effects of hormones were once and control that hormones exert; Section 8-4,
believed to be expressed only in the course of development, current belief is that adult their organizing effects during development;
neurons also can respond to hormonal manipulations with dramatic structural changes. We Section 12-5, their activating effects in
consider the actions of gonadal hormones and stress hormones here. adulthood.
Research findings have established that structural differences in cortical neurons of male
and female rats depend on gonadal hormones. More surprising, perhaps, is that gonadal hor-
mones continue to influence cell structure and behavior in adulthood. Elizabeth Hampson
and Doreen Kimura (1988) showed that women’s performance on various cognitive tasks
changes throughout the menstrual cycle as their estrogen levels fluctuate.
Changes in estrogen level appear to alter the structure of neurons and astrocytes in the
neocortex and hippocampus, which probably accounts for at least part of the performance
fluctuation. Figure 14-25 illustrates changes in dendritic spines in the hippocampal
cells of female rats at different phases of their 4-day estrous cycle. As the estrogen
Estrogen Estrogen
level rises, the number of synapses rises; as the estrogen level drops, the number of
levels high levels low
synapses declines.
Curiously, estrogen’s influence on cell structure may differ in the hippocampus
and neocortex. Jane Stewart found, for example, that when the ovaries of middle-aged
female rats are removed, estrogen levels drop sharply, producing increased numbers of
spines on pyramidal cells throughout the neocortex but decreased spine density in the
Figure 14-25 Hormones and
hippocampus (Stewart & Kolb, 1994). How these synaptic changes might influence processes
Neuroplasticity Sections of dendrites
such as memory is not immediately obvious, but the question is reasonable, especially be- from hippocampal cells during times of
cause menopausal women also experience sharp drops in estrogen levels and a corresponding high and low estrogen levels during the
decline in verbal memory ability. rat’s 4-day estrous cycle reveal many
This question is also relevant to middle-aged men, who show a slow decline in testosterone more dendritic spines when estrogen
levels are high. Information from C. S. Woolley,
levels that correlates with a drop in spatial ability. Rats that are gonadectomized in adulthood
E. Gould, M. Frankfurt, & B. S. McEwen (1990).
show increased cortical spine density, much like the ovariectomized females. Although we Naturally occurring fluctuation in dendritic spine
do not know how this change relates to spatial behavior, a reasonable supposition is that density on adult hippocampal pyramidal neurons.
testosterone levels might influence spatial memory throughout life. Journal of Neuroscience, 10, p. 4038.
510 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
When the body is stressed, the pituitary gland produces adrenocorticotrophic hormone
(ACTH), which stimulates the adrenal cortex to produce steroid hormones, the glucocorticoids.
Important in protein and carbohydrate metabolism, controlling sugar levels in the blood, and
the absorption of sugar by cells, glucocorticoids have many actions on the body, including the
brain. Robert Sapolsky (1992) proposed that glucocorticoids can sometimes be neurotoxic.
In particular, he found that with prolonged stress, glucocorticoids appear to kill hippo-
campal cells. Elizabeth Gould and her colleagues (1998) showed that even brief periods of
Figure 6-23 illustrates the body’s stress stress can reduce the number of new granule cells produced in the hippocampi of monkeys,
response. presumably through the actions of stress hormones. Evidence of neuron death and reduced
neuron generation in the hippocampus has obvious implications for animal behavior, espe-
cially for processes such as spatial memory. Finally, Richelle Mychasiuk and her colleagues
(2015) showed that stress has contrasting epigenetic effects in the hippocampus and prefron-
tal cortex, with virtually no overlap between males and females.
In sum, hormones can alter the brain’s synaptic organization and even the number of
neurons in the brain. Little is known today about the behavioral consequences of such
changes. It is likely that hormones can alter the course of plastic changes in the brain, pos-
sibly through epigenetic mechanisms.
Neurotrophic Factors and Plasticity
Neurotrophic factors, chemical compounds listed in Table 14-2 that signal stem cells to de-
velop into neurons or glia, also act to reorganize neural circuits. The first, nerve growth factor
(NGF), was discovered in the peripheral nervous system more than a generation ago. NGF
Section 8-2 explains how neurotrophic is trophic (nourishing) in the sense that it stimulates neurons to grow dendrites and synapses
factors send these signals. and in some cases promotes neuronal survival.
Trophic factors produced in the brain by neurons and glia can affect neurons both
through cell membrane receptors and by actually entering the neuron to act internally on
A Hebb synapse—one that changes with use its operation. Trophic factors may be released postsynaptically, for example, to act as signals
so that learning takes place—hypothetically that can influence the presynaptic cell. Experience stimulates their production, so neuro-
employs just such a mechanism; see trophic factors have been proposed as agents of synaptic change. For example, brain-derived
Section 5-4. neurotrophic factor (BDNF) increases when animals solve specific problems such as mazes.
This finding has led to speculation that BDNF release may enhance such plastic changes as
the growth of dendrites and synapses.
taBLe 14-2molecules exhibiting
Although many researchers would like to conclude that BDNF has a role in learning, this
neurotrophic activities
conclusion does not necessarily follow. When animals solve mazes, their behavior differs
Proteins initially characterized as from their behavior when they remain in cages. So we must first demonstrate that changes
neurotrophic factors
in BDNF, NGF, or any trophic factor are actually related to forming new synapses. Neverthe-
Nerve growth factor (NGF) less, if we assume that trophic factors do act as synaptic change agents, then we should be
Brain-derived neurotrophic factor (BDNF) able to use increased trophic factor activity during learning as a marker for where to look for
Neurotrophin 3 (NT-3) changed synapses associated with learning and memory.
Ciliary neurotrophic factor (CNTF)
Growth factors with neurotrophic activity
Psychoactive Drugs and Plasticity
Many people regularly use the stimulant caffeine, and some use more stimulating psychoac-
Fibroblast growth factor, acidic (aFGF
or FGF-1) tive drugs such as nicotine, amphetamine, or cocaine. The long-term consequences of abus-
ing psychoactive drugs are now well documented, but the question of why these drugs cause
Fibroblast growth factor, basic (bFGF
or FGF-2) problems remains to be answered. One explanation for the behavioral changes associated
Epidermal growth factor (EGF) with chronic psychoactive drug abuse is that the drugs change the brain.
One experimental demonstration of these changes is drug-induced behavioral sensitiza-
Insulinlike growth factor (ILGF)
tion, often referred to simply as behavioral sensitization, the progressive increase in behav-
Transforming growth factor (TGF)
ioral actions in response to repeated administration of a drug. Behaviors increase even when
Lymphokines (interleukin 1, 3, 6 or IL-1,
the amount given in each dose does not change. Behavioral sensitization occurs with most
IL-3, IL-6)
psychoactive drugs, including amphetamine, cocaine, morphine, and nicotine.
Protease nexin I, II
The sea slug Aplysia becomes more sensitive to a stimulus after repeated exposure. Psy-
Cholinergic neuronal differentiation factor choactive drugs appear to have a parallel action: they lead to increased behavioral sensitivity
14-4 • Structural Basis of Brain Plasticity 511
to their actions. For example, a rat given a small dose of am- ExPErimEnt 14-3
phetamine may show increased activity. When the rat is given
Question: What effect do repeated doses of amphetamine, a
the same dose of amphetamine on subsequent occasions, the
psychomotor stimulant, have on neurons?
increase in activity is progressively larger. If no drug is given
for weeks or even months and then amphetamine is given Procedure
in the same dose as before, behavioral sensitization picks up
where it left off and continues to progress. Some long-lasting Animals received multiple doses of
change must have taken place in the brain in response to the amphetamine. Neurons were drawn from
drug. Drug-induced behavioral sensitization can therefore be nucleus accumbens.
viewed as a memory for a particular drug.
Results
The parallel between drug-induced behavioral sensi- Amphetamine Saline
tization and other forms of memory leads us to ask if the
changes in the brain after behavioral sensitization are similar
to those found after other forms of learning. They are. For
example, there is evidence of increased numbers of receptors
at synapses and of more synapses in sensitized animals.
In a series of studies, Terry Robinson and his colleagues
found dramatic increases in dendritic growth and spine den- Nucleus
accumbens Rats that show sensitization …relative to saline-
sity in rats sensitized to amphetamine, cocaine, or nicotine to amphetamine have treated rats that
relative to rats that received injections of a saline solution increased dendritic growth served as controls.
(Robinson & Kolb, 2004). Experiment 14-3 compares the and spine density…
effects of amphetamine and saline treatments on cells in
the nucleus accumbens in the basal ganglia. Neurons in Conclusion: The sensitization induced by repeated exposure to
amphetamine-treated brains have more dendritic branches amphetamine changes the structure of neurons in certain brain
and increased spine density. Repeated exposure to psychoac- areas.
tive stimulants thus alters the structure of brain cells. These Information from T. E. Robinson & B. Kolb (1997). Persistent structural adaptations in nucleus
accumbens and prefrontal cortex neurons produced by prior experience with amphetamine.
changes in turn may be related to learned addictions. Journal of Neuroscience, 17, p. 8496.
These plastic changes were not found throughout the
brain. Rather, they were localized to regions such as the
prefrontal cortex and nucleus accumbens that receive a large dopamine projection. Dopa-
mine is believed to factor significantly in the rewarding properties of drugs (Wise, 2004).
Other psychoactive drugs also appear to alter neuronal structure. Marijuana, morphine,
nerve growth factor (nGF) Neurotrophic
and certain antidepressants change dendritic length and spine density, although in ways
factor that stimulates neurons to grow
different from those of stimulants. Morphine, for example, reduces dendritic length and
dendrites and synapses and in some cases
spine density in the nucleus accumbens and prefrontal cortex (Robinson & Kolb, 2004).
promotes the survival of neurons.
What do drug-induced changes in synaptic organization mean for later experience-
behavioral sensitization Escalating
dependent plasticity? If rats are given amphetamine, cocaine, or nicotine for 2 weeks before
behavioral response to the repeated
being placed in a complex environment, the expected increases in dendritic length and spine
administration of a psychomotor stimulant
density in the cortex do not happen (Kolb et al., 2003). This is not because the brain can no lon-
such as amphetamine, cocaine, or nicotine;
ger change: giving the animals additional drug doses can still produce change. Rather, some- also called drug-induced behavioral
thing about prior drug exposure alters the way in which the brain later responds to experience. sensitization.
Why prior drug exposure has this effect is as yet unknown, but obviously drug taking
can have long-term effects on brain plasticity. One possible explanation is epigenetic. Giv-
ing animals repeated doses of amphetamine or nicotine decreases methylation in both the Figure 12-30 shows enhanced connectivity
prefrontal cortex and the nucleus accumbens, and decreased methylation is related to drug- in prefrontal and limbic circuits in nicotine-
and region-specific increases in gene expression (Mychasiuk et al., 2013). These epigenetic dependent smokers.
changes may render the synapses less able to change in response to later experiences.
Some Guiding Principles of Brain Plasticity
Brain plasticity will continue as a fundamental concept underlying research into brain–
behavior relationships through the coming decades. Some basic rules have emerged to guide
this research (see Kolb and Gibb, 2014, for more details). Here we list seven.
512 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
1. Behavioral Change Reflects Brain Change
The brain’s primary function is to produce behavior, but behavior is not static. We learn and
remember, we think new thoughts or visualize new images, and we change throughout life.
All these processes require changes in neural networks. Whenever neural networks change,
behavior, including mental behavior, also changes. A corollary is especially important as
neuroscientists search for treatments for brain injuries or behavioral disorders: To change
behavior, we must change the brain.
2. All Nervous Systems Are Plastic in the Same
General Way
Even the simplest animals, such as the roundworm C. elegans, can show simple learning
that correlates with neuronal plasticity. The molecular details may differ between simple
Investigators study neuroplasticity in species and complex systems, but the principles of neuroplasticity appear to be conserved across
ranging from worms and insects to fish, birds, both simple and complex animals. This conservation allows more studies of neural plasticity
and mammals. among a wider range of animal species than in most areas of neuroscience.
3. Plastic Changes Are Age-Specific
Section 8-4 traces how brain organization The brain responds to the same experiences differently at different ages—and especially dur-
details change rapidly—and sometimes ing development. The prefrontal cortex is late to mature, for example, so the same experience
critically—during development. affects this region differently in infancy than it does in adolescence and on throughout life.
4. Prenatal Events Can Influence Brain Plasticity
Throughout Life
Prenatal experiences can alter brain organization. Potentially negative experiences, such as
Section 8-4 recounts benefits of tactile prenatal exposure to recreational or prescription drugs, and positive experiences, such as tac-
stimulation; Focus 8-2, epigenetic factors in tile stimulation of the mother’s skin, may alter gene expression or induce other epigenetic
the autism spectrum; Focus 6-2, the tragedy effects that produce enduring effects on brain organization. Even paternal or maternal
of fetal alcohol spectrum disorder. experiences before conception can alter later offsprings’ brain development and organization.
5. Plastic Changes Are Brain Region Dependent
Although we are tempted to expect plastic changes in neuronal networks to be fairly gen-
eral, it is becoming clear that many experience-dependent changes are highly specific. We
saw this specificity in the effects of psychoactive drugs on the prefrontal cortex but not on
other cortical regions. Not only do drugs selectively change the prefrontal cortex but the
Figure 12-19 diagrams these prefrontal regions. dorsolateral and orbital prefrontal areas also show opposite changes—the precise changes
varying with the particular drug. For example, stimulants such as amphetamine increase
spine density in the dorsolateral region but decrease it in the orbital region.
6. Experience-Dependent Changes Interact
Metaplasticity is a property of a lifetime’s interaction among different plastic changes in the
brain. As an animal travels through life, infinite experiences can alter its brain organization.
A lifetime’s experiences might interact. Housing animals in complex environments produces
profound changes in their neural network organization, but prior exposure to psychoactive
drugs completely blocks the enrichment effect. Conversely, although complex housing does
not block drug effects, enrichment markedly attenuates them. Prenatal events can affect
later drug effects: prenatal tactile stimulation of the mother, for example, reduces the later
effects of psychoactive drugs on the child.
7. Plasticity Has Pros and Cons
We have mainly emphasized the neuroplastic changes that can support improved motor and
cognitive function. But as noted for the effects of psychoactive drugs, plastic changes in neu-
metaplasticity Interaction among different ral networks can also interfere with behavior. Drug addicts whose prefrontal cortex has been
plastic changes in the brain. altered are prone to poor judgment in their personal life. People who have posttraumatic
14-5 • Recovery from Brain Injury 513
stress disorder show altered blood flow in the amygdala and cingulate cortex. That’s the
bad news.
Encouraging plastic changes that reverse these prefrontal alterations is the good news,
and it is associated with a loss of the prefrontal disorder. Age-related dementia is related to
synaptic loss that various forms of cognitive therapy can reverse (e.g., Mahncke, Bronstone, &
Merzenich, 2006).
14-4 reVieW
Structural Basis of Brain Plasticity
Before you continue, check your understanding.
1. Repeated high-frequency stimulation of excitatory neurons leads to the phenomenon of
, whereas repeated low-frequency stimulation leads to .
2. LTPi and LTDi are found in neurons.
3. Structural changes underlying memory include changes in both and
.
4. Learning complex spatial information has been linked to increased gray matter in the
.
5. The progressive increase in behavioral actions in response to repeated administration of
a drug is called .
6. How can plastic changes in the brain produce adverse effects?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
14-5 Recovery from Brain Injury
The nervous system appears conservative in its use of mechanisms related to behavioral
change. If neuroscientists wish to change the brain, as after injury or disease, then they
should look for treatments that will produce plastic changes related to learning, memory,
and other behaviors.
Recall that H. M. failed to recover his lost memory capacities, even after 55 years of prac-
tice in trying to remember information. Relearning simply was not possible for H. M. He had
lost the requisite neural structures. But other people do show some recovery.
An average person would probably say that the recovery process after brain trauma re-
quires the injured person to relearn lost skills, whether walking, talking, or using the fingers.
But what exactly does recovery entail? Partial recovery of function is common after brain
injury, but a person with brain trauma or brain disease has lost neurons. The brain may be
missing structures critical for relearning or remembering.
Donna’s Experience with Traumatic
Brain Injury
Donna started dancing when she was 4 years old, and she was a natural. By the time she
finished high school, she had the training and skill necessary to apprentice with and later
join a major dance company. Donna remembers vividly the day she was chosen to dance a
leading role in The Nutcracker. She had marveled at the costumes as she watched the popular
Christmas ballet as a child, and now she would dance in those costumes!
The births of two children interrupted her career as a dancer, but Donna never lost the
interest. In 1968, when both her children were in school, she began dancing again with a
local company. To her amazement, she could still perform most of the movements, although
514 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
she was rusty on the choreography of the classical dances that she had once memorized so
meticulously. Nonetheless, she quickly relearned. In retrospect, she should not have been so
surprised, because she had always had an excellent memory.
One evening in 1990, while on a bicycle ride, a drunk driver struck Donna. She was wear-
ing a helmet but received a brain-damaging blow to the head—a traumatic brain injury, or
TBI. She was comatose for several weeks. As she regained consciousness, she was confused
Focus 1-1 and Section 1-2 introduce and had difficulty talking to and understanding others. Her memory was very poor; spatial
consequences of and treatments for TBI, disorientation meant she often got lost; she endured various motor disturbances; and she had
which we elaborate here and in Section 16-3. difficulty recognizing anyone but her family and closest friends.
Over the ensuing 10 months, Donna regained most of her motor abilities and language
skills, and her spatial abilities improved significantly. Nonetheless, she was short-tempered
and easily frustrated by the slowness of her recovery, symptoms typical of people with brain
trauma. She had periods of depression.
Donna also found herself prone to inexplicable surges of panic when doing simple things.
On one occasion early in her rehabilitation, she was shopping in a large supermarket and
became overwhelmed by the number of salad dressing choices. She ran from the store, and
only after she sat outside and calmed herself could she go back inside to continue shopping.
Two years later, Donna was dancing once again, but now she found learning and remem-
bering new steps difficult. Her emotions were still unstable, which put a strain on her family,
but her episodes of frustration and temper outbursts grew far less frequent. A year later, they
were gone, and her life was not obviously different from that of other middle-aged women.
Even so, some cognitive changes persisted. Donna seemed unable to remember
the names or faces of new people she met. She lost concentration if background
distractions such as a television or a radio playing intruded. She could not dance as
she had before her injury, but she did work at it diligently. Her balance on sudden
turns gave her the most difficulty. Rather than risk falling, she retired from her
life’s first love.
Donna’s case demonstrates the human brain’s capacity for continuously chang-
ing its structure and ultimately its function throughout a lifetime. From what we
dean berry/getty images
have learned in this chapter, we can identify three ways in which Donna could re-
cover from her brain injury: she could learn new ways to solve problems, she could
reorganize the brain to do more with less, and she could generate new neurons to
produce new neural circuits. We briefly examine each possibility.
The brain changes in response to these
dancers’ new experiences and new
abilities. After her accident, Donna’s brain
Three-Legged Cat Solution
had to change to allow her to regain her Cats that lose a leg quickly learn to compensate for the missing limb and once again become
lost abilities, but she never recovered the mobile. They show recovery of function: the limb is gone, but behavior has changed to
ability these young women have to learn compensate. This simplest solution to recovery from brain injury we call the three-legged
new dances. cat solution.
A similar explanation can account for many instances of apparent recovery of function after
TBI. Imagine that a right-handed person has a stroke that costs her the use of her right hand
and arm. Unable to write with the affected limb, she switches to her left hand. Such behavioral
compensation presupposes that some nervous system changes underlie this new skill.
New-Circuit Solution
A second way to recover from brain damage is for the brain to form new connections that
allow it to do more with less. This change is most easily accomplished by processes similar to
those we considered for other forms of plasticity. The brain changes its neural connections
to overcome the loss.
Without some intervention, recovery from most brain injuries is relatively modest. Re-
traumatic brain injury (tBi) Damage to the covery can increase significantly if the person engages in behavioral, pharmacological, or
brain that results from a blow to the head. brain-stimulation therapy that encourages the brain to make new connections.
14-5 • Recovery from Brain Injury 515
ExPErimEnt 14-4
Question: Does nerve growth factor stimulate recovery from stroke, influence
neural structure, or both?
Procedure
Animals received a cortical stroke. Some were treated with
NGF; others were not. Skilled reaching was assessed.
Results
NGF increases dendrites
Motor cortex and spines.
Control NGF
Remaining Lesion reduces NGF after a stroke reverses
motor cortex dendrites and spines. loss of dendrites and spines.
Lesion NGF + lesion
Stroke
bryan kolb
Conclusion: Nerve growth factor stimulates dendritic growth and increased spine
density in both healthy and injured brains. These neuronal changes correlate with
improved motor function after stroke.
Information from B. Kolb, S. Cote, A. Ribeiro-da-Silva, & A. C. Cuello (1997). Nerve growth factor treatment prevents
dendritic atrophy and promotes recovery of function after cortical injury. Neuroscience, 76, p. 1146.
Behavioral therapy—speech therapy, physiotherapy, and music therapy are examples—
presumably increases brain activity, which facilitates neural changes. In a pharmacological
intervention, the patient takes a drug, such as nerve growth factor, known to influence
brain plasticity. When NGF is given to animals with strokes that damaged the motor cortex,
their motor functions improve (Experiment 14-4). The behavioral changes correlate with
a dramatic increase in dendritic branching and spine density in the remaining intact motor
regions. The morphological changes correlate with improved motor functions, such as reach-
ing with the forelimb to obtain food, as illustrated in Experiment 14-2 (Kolb, Cote, et al.,
1997). But because brain tissue is still missing, recovery is by no means complete.
516 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
In principle, we might expect that any drug that stimulates the growth of new connec-
epidermal growth factor (EGF)
tions would help people recover from brain injury. However, that neural growth must occur
Neurotrophic factor; stimulates the
in brain regions that can influence a lost function. A drug that stimulates synaptic growth on
subventricular zone to generate cells that
migrate into the striatum and eventually cells in the visual cortex, for example, would not enhance recovery of hand use. The visual
differentiate into neurons and glia. neurons play no direct role in moving the hand.
A third strategy to generate new neural circuits uses either deep brain stimulation (DBS)
or direct electrical stimulation of perilesional regions. The goal of electrical stimulation is to
directly increase activity in remaining parts of specific damaged neural networks. In DBS,
it is to put the brain into a more plastic (trainable) state so that rehabilitation therapies work
better. Both strategies are in preliminary clinical trials.
Lost Neuron Replacement Solution
The third strategy a patient like Donna could pursue is to generate new neurons to produce
new neural circuits. The idea that brain tissue could be transplanted from one animal to
Focus 5-4 recounts a successful case of another goes back a century. The evidence is good that tissue transplanted from fetal brains
fetal stem cell transplantation. Section 13-2 will grow and form some connections in the new brain.
describes SCN cell replacement. Unfortunately, in contrast with transplanted hearts or livers, transplanted brain tissue
functions poorly. The procedure seems most suited to conditions in which a small number of
functional cells are required, as in the replacement of dopamine-producing cells in Parkinson
disease or in the replacement of suprachiasmatic cells to restore circadian rhythms.
By 2004, dopamine-producing cells had been surgically transplanted into the striata of
The striatum, a region in the basal ganglia,
many Parkinson patients. Although the disease has not been reversed, some patients, espe-
includes the caudate nucleus and putamen.
cially the younger ones, have shown functional gains that justify the procedure. Nonetheless,
ethical issues will remain as long as the tissue is taken from aborted human fetuses.
Even in adults, neural stem cells line Adult stem cells offer a second way to replace lost neurons. Investigators know that the
the subventricular zone, diagrammed in brain is capable of making neurons in adulthood. The challenge is to get the brain to do so after
Figure 8-10A. an injury. Brent Reynolds and Sam Weiss (1992) made the first breakthrough in this research.
Cells lining the ventricles of adult mice were removed and placed in a culture medium.
The researchers demonstrated that if the correct trophic factors are added, the cells begin to
divide and can produce new neurons and glia. Furthermore, if the trophic factors—particu-
larly epidermal growth factor (EGF)—are infused into the ventricle of a living animal, the
subventricular zone generates cells that migrate into the striatum and eventually differenti-
ate into neurons and glia.
In principle, it ought to be possible to use trophic factors to stimulate the subventricular
zone to generate new cells in the injured brain. If these new cells were to migrate to the site
of injury and essentially regenerate the lost area, as shown in Figure 14-26, then it might
be possible to restore at least some lost function. Not all lost behaviors could be restored,
however, because the new neurons would have to establish the same connections with the
rest of the brain that the lost neurons once had.
This task would be daunting: connections would have to be formed in an adult brain that al-
ready has billions of connections. Nonetheless, such a treatment might someday be feasible. Cock-
tails of trophic factors are effective in stimulating neurogenesis in the subventricular zone after
Figure 14-26Stem Cells Do the
Trick Left: After cortical stroke—damage
is visible at upper right—infusion of
epidermal growth factor into a rat’s lateral
ventricle induced neurogenesis in the
subventricular zone. Right: The stem cells
migrated to the site of injury and filled
bryan kolb
in the damaged area. But the cytological
organization is abnormal.
Summary 517
brain injury. For example, in Figure 14-26 at left, animals first received ischemic injuries (strokes),
then received intraventricular infusions of trophic factors for 14 days. New cells migrated to the
site of injury, as shown at right in Figure 14-26, and many differentiated into immature neurons.
Although they did not integrate well into the existing brain, the new cells influenced
behavior and led to functional improvement (Kolb et al., 2007). The mechanism of influ-
ence is poorly understood. The new neurons apparently had some trophic influence on the
surrounding uninjured cortex. Preliminary clinical trials with humans are under way and so
far show no ill effects in volunteers.
14-5 reVieW
Recovery from Brain Injury
Before you continue, check your understanding.
1. Three ways to compensate for the loss of neurons are (1) ,
(2) , and (3) .
2. Two ways of using electrical stimulation to enhance postinjury recovery are
and .
3. Endogenous stem cells can be recruited to enhance functional improvement by using
factors.
4. What is the lesson of the three-legged cat?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
Summary
14-1 Connecting Learning and Memory memory also are unique in that they include the amygdala. The chart
Learning is a change in an organism’s behavior as a result of summarizes broad categories within these multiple memory systems.
experience. Memory is the ability to recall or recognize previous For memories to become established in the brain—the process
experience. For more than a century, laboratory studies using animals of consolidation—experiences must change neural connections, and
have uncovered two diverse types of learning: Pavlovian (or classical) these changes must become relatively permanent. When memories
and operant (or instrumental). are revisited, neural connectivity can become less fixed, allowing for
The two basic types of memory are implicit (unconscious) and the neural networks and thus the memory to be modified, a process
explicit (conscious). Episodic memory includes not only a record of called reconsolidation.
events (episodes) that occurred but also our presence there and our
role in the events. The frontal lobe likely plays a unique role in this Implicit Emotional
Explicit (unconscious) (conscious and
autobiographical memory. (conscious) Skills unconscious)
Episodic: Semantic: Habits Attraction
Personal Facts Priming Avoidance
14-2 Dissociating Memory Circuits Autobiographical Knowledge Conditioning Fear
Multiple subsystems control different aspects of memory within the
explicit and implicit systems. People with damaged explicit memory
circuits have impaired recall for facts and events. People with
Long-term memory
damaged implicit memory circuits are impaired in their recall and/or
performance of skills and habits.
Short-term memory
14-3 Neural Systems Underlying Sensory, motor, cognitive
Explicit and Implicit Memories Multiple Memory Systems
The neural circuits underlying implicit and explicit memory are distinctly
different: the reciprocal system for explicit memory includes medial 14-4 Structural Basis of Brain Plasticity
temporal structures; the unidirectional system for implicit memory The brain has the capacity for structural change, and structural
includes the basal ganglia. Emotional memory has characteristics change presumably underlies functional change. The brain changes
of both implicit and explicit memory. Neural circuits for emotional structure in two fundamental ways in response to experience.
518 Chapter 14 • HOW DO WE LEARN AND REMEMBER?
some guiding principles of brain plasticity is epigenetic: specific sites in the neuronal DNA in modified circuits
can exist in either methylated or unmethylated states.
1. Behavioral change reflects brain change.
Neuronal activity is key to brain plasticity: through it, synapses
2. All nervous systems are plastic in the same general way. form and change. Neuronal activity can be induced by general or
3. Plastic changes are age-specific. specific experience as well as by electrical or chemical stimulation.
4. Prenatal events can influence brain plasticity throughout life. Chemical stimulation may range from hormones and neurotrophic
compounds to psychoactive drugs.
5. Plastic changes are brain region dependent.
Much of the brain is capable of plastic change with experience.
6. Experience-dependent changes interact. Different experiences lead to changes in different neural systems.
7. Plasticity has pros and cons. The table summarizes seven principles that guide research about
brain plasticity and behavior.
First, existing neural circuits change largely by modifying synaptic 14-5 Recovery from Brain Injury
connections. One proposed mechanism of synaptic change is long- Plastic changes after brain injury parallel those seen when the
term potentiation (LTP), reflected in modification of EPSPs following brain changes with experience. Changes related to recovery do
learning. not always occur spontaneously, however, but must be stimulated
Second, novel neural circuits form both by forging new connections by behavioral training, by the effects of psychoactive drugs or
among existing neurons and by generating new neurons. Generating neurotrophic factors, or by electrical brain stimulation. The key
new neurons in the hippocampus is one mechanism for establishing to stimulating recovery from brain injury is to increase the plastic
novel circuits. A likely mechanism for maintaining synaptic changes changes underlying the recovery.
Key termS
amnesia, p. 483 entorhinal cortex, p. 491 long-term depression (LTD), perirhinal cortex, p. 491
anterograde amnesia, p. 497 epidermal growth factor (EGF), p. 500 priming, p. 485
associative learning, p. 500 p. 516 long-term potentiation (LTP), procedural memory, p. 485
p. 500
behavioral sensitization, p. 511 episodic memory, p. 487 reconsolidation, p. 497
conditioned response (CR), memory, p. 481
explicit memory, p. 485 retrograde amnesia, p. 497
p. 483 metaplasticity, p. 512
eyeblink conditioning, p. 483 traumatic brain injury (TBI),
conditioned stimulus (CS), nerve growth factor (NGF), p. 514
p. 483 fear conditioning, p. 483 p. 511
unconditioned response (UCR),
consolidation, p. 497 implicit memory, p. 483 neuritic plaque, p. 493 p. 483
declarative memory, p. 485 Korsakoff syndrome, p. 495 operant conditioning, p. 483 unconditioned stimulus (UCS),
dyslexia, p. 481 learning, p. 481 parahippocampal cortex, p. 491 p. 483
emotional memory, p. 498 learning set, p. 485 Pavlovian conditioning, p. 481 visuospatial memory, p. 493
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
15 How Does the Brain
ReseaRch Focus 15-1 Split Brain
15-1 The NaTuRe oF ThoughT
CharaCteriStiCS of human thought
Think? neural unit of thought
compaRaTive Focus 15-2 animal intelligenCe
expeRimeNT 15-1 QueStion: how do individual neuronS
mediate Cognitive aCtivity?
15-2 cogNiTioN aNd The associaTioN coRTex
Knowledge aBout oBjeCtS
multiSenSory integration
Spatial Cognition
attention
expeRimeNT 15-2 QueStion: Can neuronS learn to reSpond
SeleCtively to Stimuli?
planning
imitation and underStanding
ReseaRch Focus 15-3 the riSe and fall of mirror neuronS
15-3 expaNdiNg FRoNTieRs oF cogNiTive NeuRoscieNce
cliNical Focus 15-4 neuropSyChologiCal aSSeSSment
mapping the Brain
Cognition and the CereBellum
SoCial neuroSCienCe
neuroeConomiCS
15-4 ceRebRal asymmeTRy iN ThiNkiNg
anatomiCal aSymmetry
funCtional aSymmetry in neurologiCal patientS
funCtional aSymmetry in the healthy Brain
funCtional aSymmetry in the Split Brain
expeRimeNT 15-3 QueStion: will Severing the CorpuS CalloSum
affeCt the way in whiCh the Brain reSpondS?
explaining CereBral aSymmetry
expeRimeNT 15-4 (a) QueStion: how Can the right hemiSphere
of a Split-Brain SuBjeCt Show that it KnowS information?
(B) QueStion: what happenS if Both hemiSphereS are aSKed to
reSpond to Competing information?
left hemiSphere, language, and thought
15-5 vaRiaTioNs iN cogNiTive oRgaNizaTioN
Sex differenCeS in Cognitive organization
handedneSS and Cognitive organization
cliNical Focus 15-5 Sodium amoBarBital teSt
SyneStheSia
cliNical Focus 15-6 a CaSe of SyneStheSia
15-6 iNTelligeNce
ConCept of general intelligenCe
multiple intelligenCeS
divergent and Convergent intelligenCe
intelligenCe, heredity, epigenetiCS, and the SynapSe
15-7 coNsciousNess
why are we ConSCiouS?
Katherine Streeter
expeRimeNT 15-5 QueStion: Can people alter their movementS
without ConSCiouS awareneSS?
what iS the neural BaSiS of ConSCiouSneSS?
519
520 Chapter 15 • HOW DOES THE BRAIN THINK?
ReseaRch F cus 15-1
Split Brain
Epileptic seizures may begin in a restricted region of one
brain hemisphere and spread through the fibers of the cor-
pus callosum to the corresponding location in the opposite
hemisphere. To prevent the spread of seizures that cannot
be controlled through medication, neurosurgeons sometimes
sever the 200 million nerve fibers of the corpus callosum. Sample
The procedure is medically beneficial for many people card
with epilepsy, leaving them virtually seizure free, with only
minimal effects on their everyday behavior. In special cir-
cumstances, however, the aftereffects of a severed cor-
pus callosum become more readily apparent, as extensive Blocks
psychological testing by Roger Sperry, Michael Gazzaniga,
and their colleagues (Sperry, 1968; Gazzaniga, 1970) has Using his right hand, the subject is …but with his left hand, the
unable to duplicate the pattern... split-brain patient performs the
demonstrated.
task correctly.
On close inspection, such split-brain patients reveal a
unique behavioral syndrome that offers insight into the nature In this experiment, a split-brain patient’s task is to arrange a set of blocks to match the
of cerebral asymmetry. Cortical asymmetry is essential for pattern shown on a card. Information from M. S. Gazzaniga, R. B. Ivry, and G. R. Mangun (1999).
such integrative tasks as language and body control. Cognitive Science: The Biology of the Mind (p. 323). New York: Norton.
One split-brain subject was presented with several
blocks. Each block had two red sides, two white sides, and two half-red Findings from studies of other split-brain patients have shown
and half-white sides, as illustrated. The task was to arrange the blocks that, as tasks of this sort become more difficult, left-hand superiority
to form patterns identical with those shown on cards. increases. Participants whose brain is intact perform equally well with
When the subject used his right hand to perform the task, he had either hand, indicating the intact connection between the two hemi-
great difficulty. His movements were slow and hesitant. In contrast, when spheres. But in split-brain subjects, each hemisphere works on its own.
he performed the task with his left hand, his solutions were not only Apparently, the right hemisphere, which controls the left hand, has
accurate but also quick and decisive. visuospatial capabilities that the left hemisphere does not.
Studies of split-brain patients reveal that the left and right cerebral hemispheres
engage in fundamentally different types of thinking. Yet typically we are unaware of these
brain asymmetries. In this chapter we examine the neural systems and subsystems that con-
trol thinking. In the mammalian brain these systems are in the cortex.
Our first task is to define the mental processes we wish to study—to ask, what is the
nature of thought? Then we consider the cortical regions—for vision, audition, movement,
and associative function—that play major roles in thinking. We examine how these cortical
connections are organized into such systems and subsystems as the dorsal and ventral visual
streams and how neuroscientists study them.
Next we explore the brain’s asymmetrical organization and delve deeper into split-brain
phenomena. Another distinguishing feature of human thought is the different ways that
individual people think. We consider several sources of these differences, including those
related to gender and to what we call intelligence. Finally, we address consciousness and how
it may relate to the neural control of thought.
15-1 The Nature of Thought
Studying abstract mental processes such as thought, language, memory, emotion, and moti-
vation is tricky. They cannot be seen but can only be inferred from behavior and are best
thought of as psychological constructs, ideas that result from a set of impressions. The mind
constructs the idea as being real, even though it is not tangible.
15-1 • The Nature of Thought 521
We run into trouble when we try to locate constructs such as thought or memory in the
split brain Surgical disconnection of the
brain. That we have words for these constructs does not mean that the brain is organized
hemispheres by severing the corpus callosum.
around them. Indeed, it is not. For instance, although people talk about memory as a unitary
thing, the brain neither treats memory as unitary nor localizes it in one particular place. The psychological construct Idea or set of
impressions that some mental ability exists as
many forms of memory are each treated differently by widely distributed brain circuits. The
an entity; memory, language, and emotion are
psychological construct of memory that we think of as being a single thing turns out not to
examples.
be unitary at all.
Assuming a neurological basis for psychological constructs such as memory and thought cognition Act or process of knowing or
coming to know; in psychology, refers to
is risky, but we certainly should not give up searching for where and how the brain produces
thought processes.
them. After all, thought, memory, emotion, motivation, and other such constructs are the
most interesting activities the brain performs. syntax Ways in which words are put together;
Psychologists typically use the term cognition (knowing) to describe thought processes, proposed to be unique to human language.
that is, how we come to know about the world. For behavioral neuroscientists, cognition
usually entails the ability to pay attention to stimuli, whether external or internal, to identify
stimuli, and to plan meaningful responses to them. External stimuli cue neural activity in Section 14-1 details types of memory,
our sensory receptors. Internal stimuli can spring from the autonomic nervous system (ANS) Section 14-4 how neuroplasticity contributes
as well as from neural processes—from constructs such as memory and motivation. to memory processing and storage.
Characteristics of Human Thought
Human cognition is widely believed to have unique characteristics. One is that human
thought is verbal, whereas the thought of other animals is nonverbal. Language is presumed
to give humans an edge in thinking, and in some ways it does:
• Language provides the brain a means of categorizing information. It allows us easily to The appearance of human language
group together objects, actions, and events that have common factors. correlates with a dramatic brain size increase;
see Section 2-3. Section 10-4 explains
• Language provides a means of organizing time, especially future time. It enables us to plan
foundations underlying all languages.
our behavior around time (say, Monday at 3:00 p.m.) in ways that nonverbal animals cannot.
• Perhaps most important, human language has syntax—sets of rules for putting words
together to create meaningful utterances.
Linguists argue that although other animals, such as chimpanzees, can use and recognize
vocalizations (about three dozen for chimps), they do not rearrange these sounds to produce
new meanings. This lack of syntax, linguists maintain, makes chimpanzee language literal Before you accept the linguists’ position,
and inflexible. Human language, in contrast, has enormous flexibility that enables us to talk review Focus 1-2, featuring the chimp Kanzi.
about virtually any topic, even highly abstract ones like psychological constructs. In this way,
our thinking is carried beyond a rigid here and now.
Neurologist Oliver Sacks illustrated the importance of syntax to human thinking in his
description of Joseph, an 11-year-old deaf boy who was raised without sign language for his
first 10 years and so was never exposed to syntax. According to Sacks:
Joseph saw, distinguished, used; he had no problems with perceptual categorization or
generalization, but he could not, it seemed, go much beyond this, hold abstract ideas in mind,
reflect, play, plan. He seemed completely literal—unable to juggle images or hypotheses or
possibilities, unable to enter an imaginative or figurative realm. . . . He seemed, like an animal,
or an infant, to be stuck in the present, to be confined to literal and immediate perception.
(Sacks, 1989, p. 40)
Language, including syntax, develops innately in children because the human brain is pro-
grammed to use words in a form of universal grammar. But in the absence of words—either
spoken or signed—no grammar can develop. Without the linguistic flexibility that grammar
allows, no “higher-level” thought can emerge. Without syntactical language, thought is stuck
in the world of concrete, here-and-now perceptions. Syntax, in other words, influences the
very nature of our thinking.
In addition to arranging words in syntactical patterns, the human brain has a passion
for stringing together events, movements, and thoughts. We combine musical notes into
melodies, movements into dance, images into videos. We design elaborate rules for games
522 Chapter 15 • HOW DOES THE BRAIN THINK?
and governments. To conclude that the human brain is organized to chain together events,
movements, and thoughts seems reasonable. Syntax is merely one example of this innate
human way of thinking about the world.
We do not know how this propensity to string things together evolved, but one possibility
is natural selection: stringing movements together into sequences is highly adaptive. It would
allow for building houses or weaving threads into cloth, for instance.
William Calvin (1996) proposed that the motor sequences most important to ancient
humans were those used in hunting. Throwing a rock or a spear at a moving target is a com-
plex act that requires much planning. Sudden ballistic movements, such as throwing, last
Figure 11-2 diagrams the frontal lobe less than an eighth of a second and cannot be corrected by feedback. The brain has to plan
hierarchy that initiates motor sequences. every detail and then spit them out as a smooth-flowing sequence.
Today, a football quarterback does just this when he throws a football to a receiver run-
ning a zigzag pattern to elude a defender. A skilled quarterback can hit the target on virtually
every throw, stringing movements together rapidly in a continuous sequence with no pauses
or gaps. This skill is uniquely human. Chimpanzees can throw, but their throws are inac-
curate. No chimpanzee could learn to throw a ball to hit a moving target.
The human predisposition to sequence movements may have encouraged language
development. Spoken language, after all, is a sequence of movements involving the throat,
tongue, and mouth muscles. Viewed in this way, language is the by-product of a brain that
was already predisposed to operate by stringing movements, events, or even ideas, together.
A critical characteristic of human motor sequencing is our ability to create novel sequences
with ease. We constantly produce new sentences. Composers and choreographers earn their
living making new music and dance sequences. Novel movement or thought sequences are
a product of the frontal lobe.
People with frontal lobe damage have difficulty generating novel solutions to problems.
They are described as lacking imagination. The frontal lobes are critical not only for orga-
nizing behavior but also for organizing thinking. One major difference between the human
brain and other primates’ brains is the size of the frontal lobes.
Neural Unit of Thought
What exactly goes on within the brain to produce what we call thinking? Is thought an attri-
bute exclusive to humans? Before you answer, consider the mental feats of Alex the parrot,
profiled in Comparative Focus 15-2, Animal Intelligence.
Alex’s cognitive abilities are unexpected in a bird. In the past 40 years, the intellectual
capacities of chimpanzees and dolphins have provoked great interest, but Alex’s mental life
appears to have been just as rich as the mental life of those two large-brained
Cerebrum Cerebellum Cerebrum Cerebellum mammals.
The fact that birds are capable of thought is a clue to the neural basis of
thought. A logical presumption may be that thinking, which humans are so
good at, must be due to some special property of the massive human neocortex.
But birds do not possess a neocortex. Rather, they evolved specific brain nuclei
that function much as the layers of the human cortex do. This organizational
Parrot Human difference in the forebrain of birds and mammals implies that thinking must
be an activity of complex neural circuits, not of some particular brain region.
The idea of neural circuits is the essence of Donald Hebb’s (1949) concept
that cell assemblies (networks of neurons) represent objects or ideas, and the interplay
among the networks results in complex mental activity such as cognition. Connections
cell assembly Hypothetical group of neurons among neurons are not random but rather are organized into systems and subsystems.
that become functionally connected via Thinking must result from the activity of these complex neural circuits. One way to iden-
common sensory inputs; proposed by Hebb tify their role is to consider how individual neurons respond during cognitive activity.
as the basis of perception, memory, and William Newsome and his colleagues (1995) took this approach in training monkeys to
thought. identify apparent motion in a set of moving dots on a television screen. The Procedure
15-1 • The Nature of Thought 523
compaR ative F cus 15-2
Animal Intelligence
Intelligent animals think. We all know that parrots can talk, but most of
us assume that no real thought lies behind their words. An African grey
parrot named Alex proved otherwise. Irene Pepperberg, pictured here
with Alex, studied his ability to think and use language for more than
three decades (Pepperberg, 1990, 1999, 2006).
A typical session with Alex and Pepperberg proceeded roughly as
follows (Mukerjee, 1996): Pepperberg would show Alex a tray with four
corks. “How many?” she would ask. “Four,” Alex would reply. She then
might show him a metal key and a green plastic one.
“What toy?”
“Key.”
“How many?”
“Two.”
“What’s different?”
wm. munoz
“Color.”
Alex did not just have a vocabulary: words had meaning to him. He
correctly applied English labels to numerous colors (red, green, blue, The African grey parrot Alex, shown here with Irene Pepperberg and a
yellow, gray, purple, orange), shapes (two-, three-, four-, five-, six- sampling of the items he could count, describe, and answer questions
cornered), and materials (cork, wood, rawhide, rock, paper, chalk, wool). about. Alex died in 2007 at the age of 31.
He also labeled various items made of metal (chain, key, grate, tray, toy
truck), wood (clothespin, block), and plastic or paper (cup, box).
Most surprisingly, Alex used words to identify, request, and refuse Alex could not respond just to one attribute. Rather, he had to com-
items. He responded to questions about abstract ideas, such as the color, bine the concepts of rawhide and purple and find the object that pos-
shape, material, relative size, and quantity of more than 100 objects. sessed them both. Then he had to figure out the object’s shape. Clearly,
Alex’s thinking was often quite complex. Presented with a tray that considerable mental processing was required, but Alex succeeded at
contained seven items—a circular rose-colored piece of rawhide, a piece such tasks time and again.
of purple wool, a three-cornered purple key, a four-cornered yellow piece Alex also demonstrated that he understood what he said. If he
of rawhide, a five-cornered orange piece of rawhide, a six-cornered requested one object and was presented with another, he was likely
purple piece of rawhide, and a purple metal box—and then asked, “What to say no and repeat his original request. In fact, when given incor-
shape is the purple hide?” Alex would answer correctly, “Six-corner.” rect objects on numerous occasions in formal testing, he said no and
To come up with this answer, Alex had to comprehend the ques- repeated his request 72 percent of the time, said no without repeating
tion, locate the correct object of the correct color, determine the answer his request 18 percent of the time, and made a new request the other 10
to the question about the object’s shape, and encode his answer into percent of the time.
an appropriate verbal response. This task was not easy. After all, four These responses suggest that Alex’s requests led to an expectation
objects were pieces of rawhide and three objects were purple. in his mind. He knew what he was asking for, and he expected to get it.
section of Experiment 15-1 on page 524 shows how the researchers varied the difficulty of
the task by manipulating the number of dots that moved in the same direction. If all the dots
move in the same direction, perceiving the whole array as moving is very easy. If only a small
percentage of the dots move in the same direction, however, perceiving apparent motion in
that direction is much more difficult.
In fact, a threshold number of dots moving together is required to make directional
motion apparent. If too few dots are moving in the same direction, the viewer gets an impres-
sion of random movement. Apparently, on the basis of the proportion of dots moving in the
same direction, the brain decides whether dots are moving in a consistent direction.
After the monkeys were trained in the task, the investigators recorded from single neu- Figure 9-16 locates visual regions V1 through
rons in visual area V5. V5 contains cells sensitive to movement in a preferred direction. When V5 in the occipital lobe.
vertical movement crosses its receptive field, a neuron that is sensitive to vertical motion
responds with a vigorous burst of action potentials. But just as the observer has a threshold
524 Chapter 15 • HOW DOES THE BRAIN THINK?
ExpErimEnt 15-1
Question: How do individual neurons mediate cognitive activity?
Procedure
Monkeys were trained to identify apparent motion in a
set of moving dots on a TV screen.
Semirandom Semicoordinated dot Coordinated
Random dot movement dot movement movement (threshold level dot movement
(no apparent motion (still no apparent needed to perceive (apparent motion
perceived) motion perceived) apparent motion) strongly perceived)
Results
After the monkeys were trained in the task, investigators recorded from single neurons in
visual area V5, which contains cells that are sensitive to motion in a preferred direction.
The neural responses to the four different patterns of movement are shown below.
Baseline response Baseline response Moderate response Strong response
Conclusion: The increase in neuronal firing rate correlates with the
monkey’s perception of motion, suggesting that individual neurons, not the
summed activity of many neurons, influence perception.
for perceiving coherent motion in one direction, so too does the neuron. If at some point
the random activity of the dots increases to a level that obscures movement in a neuron’s
preferred direction, the neuron will stop responding because it does not detect any consistent
pattern.
So how does the activity of any given neuron correlate with the perceptual threshold for
apparent motion? On the one hand, if our perception of apparent motion results from the
summed activity of many dozens or even thousands of neurons, little correlation would exist
between the activity of any one neuron and the perception. On the other hand, if individual
neurons influence our perception of apparent motion, then a strong correlation would exist
between the activity of a single cell and the perception.
The results of Experiment 15-1 are unequivocal: the sensitivity of individual neurons is
very similar to the perceptual sensitivity of the monkeys to apparent motion. As shown in the
Results section, if individual neurons failed to respond to the stimulus, the monkeys behaved
as if they did not perceive any apparent motion.
This finding is curious. Given the large number of V5 neurons, it seems logical that
perceptual decisions are based on the responses of a large pool of neurons. But Newsome’s
results show that the activity of individual cortical neurons is correlated with perception
rather than perception being the property of a particular brain region.
Still, Hebb’s idea of a cell assembly—an ensemble of neurons that represents a com-
plex concept—suggests some way of converging the inputs of individual neurons to arrive
at a consensus. Here, the neuronal ensemble represents a sensory event (apparent motion)
that the activity of the ensemble detects. Cell assemblies could be distributed over fairly
Figures 9-33 to 9-35 diagram functional large regions of the brain, or they could be confined to smaller areas, such as cortical
columns in occipital and temporal cortices. columns.
15-2 • Cognition and the Association Cortex 525
Via computer modeling, cognitive scientists have demonstrated
the capacity of cell assembly circuits to perform sophisticated sta-
tistical computations. Other complex tasks, such as Alex the par-
rot’s detecting an object’s color, also are believed to entail neuronal
ensembles. Cell assemblies provide the basis for cognition. Dif-
ferent ensembles come together, much like words in language, to
produce coherent thoughts.
What do individual neurons contribute to a cell assembly? Each
acts as a computational unit. As Experiment 15-1 shows, even one
solitary neuron can decide on its own when to fire if its summed
inputs indicate that movement is taking place. Neurons are the only
elements in the brain that combine evidence and make decisions.
Neurons are the foundation of cognitive processes and of thought.
The combination of individual neurons into novel neural networks
produces complex mental representations—ideas, for instance.
15-1 review Hebb’s Cell Assembly “Cells that fire
together wire together.” Image from D. O. Hebb (1949).
The Nature of Thought The Organization of Behavior (Figure 9, p. 71). New York:
Before you continue, check your understanding. McGraw-Hill.
1. Cognition, or thought, entails the abilities of , , and
stimuli.
2. Unlike thought in other animals, humans have the added advantage of ,
which adds to thought.
3. The is the basic unit of thought production.
4. Describe the most important way in which human thought differs from thinking in other
animals.
Answers appear at the back of the book.
For additional study tools, visit LaunchPad:
www.macmillanhighered.com/launchpad/kolb5e
15-2 Cognition and the
Association Cortex
Altogether, the primary sensory and motor cortical regions occupy
about a third of the neocortex (Figure 15-1). The remaining two-
thirds, located in the frontal, temporal, parietal, and occipital lobes, is
referred to generally as the association cortex. It functions to produce KEY (cortical areas)
cognition. Primary motor Primary visual Primary olfactory
A fundamental difference between association cortex and primary Primary sensory Primary auditory and taste
sensory and motor areas is that the association cortex has a distinctive
FiGUre 15-1 Cortical Functions Lateral
pattern of connections. A major source of input to all cortical areas is
view of the left hemisphere and medial
the thalamus, which rests atop the brainstem. The primary sensory cortex receives inputs
view of the right hemisphere, showing
from thalamic nuclei that receive information from the body’s sense organs. But inputs to the primary motor and sensory areas. All
the association cortex come from thalamic areas that receive their inputs from other corti- remaining cortical areas are collectively
cal regions. As a result, inputs to the association cortex are already highly processed. So referred to as the association cortex, which
this information must be fundamentally different from the raw information reaching the functions in thinking.
primary sensory and motor cortex. The association regions contain knowledge either about
our external or internal world or about movements. association cortex Neocortex outside
Owing to its close relationship to the visual and auditory sensory regions, the tempo- primary sensory and motor cortices;
ral association regions tend to produce cognition related to visual and auditory processing. functions to produce cognition.
526 Chapter 15 • HOW DOES THE BRAIN THINK?
FiGUre 15-2 Prefrontal Association (A) Lateral view (B) Medial view
Cortex Lateral view of the brain’s left Dorsolateral prefrontal Dorsomedial Anterior cingulate
hemisphere (A) and medial view of the cortex prefrontal cortex
right hemisphere (B) represent regions cortex
of the prefrontal cortex (PFC) in relation
to the associated anterior cingulate
allocortex, shown in (B). Figure 12-19
illustrates how these areas function in
producing emotional behavior.
Ventromedial
Orbital prefrontal prefrontal cortex
cortex
Similarly, the parietal cortex is closely related to somatosensation and movement control. In
contrast, the frontal cortex coordinates information coming from the parietal and temporal
association regions with information coming from subcortical regions.
As diagrammed in Figure 15-2, the multiple subdivisions of the prefrontal cortex (PFC)
encompass its dorsal, lateral, orbital, and medial regions. Activity in each prefrontal region is
associated with the types of cognitive processing that we describe throughout this chapter.
An additional frontal lobe region shown in Figure 15-2 is the anterior cingulate cortex (ACC).
Although the ACC was once believed only to play a role in emotion, it is becoming clear that
it functions as an interface between emotion and cognition.
To understand the types of knowledge that the association areas contain, we next con-
sider discrete cognitive behaviors, then trace these behaviors to different parts of the asso-
ciation cortex.
Knowledge about Objects
Visualize a milk carton sitting on a counter directly in front of you. What do you see? Now
imagine moving the carton a few inches off to one side as you continue to stare directly
ahead. What do you see now? Next, imagine that you tilt the carton toward you at a 45° angle.
Again, what do you see? Probably you answered that you saw the same thing in each situa-
tion: a rectangular box with lettering on it.
Intuitively, you feel that the brain must see the object much as you have perceived it.
The brain’s seeing, however, is more compartmentalized than are your perceptions. Com-
partmentalization is revealed in people with damage to various regions of the occipital
cortex, many of whom lose one particular aspect of visual perception. For instance, those
with damage to visual area V4 can no longer perceive color, whereas those with damage
to area V5 can no longer see movement (when the milk carton moves, it becomes invisible
to them).
Moreover, your perception of the milk carton’s consistently rectangular shape does not
always match the forms your visual system is processing. When you tip the carton toward
you, you still perceive it as rectangular, even though it is no longer presenting a rectangular
shape to your eyes. Your brain has somehow ignored the change in information about shape
that your retinas have sent it and concluded that this object, no matter its apparent shape,
remains the same milk carton.
There is more to your conception of the milk carton than merely perceiving and processing
its physical characteristics. You also know what a milk carton is, what it contains, and where
you can get one. The knowledge about milk cartons that you have acquired is represented in
the temporal association cortex, which forms the ventral stream of visual processing. If the
Section 9-4 recounts cases illustrative of temporal association regions are destroyed, a person loses visual knowledge not only about
various visual-form agnosias. milk cartons but also about all other objects. The person becomes agnosic (unknowing).
15-2 • Cognition and the Association Cortex 527
Knowledge about objects includes even more than how they look and what they are used Parietal lobe
for. It depends on what will be done with the information—how to pick up the milk carton,
Occipital
for example. Knowledge of what things are is temporal; knowledge of how to grasp the object lobe
Do
is parietal (Figure 15-3). rsa
ls
tr e
am
Multisensory Integration Ventral stream
Our knowledge about the world comes through multisensory channels. When we see and
hear a barking dog, the visual information and auditory information fit together seamlessly. Temporal
lobe
How do all our neural systems and functional levels combine to afford us a unified conscious Striate
cortex (region V1)
experience?
Philosophers, impressed with this integrative capacity, identified the binding problem, Streaming Visual
FiGUre 15-3
which asks how the brain ties its single and varied sensory and motor events together into Information The dorsal visual
a unified perception or behavior. It is gradually becoming clear how the brain binds up our stream mediates vision for action. The
perceptions and how this ability is gradually acquired in postnatal life (see the review by ventral stream mediates vision for object
Stein & Rowland, 2011). recognition.
One solution to the sensory integration aspect of the binding problem lies in multimodal
regions of the association cortex, that is, regions populated by neurons that respond to infor- binding problem Philosophical question
mation from more than one sensory modality, as illustrated in Figure 15-4. Investigators focused on how the brain ties single and
presume that multimodal regions combine characteristics of stimuli across different senses varied sensory and motor events together
when we encounter them separately or together. For example, the fact that we can visually into a unified perception or behavior.
identify objects that we have only touched implies a common perceptual system linking
the visual and somatic circuits. In Section 15-5, Clinical Focus 15-6 profiles a man in whom The senses of smell and taste combine to
stimulation from one sensory modality (taste) concurrently induces the experience of a dif- produce the experience of flavor; see
ferent modality (touch). Section 12-2.
Somatosensory Ventral intraparietal Lateral intraparietal FiGUre 15-4 Multisensory Areas in
areas 3b and 1 area area the Monkey Cortex Color-coded
Ventral premotor Temporoparietal area areas represent regions where anatomical
cortex data and/or electrical stimulation
Visual area demonstrate multisensory interactions.
Principal medial temporal
sulcus Dashed lines represent multimodal areas
Primary and secondary revealed when sulci are opened. Information
Ventrolateral visual areas from A. A. Ghanzanfar & C. E. Schroeder (2006). Is
prefrontal cortex neocortex essentially multisensory? Trends in Cognitive
Caudomedial auditory Science, 10, pp. 278–285.
Auditory core and
belt area
lateral belt areas
Superior temporal
sulcus
KEY (multimodal cortex)
Auditory, visual, and Auditory and visual Auditory and
somatosensory somatosensory
Spatial Cognition
The location of objects is just one aspect of what we know about space. Spatial cognition
encompasses a whole range of mental functions that vary from navigational ability (getting
from point A to point B) to mentally manipulating complex visual arrays like those shown
in Figure 15-5.
Imagine going for a walk in an unfamiliar park. You do not go around and around in
circles. Rather, you proceed in an organized, systematic way. You also need to find your way FiGUre 15-5 Spatial Cognition
These two figures are the same but are
back. These abilities require a representation of the physical environment in your mind’s eye.
oriented differently in space. Researchers
At some time during the walk, let’s assume you are uncertain where you are—a common test spatial cognition by giving subjects
problem. One solution is to make a mental image of your route, complete with various land- pairs of stimuli like this and asking if the
marks and turns. It is a small step from mentally manipulating these kinds of navigational shapes are the same or different.
528 Chapter 15 • HOW DOES THE BRAIN THINK?
landmarks and movements to manipulating other kinds of images in your mind. Thus the
ability to mentally manipulate visual images seems likely to have arisen in parallel with the
ability to navigate in space.
The evolution of skill in mental manipulation is also closely tied to the evolution of physi-
The Basics, Section 1-3, traces nervous cal movements. It is likely that animals first moved using whole-body movements (the swim-
system evolution across the animal kingdom. ming motion of a fish), then developed coordinated limb movements (quadrupedal walking),
and finally mastered discrete limb movements, such as a human arm reaching out. As the
guidance strategies for controlling movements became more sophisticated, cognitive abilities
evolved to support the guidance systems.
It seems unlikely that more sophisticated cognitive abilities evolved on their own. Why
would a fish, say, be able to manipulate an object in its mind that it could not manipulate in
the real world? But a human, who can manipulate objects by hand, should be able to imagine
Alex the parrot manipulated objects with his such manipulations. After all, we are constantly observing our hands or feet manipulating
beak. things: we must have many mental representations of such activities.
Once the brain can manipulate objects that are physically present, it seems a small step
to manipulating imagined objects—to solve problems like the one depicted in Figure 15-6.
The ability to manipulate an object in the mind’s eye probably flows from the ability to
manipulate tangible objects with the hands.
Research findings provide clues to the brain regions participating in various aspects of
spatial cognition. For instance, the dorsal stream in the parietal lobes is central in controlling
vision for action. Humans make discrete limb movements to points in space, so a reasonable
a supposition is that the dorsal stream’s evolutionary development provided a neural basis
b for such spatial cognitive skills as mentally rotating objects. In fact, people with damaged
c
parietal association regions, especially in the right hemisphere, have deficits in processing
FiGUre 15-6 Mental Manipulation complex spatial information, both in the real world and in their imagination.
Try this sample test item used to measure By tracing the evolutionary development of the human brain, we find that the parietal
spatial orientation. Compare the three association regions expanded considerably more in humans than in other primates. This
cubes on the right with the one on the left.
expanded brain region functions in part to perform the complex spatial operations just dis-
No letter appears on more than one face of
a given cube. Which cube—a, b, or c—could cussed. Humans have a capacity for building that far exceeds that of our nearest relative, the
be a different view of the cube on the left? chimpanzee. You may consider it a long leap of logic, but perhaps our increased capacity for
The correct answer is at the bottom of the building and manipulating objects played heavily into our developing cognitive spatial abilities.
page.
Attention
Imagine you’re meeting some friends at a football game. You search for them as you meander
through the crowd in the stadium. Suddenly you hear one friend’s distinctive laugh and turn
to scan in that direction. You see your group and rush to join them.
This everyday experience demonstrates the nature of attention, selective narrowing or
attention Narrowing or focusing awareness
focusing of awareness to part of the sensory environment or to a class of stimuli. Even as
to a part of the sensory environment or to a
sounds, smells, feelings, and sights bombard you, you still can detect a familiar laugh or spot
class of stimuli.
a familiar face: you can direct your attention.
contralateral neglect Ignoring a part of More than 100 years ago, William James (1890) defined attention: “It is the taking posses-
the body or world on the side opposite
sion by the mind in clear and vivid form of one out of what seem several simultaneous objects
(contralateral to) that of a brain injury.
or trains of thought.” James’s definition goes beyond our example of locating friends in a
extinction In neurology, neglect of crowd, inasmuch as he notes that we can attend selectively to thoughts as well as to sensory
information on one side of the body when stimuli. Who hasn’t at some time been so preoccupied with a thought as to exclude all else
presented simultaneously with similar
from mind? So attention can be directed inward as well as outward.
information on the other side of the body.
Selective Attention
As with many other inferred mental processes, studying the neural basis of attention is chal-
lenging. Research with monkeys trained to attend to particular locations or visual stimuli,
however, has identified neurons in the cortex and midbrain that show enhanced firing rates
The answer to the mental manipulation in to particular locations or visual stimuli. Significantly, the same stimulus can activate a neu-
Figure 15-6 is a. ron at one time but not at another, depending on the monkey’s learned focus of attention.
15-2 • Cognition and the Association Cortex 529
In the study shown in Experiment 15-2, James Moran and Robert ExpErimEnt 15-2
Desimone (1985) trained monkeys to hold a bar while gazing at a fixation
Question: Can neurons learn to respond selectively to
point on a screen. A sample stimulus (e.g., a vertical red bar) appeared stimuli?
briefly at one location in the visual field, followed about 500 milliseconds
later by a test stimulus at the same location. When the test stimulus was Procedure
identical with the initial sample stimulus, an animal was rewarded if it
Monkeys were trained to release a bar when a certain
immediately released the bar. stimulus was presented in a certain location. The
Each animal was trained to attend to stimuli presented in one particu- monkeys learned to ignore stimuli in all other locations.
lar area of the visual field and to ignore stimuli in any other area. In this Fixation point Stimulus
way, the same visual stimulus could be presented to different regions of
a neuron’s receptive field to test whether the cell’s response varied with
stimulus location.
As the animals performed the task, the researchers recorded neurons fir-
ing in visual area V4. Neurons in V4 are sensitive to color and form, and dif-
ferent neurons respond to different combinations of the two variables (e.g,, a
red vertical bar or a green horizontal bar). Visual stimuli were presented either
in the correct location for a reward or in an incorrect location for no reward.
As diagrammed in the Results section of Experiment 15-2, neurons
responded only when a visual stimulus was in the reward location, even
though the same stimulus was presented in a no-reward location. Before
Results
training, the neurons responded to all stimuli in both locations. This find-
During performance of this task, researchers recorded
ing tells us that attending to specific parts of the sensory world is a property
the firing of neurons in visual area V4, which are
of single neurons: more evidence that the neuron is the computational unit sensitive to color and form. Stimuli were presented in
of cognition. either rewarded or unrewarded locations.
Deficits of Attention Pretraining recordings:
Attention is probably a property of neurons throughout the brain, with Rewarded location Unrewarded location
some regions playing more prominent roles than others. The frontal lobes, Strong response Strong response
for instance, are central in attention. People with frontal lobe injuries tend
to become overly focused on environmental stimuli. They seem to selec-
tively direct attention to an excessive degree or to have difficulty shifting
attention. Studies of these people suggest that the frontal association cor- Before training, neurons responded
to stimuli in all locations.
tex controls the ability to direct attention flexibly to where it is needed.
Indeed, planning, a key frontal lobe function, requires this ability. Posttraining recordings:
That the parietal association cortex is key in other aspects of attention Rewarded location Unrewarded location
is perhaps best illustrated by the attention deficit referred to as neglect. Strong response Baseline response
Neglect occurs when a brain-injured person ignores sensory information
that should be considered important. Usually the condition affects only one
side of the body and is called contralateral neglect. We observed a dog that
After training, neurons responded only when
had developed a right-hemisphere tumor and ate only the food on the right the visual stimuli were in the rewarded location.
side of its dish, ignoring the food on the left side. Neglect is a fascinating
Conclusion: Neurons can learn to respond selectively to information in their
symptom because often no damage to sensory pathways accompanies it. receptive field.
Rather, neglect is a failure of attention.
People with damage to the parietal association cortex of the right hemi-
sphere may have particularly severe neglect of objects or events in the left side of their world.
For example, one man dressed only the right side of his body, shaved only the right side of his
face, and read only the right side of a page (if you can call that reading). He could move his left
limbs spontaneously, but when asked to raise both arms, he would raise only the right. When
pressed, he could be induced to raise the left arm, but he quickly dropped it to his side again.
As people with contralateral neglect begin to recover, they show another interesting
symptom. They neglect information on one side of the body when it is simultaneously pre-
sented with similar information on the other side of the body. Figure 15-7 shows a common
clinical test for this symptom, called extinction.
530 Chapter 15 • HOW DOES THE BRAIN THINK?
When shown two identical objects In an extinction test, the patient is asked to keep his or her eyes fixed on the
examiner’s face and to report objects presented in one or both sides of the visual
Patient’s right Patient’s left
visual field visual field
field. When presented with a single object (a fork) to one side or the other, the
patient orients himself or herself toward the appropriate side of the visual field,
Patient
so we know that he or she cannot be blind on either side. But now suppose that
sees only
the object two forks are presented, one on the left and one on the right. The patient ignores
in his right the fork on the left and reports the one on the right. When asked about the left
visual field. side, the patient is quite certain that nothing appeared there and that only one
fork was presented, on the right.
Perhaps the most curious aspect of neglect is that people who have it fail to
When shown two different objects pay attention not only to one side of the physical world around them but also to
one side of the world represented in their mind. We studied one woman who had
complete neglect for everything on her left side. She complained that she could
Patient sees not use her kitchen because she could never remember the location of anything
the object
on her left.
in both
visual fields. We asked her to imagine standing at the kitchen door and to describe what was
in the various drawers on her right and left. She could not recall anything on her
left. We then asked her to imagine walking to the end of the kitchen and turning
around. We again asked her what was on her right, the side of the kitchen that
had previously been on her left. She broke into a big smile and tears ran down her
face as she realized that she now knew what was on that side of the room. All she
When shown two kinds of an object had to do was reorient her body in her mind’s eye. She later wrote and thanked
us for changing her life, because she was now able to cook again. Clearly, neglect
can exist in the mind as well as in the physical world.
Although complete contralateral neglect is usually associated with parietal
Patient lobe injury, specific forms of neglect can arise from other injuries. Ralph Adolphs
sees only and his colleagues (2005) describe the case of S. M., a woman with bilateral amyg-
the object
in his right dala damage who could not recognize fear in faces. On further study, the reason
visual was discovered: S. M. failed to look at the eyes when she looked at faces; instead,
field. she looked at other facial features such as the nose. Because fear is most clearly
identified in the eyes, not the nose, she did not identify the emotion. When she
was specifically instructed to look at the eyes, her recognition of fear became
FiGUre 15-7 Testing for Extinction
entirely normal. Thus, the amygdala plays a role in directing attention to the eyes to identify
A stroke patient who shows neglect for
facial expressions.
information presented to his left responds
differently depending on whether objects
in the left and right visual fields are similar Planning
or different. At noon on a Friday, a friend proposes that she and you go to a nearby city for the weekend
to attend a concert. She will pick you up at 6:00 p.m. and you will drive there together.
Because you are completely unprepared for this invitation and because you are going to
be busy until 4:00, you must rush home and get organized. En route you stop at a fast food
restaurant so that you won’t be hungry on the 2-hour drive. You also need cash, so you head
to the nearest ATM. When you get home, you grab various pieces of clothing appropriate for
the concert and the trip. You also pack your toiletries. You somehow manage to get ready by
6:00, when your friend arrives.
Although the task of getting ready in a hurry may make us a bit harried, most of us can man-
age it. People with frontal lobe injury cannot. To learn why, let’s consider what the task requires.
1. To plan your behavior, you must select from many options. What do you need to take
with you? Cash? Then which ATM is closest, and what is the quickest route to it? Are you
hungry? Then what is the fastest way to get food on a Friday afternoon?
2. In view of your time constraint, you have to ignore irrelevant stimuli. If you pass a sign
advertising a sale in your favorite store, for instance, you have to ignore it and persist with
the task at hand.
15-2 • Cognition and the Association Cortex 531
3. You have to keep track of what you have done already, a requirement especially important
while you are packing. You do not want to forget anything or pack duplicates. You do not
want to take four pairs of shoes but no toothbrush.
The task’s general requirements can be described as the temporal (time) organization of
behavior. You are planning what you need to do and when you need to do it. Temporal plan-
ning is the general function of the frontal lobes, especially the prefrontal cortex.
But to plan, you also need to recognize objects (an occipital and temporal lobe function)
and to make appropriate movements with respect to them (a parietal lobe function). You
can therefore think of the frontal lobes as acting like an orchestra conductor. The frontal
lobes make and read a motor plan to organize behavior in space and time—a kind of score,
analogous to the musical score a conductor uses. People with frontal lobe injuries are simply
unable to organize their behavior.
Performance on the Wisconsin Card Sorting Test exemplifies the deficits frontal lobe
injury causes. Figure 15-8 shows the testing materials. The subject is presented with four
stimulus cards bearing designs that differ in color, form, and number of elements, thus set-
ting up three possible sorting categories. The subject must sort a deck of cards into piles in
front of the various stimulus cards, depending on the sorting category called for. But the
FiGUre 15-8 Wisconsin Card
correct sorting category is never stated. The subject is simply told after placing each card
Sorting Test The subject receives a
whether the choice is correct or incorrect. deck of cards containing multiple copies of
In one trial, for example, the first correct sorting category is color. After the subject has those represented here and is presented
sorted a number of cards by color, the correct solution switches, without warning, to form. with a row of four cards selected from
When the subject has started to sort by form, the correct solution again changes unexpect- among them. The task is to place each
card in the pile under the appropriate
edly, this time to the number of items on each card. The sorting rule later becomes color
card in the row, sorting by one of three
again, and so on, with each change in rule coming unannounced. possible categories. Subjects are never
Shifting response strategies is particularly difficult for people with frontal lobe lesions: explicitly told what the correct sorting
they may continue responding to the original stimulus (color) for as many as 100 cards until category is—color, number, or form; they
the test ends. This pattern, known as perseveration, is the tendency to emit repeatedly the are told only whether their responses are
same verbal or motor response to varied stimuli. correct or incorrect. After subjects have
begun sorting by one category, the tester
Frontal lobe subjects may even comment that they know that color is no longer the cor-
unexpectedly changes to another category.
rect category, but they continue to sort by color. One stated: “Form is probably the correct
solution now so this [sorting by color] will be wrong, and this will be wrong, and wrong again.”
Despite knowing the correct sorting category, the frontal lobe patient cannot shift behavior
in response to the new external information.
Imitation and Understanding
In all communication—verbal and nonverbal—the sender and receiver must share an under-
standing of what counts. If a person speaks a word or makes a gesture, another person will perseveration Tendency to emit repeatedly
understand only if he or she interprets it correctly. To accomplish this coordination in com- the same verbal or motor response to varied
munication, the processes of producing and perceiving a message must share a common stimuli.
representation in the sender’s and the receiver’s brains.
How do both sender and receiver of a potentially ambiguous gesture, such as a raised hand
or a faint smile, achieve a common understanding? Giacomo Rizzolatti and his colleagues
(Rizzolatti, 2007; Rizzolatti & Craighero, 2004) proposed an answer. In monkeys’ frontal
lobes they identified neurons that discharge during active movements of the hand or mouth
or both. These neural discharges do not precede the movements but instead occur in syn-
chrony with them. But it takes time for a neural message to go from a frontal lobe to a hand,
so we would predict that, if these cells are controlling the movements, they will discharge
before the movements take place. The cells must therefore be recording a movement that is
taking place.
In the course of his studies, Rizzolatti also found that many “movement” neurons located
in the inferior frontal and posterior parietal cortex discharge when a monkey sees other
monkeys make the same movements. They also discharge when the monkey sees the
532 Chapter 15 • HOW DOES THE BRAIN THINK?
experimenter make the movements. Rizzolatti called them mirror neurons. The researchers
mirror neuron Cell in the primate premotor
proposed that mirror neurons represent actions, one’s own or those of others. Such neural
and parietal cortex that fires when an
representations could be used both for imitating others’ actions and for understanding their
individual observes an action taken by
another individual. meanings, thus enabling appropriate responses. Mirror neurons therefore could provide the
link between the sender and the receiver of a communication.
Rizzolatti and his colleagues used PET to look for these same neuron populations in
humans. Participants were asked to watch a movement, to make the same movement, or
to imagine the movement. Each condition activated a region of the lateral frontal lobe in
the left hemisphere, including Broca’s area. Taken together with the results of the monkey
studies, this finding suggests that primates have a fundamental mechanism for recognizing
action. People apparently recognize others’ actions, because the neural patterns produced
when they observe those actions are similar to those produced when they themselves make
those same actions. Research Focus 15-3, The Rise and Fall of Mirror Neurons, frames the
debate on mirror neuron function.
ReseaRch F cus 15-3
The Rise and Fall of Mirror Neurons
Rizzolatti and colleagues’ discovery of mirror neurons in the 1990s was perceived as among the most important discoveries in neuroscience in
serendipitous (e.g., Rizzolatti, 2007). The group was investigating how the past generation.
neurons in the premotor cortex of macaque monkeys control grasping But by the early 2000s, cracks began to show in the mirror. Greg-
actions. The monkeys were trained to make different grasping move- ory Hickok (2014) has argued that mirror neurons do not make actions
ments to retrieve bits of food. When the animals reached for the food, understandable, but they do refine movement control. Hickok and others
cells in the premotor cortex were highly active, revealing their role in suggest that mirror neurons do not “understand” action, but rather their
movement control. function arises from an association between executing an action and the
Between reaching trials the monkeys could observe an investigator self-observation of the action.
making reaching movements similar to those the monkey had made. Thus, the neurons learn to mirror. But why? What is the benefit?
Unexpectedly, many of the same neurons fired in response to the mon- One possibility is that because the actions of others are relevant to one’s
keys observing the experimenter’s reaching: the cells appeared to mirror own actions, having a system to link others’ perceived actions with one’s
others’ behavior. The name mirror neurons stuck. Studies using non- own appropriate actions is adaptive. An extension of this idea is that
invasive imaging demonstrated similar neuronal populations, although mirror neurons are activated after an action is understood by other
apparently more widespread, in humans. brain regions as a way to make predictions about future actions (Hickok,
Over the ensuing decade, mirror neurons were hypothesized to 2013). In this view, mirror neurons simply reflect the fact that the brain
be the basis of understanding actions rather than merely recognizing understands actions (Csibra, 2007). The advantage of this type of mirror
them. This possibility had profound implications and led to propositions system is that with this knowledge we can make movements faster and
that mirror neurons were the basis of speech and language, empathy, more accurately.
social cognition, theory of mind—even civilization! Dysfunction of the The lessons from the rise and fall of mirror neurons: First, although
mirror neuron system was proposed as a basis for disorders such as the mirror neuron theory of functioning to understand action may be
the broken mirror hypothesis of autism (Ramachandran & Oberman, wrong, it has served the field well by stimulating new research. That
2006). research has led to better understanding of how the brain thinks. A
The lure of mirror neurons spread well beyond neuroscience and into second lesson is vigilance: some scientists and media can push scientific
the popular media. All the hype resulted in mirror neurons being widely theories well beyond the data.
15-2 review
Cognition and the Association Cortex
Before you continue, check your understanding.
1. The association cortex contains and functions to produce .
2. As a general rule, the lobes generate knowledge about objects, whereas
the lobes produce various forms of spatial cognition.
3. The frontal lobes function not only to make movements but also to and to
.
15-3 • Expanding Frontiers of Cognitive Neuroscience 533
4. neurons in the frontal and parietal lobes represent actions, one’s own or
those of others.
5. Describe the function of multimodal cortex.
Answers appear at the back of the book.
For additional study tools, visit LaunchPad:
www.macmillanhighered.com/launchpad/kolb5e
15-3 Expanding Frontiers of
Cognitive Neuroscience
Sophisticated noninvasive stimulation and recording techniques for measuring the brain’s
electrical activity and noninvasive brain imaging methods led to a major shift in studying
cognitive neuroscience Study of the neural
brain and behavior: cognitive neuroscience, the field that studies the neural bases of cogni-
bases of cognition.
tion. Cognitive neuroscience focuses on high-tech research methods but continues to rely
on the decidedly low-tech tools of neuropsychological assessment—behavioral tests that com-
pare the effects of brain injuries on performing particular tasks. Clinical Focus 15-4, Neuro-
psychological Assessment, illustrates its benefits.
clinical F cus 15-4
Neuropsychological Assessment
In this high-tech age of PET, fMRI, and ERP, low-tech behavioral assess- Card Sorting Test, which assesses abstract reasoning (see Figure 15-8).
ment endures as among the best, simplest, most economical ways to Finally, all were given a reading test.
measure cognitive function. The first patient, J. N., was a 28-year-old man who had developed a
To illustrate the nature and power of neuropsychological assess- tumor in the anterior and medial left temporal lobe. His preoperative psy-
ment, we compare three patients’ test performance on an array of tests chological tests showed superior intelligence scores. His only significant
selected from among those used in a complete neuropsychological deficits appeared on tests of verbal memory.
assessment. The five tests presented here measure verbal and visual When we saw J. N. a year after surgery that successfully removed
memory, verbal fluency, abstract reasoning, and reading. Performance the tumor, he had returned to his job as a personnel manager. His intel-
was compared with that of a healthy control participant. ligence was still superior, but as the score summary shows, he was
In the delayed memory tests—one verbal, the other visual—the impaired on the delayed verbal memory test, recalling only about 50
patients and the control were read a list of words and two short stories. percent as much as the control and other subjects.
They were also shown a series of simple drawings. Their task: repeat The second patient, E. B., was a college senior majoring in psychol-
the words and stories immediately after hearing them and draw the ogy. An aneurysm in her right temporal lobe had burst due to a bulge in
simple figures. the artery. The anterior part of that lobe had been removed. E. B. was of
Half an hour later, without warning, they were asked to perform the above-average intelligence and completed her undergraduate degree with
tasks again. Their performance on these tests yielded the delayed verbal good grades. Her score on the delayed visual memory test, just over half
and visual memory scores listed in the table. the scores of the other test-takers, clearly showed her residual deficit.
In the delayed verbal fluency test, patients and control had 5 minutes The third patient, also of above-average intelligence, was J. W., a
to write down as many words as they could think of that start with the let- 42-year-old police detective who had a college degree. A benign tumor
ter s, excluding numbers and people’s names. Then came the Wisconsin had been removed from his left frontal lobe.
We saw J. W. 10 years after his surgery. He was still on the police
force but working a desk job. His verbal fluency was markedly reduced,
Subjects’ Scores as was his ability to solve the card-sorting task. His reading skill, how-
ever, was unimpaired. This was also true of the other patients.
test control J. N. e. B. J. w.
Two principles emerge from the results of these three neuropsycho-
Delayed verbal memory 17 9* 16 16 logical assessments:
Delayed visual memory 12 14 8* 12
1. Brain functions are localized. Damage to different brain regions pro-
Verbal fluency 62 62 66 35* duces different symptoms.
Card-sorting errors 9 10 12 56* 2. Brain organization is asymmetrical. Left-hemisphere damage prefer-
Reading 15 21 22 17 entially affects verbal functions; right-hemisphere damage preferen-
*Atypically poor score. tially affects nonverbal functions.
534 Chapter 15 • HOW DOES THE BRAIN THINK?
Sophisticated imaging techniques are helping cognitive neuroscientists map the human
brain. Its methods assist social psychologists in discovering how the brain mediates social
interactions and economists in discovering how the brain makes decisions.
Mapping the Brain
Among the great scientific challenges of the twenty-first century, mapping the human
brain connectome may be the most intriguing. Toward this end, the U.S. National Institutes
of Health (NIH) awarded grants totaling $40 million to map the complete structural and
functional fiber pathway connections of the human brain in vivo. Researchers participating
in the Human Connectome Project (HCP) are combining diffusion tensor imaging (DTI) and
functional connectivity magnetic resonance imaging (fcMRI) to plot these connections in
the living human brain. By the end of 2015 HCP investigators had completed scanning 1200
healthy adults’ brains, including 300 twin pairs.
The HCP’s goal is to provide a reference atlas for those seeking to understand human
For more on the HCP, including brain function and dysfunction. It has attracted considerable public interest, and an explo-
connectome images, go to sion of studies outside the HCP also seeks to map the human brain. For example, in a review,
www.humanconnectomeproject.org. Roser Sala-Llonch and colleagues (2015) report that as people age, they show reduced func-
National Geographic published an accessible tional connectivity compared to young adults. The investigators hypothesize that this find-
article in February 2014. ing could explain age-related cognitive changes.
Using fMRI in Brain Mapping
The fcMRI technique uses resting-state fMRI (rs-fMRI) to measure functional correlations
between brain regions. Pooling rs-fMRI data across thousands of healthy young adults makes
it possible to identify consistent patterns of connectivity, or nerve tracts, in the brain. Utiliz-
ing rs-fMRI data from 1000 participants, Thomas Yeo and colleagues (2011) parcellated the
human cerebral cortex into the 17 networks illustrated in Figure 15-9.
The cerebral cortex is made up of primary sensory and motor networks as well as the mul-
tiple, large-scale networks that form the association cortex. The sensory and motor networks
are largely local: adjacent areas tend to show strong functional coupling with one another.
In Figure 15-9, the turquoise and blue/gray regions in somatosensory and motor cortex and
the purple region in visual cortex illustrate these couplings.
In contrast, the association networks include areas distributed throughout the prefron-
tal, parietal, anterior temporal, and midline regions. In Figure 15-9, the distributed yellow
regions show prefrontal–posterior parietal connectivity. Some distributed networks, shown
in light red, include temporal, posterior parietal, and prefrontal regions.
Unlike DTI, fcMRI does not measure static anatomical connectivity but rather uses tem-
poral (time-based) correlations between neurophysiological activities in different regions to
infer functional connectivity. One obvious direction of investigations based on fcMRI is
searching for individual phenotypic variations. Such mapping will allow examination of
FiGUre 15-9 Parcellation of Cerebral
Cortical Networks An estimate
of 17 cortical networks based on fcMRI
data from 1000 participants. Each color
represents a network. Some, such as the
blue auditory areas in temporal lobe, are
localized; others are widely distributed,
such as the yellow regions, which reveal
prefrontal–posterior parietal connectivity.
Republished with permission of the American
Physiological Society from B. T. T. Yeo, F. M. Fienen,
J. Sepulcre, M. R. Sabuncu, D. Lashkari, et al., “The
Organization of the Human Cerebral Cortex Estimated
by Intrinsic Functional Connectivity,” 2011, Journal of
Neurophysiology, 106, pp. 1125–1165. Permission conveyed
through Copyright Clearance Center, Inc. Left hemisphere, lateral view Left hemisphere, Medial view
15-3 • Expanding Frontiers of Cognitive Neuroscience 535
specific traits (e.g., musical ability) or psychiatric diagnoses (see the review by Kelly and col-
brain connectome Map of the complete
leagues, 2012).
structural and functional fiber pathways of the
Tractography Using Diffusion Tensor Imaging human brain in vivo.
DTI studies provide results, often called tractography, that complement the networks mapped hyperconnectivity Increased local
by fcMRI. Tractography measures actual neuroanatomical pathways that can be related to connections between two related brain
specific traits. Traditional postmortem tract tracing was performed on single brains. Today, regions.
tractography can be performed quickly on many living brains, and measurements can be
made simultaneously in the entire brain. This advance allows researchers to correlate spe-
cific behavioral traits with specific patterns of connectivity.
Psyche Loui and her colleagues (2011) were interested in the neural basis of perfect (or
absolute) pitch, the ability not only to discriminate among musical notes but also to name any
note heard. Perfect pitch is rare among humans but shared by people with remarkable musi-
cal talents. Think Mozart. Development of perfect pitch is sensitive to early experiences,
including musical training and exposure to tonal languages such as Japanese.
Loui’s team studied musicians, with and without absolute pitch, who were matched in
gender, age, handedness, ethnicity, IQ score, and years of musical training. Participants
were given a test of pitch-labeling that allowed the researchers to place the musicians
with absolute pitch into two categories: more accurate and less accurate. The less accu-
rate group was superior to participants without absolute pitch, who could not accurately
identify the note.
The investigators hypothesized that absolute pitch could be related to increased con-
nectivity in brain regions that process sounds. They used DTI to reconstruct white-matter
tracts connecting two temporal cortex regions involved in auditory processing, the superior
and middle temporal gyri, and regions not involved in auditory processing (corticospinal
tract). The results, reproduced in Figure 15-10, show that people with absolute pitch have
greater connectivity in temporal lobe regions responsible for pitch perception than do people
without it. The effect is largest in people in the more accurate group.
Although enhanced connectivity appears in both hemispheres of the musicians, when
the investigators correlated performance on a test of absolute pitch with tract volume,
only left-hemisphere tract volume predicted performance. It appears that having more
local connections, or hyperconnectivity, in the left hemisphere is responsible for absolute
pitch.
It is tempting to speculate that other exceptional talents, such as creativity, might be
related to hyperconnectivity in cerebral regions. Conversely, we can speculate that reduced
structural and functional connectivity is related to cognitive impairments after acquired
brain injuries and/or neurodevelopmental and psychiatric disorders.
Cognition and the Cerebellum FiGUre 15-10 Tractography of
Temporal Lobe Auditory
So far we have emphasized the role of the neocortex in cognitive functions, in part because Circuits Color overlaid on DTI images
of its marked expansion in size and neuron numbers in primate brains. Yet the human demonstrates tracts between the superior
temporal gyrus and middle temporal gyrus
in three individuals. Participants A and
B had more accurate and less accurate
(A) More accurate perfect pitch (B) Less accurate perfect pitch (C) Lacking perfect pitch
perfect pitch, respectively; Case C did
not. The tracts that connect the regions
in the left hemisphere (orange) are larger
in participants A and B than in C. Tracts
colored purple connect the regions in the
right hemisphere. Copyright © 2011, Massachusetts
Institute of Technology. Loui, P., Li, H. C., Hohmann, A.,
& Schlaug, G. (2011). Enhanced Connectivity in Absolute
Pitch Musicians: A Model of Hyperconnectivity. Journal
Left Right Left Right Left Right of Cognitive Neuroscience 23(4), 1015-1026. Permission
hemisphere hemisphere hemisphere hemisphere hemisphere hemisphere conveyed through Copyright Clearance Center, Inc.
536 Chapter 15 • HOW DOES THE BRAIN THINK?
Research Focus 2-1 describes the effects of cerebellum accounts for 80 percent of the brain’s neurons. The cerebellum has long been
cerebellar agenesis. known to play a central role in motor control and motor learning, but the concurrent evolu-
tion of neocortex, cerebellum, and cognitive complexity in primates suggests that the cer-
ebellum may play a larger role in cognitive processes than investigators have appreciated
(e.g., Barton, 2012).
The extensive neocortex–cerebellum interconnections include prefrontal cortex, Broca’s
area, and neocortical regions that have sensory or perceptual functions. Thus, the cerebel-
lum appears to be critical in producing fine movements and perception, but some executive
function also may be associated with working memory, attention, language, music, and deci-
sion-making processes (Bauman et al., 2015). No single coherent model of cerebellar activity
in cognition has emerged, partly because researchers interested in cognitive functions have
neglected the cerebellum for decades. Undoubtedly, the coming decade will deliver an abun-
dance of new information, allowing for a better- informed model of cerebellar functions in
cognition.
Social Neuroscience
By combining cognitive neuroscience tools, especially functional neuroimaging, with
social neuroscience Interdisciplinary field
abstract constructs from social psychology, social neuroscience seeks to understand how
that seeks to understand how the brain
the brain mediates social interactions. Matthew Lieberman (2007) identified broad themes
mediates social interactions.
that attempt to encompass all cognitive processes involved in understanding and interacting
theory of mind Ability to attribute mental
with others and in understanding ourselves.
states to others.
Understanding Others
Animals’ mind and experiences are not open to direct inspection. We infer animals’ mind
in part by observing their behaviors and peoples’ mind by listening to their words. In doing
so, we may develop a theory of mind, the attribution of mental states to others. Theory of
mind includes an understanding that others may have feelings and beliefs different from our
own. This broader understanding has led some investigators to conclude that theory of mind
may be uniquely human. But many researchers who study apes strongly believe that other
apes, too, possess a theory of mind.
Many fMRI studies over the past decade suggest that the brain region believed most
closely associated with theory of mind is the dorsolateral prefrontal cortex (see Figure 15-2).
Human prefrontal regions are disproportionately large as cor-
rected for brain size, but other apes also have large prefrontal
regions. The anatomy supports the likelihood that they also
possess a theory of mind.
The capacity to understand others can also be inferred
from the presence of empathy. For example, when partici-
pants watch videos of others smelling disgusting odors, they
report a feeling of disgust. Lieberman and his colleagues
(Rameson et al., 2012) used fMRI to assess the neural cor-
relates of empathy by asking participants to empathize with
sad images. Empathy correlated with increased activity in the
medial prefrontal region, suggesting that the area is critical
for empathic experience.
the povinelli group llC
Understanding Oneself
Not only are we humans aware of others’ intentions, we also
have a sense of self. Humans and apes have the ability to rec-
ognize themselves in a mirror, an ability that human infants
Looking at its reflection and pointing to a dot placed on its forehead, this chimpanzee demonstrate by about 21 months of age. Studies using fMRI
displays self-recognition, a cognitive ability possessed by higher primates. show that when we recognize our own face versus the face of
15-3 • Expanding Frontiers of Cognitive Neuroscience 537
familiar others, brain activity increases in the right lateral prefrontal cortex and in the lateral
parietal cortex. The parietal cortex activation is thought to reflect the body’s recognition of
what itself feels like.
But self-recognition is only the beginning of understanding oneself. People also have a
self-concept that includes beliefs about their own personal traits (e.g., kind, intelligent). When
participants are asked to determine whether trait words or sentences are self- descriptive,
brain activity in medial prefrontal regions increases.
Self-Regulation
Self-regulation is the ability to control emotions and impulses as a means of achieving long-
term goals. We may wish to yell at the professor because an exam was unfair, but most of us
recognize that this course will not be productive. Dynamic imaging studies again reveal that
prefrontal regions are critical in social cognition, in this case in self-regulation.
Children are often poor self-regulators, which probably reflects slow development of the Section 8-2 describes unique aspects of
prefrontal regions responsible for impulse control. A uniquely human ability to self-regulate frontal lobe development that extend beyond
is by putting feelings into words, a strategy that allows us to control emotional outbursts. childhood—up to age 30.
Curiously, such verbal labeling is associated with increased activity in the right lateral pre-
frontal regions but not in the left.
Not only can humans control their emotions; they also have expectations about how
a stimulus might feel (e.g., an injection by syringe). Our expectations can alter the actual
feeling of an event. It is common for people to say ouch when they do something like stub
a toe, even if they actually feel no pain. Nobukatsu Sawamoto and colleagues (2000) found
that when participants expect pain, activity increases in the anterior cingulate cortex (see Feeling and treating physical pain is a topic in
Figure 15-2B), a region associated with pain perception, even if the stimulus turns out not Section 11-4. Focus 12-1 reports on emotional
to be painful. pain.
Living in a Social World
We spend much of our waking time interacting with others socially. In a sense, our under-
standing of our self and our social interactions link together into a single mental action. One
important aspect of this behavior includes forming attitudes and beliefs about ourselves
and about others. When we express attitudes (including prejudices) toward ideas or human
groups, brain imaging shows activation in prefrontal, anterior cingulate, and lateral parietal
regions.
Samuel McLure and colleagues (2004) took advantage of the fact that many people have
strong attitudes toward cola-flavored sodas. Coca-Cola and Pepsi Cola are nearly identical
in chemical composition, yet subjectively, people routinely prefer one to the other. The
researchers ran blind taste tests among people who stated a cola brand preference.
As a group, participants failed to discriminate the drinks accurately when they were pre-
sented in a blind taste test. Brain activity was also equivalent for each cola in the blind con-
dition. However, when participants believed that they were drinking Coca-Cola, significant
changes in brain activity were recorded in many regions, including the hippocampus and
dorsolateral prefrontal cortex. The investigators concluded that cultural information biases
brain systems, which in turn biases attitudes.
Social Cognition and Brain Activity
Social cognitions running the gamut from understanding ourselves to understanding others
clearly are associated with activation of specific brain regions, especially prefrontal regions.
The obvious conclusion is that prefrontal activity produces our social cognitions, just as
activity in visual regions produces our visual perceptions. But this conclusion has proved
controversial. Ed Vul and colleagues (2009, 2012) go so far as to suggest that “correlations in
social neuroscience are voodoo.” Their assertion has led to strong disputations (e.g., Lieber-
man et al., 2012). The arguments are complex, focus on the nature of the analysis of fMRI
538 Chapter 15 • HOW DOES THE BRAIN THINK?
data, and will certainly continue. In our view, the debate does not impugn the general con-
clusion that brain states produce behavioral states.
Neuroeconomics
Historically, economics was a discipline based on the “rational actor,” the belief that
Leonard Mlodinow’s wonderful 2009 book, people make rational decisions. In the real world, people often make decisions based on
The Drunkard’s Walk: How Randomness Rules assumption or intuition, as is common in gambling. Why don’t people always make rational
Our Lives, offers many everyday examples. decisions?
The cerebral processes underlying human decision making are not easily inferred from
behavioral studies. But investigators in the field of neuroeconomics, which combines ideas
from economics, psychology, and neuroscience, attempt to explain those processes by study-
ing patterns of brain activity as people make decisions in real time. The general assumption
among neuroeconomists is that two neural decision pathways influence our choices. One is
deliberate, slow, rule-driven, and emotionally neutral; it acts as a reflective system. The other
pathway—fast, automatic, emotionally biased—forms a reflexive system.
If people must make quick decisions they believe will provide immediate gain, widespread
Figure 6-17 maps the dopaminergic pathways activity appears in the dopaminergic reward system. This includes the ventromedial prefron-
associated with reward. tal cortex and ventral striatum (nucleus accumbens): the reflexive pathway. If slower, delib-
erative decisions are possible, activity is greater in the lateral prefrontal, medial temporal,
and posterior parietal cortex, the areas that form the reflective pathway.
Neuroeconomists are looking to identify patterns of neural activity in everyday decision
making, patterns that may help account for how people make decisions about their finances,
social relations, and other personal choices. Although most neuroeconomic studies to date
have used fMRI, in principle these studies could also use other noninvasive imaging technol-
ogies. Epigenetic factors probably contribute to developing the balance between the reflec-
tive and reflexive systems in individuals. Epigenetic studies therefore may help explain why
many people make decisions that are not in their long-term best interest.
neuroeconomics Interdisciplinary field that Because of predictions that all mammals will have similar reflective and reflexive decision
seeks to understand how the brain makes systems and because all animals make decisions, the neural bases of decision processes in
decisions. nonhumans undoubtedly will receive more study in the future.
15-3 review
Expanding Frontiers of Cognitive Neuroscience
Before you continue, check your understanding.
1. Noninvasive imaging techniques enable cognitive psychologists to investigate the neural
bases of thought in the “normal” brain, leading to the field called .
2. Imaging methods such as DTI and fcMRI are allowing researchers to develop a
, a map of the complete structural and functional fiber pathway connections
in the living human brain.
3. The role of the in cognition, formerly unappreciated, is now attracting
researchers’ attention.
4. Social neuroscience is an interdisciplinary field that seeks to understand how the brain
mediates .
5. Our attribution of mental states to others is known as .
6. Neuroeconomics seeks to understand the neural bases of .
7. List four general themes of social neuroscience research.
Answers appear at the back of the book.
For additional study tools, visit LaunchPad:
www.macmillanhighered.com/launchpad/kolb5e
15-4 • Cerebral Asymmetry in Thinking 539
15-4 Cerebral Asymmetry
in Thinking
Fundamental to behavioral neuroscience was the finding by Paul Broca and his contempo-
raries in the mid-1800s that language is lateralized to the brain’s left hemisphere. But the
implications of lateralized brain functions were not really understood until the 1960s, when
Roger Sperry (1968) and his colleagues began to study people who, as described in Research Seizing on Sperry’s findings, the 1980s saw
Focus 15-1, had undergone surgical separation of the two hemispheres as a treatment for an avalanche of self-help books about “left-
intractable epilepsy. It soon became apparent that the cerebral hemispheres are more func- brained” and “right-brained” people. The
tionally specialized than researchers had previously realized. Before considering how the novelty wore off, but cerebral asymmetry
brain’s two sides cooperate in generating cognitive activity, we look at the anatomical differ- remains important to understanding how the
ences between the left and right hemispheres. human brain thinks.
Anatomical Asymmetry
Building on Broca’s findings, investigators have learned how the language- and music-related
areas of the left and right temporal lobes differ anatomically. In particular, the primary audi-
tory area is larger on the right, whereas the secondary auditory areas are larger on the left in
most people. Other brain regions also are asymmetrical.
Figure 15-11 shows that the lateral fissure, which partly separates the temporal and pari-
etal lobes, has a sharper upward course in the right hemisphere relative to the left. As a
result, the posterior right temporal lobe is larger than the same region on the left, as is the
left parietal lobe relative to the right.
Among the anatomical asymmetries in the frontal lobes, the region of sensorimotor cor-
tex representing the face is larger in the left hemisphere than in the right, a difference that
presumably corresponds to the left hemisphere’s special role in talking. Broca’s area is orga-
nized differently on the left and the right. The area visible on the brain’s surface is about
one-third larger on the right than on the left, whereas the cortical area buried in the sulci of
Broca’s area is greater on the left than on the right.
Not only do these gross anatomical differences exist but so too do hemispheric differences
in the details of their cellular and neurochemical structures. For example, neurons in Broca’s
area on the left have larger dendritic fields than do corresponding neurons on the right. The
discovery of structural asymmetries told us little about the reasons for such differences, but
ongoing research is revealing that they result from underlying differences in cognitive pro-
cessing by the brain’s two sides.
Although many anatomical asymmetries in the human brain are related to language,
brain asymmetries are not unique to humans. Most if not all mammals have asymmetries,
as do many bird species. The functions of cerebral asymmetry therefore cannot be limited
to language processing. Rather, human language likely evolved after the brain became asym-
metrical. Language simply took advantage of processes, including the development of mirror
neurons, that had already been lateralized by natural selection in earlier members of the
human lineage.
Lateral fissure
Parietal
lobe FiGUre 15-11 Cerebral
Asymmetry The lateral fissure takes
a flatter course in the left hemisphere
than in the right. As a result, the posterior
Temporal right temporal lobe is larger than the same
lobe region on the left side, and the inferior
parietal region is larger on the left than on
Left hemisphere Right hemisphere the right.
540 Chapter 15 • HOW DOES THE BRAIN THINK?
Functional Asymmetry in Neurological
Patients
The specialized functions of the cerebral hemispheres become obvious in people with dam-
age to the left or right side of the brain. To see these functional differences clearly, compare
the cases of G. H. and M. M.
Right Parietal Damage
When G. H. was 5 years old, as he was hiking with his family, a large rock rolled off an
embankment and hit him on the head. He was unconscious for a few minutes and had a
severe headache for a few days but quickly recovered. Around age 18, however, he started
having seizures. Neurosurgical investigation revealed that G. H. had had a right posterior
parietal injury from the rock accident. Figure 15-12A shows the area affected. After surgery
to remove this area, G. H. had weakness on the left side of his body and showed contralateral
neglect. But these symptoms lessened fairly quickly, and a month after the surgery, they had
completely cleared.
Nevertheless, G. H. had chronic difficulties in copying drawings; 4 years later, he still
performed this task at about the level of a 6-year-old. He also had trouble assembling puzzles,
a pastime he enjoyed before his surgery. When asked to perform mental manipulations like
the one in Figure 15-6, he became very frustrated and refused to continue. G. H. also had
difficulty finding his way around familiar places. The landmarks he had used to guide his
travels before the surgery no longer worked for him. G. H. now has to learn street names and
use a verbal strategy to go from one place to another.
FiGUre 15-12 Contrasting Parietal (A) Participant G. H. (B) Participant M. M.
Lobe Injuries Injury to this area of the right Injury to this area of the left
hemisphere caused difficulties hemisphere caused difficulties in
in copying drawings, language, copying movements,
assembling puzzles, and finding reading, and generating names
the way around a familiar city. of objects or animals.
Left Parietal Damage
M. M.’s difficulties were quite different. A meningioma had placed considerable pressure on
Meningioma is imaged in Focus 3-3. the left parietal region. The tumor was surgically removed when M. M. was 16 years old. It
had damaged the area shown in Figure 15-12B.
After the surgery, M. M. had various problems, including aphasia, impaired language use.
The condition lessened over time: a year after the surgery, M. M. spoke fluently. Unfortu-
nately, other difficulties persisted. In solving arithmetic problems, in reading, and even in
simply calling objects or animals by name, M. M. performed at about a 6-year-old level. She
had no difficulty making movements spontaneously, but when asked to copy a series of arm
Section 10-4 describes how left-hemisphere movements, such as those diagrammed in Figure 15-13, she had great difficulty. She could
damage causes aphasias. Section 11-5 not figure out how to make her arm move to match the example. A general impairment in
explains how somatosensory cortex damage making voluntary movements in the absence of paralysis or a muscular disorder is a symptom
contributes to apraxia. of apraxia, the inability to complete a plan of action accurately.
15-4 • Cerebral Asymmetry in Thinking 541
Series 1 Two Arm Movement
FigurE 15-13
Series Subjects observe the tester
perform each sequence, then copy it
as accurately as they can. People with
left-hemisphere injury, especially in the
posterior parietal region, are impaired at
copying such movements.
Series 2
Lessons from Patients G. H. and M. M.
What can we learn about brain function by comparing G. H. and M. M.? Their lesions were
in approximately the same location but in opposite hemispheres, and their symptoms were
very different.
Judging from G. H.’s difficulties, the right hemisphere contributes to controlling spatial
skills, such as drawing, assembling puzzles, and navigating in space. In contrast, M. M.’s con-
dition reveals that the left hemisphere seems to contribute to controlling language functions
and cognitive tasks related to schoolwork—namely, reading and arithmetic. In addition, the
left hemisphere’s role in controlling voluntary movement sequences differs from the right
hemisphere’s role.
To some extent, then, the left and right hemispheres think about different types of informa-
tion. The question is whether these functional differences can be observed in a healthy brain.
Functional Asymmetry in the Healthy Brain
In the course of studying the auditory capacity of people with a temporal lobe lesion, Doreen
dichotic listening Experimental procedure
Kimura (1967) found something unexpected. She presented her control participants with two
for simultaneously presenting a different
strings of digits, one played into each ear, a procedure known as dichotic listening. The task
auditory input to each ear through
was to recall as many digits as possible. stereophonic earphones.
Kimura found that the controls recalled more digits presented to the right ear than to the
left. This result is surprising because the auditory system crosses repeatedly, beginning in
the midbrain. Nonetheless, information coming from the right ear seems to have preferential
access to the left (speaking) hemisphere.
In a later study, Kimura (1973) played two pieces of music for participants, one to each
ear. She then gave the participants a multiple-choice test, playing four bits from musical
selections and asking the participants to pick out the bits they had heard before. In this test,
she found that participants were more likely to recall the music played to the left ear than
to the right. This result implies that the left ear has preferential access to the right (musical)
hemisphere.
The demonstration of this functional asymmetry in the healthy brain provoked much
interest in the 1970s, leading to demonstrations of functional asymmetries in the visual
and tactile systems as well. Consider the visual system. If we fixate on a target, such as a
dot positioned straight ahead, all the information to the left of the dot goes to the right
542 Chapter 15 • HOW DOES THE BRAIN THINK?
hemisphere and all the information to the right of the dot goes to the left hemisphere, as
shown in Figure 15-14.
If information is presented for a relatively long time—say, 1 second—we can easily report
what was in each visual field. If, however, the presentation is brief—say, only 40 milliseconds—
then the task is considerably harder. This situation reveals a brain asymmetry.
Words presented briefly to the right visual field and hence sent to the left hemisphere
are more easily reported than are words presented briefly to the left visual field. Similarly,
if complex geometric patterns or faces are shown briefly, those presented to the left visual
field and hence sent to the right hemisphere are more accurately reported than are those
presented to the right visual field.
Apparently, the hemispheres not only think about different types of information, they
also process information differently. The left hemisphere seems biased toward processing
language-related information, whereas the right hemisphere seems biased toward processing
nonverbal, and especially spatial, information.
A word of caution: Although asymmetry studies are fascinating, what they tell us about
the differences between the hemispheres is not entirely clear. They tell us something is dif-
Those popular left brain–right brain accounts
ferent, but it is a broad leap to conclude that the hemispheres house entirely different skill
of the 1980s ignored the many functions the
sets.
hemispheres have in common.
The hemispheres have many common functions, such as controlling movement in the
contralateral hand and processing sensory information through the thalamus. Still, differ-
Fixation point ences in the hemispheres’ cognitive operations do exist. We can better understand these
Left visual field Right visual field differences by studying split-brain patients, whose cerebral hemispheres have been surgically
separated for medical treatment.
“Anne”
Functional Asymmetry in the Split Brain
Before considering the details of split-brain studies, let us review what we already know
about cerebral asymmetry. First, the left hemisphere has speech; the right hemisphere does
not. Second, as demonstrated in Research Focus 15-1, on page 520, the right hemisphere
performs better than the left on certain nonverbal tasks, especially those that engage visuo-
spatial skills.
But how does a severed corpus callosum affect how the brain thinks? After the
corpus callosum has been cut, the hemispheres have no way of communicating with
Retina Retina one another. The left and right hemispheres are therefore free to think about different
things. In a sense, a split-brain patient has two brains.
Optic One way to test the hemispheres’ cognitive functions in a split-brain patient takes
chiasm advantage of the fact that information in the left visual field goes to the right hemisphere
Left Right and information in the right field goes to the left hemisphere (see Figure 15-14). With the
hemisphere hemisphere corpus callosum cut, however, information presented to one side of the brain has no way
of traveling to the other side. It can be processed only in the hemisphere that receives it.
Experiments 15-3 and 15-4 show some basic testing procedures based on this dichot-
“Anne”
omy. The split-brain subject fixates on the dot in the center of the screen while informa-
tion is presented to the left or right visual field. The person must respond with the left
Corpus callosum
hand (controlled by the right hemisphere), with the right hand (controlled by the left
FigurE 15-14 Visual Pathways to the hemisphere), or verbally (also a left-hemisphere function). In this way, researchers can
Hemispheres When fixating at a point, each observe what each hemisphere knows and what it is capable of doing.
eye sees both visual fields but sends information As illustrated in Experiment 15-3, for instance, a picture—say, of a spoon—might be
about the right visual field only to the left
flashed and the subject asked to state what he or she sees. If the picture is presented to
hemisphere. Information about the left visual field
proceeds only to the right hemisphere. In healthy the right visual field, the person will answer, “Spoon.” If the picture is presented to the
participants given short exposures to stimuli left visual field, however, the person will say, “I see nothing.” The subject responds in
(well under 1 second), the left hemisphere is this way for two reasons:
more accurate at perceiving words, whereas the
1. The right hemisphere (which receives the visual input) does not talk, so it cannot
right hemisphere is more accurate at perceiving
objects, including faces. respond verbally, even though it sees the spoon in the left visual field.
15-4 • Cerebral Asymmetry in Thinking 543
2. The left hemisphere does talk, but it does not see the spoon, so it ExpErimEnt 15-3
answers—quite correctly, from its own perspective—that nothing was
Question: Will severing the corpus callosum affect the way
presented.
in which the brain responds?
Now suppose the task changes. In Experiment 15-4A, the picture of a
spoon is still presented to the left visual field, but the subject is asked to use Procedure
the left hand to pick out the object shown on the screen. In this case, the The split-brain subject fixates on the dot in the center of
left hand, controlled by the right hemisphere, which sees the spoon, read- the screen while an image is projected to the left or right
ily picks out the correct object. Can the right hand also choose correctly? visual field. He is asked to identify verbally what he sees.
No, because it is controlled by the left hemisphere, which cannot see the Projector
Screen
spoon. If the person in this situation is forced to select an object with the
right hand, the left hemisphere does so at random.
Now let’s consider an interesting twist. In the Procedure for Experi-
ment 15-4B, each hemisphere is shown a different object—say, a spoon to
the right hemisphere and a pencil to the left. The subject is asked to use
both hands to pick out “the object.” The problem here is that the right and
left hands do not agree. While the left hand tries to pick up the spoon, the
right hand tries to pick up the pencil or tries to prevent the left hand from
picking up the spoon.
This conflict between the hemispheres can be seen in the everyday
behavior of some split-brain subjects. One woman, P. O. V., reported fre- Results
quent interhemispheric competition for at least 3 years after her surgery. “I If the spoon is presented If the spoon is presented
open the closet door. I know what I want to wear. But as I reach for some- to the right visual field, to the left visual field, the
the subject answers, subject answers, “I see
thing with my right hand, my left comes up and takes something different.
“Spoon.” nothing.”
I can’t put it down if it’s in my left hand. I have to call my daughter.”
Left visual field Right visual field Left visual field Right visual field
We know from Experiment 15-3 that the left hemisphere is capable of
using language, and Research Focus 15-1 reveals that the right hemisphere
has visuospatial capabilities that the left hemisphere does not. Although
findings from half a century of studying split-brain patients show that the
hemispheres process information differently, another word of caution is
needed. There is more functional overlap between the hemispheres than
was at first suspected. The right hemisphere, for instance, does have some
language functions, and the left hemisphere does have some spatial abili-
ties. Nonetheless, the two undoubtedly are different.
Explaining Cerebral Asymmetry
Various hypotheses propose to explain hemispheric differences. One idea,
that the left hemisphere is important in controlling fine movements, dates
back a century. Recall M. M., the meningioma patient with left parietal
lobe damage and apraxia (see Figure 15-12B). Although the apraxia sub-
Severed corpus callosum
sided, she was left with chronic trouble in copying movements.
Perhaps one reason that the left hemisphere has a role in language is Conclusion: When the left hemisphere, which can speak,
that speaking requires fine motor movements of the mouth and tongue. sees the spoon in the right visual field, the subject responds
Significantly, damage to the language-related areas of the left hemisphere correctly. When the right hemisphere, which cannot speak,
sees the spoon in the left visual field, the subject does not
almost always interferes with both language and movement, whether the
respond.
person speaks or signs. Reading Braille, however, may not be so affected
by left-hemisphere lesions. Most people prefer to use the left hand to read
Braille, which essentially consists of spatial patterns, so processes related
to reading Braille may reside in the right hemisphere.
That said, another clue that the left hemisphere’s specialization for language may be h ou s e
related to its special role in controlling fine movements comes from investigating where
the brain processes certain parts of speech. Recall that cognitive systems for represent- Braille
ing abstract concepts likely are related to systems that produce more concrete behaviors.
ExpErimEnt 15-4
(A) Question: How can the right hemisphere of a split-brain (B) Question: What happens if both hemispheres are asked to
subject show that it knows information? respond to competing information?
Procedure Procedure
The split-brain participant is asked to use his left hand to pick out the Each visual field is shown a different object—a spoon to the left
object shown on the screen to the left visual field (right hemisphere). and a pencil to the right. The split-brain participant is asked to use
both hands to pick up the object seen.
Results Results
The participant chooses the spoon with his left hand because the In this case, the right and left hands do not agree. They may each
right hemisphere sees the spoon and controls the left hand. If the pick up a different object, or the right hand may prevent the left
right hand is forced to choose, it will do so by chance because no hand from performing the task.
stimulus is shown to the left hemisphere.
Left visual field Right visual field Left visual field Right visual field
Severed Severed
corpus callosum corpus callosum
Conclusion: Each hemisphere is capable of responding independently. The left hemisphere
may dominate in a competition, even if the response is not verbal.
Consequently, we might expect that the left hemisphere would participate in forming con-
cepts related to fine movements.
Concepts that describe movements are the parts of speech we call verbs. A fundamental
difference between left- and right-hemisphere language abilities is that verbs seem to be
processed only in the left hemisphere, whereas nouns are processed in both hemispheres.
544
15-4 • Cerebral Asymmetry in Thinking 545
In other words, not only does the left hemisphere specialize in producing actions, it also
produces mental representations of actions in the form of words.
If the left hemisphere excels at language because it is better at controlling fine move-
ments, what is the basis of the right hemisphere’s abilities? One idea is that the right hemi-
sphere specializes in controlling movements in space. In a sense, this role elaborates the
functions of the dorsal visual stream (diagrammed in Figure 15-3).
Once again, we can propose a link between movement at a concrete level and movement
at a more abstract level. If the right hemisphere is producing movements in space, then it is
also likely to produce mental images of such movements. We would therefore predict impair-
ment of right-hemisphere patients’ ability both to think about and to make spatially guided
movements. And they are thus impaired.
Bear in mind that theories about the reasons for hemispheric asymmetry are highly specu-
lative. The brain has evolved to produce movement and to construct a sensory reality, so The nervous system produces movement
the observed asymmetry must somehow relate to these overriding functions. That is, more within a perceptual world the brain
recently evolved functions, such as language, likely are extensions of preexisting functions. constructs.
So the fact that language is represented asymmetrically does not mean that the brain is asym-
metrical because of language. After all, other species that do not talk have an asymmetrical
brain.
Left Hemisphere, Language, and Thought
As we end our examination of brain asymmetry, consider one more provocative idea. Michael
Gazzaniga (1992) proposed that the left hemisphere’s superior language skills are impor-
tant for understanding the differences between humans’ and other animals’ thinking. He
called the speaking hemisphere the interpreter. The following experiment, using split-brain
patients as subjects, illustrates what Gazzaniga meant.
Each hemisphere is shown a picture of a match followed by a picture of a piece of wood,
for example. Another set of pictures is then shown. The task is to pick from this set a third
picture that has an inferred relation to the first two. In this example, the third related picture
might be a bonfire. The right hemisphere is incapable of making the inference that a match
struck and held to a piece of wood could start a bonfire, whereas the left hemisphere easily
arrives at this interpretation.
An analogous task uses words. One or the other hemisphere might be shown the words
pin and finger then be asked to pick out a third word related to the other two. In this case,
the correct answer might be bleed.
The right hemisphere cannot make this connection. Although it has enough language
ability to pick out close synonyms for pin and finger (needle and thumb, respectively), it can-
not make the inference that pricking a finger with a pin will result in bleeding.
Again, the left hemisphere has no difficulty with this task. Apparently, the left hemi-
sphere’s language capability gives it a capacity for interpretation that the right hemisphere
lacks. One reason may be that language serves to label and express the computations of other
cognitive systems.
Gazzaniga goes even further. He suggests that the evolution of left-hemisphere lan-
guage abilities makes humans a “believing” species: humans can make inferences and
have beliefs about sensory events. By contrast, Alex, the African grey parrot profiled in
Comparative Focus 15-2, would not have been able to make inferences or hold beliefs
because he did not have a system analogous to our left-hemisphere language system. Alex
could use language but could not make inferences about sensory events with language.
Gazzaniga’s idea is intriguing. It implies a fundamental difference in the nature of cere-
bral asymmetry—and therefore in the nature of cognition—that exists between humans
and other animals because of the nature of human language. We return to this idea in
Section 15-7.
546 Chapter 15 • HOW DOES THE BRAIN THINK?
15-4 review
Cerebral Asymmetry in Thinking
Before you continue, check your understanding.
1. The right hemisphere plays a role in and .
2. The left hemisphere plays a role in and .
3. The split brain results from cutting apart the .
4. Why does it matter that the two cerebral hemispheres process information differently?
Answers appear at the back of the book.
For additional study tools, visit LaunchPad:
www.macmillanhighered.com/launchpad/kolb5e
15-5 Variations in Cognitive
Organization
No two brains are identical. Some differences are genetically determined; others result from
plastic changes caused, for example, by experience and learning or epigenetic factors. Some
brain differences are idiosyncratic (unique to a particular person); many others are system-
atic and common to whole categories of people. In this section, we consider two systematic
variations in brain organization, those related to sex and handedness, and one idiosyncratic
variation, the fascinating sensory phenomenon synesthesia.
Sex Differences in Cognitive Organization
The idea that men and women think differently probably originated with the first men
and women. Science backs it up. Books, including one by Doreen Kimura (1999), present
persuasive evidence for marked differences between men’s and women’s performance on
many cognitive tests. As illustrated in Figure 15-15, paper-and-pencil tests consistently
show that on average females have better verbal fluency than males do, whereas males do
better on tests of spatial reasoning. Our focus here is on how such differences relate to
the brain.
Neural Bases of Sex Differences
Considerable evidence points to sex differences, both in the brain’s gross cerebral struc-
ture and at a neuronal level. Jill Goldstein and her colleagues (2001) conducted a large
MRI study of sexual dimorphism in the human brain. They found that women have larger
volumes of dorsal prefrontal and associated paralimbic regions, whereas men have larger
volumes of more ventral prefrontal regions (Figure 15-16). (Brain size is related to body
size, and on average, male brains are bigger than female brains, so the investigators cor-
rected for size.)
Another way to measure sex differences is cortical thickness independent of volume.
Figure 15-17 shows that relative to men, women have increased cortical gray matter con-
centration in many cortical regions. Men’s gray matter concentration, by contrast, is more
uniform across the cortex. The MRI studies represented in Figures 15-16 and 15-17 thus point
to differences between men’s and women’s cortical organization.
Sex differences in neuronal structure also exist. Gonadal hormones influence the struc-
ture of neurons in the prefrontal cortices of rats (Kolb & Stewart, 1991). The cells in one pre-
frontal region, located along the midline, have larger dendritic fields (and presumably more
synapses) in males than in females, as shown in the top row of Figure 15-18 on page 548.
In contrast, the cells in the orbitofrontal region have larger dendritic fields (and presumably
more synapses) in females than in males, as shown in the bottom row. These sex differences
15-5 • Variations in Cognitive Organization 547
(A) Spatial relation–type task (C) Short-term-memory–type task
Tasks That Reliably
FigurE 15-15
Show Sex-Related Cognitive
Participants were asked Participants were asked to fill in the Differences
to draw a line to indicate empty boxes with the appropriate
waterline in tipped glass. symbols from the top row.
1 2 3 4 5 6 7 8 9
Waterline Correct
response
2 8 3 2 1 4 2 3 5 9 2 1 7 3 6
Incorrect 9 7 2 3 1 4 6 1 9 7 4 3 1 6 8
response
This response indicates no comprehension of
the concept of horizontality of fluid level. When given a larger number of boxes to fill
Males are generally more accurate at making in and a time limit, females complete from
this judgment than are females. 10 to 20 percent more items than males do.
(B) Mental rotation–type task (D) Verbal fluency–type task
Lateral view
Participants were asked to choose the Participants were asked to fill in each blank
block that could be made from a plan. to form words that make a sentence.
1. F M A J
Plan
2. C B E S
3. D I J K
a b c d
Medial view
Males are generally more accurate Females are generally faster at
than females at this task. this type of test than males are. Sex Differences in
FigurE 15-16
Brain Volume Women’s brain volume
in prefrontal and medial paralimbic regions
(orange) is significantly higher than men’s.
Men have larger relative volumes in the
are not found in rats that have had their testes or ovaries removed at birth. Presumably, sex medial and orbitofrontal cortex and the
hormones somehow change the brain’s organization and ultimately its cognitive processing. angular gyrus (green). Orange areas
Stewart and Kolb (1994) found that the presence or absence of gonadal hormones affects correspond to regions that have high levels
the brain in adulthood as well as in early development. In this study, which focused on of estrogen receptors during development,
green to regions high in androgen
how hormones affect recovery from brain damage, middle-aged female rats’ ovaries were
receptors during development. Information from
removed. On examining the brains of these rats and those of control rats some months later, J. M. Goldstein, L. J. Seidman, N. J. Horton, N. Makris,
researchers observed that the cortical neurons of the rats whose ovaries had been removed— D. N. Kennedy, et al. (2001). Normal sexual dimorphism
especially the prefrontal neurons—had undergone structural changes. The cells had grown of the adult human brain assessed by in vivo magnetic
30 percent more dendrites, and their spine density increased compared with the control rats’ resonance imaging. Cerebral Cortex 11, pp. 490–497.
cells. Clearly, gonadal hormones can affect the brain’s neuronal structure at any point in an
animal’s life.
An additional way to consider the neural
Courtesy dr. arthur toga, laboratory of neuro
basis of sex differences is to look at the effects
of cortical injury in men and women. If sex
differences exist in the neural organization of
cognitive processing, differences in the effects
FigurE 15-17 Sex Differences in Gray
of cortical injury in the two sexes should
Matter Concentration Women
appear. Doreen Kimura (1999) conducted this
imaging at uSC
show increased gray matter concentration
kind of study and showed that the pattern of in the cortical regions, shown in color
cerebral organization within each hemisphere on this MRI. Gray-shaded regions are not
may in fact differ between the sexes. Left hemisphere statistically different in males and females.
548 Chapter 15 • HOW DOES THE BRAIN THINK?
Investigating people who had a cortical stroke in adulthood, Kimura tried to match the
location and extent of injury in her male and female subjects. She found that men and
women were almost equally likely to be aphasic subsequent to left-hemisphere lesions of
some kind. But men were more likely to be aphasic and apraxic after damage to the left pos-
terior cortex, whereas women were far more likely to be aphasic and apraxic after lesions to
the left frontal cortex. These results, summarized in Figure 15-19, suggest a sex difference
in intrahemispheric organization, a conclusion supported by a later study (Figure 15-20)
using diffusion tensor analysis of brain networks in over 900 participants. The population,
comprising nearly equal numbers of each sex, showed that females have greater interhemi-
spheric connectivity, whereas males’ intrahemispheric connectivity is greater (Ingalhalikar
et al., 2013).
Evidence strongly favors a neural basis for gender identity, including transgender identity.
Section 12-5 describes the gender identity Georg Krantz and colleagues (2014) used diffusion tensor analysis to compare brain networks
spectrum. of female-to-male and male-to-female transsexuals with those of gender-typical females and
males. The imaging replicated the distinctly different pattern of hemispheric connectivity
in gender-typical females and males. The pattern of connectivity in transsexuals, however,
falls halfway between those of females and males.
That is, DTIs of the white matter microstructure of transgender females and males falls
halfway between that of gender-typical females and males. The investigators take these pat-
terns as evidence that neural white matter microstructure is influenced by the hormonal
environment during late prenatal and early postnatal brain development. This is the time,
they hypothesize, that determines gender identity. But genital differentiation is determined
earlier in development. The timing difference thus makes a genital–gender mismatch
possible.
Evolution of Sex-Related Cognitive Differences
Although gonadal hormones have taken center stage in explaining sex differences in cog-
nitive function, we are still left to question how these differences arose. To answer this
question, we must look back at human evolution. Mothers pass their genes to both sons and
daughters, and fathers do the same. Ultimately then, males and females of a species have
virtually all their genes in common.
The only way a gene can affect one sex preferentially is for the animal’s
Male rat Female rat
gonadal hormones to influence the gene’s activities. Gonadal hormones are in
turn determined by the presence or absence of the Y chromosome, which car-
ries a gene called the testes-determining factor. TDF stimulates the body to pro-
duce testes, which then manufacture androgens, which in turn influence other
Cells from medial genes’ activities.
frontal cortex Like other body organs, the brain is a potential target of natural selection.
We should therefore expect to find sex-related differences in the brain whenever
the sexes differ in the adaptive problems they have faced in their species’ evolu-
tion. Aggressive behavior is a good example. Males in most mammalian species
typically are more physically aggressive than females. This trait presumably
improved males’ reproductive success by selecting against individuals with lesser
aggressiveness. Producing higher levels of aggression entails male hormones. We
know from studies of nonhuman species that aggression is related directly to
the presence of androgens and to their effects on gene expression, both during
brain development and later in life. In this case, therefore, natural selection has
Cells from orbito-
worked on gonadal hormone levels to favor aggressiveness in males.
frontal region
FigurE 15-18 Sex Differences in Neuronal Architecture In the
frontal cortices of male and female rats, cells in the midline frontal region
(top two drawings) are more complex in males than in females, whereas the
opposite is true of the orbitofrontal region (bottom two drawings).
15-5 • Variations in Cognitive Organization 549
Area of stroke Evidence for Sex
FigurE 15-19
Differences in Cortical
Organization Apraxia and aphasia are
Broca’s Wernicke’s associated with frontal damage to the left
area area hemisphere in women and with posterior
damage in men. Information from D. Kimura (1999).
KEY Sex and Cognition, Cambridge, MA: MIT Press.
Females
Males
Apraxia Aphasia
Sex-related frequency (%)
80 80
60 60
40 40
20 20
0 0
Left frontal Left posterior Left frontal Left posterior
area area area area
Explaining sex-related differences in cognitive processes, such as language or spatial
skills, is more speculative than explaining sex-related differences in aggressive behavior.
Nevertheless, some hypotheses come to mind. We can imagine, for instance, that in the
(A) Male brain
history of mammalian evolution, males have tended to range over larger territories than
have females. This behavior requires spatial abilities, so evolution would have favored these
skills in males.
Support for this hypothesis comes from comparing spatial problem solving in males of
closely related mammalian species—species in which the males range over large territories
versus species in which the males’ range is not extensive. Pine voles, for example, have a
restricted range and no sex-related difference in range, whereas meadow voles have a range
about 20 times as large as pine voles’, and male meadow voles range more widely than the
females.
Meadow voles display far superior spatial skills to those of pine voles. A sex difference in
spatial ability among meadow voles favors males, but pine voles have no such sex difference.
The hippocampus is implicated in spatial navigation skills. Significantly, the hippocampus (B) Female brain
is larger in meadow voles than in pine voles, and it is larger in male meadow voles than in
females (Gaulin, 1992). A similar logic could help explain sex-related differences in spatial
abilities between human males and females (see Figure 15-15).
Explaining sex-related differences in language skills also is speculative. One hypothesis
holds that if males were hunters and often away from home, home-based females formed
social groups selectively favored to develop tools, one of which is language, for social inter-
actions. We might also argue that females with superior fine motor skills (such as foraging
for food and making clothing and baskets) had a selective advantage. The relation between
language and fine motor skills may have favored enhanced language capacities in females.
Although such speculations are interesting, they are not testable. We will probably never
know with certainty why sex-related differences in brain organization developed. FiGUre 15-20 Sex Differences in the
Connectome DTI analysis of brain
Handedness and Cognitive Organization networks in these dorsal views reveals
greater intrahemispheric connections in
Nearly everyone prefers one hand to the other for writing or throwing a ball. Most people males (A) and greater interhemispheric
prefer the right hand. In fact, left-handedness has historically been viewed as odd. But it connections in females (B). Image from M.
Ingalhalikar, A. Smith, D. Parker, P. D. Satterthwaite, M.
is not rare. An estimated 10 percent of the human population worldwide is left-handed.
A. Elliott, K. Ruparel, et al. (2013). Sex differences in the
This proportion represents only the number of people who write with the left hand. When structural connectome of the human brain. Proceedings
broader criteria are used to determine left-handedness, estimates range from 10 percent to of the National Academy of Sciences U S A, 111, 823–828,
30 percent of the population. Fig. 2.
550 Chapter 15 • HOW DOES THE BRAIN THINK?
clinical F cus 15-5
Sodium Amobarbital Test
Guy, a 32-year-old lawyer, had a vascular malformation over the region one to make sure that no residual drug effect lingers. In the brief
corresponding to the posterior speech zone. The malformation was period of drug action, the patient is given a series of simple tasks
beginning to cause neurological symptoms, including seizures. The ideal requiring the use of language, memory, and object recognition. To
surgical treatment was removal of the abnormal vessels. test speech, the patient is asked to name some common objects pre-
The complication with this surgery is that removing vessels sitting sented in quick succession, to count, to recite the days of the week
over the posterior speech zone poses a serious risk of permanent apha- forward and backward, and to spell simple words.
sia. Because Guy was left-handed, his speech If the injected hemisphere is nondominant
areas could be in the right hemisphere. If so, the for speech, the patient may continue to carry
surgical risk would be much lower. out the verbal tasks, although there is often a
To achieve certainty in such doubtful cases, period as long as 30 seconds during which he
Jun Wada and Ted Rasmussen (1960) pioneered or she appears confused and is silent but can
the technique of injecting sodium amobarbital, resume speech with urging. When the injected
a barbiturate, into the carotid artery to briefly hemisphere is dominant for speech, the patient
anesthetize the ipsilateral hemisphere. (Injec- typically stops talking and remains completely
tions are now usually made through a catheter aphasic until recovery from the anesthesia is well
inserted into the femoral artery.) The procedure along, somewhere in the range of 4 to 10 minutes.
enables an unequivocal localization of speech Guy was found to have speech in the left hemi-
because injection into the speech hemisphere sphere. During the test of his left hemisphere, he
results in speech arrest lasting as long as sev- Left carotid
could not talk. Later, he said that when he was
artery
eral minutes. As speech returns, it is character- asked about a particular object, he wondered
Sodium
ized by aphasic errors. just what the question meant. When he finally
amobarbital
Injection into the nonspeaking hemisphere had some vague idea, he had no idea of what the
may produce no or only brief speech arrest. answer was or how to say anything. By then he
The amobarbital procedure has the advantage realized that he had been asked all sorts of other
of allowing each hemisphere to be studied sepa- questions to which he had also not responded.
rately in the functional absence of the other When asked which objects he had been
To avoid damaging speech zones in
(anesthetized) hemisphere. Because the period of shown, he said he had no idea. However, when
patients about to undergo brain surgery,
anesthesia lasts several minutes, a variety of func- given an array of objects and asked to choose
surgeons inject sodium amobarbital into
tions, including memory and movement, can be the carotid artery. The drug anesthetizes with his left hand, he identified the objects by
studied to determine a hemisphere’s capabilities. the hemisphere where it is injected (here, pointing because his nonspeaking right hemi-
The sodium amobarbital test is always per- the left), allowing the surgeon to determine sphere controlled that hand. In contrast, his
formed bilaterally, with the second cerebral hemi- whether that hemisphere is dominant for speaking left hemisphere had no memory of the
sphere being injected several days after the first speech. objects: it had been asleep.
Because the left hemisphere controls the right hand, the general assumption is that right-
handedness is somehow related to the presence of speech in the left hemisphere. If this were
so, language would be located in the right hemisphere of left-handed people. This hypothesis
is easily tested, and it turns out to be false.
In the course of preparing patients with epilepsy for surgery to remove the abnormal tis-
sue causing their seizures, Ted Rasmussen and Brenda Milner (1977) injected the left or right
hemisphere with sodium amobarbital. This drug produces a short-acting anesthesia of the
entire hemisphere, making it possible to determine where speech originates. As described in
Clinical Focus 15-5, Sodium Amobarbital Test, if a person becomes aphasic when the drug
is injected into the left hemisphere but not when the drug is injected into the right, then
speech must reside in that person’s left hemisphere.
Rasmussen and Milner found that in virtually all right-handed people, speech was local-
ized in the left hemisphere, but the reverse was not true for left-handed people. About 70
percent of left-handers also had speech in the left hemisphere. Of the remaining 30 percent,
about half had speech in the right hemisphere and half had speech in both hemispheres.
15-5 • Variations in Cognitive Organization 551
Findings from neuroanatomical studies have subsequently shown that left-handers with
anomalous speech representation
speech in the left hemisphere have asymmetries similar to those of right-handers. By contrast,
Condition in which a person’s speech zones
in left-handers with speech originating in the right hemisphere or in both hemispheres—
are located in the right hemisphere or in both
known as anomalous speech representation—the anatomical symmetry is reversed or absent. hemispheres.
Sandra Witelson and Charlie Goldsmith (1991) asked whether any other gross differences
synesthesia Ability to perceive a stimulus
in the brain structure of right- and left-handers might exist. One possibility is that the con-
of one sense as the sensation of a different
nectivity of the cerebral hemispheres may differ. To test this idea, the investigators studied
sense, as when sound produces a sensation
the hand preference of terminally ill subjects on a variety of one-handed tasks. They later of color; literally, feeling together.
performed postmortem studies of these patients’ brains, paying particular attention to the
size of the corpus callosum. They found that the callosal cross-sectional area was 11 percent
greater in left-handed and ambidextrous (little or no hand preference) people than in right-
handed people.
Whether this enlarged callosum is due to a greater number of fibers, to thicker fibers,
or to more myelin remains to be seen. If the larger corpus callosum is due to more fibers,
the difference would be on the order of 25 million more fibers. Presumably, such a differ-
ence would have major implications for the organization of cognitive processing in left- and
right-handers.
Synesthesia
Some variations in brain organization are idiosyncratic rather than systematic. Synesthesia
is an individual’s capacity to join sensory experiences across sensory modalities, as discussed
in Clinical Focus 15-6, A Case of Synesthesia. Examples include the ability to hear colors or
taste shapes. Edward Hubbard (2007) estimated the incidence of synesthesia at about 1 in 23
people, although for most it likely is limited in scope.
Synesthesia runs in families—the family of Russian novelist Vladimir Nabokov, for
example. As a toddler, Nabokov complained to his mother that the letter colors on his
clinical F cus 15-6
A Case of Synesthesia When Cytowic quizzed him about this strange remark, Watson
said that all flavors had shape for him. “I wanted the taste of this
Michael Watson tastes shapes. His sensory joining first came to the chicken to be a pointed shape, but it came out all round. Well, I
attention of neurologist Richard Cytowic over dinner. After tasting a mean it’s nearly spherical. I can’t serve this if it doesn’t have points”
sauce he was making for roast chicken, Watson blurted out, “There (Cytowic, 1998, p. 4).
aren’t enough points on the chicken.” Watson has synesthesia, which literally means feeling together.
All his life Watson has experienced the feeling of shape when he
tastes or smells food. When he tastes intense flavors, he reports an
22 experience of shape that sweeps down his arms to his fingertips.
3 21
2 4 23 He experiences the feeling of weight, texture, warmth or cold, and
5 shape, just as though he were grasping something.
1 20
The feelings are not confined to his hands, however. Watson
13 6 19 experiences some taste shapes, such as points, over his whole
body. He experiences others only on the face, back, or shoulders.
These impressions are not metaphors, as other people might
7 18 use when they say that a cheese is sharp or a wine is textured.
Such descriptions make no sense to Watson. He actually feels the
12 17 shapes.
8
16 Cytowic systematically studied Watson to determine whether
11 9 14
15 his feelings of shape were always associated with particular fla-
10
vors and found that they were. Cytowic devised the set of geo-
Neurologist Richard Cytowic devised this set of figures to help
Michael Watson communicate the shapes he senses when he
metric figures shown here to allow Watson to communicate which
tastes food. shapes he associated with various flavors.
552 Chapter 15 • HOW DOES THE BRAIN THINK?
Musician–composer Stevie Wonder is a wooden alphabet blocks were all wrong. His mother understood what he meant, because
synesthete, as were music legends Duke she too perceived letters and words in particular colors. Nabokov’s son is synesthetic in the
Ellington and Franz Liszt and Nobel Prize– same way.
winning physicist Richard Feynman. If you’ve shivered on hearing a particular piece of music or the noise of fingernails scratch-
ing across a chalkboard, you have felt sound. Even so, other sensory blendings may be dif-
ficult to imagine. How can sounds or letters possibly produce colors? Studies of synesthetes
show that the same stimuli always elicit the same experiences for them.
The most common form of synesthesia is colored hearing. For many synesthetes, this
means hearing both speech and music in color—perceiving a visual mélange of colored
shapes, movement, and scintillation. The fact that colored hearing is more common than
other types of synesthesia is curious.
The five primary senses (vision, hearing, touch, taste, and smell) all generate synesthetic
pairings. Most, however, are in one direction. For instance, whereas synesthetes may see
colors when they hear, they do not hear sounds in colors. Furthermore, some sensory combi-
nations occur rarely, if at all. In particular, taste or smell rarely triggers a synesthetic response
like Michael Watson’s.
Because each case is idiosyncratic, synesthesia’s neurological basis is difficult to investi-
gate. Few studies have related it directly to brain function or brain organization, and differ-
ent people may experience it for different reasons. Various hypotheses have been advanced
to account for synesthesia:
• Extraordinary neural connections between the sensory regions are related in a
particular synesthete.
• Activity is increased in the frontal lobe multimodal cortex, which receives inputs from
more than one sensory area.
• Particular sensory inputs elicit unusual patterns of cerebral activation.
Whatever the explanation, when it comes to certain sensory inputs, the brain of a synes-
thete certainly works differently from other people’s brains.
15-5 review
Variations in Cognitive Organization
Before you continue, check your understanding.
1. The two major contributors to organizational differences in individual brains are
and .
2. Differences in the cerebral organization of thinking are probably related to differences in
the that underlie different types of cognitive processing.
3. People who experience certain sensations in more than one sensory modality are said to
have .
4. What roles do gonadal hormones play in brain organization and function?
Answers appear at the back of the book.
For additional study tools, visit LaunchPad:
www.macmillanhighered.com/launchpad/kolb5e
15-6 Intelligence
Intelligence exerts a major influence on anyone’s thinking ability. It is easy to identify in
people and even easy to observe in other animals. Yet intelligence is not at all easy to define.
Despite a century of study, researchers have not yet reached agreement on what intelligence
entails. We therefore begin this section by reviewing some hypotheses of intelligence.
15-6 • Intelligence 553
Concept of General Intelligence
In the 1920s, Charles Spearman proposed that although different kinds of intelligence may
exist, there is also an underlying general intelligence, which he called the g factor. Consider
for a moment what a general intelligence factor might mean for the brain. Presumably, brains
with high or low g would have some general difference in brain architecture—perhaps in Cytoarchitectonics refers to brain cell
gyral patterns, cytoarchitectonics, vascular patterns, or neurochemistry, for example. organization, structure, and distribution.
This difference could not be something as simple as size, because human brain size
(which varies from about 1000 to 2000 grams) correlates poorly with intelligence. Another Section 1-5 reveals fallacies inherent in
possibility is that g is related to special cerebral connectivity or even to the ratio of neurons correlating human brain size with intelligence.
to glia. Still another possibility is that g is related to the activation of specific brain regions,
possibly in the frontal lobe (Duncan et al., 2000; Gray & Thompson, 2004).
The results of preliminary studies of Albert Einstein’s brain implied that cerebral con-
nectivity and ratio of glia to neuron may be important. Sandra Witel-
son and her colleagues (Witelson et al., 1999) found that although
Einstein’s brain is the same size and weight as the average male brain,
its lateral fissure is short, and both the left and the right lateral fis-
sures take a particularly striking upward deflection (Figure 15-21;
compare Figure 15-11). This arrangement essentially fuses the infe-
rior parietal area with the posterior temporal area.
The inferior parietal cortex has a role in mathematical reasoning,
so it is tempting to speculate that Einstein’s mathematical abilities
were related to neural rearrangements in this area. But another important difference may FigurE 15-21 Einstein’s Brain The
distinguish Einstein’s brain. Marion Diamond and her colleagues (1985) looked at its glia- lateral fissure of Einstein’s brain takes
an exaggerated upward course relative
to-neuron ratio versus the mean for a control population. They found that Einstein’s ratio
to its course in typical brains, essentially
in the inferior parietal cortex was higher than average: each neuron in this region had an fusing the posterior temporal regions with
unusually high number of glial cells supporting it. the inferior parietal regions. The arrow
The glia-to-neuron ratio was not unusually high in any other cortical areas of Ein- in each hemisphere indicates Einstein’s
stein’s brain measured by these researchers. Possibly, then, certain types of intelligence ascending lateral fissure as it runs into the
postcentral sulcus. Republished with permission
could be related to differences in cell structure in localized brain regions. But even if this
of Elsevier Science and Technology Journals from The
hypothesis proves correct, it offers little neural evidence in favor of a general intelligence Exceptional Brain of Albert Einstein, S. Witelson, D. Kigar,
factor. T. Harvey, The Lancet, June 19, 1999, Vol. 353, p. 2151.
One possibility is that g is related to the brain’s language processes, because language Permission conveyed through Copyright Clearance
ability qualitatively changes the nature of cognitive processing in humans. So perhaps people Center, Inc.
with very good language skills also have an advantage in general thinking ability.
Multiple Intelligences
Many other hypotheses on intelligence have been set forth since Spearman’s, but few have
considered the brain directly. One exception, proposed by Howard Gardner (1983), a neu-
ropsychologist at Harvard, considers the effects of neurological injury on people’s behavior.
Gardner concludes that seven distinct forms of intelligence exist and that brain injury can
selectively damage any form. The idea of multiple human intelligences should not be surpris-
ing given the varied cognitive operations the human brain can perform.
Gardner’s seven categories of intelligence are linguistic, musical, logical-mathematical,
spatial, bodily-kinesthetic, intrapersonal, and interpersonal. Linguistic and musical intel-
ligence are straightforward concepts, as is logical-mathematical intelligence. Spatial intel-
ligence refers to abilities discussed in this chapter, especially navigating in space, and to the
ability to draw and paint. Bodily-kinesthetic intelligence refers to superior motor abilities,
such as those exemplified by skilled athletes and dancers.
The two types of “personal” intelligence are less obvious. They refer to the frontal and
temporal lobe operations required for success in a highly social environment. The intra-
personal aspect is awareness of one’s own feelings, whereas the interpersonal aspect entails
554 Chapter 15 • HOW DOES THE BRAIN THINK?
recognizing others’ feelings and responding appropriately. Gardner’s definition of intelli-
gence has the advantage not only of being inclusive but also of acknowledging forms of
intelligence not typically recognized by standard intelligence tests, abilities such as theory
of mind, described in Section 15-3.
One prediction stemming from Gardner’s analysis of intelligence is that brains ought
to differ in some way when people have more of one form of intelligence and less of
another. Logically, we could imagine that if a person were higher in musical intelli-
gence and lower in interpersonal intelligence, then the brain regions for music (espe-
cially the temporal lobe) would differ in some fundamental way from the “less efficient”
regions for interpersonal intelligence. One way to examine such differences is to use
fcMRI or DTI to identify differences in pathways, as in the example of absolute pitch
(see Figure 15-10).
Divergent and Convergent Intelligence
One clear difference between lesions in the parietal and temporal lobes and lesions in the
frontal lobes is in the way they affect performance on standardized intelligence tests. Pos-
terior lesions produce reliable and often large decreases in intelligence test scores, whereas
frontal lesions do not. This is puzzling. If frontal lobe damage does not diminish a person’s
intelligence test score, why do people with this kind of damage often do stupid things? The
answer lies in the difference between two kinds of intelligence.
According to J. P. Guilford (1967), traditional intelligence tests measure
convergent thinking—applying knowledge and reasoning skills to narrow the range of pos-
sible solutions to a problem, then zeroing in on one correct answer. Typical intelligence
test items using vocabulary words, arithmetic problems, puzzles, block designs, and so
forth all require convergent thinking. They demand a single correct answer that can be
easily scored.
In contrast, divergent thinking reaches outward from conventional knowledge and reasoning
skills to explore new, more unconventional solutions to problems. Divergent thinking assumes a
variety of possible approaches and answers to a question rather than a single “correct” solution.
A task that requires divergent thinking is to list all the possible uses you can imagine for a coat
hanger.
Clearly, a person who is very good at divergent thinking might not necessarily be good at
convergent thinking and vice versa. The distinction is useful because it helps us to under-
stand the effects of brain injury on thought. Frontal lobe injury is believed to interfere with
divergent thinking. The convergent thinking measured by standardized IQ tests is often
impaired in people with damage to the temporal and parietal lobes.
Injury to the left parietal lobe in particular causes devastating impairment in the
ability to perform cognitive processes related to academic work. People with this kind of
injury may be aphasic, alexic, and apraxic. Many have severe deficits in arithmetic abil-
ity. All such impairments would interfere with school performance and performance at
most jobs.
Patient M. M., discussed in Section 15-4, had left parietal lobe injury and was unable to
return to school. In contrast with people like M. M., those with frontal lobe injuries seldom
have deficits in reading, writing, or arithmetic. And they show no decrement in standardized
IQ tests. C. C.’s case provides a good example.
C. C. had a meningioma along the midline between the frontal lobes. Extracting it
required removing brain tissue from both hemispheres. Before his surgery C. C. was a prom-
inent lawyer. Afterward, although he still had a superior IQ and superior memory, he was
unable to work, in part because he no longer had any imagination. He could not generate the
novel solutions to legal problems that had characterized his career before the surgery. Thus,
both M. M. and C. C. had problems that prevented them from working, but their problems
differed because their injuries affected different kinds of thinking.
15-6 • Intelligence 555
Intelligence, Heredity, Epigenetics,
and the Synapse
Donald Hebb proposed another way to categorize human intelligence. Like Guilford,
Hebb thought of people as having two forms, which he called intelligence A and intelli-
gence B. Unlike Guilford’s convergent–divergent dichotomy, Hebb’s intelligence A refers
to innate intellectual potential, which is highly heritable: it has a strong genetic compo-
nent. Intelligence B is observed intelligence, which is influenced by experience as well as
other factors, such as disease, injury, or exposure to environmental toxins, especially during
development.
Hebb (1980) understood that experience can influence brain cell structure significantly. Review Focus 8-1. Section 8-4 recounts
In his view, experiences influence brain development, and thus observed intelligence, Hebb’s pioneering work on enriched
because they alter the brain’s synaptic organization. It follows that appropriate postnatal environments’ importance in early childhood
experiences can enhance development of intelligence B in people with lower than average education.
intelligence A, whereas a poor or underresourced environment can hinder the development
of intelligence B in people with higher than average intelligence A. The task is to identify
a good and a bad environment so as to stimulate people to reach their highest potential convergent thinking Form of thinking that
intelligence. searches for a single answer to a question
One implication of Hebb’s view of intelligence: the brain’s synaptic organization is key. (such as 2 + 2 = ?); contrasts with divergent
Synaptic organization is partly directed by a person’s genes but is also affected by epigenetic thinking.
factors. Variations in the experiences to which people are exposed, coupled with variations divergent thinking Form of thinking that
in genetic patterns, undoubtedly contribute to the individual differences in intelligence that searches for multiple solutions to a problem
we observe—both quantitative differences (as measured by IQ tests) and qualitative differ- (how many ways can a pen be used?);
ences (as in Gardner’s view). contrasts with convergent thinking.
Hikaru Takeuchi and colleagues (2012) used f MRI to characterize brain activation while intelligence A Hebb’s term for innate
participants performed working memory tasks of varied complexity. Performance on IQ tests intellectual potential, which is highly heritable
and memory are highly correlated, so the investigators reasoned that brain activity during and cannot be measured directly.
memory tests might reflect brain differences related to IQ score. intelligence B Hebb’s term for observed
Performance speed correlated with increased activation in the right dorsolateral prefron- intelligence, influenced by experience and
tal cortex as well as an increase in the interaction between the prefrontal cortex and right other factors in the course of development;
posterior parietal cortex. Gray matter volume in the right dorsolateral prefrontal region cor- measured by intelligence tests.
related with the participant’s accuracy in working memory tasks, which in turn correlated
with psychometric intelligence measures.
Others have obtained parallel results using event-related potentials (e.g., Langer et al., Section 7-2 describes ERP’s use in mapping
2009). The general conclusion from ERP studies is that general intelligence is related to the brain function.
efficiency of cortical networks linking prefrontal and parietal regions. We can speculate that
the efficiency of different neural networks, as might be seen in fcMRI studies, will underlie
the variation in each of Gardner’s seven forms of intelligence.
Finally, neuropsychological studies using tests of executive (frontal lobe) function show
an advantage for bilingual speakers relative to monolinguals. The difference is hypothesized
to reflect bilinguals’ consistent need to select language-appropriate words and to inhibit
language-inappropriate words. Further, learning two languages early in life appears to confer
an even greater advantage than acquiring a second language later in life. Focus 8-3 backs up these ideas about
Olulade and colleagues (2015) found that, versus monolinguals, increased gray matter bilingual speakers.
volume in the frontal lobe of adults who learned two languages before age 6 reflects this
behavioral advantage. No such difference appeared when the investigators compared indi-
viduals who acquired an oral language and American Sign Language. The finding is con-
sistent with the idea that the challenge of selecting language-appropriate words is critical.
How the increased gray matter volume correlates with other measures of intelligence is
unknown, but the results are consistent with evidence showing long-term cognitive advan-
tages in elderly bilinguals. This suggests a broader advantage for bilinguals than in executive
functions alone.
556 Chapter 15 • HOW DOES THE BRAIN THINK?
15-6 review
Intelligence
Before you continue, check your understanding.
1. Different concepts of intelligence include Spearman’s , Gardner’s
, Guilford’s concepts of and thinking, and
Hebb’s and .
2. Each form of intelligence that humans possess is probably related to the brain’s
organization as well as to its efficiency.
3. No two brains are alike. They differ, for example, in , , and
.
4. Evidence that Hebb’s intelligence A and intelligence B can be altered by experience is
evidence of influences on brain organization.
5. How might intelligence be related to brain activity?
Answers appear at the back of the book.
For additional study tools, visit LaunchPad:
www.macmillanhighered.com/launchpad/kolb5e
15-7 Consciousness
Our conscious experience is familiar and intimate yet remains largely a mysterious product
of the brain. Everyone has an idea of what it means to be conscious, but like thinking and
intelligence, consciousness is easier to identify than to define. Definitions range from a mere
manifestation of complex thought processes to more slippery notions that see it as the subjec-
tive experience of awareness or the “inner self.”
Despite the difficulty of defining consciousness, scientists generally agree that it is a
process, not a thing. And consciousness is probably not a single process but several, such as
are associated with seeing, talking, thinking, emotion, and so on.
Consciousness is not unitary but can take various forms. A person is not necessarily
equally conscious at all stages of life. We don’t think of a newborn baby as being conscious
in the same way that a healthy older child or adult is. Indeed, we might say that part of
the maturation process is becoming fully conscious. The level of consciousness even
Section 13-3 explores sleep stages and dream changes across the span of a day as we pass through various states of drowsiness, sleep,
states. and waking. One trait that characterizes consciousness, then, is its constant variability.
Why Are We Conscious?
Countless people, including neuroscience researchers, have wondered why we experience
consciousness, the mind’s level of responsiveness to impressions made by the senses. The
simplest explanation is that consciousness provides an adaptive advantage. Either our con-
Investigators’ conclusions from sensory
deprivation experiments: the brain inherently struct of the sensory world or our selection of behavior is enhanced by being conscious.
needs stimulation; see Figure 12-1. Consider visual consciousness.
According to Francis Crick and Christof Koch (1998), an animal such as a frog acts
a bit like a zombie when it responds to visual input. Frogs respond to small, preylike
objects by snapping and to large, looming objects by jumping. These responses are con-
trolled by different visual systems and are best thought of as reflexive rather than con-
scious. And these visual systems work well for the frog. So why would humans need to
add consciousness?
consciousness The mind’s level of Crick and Koch suggest that reflexive systems are fine when their number is limited,
responsiveness to impressions made by the but as their numbers grow, reflexive arrangements become inefficient, especially when
senses. two or more systems conflict. As the amount of information about an event increases,
15-7 • Consciousness 557
it becomes advantageous to produce a single complex representation and make it ExpErimEnt 15-5
available for a sufficient time to the parts of the brain—such as the frontal lobes—
Question: Can people alter their movements
that choose among many possible action plans. This sustained, complex representa-
without conscious awareness?
tion is consciousness.
Of course, to survive we must retain the ability to respond quickly and uncon- Procedure
Volunteers were
sciously when we need to. This reflexive ability exists alongside our ability to pro-
required to move
cess information consciously. The ventral visual stream is conscious, but the dorsal 1
2 their hands and grasp
stream, which acts more rapidly, is not. Athletes model the unconscious action of the 3 the illuminated rod
online dorsal stream. To hit a baseball or tennis ball traveling at more than 100 miles as quickly as possible.
per hour requires athletes to swing before they are consciously aware of actually see-
ing the ball. Conscious awareness of the ball comes just after hitting it. In this trial, the
In a series of experiments, Marc Jeannerod and his colleagues (Castiello et volunteer reaches for
al., 1991) found a similar dissociation between behavior and awareness in healthy illuminated rod 3.
volunteers as they make grasping movements. Experiment 15-5 illustrates a rep-
resentative experiment. Participants were required to grasp one of three rods as
quickly as possible. A light on a rod indicated it to be the correct target rod on any
given trial.
On some trials, the
On some trials, unknown to the participants, the light jumped from one target to Results
light jumps from one
another. Participants were asked to report whether such a jump had occurred. As shown target to another,…
in the Results section of the experiment, although participants were able to make the 1
2
trajectory correction, they were sometimes actually grasping the correct target before 3 … causing the
they were aware it had changed. volunteer to correct
his trajectory. Most
On some trials, the extent of dissociation between motor and vocal responses was participants found
so great that, to their surprise, participants grasped the target some 300 milliseconds that they were
before they emitted the vocal response. As with baseball players, their conscious aware- actually grasping
the new target
ness of the stimulus event occurred only after their movements took place. No thought
before they were
was required to make the movement, just as frogs catch flies without having to think aware that it had
about it.
Unconscious movements are different from those consciously directed toward a spe-
cific object, as when we reach into a bowl of jellybeans to select a candy of a certain
Conclusion: It is possible to dissociate behavior
color. In this case, we must be aware of all the different colors surrounding the color and conscious awareness.
we want. Here the conscious ventral stream is needed to discriminate among particu- Research from C. Frith, R. Perry, & E. Lumer (1999). The neural
lar stimuli and respond differentially to them. Consciousness, then, allows us to select correlations of conscious experience. Trends in Cognitive
Sciences, 3, pp. 105–114.
behaviors that correspond to an understanding of the nuances of sensory inputs.
What Is the Neural Basis of
Consciousness?
Consciousness must be related in some way to neural system activity, particularly in the
forebrain. One way to investigate these systems is to contrast two kinds of neurological
conditions.
In the first condition, a person lacks conscious awareness of some subset of informa-
tion, even though he or she processes that information unconsciously. Examples include
blindsight, visual form agnosia, implicit learning in amnesia, and visual neglect (discussed
in Section 15-2). Another example is obsessive-compulsive disorder, in which people persist Focus 9-1 describes blindsight, Section 9-4
in some checking behavior—to see that the stove is off or the door is locked—even though visual agnosias, Section 14-2 implicit learning
in amnesia, and Section 16-4, OCD.
they have already checked many times.
All these phenomena show that stimuli can be highly processed by the brain without
entering conscious awareness. This is quite different from the second neurological condi- Focus 11-5 outlines phantom limb pain,
tion, in which people are consciously aware of stimuli that are not actually there. Examples Figure 14-20 how amputation remaps the
include phantom limbs and the hallucinations of schizophrenia. In both, consciousness of cortex, Focus 8-5 brain abnormalities in
specific events, such as pain in a missing limb or hearing voices, exists even though these schizophrenia.
events clearly are not “real.”
558 Chapter 15 • HOW DOES THE BRAIN THINK?
We can draw two conclusions from these contrasting conditions. First, the representation
of a visual object or event is likely to be distributed over many parts of the visual system and
probably over parts of the frontal lobes as well. Damage to different areas not only produces
different specific symptoms, such as agnosia or neglect, but can also produce a specific loss
of visual consciousness. Disordered functioning can induce faulty consciousness, such as
hallucinations. Second, because visual consciousness can be lost, it follows that parts of the
neural circuit must produce this awareness.
In Section 15-1, we appointed the neuron the unit of thinking. It is unlikely, however, that
the neuron can be the unit of conscious experience. Instead, consciousness presumably is a
process that emerges from neural circuits, with greater degrees of consciousness associated
with increasingly complex circuitry.
For this reason, humans, with their highly complex brain circuits, are often credited with
a greater degree of consciousness than other animals have. Simple animals such as worms
are assumed to have less consciousness (if any) than dogs, which in turn are assumed to have
The Glasgow Coma Scale, described in less consciousness than humans. Brain injury may alter self-awareness in humans, as happens
Section 1-2, objectively scores degrees of in contralateral neglect, but unless a person is in a coma, he or she retains some conscious
consciousness in brain-injured people. experience.
Some people argue that language fundamentally changes the nature of consciousness.
Gazzaniga, for one, believes that the left hemisphere, with its language capabilities, acts as
an interpreter of stimuli (see Section 15-4). He maintains that this ability is an important dif-
ference between the functions of the two hemispheres.
Yet people who are aphasic have not lost consciousness. Although language may
alter the nature of our conscious experience, equating any one brain structure with
consciousness seems an unlikely hypothesis. Rather, viewing consciousness as a prod-
uct of all cortical areas, their connections, and their cognitive operations holds more
promise.
We end our discussion of thinking on an interesting, if speculative, note. David Chalm-
ers (1995) proposed that consciousness includes not only the information the brain receives
through its sensory systems but also the information the brain has stored and presumably
the information the brain can imagine. In his view, consciousness is the end product of all
the brain’s cognitive processes.
An interesting implication of Chalmers’s notion is that as the brain changes with expe-
rience, so does the state of consciousness. As our sensory experiences become richer and
our store of information greater, our consciousness may become more complex. From this
perspective, some advantage may attend growing old.
15-7 review
Consciousness
Before you continue, check your understanding.
1. Over the course of human evolution, one characteristic of sensory processing is that it
has become more .
2. is the mind’s level of responsiveness to impressions made by the senses.
3. As relative human brain size and complexity have increased, so too has our degree of
.
4. Not all behavior is under conscious control. What types of behaviors are not conscious?
Answers appear at the back of the book.
For additional study tools, visit LaunchPad:
www.macmillanhighered.com/launchpad/kolb5e
Summary 559
SUMMarY
15-1 The Nature of Thought Using noninvasive imaging techniques such as fMRI, researchers have
The complex processes we call thinking, or cognition, are products shown that social cognition primarily involves activity in the prefrontal
of both human and nonhuman brain activity. We use such words as cortex.
language and memory to describe cognitive operations, but these Neuroeconomics combines psychology, neuroscience, and
concepts are abstract psychological constructs—merely inferred economics in seeking to understand human decision making. fMRI
and not found in discrete places in the brain. They exist but have no studies reveal two decision-making pathways. One is slow and
physical form. reflective, involving diffuse regions of association cortex. The other
The brain carries out multiple cognitive operations—perception, is quick and reflexive, involving the dopaminergic reward system.
action for perception, imagery, planning, spatial cognition, and
attention. Each requires widespread activity in many cortical areas.
15-4 Cerebral Asymmetry in Thinking
The unit of cognition, however, is the neuron. Cognitive operations are organized asymmetrically in the left and right
cerebral hemispheres: each carries out complementary functions.
15-2 Cognition and the Association Cortex The most obvious functional difference is language, typically housed
The brain’s association cortex includes medial, dorsal, and orbital in the left hemisphere.
subdivisions of the prefrontal cortex, the posterior parietal cortex, Cerebral asymmetry, manifested in anatomical differences between
and anterior regions of the temporal lobe. Cell assemblies in the the two hemispheres, can be inferred from the differential effects of
association cortex specifically take part in most forms of cognition. injury to opposite sides of the brain. Asymmetry can also be seen
The frontal lobes not only plan, organize, and initiate movements in the healthy brain and in the brain that is surgically split to relieve
but also organize our behavior over time (temporally). As a general intractable epilepsy. Various syndromes result from association
rule, the temporal lobes generate knowledge about objects, whereas cortex injury, among them agnosia, apraxia, aphasia, and amnesia.
the parietal lobes produce varied forms of spatial cognition. Neurons Each includes the loss or disturbance of some cognitive function.
in both the temporal and the parietal lobes contribute to our ability to
selectively attend to sensory information.
15-5 Variations in Cognitive Organization
Regions in the frontal and parietal lobes contain mirror neurons Unique brains produce unique thought patterns. Marked variations
that represent actions—one’s own or those of others. Such neural in brain organization among individuals are exhibited in idiosyncratic
representations could be used both for imitating others’ actions and capacities such as synesthesia. Systematic differences in cognition
for moving faster and more accurately. A significant area of the cortex exist as well, manifested in the performance of females and males
is multisensory, allowing the brain to combine characteristics of on cognitive tests, especially on tests of spatial and verbal behavior.
stimuli across sensory modalities, whether we encounter the stimuli Sex differences in cognition result from gonadal hormones’ actions
together or separately. on cortical organization, possibly on the architecture of cortical
neurons, and ultimately on neural networks. Female and male cerebral
hemispheres exhibit marked differences in anatomical organization.
Expanding Frontiers of
15-3
Right- and left-handers also differ in hemispheric organization.
Cognitive Neuroscience Left-handers constitute at least three distinct groups. In one, speech
Neuropsychological studies that began in the late 1800s to examine appears to reside in the left hemisphere, as it does in right-handers.
the behavioral capacities of people and laboratory animals with The other two groups have anomalous speech representation, either
localized brain injuries did not allow investigators to study “normal” in the right hemisphere or in both hemispheres. The reasons for these
brains. Today, noninvasive brain recording systems and imaging organizational differences remain unknown.
techniques further the field of cognitive neuroscience, which studies
the neural basis of cognition by measuring brain activity while healthy 15-6 Intelligence
participants engage in cognitive tasks. Intelligence is easy to spot but difficult to define. Obvious differences
An important step in identifying the neural bases of cognition is exist across, as well as within, species, and we find varied forms
mapping cortical connections for the brain connectome. Two promising of intelligence among humans within our own culture and in other
imaging tools are functional connectivity magnetic resonance imaging cultures. Intelligence is unrelated to differences in brain size within
(fcMRI) and tractography using diffusion tensor imaging. a species or to any obvious gross structural differences among
The cerebellum, which houses 80 percent of the human brain’s members of the species. Intelligence may be related to synaptic
neurons, was long believed primarily to have motor functions. organization and processing efficiency.
Emerging data, however, reveal cerebellar involvement in a wide
range of cognitive functions as well. 15-7 Consciousness
Social neuroscience, a field that combines cognitive neuroscience The larger a species’ brain is relative to its body size, the more
with social psychology, explores how we understand others’ knowledge the brain acquires. Consciousness, the mind’s level of
intentions by constructing a theory of mind. Social neuroscience also responsiveness to impressions made by the senses, emerges from
investigates how we develop attitudes, beliefs, and a sense of self. the nervous system’s complexity.
560 Chapter 15 • HOW DOES THE BRAIN THINK?
KeY terMS
anomalous speech cognition, p. 521 extinction, p. 528 psychological construct, p. 521
representation, p. 551 cognitive neuroscience, p. 533 hyperconnectivity, p. 535 social neuroscience, p. 536
association cortex, p. 525 consciousness, p. 556 intelligence A, p. 555 split brain, p. 521
attention, p. 528 contralateral neglect, p. 528 intelligence B, p. 555 synesthesia, p. 551
binding problem, p. 527 convergent thinking, p. 555 mirror neuron, p. 532 syntax, p. 521
brain connectome, p. 535 dichotic listening, p. 541 neuroeconomics, p. 538 theory of mind, p. 536
cell assembly, p. 522 divergent thinking, p. 555 perseveration, p. 531
Visit LaunchPad to access the e-Book, videos, LearningCurve adaptive quizzing,
flashcards, and more: www.macmillanhighered.com/launchpad/kolb5e
ch a p te r
16 What Happens When ReseaRch Focus 16-1 Posttraumatic stress DisorDer
16-1 MultidisciplinaRy ReseaRch on BRain
the Brain Misbehaves?
and BehavioRal disoRdeRs
causes of DisorDereD Behavior
investigating the neuroBiology of Behavioral DisorDers
16-2 classiFying and tReating BRain and
BehavioRal disoRdeRs
iDentifying anD classifying Behavioral DisorDers
treatments for DisorDers
ReseaRch Focus 16-2 treating Behavioral DisorDers with
transcranial magnetic stimulation
16-3 undeRstanding and tReating neuRological disoRdeRs
traumatic Brain injury
clinical Focus 16-3 concussion
stroke
ePilePsy
multiPle sclerosis
neuroDegenerative DisorDers
are all Degenerative Dementias asPects of a single Disease?
age-relateD cognitive loss
16-4 undeRstanding and tReating psychiatRic disoRdeRs
schizoPhrenia sPectrum anD other Psychotic DisorDers
mooD DisorDers
ReseaRch Focus 16-4 antiDePressant action anD Brain rePair
anxiety DisorDers
16-5 is MisBehavioR always Bad?
Katherine Streeter
561
562 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
ReseaRch F cus 16-1
Posttraumatic Stress Disorder
Life is filled with stress. Routinely, we cope. But some events are so physi-
cally threatening and often emotionally shattering that long-term conse-
quences ensue. Flashbacks and nightmares persist long after any physical
danger has passed. These symptoms can lead to emotional numbness and
a diagnosis of posttraumatic stress disorder, or PTSD (Jorge, 2015).
Traumatic events that may trigger PTSD include violent assault,
natural or human-caused disaster, accident, and war. An estimated 1
in 6 veterans of the conflicts in Iraq and Afghanistan, many not directly
exposed to combat, developed symptoms of PTSD, including intrusive,
unwanted thoughts; avoiding thoughts related to stressful events; nega-
tive cognitions and moods; and altered arousal and reactivity responses.
Understanding the neural basis and identifying new PTSD treatments
has spurred intense interest. Nevertheless, treatment is often difficult,
Courtesy Albert “Skip” Rizzo, Ph.D., USC-ICT
and most sufferers receive no or little treatment.
That a beneficial therapy is to relive a traumatic event is counterintui-
tive. Yet in virtual reality (VR) exposure therapy, a controlled virtual
immersion environment combines realistic street scenes, sounds, and
odors that allow people to relive traumatic events (Gonçalves et al., 2012).
The Virtual Iraq and Afghanistan Simulation is customized for war veter-
ans to start with benign events—such as children playing—and gradually
add increasingly stressful components, culminating in such traumatic
events as a roadside bomb exploding in the virtual space around an
armored personnel carrier, illustrated here. Many unknowns related to PTSD remain, including how stress injures
To make Virtual Iraq realistic, the system pumps in smells, stepping the brain, especially the frontal lobes and hippocampus (Wingenfeld &
up from the scent of bread baking to body odor to the reek of gunpowder Wolf, 2014); why some people do not develop PTSD following extremely
and burning rubber. Speakers provide sounds while off-the-shelf sub- stressful events; and the extent to which PTSD is associated with other
woofers mounted under the subject’s chair re-create movements. VR health events, including previous stressors, diabetes, and head trauma
exposure therapy is now used prior to stress exposure for soldiers, (Costanzo et al., 2014). That said, assessment and treatment options for
police, firefighters, and other first responders, as a means of preventing most of those who endure PTSD are poor: over half of all war veterans,
PTSD (Rizzo et al., 2012). for example, receive no assessment or treatment.
current understanding of ptSD illustrates how thinking on the brain’s role in health
can shift. Largely as a result of symptoms displayed by returning Vietnam War veterans, in
1980 the DSM-III introduced PTSD as a mental disorder. Lynda Holmstrom and Ann Burgess
(1978) as well pointed out similarities in symptoms between war veterans and rape victims.
A prominent feature of PTSD diagnosis is that a traumatic external agent, rather than
internal causes, is prominent in producing the characteristic set of behavioral symptoms
described in Research Focus 16-1, Posttraumatic Stress Disorder. Neuroscientists now recog-
nize that the brain contributes to PTSD development and that traumatic experiences related
to policing, firefighting, and accidental events can contribute to the condition.
posttraumatic stress disorder (PTsD) The many discussions of behavioral disorders and organic disease presented throughout
Syndrome characterized by physiological this book serve both to illustrate the brain’s organization and functioning and to exemplify
arousal brought on by recurring memories how knowledge about brain function contributes to understanding and treating brain disor-
and dreams related to a traumatic event for der and disease. Classifying and treating organic and behavioral conditions is our focus in
months or years after the event. this chapter.
virtual reality (VR) exposure therapy We know that the brain is complex. We do not yet understand all its parts and their func-
Controlled virtual immersion environment tions, nor is it clear how the brain produces mind, a sense of well-being, and a sense of self. Still,
that, by allowing individuals to relive traumatic significant advances have led to the realization that while under some circumstances the brain
events, gradually desensitizes them to stress. copes competently with life’s challenges, under other circumstances, it is not up to the job.
563
To illustrate progress in studying brain and behavior over the past century, we can con-
trast the theories of Sigmund Freud with present-day views. Freud’s theories were based
on his observations of patients while not having the help of the anatomical or imaging data
available today. The underlying tenet of Freud’s theory is that our motivations are largely hid-
den away in our unconscious mind. Freud posited that a mysterious, repressive force actively
withholds our sexual and aggressive motivations from conscious awareness. He believed that
mental illness resulted from the failure of these repressive processes.
Freud proposed the three components of mind illustrated in Figure 16-1A:
1. Primitive functions, including the “instinctual drives” of sex and aggression, arise from
the id, the part of the mind that Freud thought operated on an unconscious level.
2. The rational part of the mind he called the ego. Freud also believed, much of the ego’s
activity to be unconscious, although experience (to him, perceptions of the world) is
conscious.
3. The superego aspect of mind acts to repress the id and to mediate ongoing interactions
between the ego and the id.
For Freudians, abnormal behaviors result from the emergence of unconscious drives into
voluntary conscious behavior. The aim of psychoanalysis, the original talk therapy, is to trace
symptoms to their unconscious roots and thus expose them to rational judgment.
By the 1970s, scientific studies of the brain made the whole notion of id, ego, and super-
ego seem antiquated. Nevertheless, some resemblance between Freud’s theory and brain
theory is apparent (Figure 16-1B). The limbic system and brainstem have properties akin
to those of the id: they produce emotional and motivated behavior, including the will to
survive and to reproduce. The posterior and the dorsolateral frontal cortices have proper-
ties akin to those of the ego: they allow us to learn and to solve everyday problems. The
prefrontal neocortex has properties akin to those of the superego, enabling us to be aware of
others and to learn to follow social norms. Furthermore, as abundantly displayed in earlier
chapters, many processes underlying these functions are unconscious: they operate outside
our awareness.
Three differences between Freud’s view and present-day neuroscience are apparent. First,
we now recognize that the brain is composed of hundreds of interacting structures, not
just three. Second, we know that the functions of these brain parts is complicated and de-
pends upon ongoing expression of genes, interactions of myriad chemicals, and functioning
and connections of glia and neurons. Third, we understand that behavioral disorders have
(A) (B)
Dorsal frontal Posterior cortex
cortex is locus generates sensory
preconscious
GO
of self-conscious representations
thought. of the world.
SUPERE
EGO
d
se
res
p
re
unconscious Ventral frontal
cortex regulates
ID inhibitions. Limbic system and
brainstem regulate
instincts and drives.
Figure 16-1 Mind Models (A) Freud based his model of the mind, drawn in 1933, solely
on clinical observations (color added). (B) In a contemporary brain imaging and lesioning
studies map, the brainstem and limbic system correlate with Freud’s depiction of the id,
the ventral frontal and posterior cortex with the ego, and the dorsal frontal cortex with the
superego. Information from a drawing by Mark Solms and Oliver Turnbull.
564 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
complex causes, including genetic abnormalities, abnormalities in nervous system develop-
ment over the life-span, and environmental and epigenetic effects that modulate genetic and
developmental expression.
Investigating the origins and treatment of disordered behavior is perhaps the most fascinat-
ing pursuit in studying the brain and behavior. Once, neurologists treated organic disorders
of the nervous system—conditions such as Parkinson disease and stroke—medically. Psychia-
trists treated mental disorders such as schizophrenia and PTSD pharmacologically. Psycho-
logical disorders were treated with counseling and other behavioral therapies. Increasingly,
practitioners are synthesizing their insights into a unified understanding of mind and brain, a
neuropyschoanalysis that views the brain as the ultimate source of behavior. When loved ones
develop brain disorders, family members usually become the primary caregivers and as such
join practitioners as participants, because they and their loved ones are those most affected.
With this synthesis of understanding about brain and behavior in mind, we first survey
how researchers investigate the neurobiology of organic and behavioral disorders. We then
examine how disorders are classified, treated, and distributed in the population and review
established and emerging treatments both for neurological and for psychiatric disorders.
16-1 Multidisciplinary Research on
Brain and Behavioral Disorders
Brain research is multidisciplinary. One way to summarize methods of studying links
between brain and behavior is to consider them from the macro level of the whole organism
Chapter 7 surveys research methods ranging down to the molecular level of neuronal excitation and inhibition. Behavioral studies by
from single-cell recordings to functional brain their nature investigate the whole organism, but understanding the whole organism requires
imaging. understanding its parts—its cells, its chemistry, and its genes.
Molecular biology offers neuroscientists varied approaches to studying behavior. Scien-
tists can breed strains of animals, such as fruit flies, fish, or mice, with either a gene knocked
out (deleted or inactivated) or a gene inserted. Knockout technology is used both to create
Section 3-3 reviews genetics, genetic animal models of human disorders and to generate treatments for neurobehavioral disorders.
engineering, and epigenetic mechanisms; Variations on this technology include methods for turning genes on or off for periods of time.
Section 7-5 explores techniques for What is clear from this research is that the genes related to disordered behavior in fruit flies,
measuring genetic and epigenetic influences. fish, and mice are largely the same as those related to similar disordered behavior in people.
Freud was limited to probing the brain with conversation. Today, brain imaging tech-
niques allow behavioral neuroscientists to describe structures and pathways in an individual
brain and the changes it undergoes during development, learning, and after damage, all with-
out directly accessing the brain. Understanding the brain’s structure and function leads to
understanding that individual brains differ—why, for example, one person may have PTSD
or any other disorder, whereas another person in similar circumstances does not.
Causes of Disordered Behavior
Neuroscientists presume that abnormal brain functioning results in disordered behavior.
Evidence for brain abnormalities is relatively straightforward in neurological disorders, and
at least in a general sense, the causes are largely known:
1. Genetic errors, as in Huntington disease
2. Epigenetic mechanisms at work prenatally, later in life, even in succeeding generations
3. Progressive cell death resulting from neurodegenerative causes, as in Parkinson or
Focus 3-4 describes Huntington disease’s Alzheimer disease
genetic basis; Focus 5-2, neural degeneration
4. Rapid cell death, as in stroke or traumatic brain injury
in Parkinson disease; Focus 2-3, symptoms
and aftereffects of stroke; and Focus 4-2, 5. Loss of neural function and connections seen in disorders such as multiple sclerosis and
myelin breakdown in MS. myasthenia gravis
16-1 • Multidisciplinary Research on Brain and Behavioral Disorders 565
In contrast to these organic neurological disorders, far less is known about neu- table 16-1 causes of selected Behavioral Disorders
robiological causes of behavioral and psychiatric disorders. But results of neuro-
cause Disorder
biological studies of pathology and newer research methods are revealing clues to
causation: changes in the brain’s structure or activity are implicated. Table 16-1 lists Genetic error Tay-Sachs disease
the most likely causal categories underlying behavioral disorders, micro to macro. Hormonal anomaly Androgenital syndrome
At the microscopic level is genetic error, such as that responsible for Tay-Sachs Developmental anomaly Schizophrenia
disease and Huntington disease. Intermediate categories include one-time events, Infection Encephalitis
such as infections, injuries, and toxins. At the macro level, nutrition, stress, and
Injury Traumatic brain injury
negative experience are prominent actors. Of course, many of these factors interact.
Genetic error is probably linked to more macro causes, such as hormonal or develop- Toxins MPTP poisoning
mental anomalies. Genetic vulnerability to stress, infection, or pollution may be the Poor nutrition Korsakoff syndrome
immediate cause of some disorders. In other cases, no direct genetic predisposition Stress Anxiety disorders
is needed: disordered behavior arises strictly from epigenetic factors, such as stress Negative experience Developmental delays among
and negative experiences, which influence gene expression and function. Romanian orphans
Investigating the Neurobiology The Index of Disorders inside the book’s front
of Behavioral Disorders cover lists where each condition in Table 16-1
is discussed.
A single brain abnormality can cause a behavioral disorder, explaining everything about it
and its treatment. Phenylketonuria (PKU) is an example. PKU results from a defect in the
gene for phenylalanine hydroxylase (PHA), an enzyme that breaks down the amino acid
phenylalanine. Babies with PKU have elevated blood levels of phenylalanine, leading to
intellectual impairments, seizures, and other physiological conditions. To inherit PKU, both
parents must carry a defective PHA gene. This recessive condition confers resistance to cer-
neuropsychoanalysis Movement within
tain fungal toxins. About 400 mutations of the PHA gene are known (Foroozani et al., 2015).
neuroscience and psychoanalysis to
Left untreated, PKU causes severe intellectual disability, but PKU can be treated just by
combine the insights of both to yield a unified
restricting dietary intake of phenylalanine—foods high in protein, including beef, fish, cheese, understanding of mind and brain.
and soy. A strict diet in infancy prevents brain damage by PKU, and controlled diet through-
phenylketonuria (PKu) Behavioral disorder
out life ensures protection. Expectant mothers who have had PKU might provide an in utero
caused by elevated levels of the amino acid
environment with high PHA levels, and this too can be controlled if the mother restricts her di-
phenylalanine in the blood and resulting
etary intake of phenylalanine. Several drugs to reduce phenylalanine levels are in development. from a defect in the gene for the enzyme
If other behavioral disorders were as simple and well understood as PKU, neuroscience phenylalanine hydroxylase; the major
research could quickly yield cures for them. Many disorders do not result from a single ge- symptom is severe developmental disability.
netic abnormality, however, and the causes of most disorders remain conjectural. The major
problem: diagnosis of a disability is based mainly on behavioral symptoms, and behavioral
symptoms give few clues to specific neurochemical or neurostructural causes.
This problem also appears in treating PKU. Table 16-2 lists what is known about PKU
at different levels of analysis: genetic, biochemical, histological, neurological, behavioral,
and social. The underlying problem becomes less apparent with the procession of entries
in the table. In fact, it is not possible to predict the specific biochemical abnormality from
information at the neurological, behavioral, or social level, exactly where the most accessible
information resides.
For most psychiatric diseases, the underlying pathology is unknown. For PKU, the dis-
tinctive smell of her baby’s urine detected by one mother was the first link in a chain of
discoveries that identified elevated PHA. The task for future study and treatment of most
behavioral disorders is to identify biological markers that will lead to similar understandings.
Challenges to Diagnosis
Knowledge about behavioral disorders is hampered by its subjective nature. Most diagnostic in-
formation gathered about a patient’s behavior comes both from patients and their families. Un-
fortunately, people seldom are objective observers of their own behavior or that of a loved one.
We tend to be selective in noticing and reporting symptoms. If we believe someone has a
memory problem, for example, we often notice memory lapses that we might ordinarily ignore.
566 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
table 16-2 Pku: neurobiological Pathogenesis of a Behavioral Disorder
level of analysis* Known information
Genetic Inborn metabolism error
Recessive defective gene (autosomal)
Biochemical Conversion of phenylalanine to tyrosine impaired, elevating levels of phe-
nylalanine and its metabolites in the blood
Abnormal tissue Abnormal cortical lamination
Decrease in neuron size and dendritic length
Lowered spine density
Neurological Severe intellectual impairment
Slow growth
Seizure
Abnormal EEG
Behavioral IQ score below 50 (in 95 percent of patients)
Social, economic Significant loss of meaningful life and productivity
Treatment Dietary intake of phenylalanine restricted
*From most to least specific
Source: Information from “Special Challenges in the Investigation of the Neurobiology of Mental Illness,” by G. R. Heninger,
1999, in The Neurobiology of Mental Illness (p. 90), edited by D. S. Charney, E. J. Nestler, and B. S. Bunney. New York: Oxford
University Press.
Nor are we often specific in identifying symptoms. Simply identifying a memory problem
is not sufficient. Treatment requires knowing exactly what type of memory deficit underlies
Sections 14-2 and 14-3 explain a range of the problem. Losses of memory for words, places, or habits—each has different underlying
memory deficits. pathologies and brain systems.
Just as patients and their loved ones make diagnosis difficult, so too do diagnosticians.
Behavioral information about patients may be interpreted differently by general physicians,
psychiatrists, neurologists, psychologists, social workers, and others. Evaluators with differ-
ent conceptual biases shape and filter the questions they ask and the information they gather.
One evaluator believes that a behavioral disorder is genetic; another believes it results
from a virus; and a third, that it can be traced to repressed sexual experiences during
childhood. Each makes different types of observations and administers different kinds of
diagnostic tests. In contrast, diagnosing organic disorders is less dependent on subjective
observations than on objective experimental methods—but these too have limitations.
Research Challenges
Even if the problems of diagnosis were solved, major obstacles to investigating behavioral
disorders would still exist. Following is a partial list.
OrganizatiOnal COmplexit y The nervous system far outstrips other body systems in
complexity. The brain has a wider variety of cell types than does any other body organ, and
nervous system cells and their connections are plastic: they change with experience. These
features add a whole new dimension to understanding healthy and disordered functioning.
SyStemiC COmplexit y As our understanding of brain and behavior has progressed, so it
has become apparent that multiple receptor systems serve widely varied functions. For ex-
ample, the brain’s major activating systems, those that employ acetylcholine, dopamine, nor-
epinephrine, serotonin, and GABA are diffuse, with little specificity between biochemistry
Figure 5-17 summarizes major neural and behavior. The neurotransmitter GABA affects some 30 percent of the brain’s synapses.
activating systems; Figure 6-7, how When people ingest a GABA agonist, such as a benzodiazepine, multiple effects on behavior
psychoactive drugs affect the GABA A become apparent. So it is with most drug treatments, which may improve a target behavior
receptor. but at the same time produce varied side effects.
neurOnal plaStiCit y The nervous system can adapt to extreme stress or injury. Even
the nigrostriatal dopaminergic system’s close relation to Parkinson disease is enigmatic. It is
impossible to tie dopamine depletion to a consistent behavioral syndrome. Two people with
16-1 • Multidisciplinary Research on Brain and Behavioral Disorders 567
Parkinson disease can exhibit vastly different symptoms, even though the common basis Frontal Corpus
of the disease is a loss of neurons from the substantia nigra (Fereshtehnejad et al., 2015). cortex callosum
Further, only when the loss of dopamine neurons exceeds about 60 percent to 80 percent do
investigators see clinical signs of Parkinson disease. Are those cells not all needed? That is Caudate nucleus
unlikely, but the result shows that the brain’s compensatory plasticity is considerable. When
a disease progresses slowly, the brain has a remarkable capacity for adapting.
COmpenSatOry plaStiCity Even the best technology produces uncertain relationships.
Magnetic resonance imaging may show that a person with multiple sclerosis has many nervous
system lesions yet displays few outward symptoms. Just as brain lesions do not always produce
Substantia nigra Cerebellum
behavioral symptoms, behavioral symptoms are not always linked to obvious neuropathology.
Clearly, people display compensatory plasticity: they can change their behavior to adapt to
Nigrostriatal Dopamine Pathways
Axons of neurons in the midbrain substantia
neural change just as they can display disordered behavior without obvious brain pathology. nigra project to the basal ganglia, supplying
teChnOlOgiCal reSOlutiOn Some people have notable behavioral problems after a brain dopamine to maintain healthy motor
behavior. Dopamine loss contributes to
trauma, yet no obvious signs of brain damage appear on an MRI. An infant’s brain may seem
muscle rigidity and dyskinesia in Parkinson
healthy only to display severe cerebral palsy later. The resolution of a technology may lack disease.
sufficient detail to detect subtle neuronal change, such as a drop in dendritic spine density or
injury so diffuse that it is hard to identify. Given the current diagnostic methods for both be-
havioral disorders and neuropathology, identifying disorders and their causes is seldom easy.
mOdeling SimpliCit y A major avenue for investigating the causes of disorders is to de-
velop and study animal models. Rats with specific lesions of the nigrostriatal dopamine
system are used to model Parkinson disease. Animal models lead to significant advances
Section 7-7 reviews the benefits of creating
in understanding neural conditions and their treatment. But the view they provide of the
animal models of disorders.
neurobiology behind behavioral disorders can be oversimplified.
The fact that a drug reduces symptoms does not necessarily mean that it is acting on a key
biochemical aspect of the pathology. Aspirin can get rid of a headache, but that does not mean
that the headache is caused by the receptors on which aspirin acts. Similarly, antipsychotic
drugs block dopamine D2 receptors, but that does not mean that schizophrenia is caused by
abnormal D2 receptors. Schizophrenia quite possibly results from a disturbance in glutamater-
gic systems, and for some reason dopamine antagonists can rectify the abnormality.
mOdeling limitatiOnS Modeling human disorders is complex, and critical thinking is
imperative when you encounter media reports about studies using animal models that point
toward possible cures for human behavioral diseases. Caution applies especially to psychi-
atric disorders whose causes remain unknown. Further, many symptoms of disorders such
as schizophrenia and anxiety are largely cognitive. Objectively identifying any cognitive
processes mimicked by a laboratory model is a difficult task.
16-1 review
Multidisciplinary Research on Brain and Behavioral Disorders
Before you continue, check your understanding.
1. Neural correlates of Freud’s id, ego, and superego could be, respectively, the
, , and .
2. Causes of disordered behavior include , , ,
, and .
3. For most psychiatric disorders, the causes are unknown, but is an exception.
4. A major challenge in diagnosing disorders is that diagnosis tends to be .
5. Describe a research conundrum for understanding brain injury.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
568 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
16-2 Classifying and Treating Brain
and Behavioral Disorders
Behavioral disorders afflict millions every year. The National Institute for Mental Disorders
estimates that in a given year about one in four people in the United States has a diagnosable
behavioral disorder, and nearly half of the population does over their lifetime. Only a minority
receive treatment of any kind, and even fewer receive treatment from a mental health special-
ist. Large-scale surveys of neurological disorders show a similar pattern of prevalence. Together,
behavioral, psychiatric, and neurological disorders are the leading cause of disability after age
Figure 8-31 pegs the peak age of onset for
15. Behavioral disorders, traditionally classified as social, psychological, psychiatric, and neu-
mental disorders at 14 years.
rological, reflect the assessment and treatment roles different professional groups play. As un-
derstanding of brain function increases, the lines between behavioral disorders are blurring.
Identifying and Classifying
Behavioral Disorders
Epidemiologists study disease distribution and causes in human populations and help define
and assess behavioral disorders of three general types—psychoses, mood, and affect. Vari-
ous professional organizations classify disorders differently, for example, as in Table 16-3.
table 16-3 summary of Dsm-5 Diagnostic classification of Disorders
Diagnostic category core features and examples of specific disorders
Neurodevelopmental disorders Disorders typically manifest early; characterized by developmental deficits that produce impairments of
personal, social, or academic functioning, including ASD, ADHD, Tourette disorder.
Schizophrenia spectrum and other Functioning deteriorates toward psychosis or loss of contact with reality defined by delusions, hallucinations,
psychotic disorders disorganized thinking, grossly disorganized or disordered motor behavior, and negative symptoms.
Bipolar and related disorders Disorders placed between schizophrenia and depressive disorders, bridging two diagnostic classes, and
characterized by periods of extreme elation and/or significant depressive symptoms.
Depressive disorders All feature sad, empty, or irritable mood, accompanied by physical and cognitive changes that significantly
affect the individual’s capacity to function. Includes major depressive disorder, dysthymia, premenstrual
dysphoric disorder.
Anxiety disorders All feature excessive fear and anxiety but differ in objects or situations that induce fear, anxiety, or avoidance
and associated cognitive ideation. Includes generalized anxiety disorder (GAD), specific phobia, agoraphobia,
panic disorder, separation anxiety disorder.
Obsessive-compulsive and related disorders Differ from developmentally normative preoccupations and rituals by excessiveness or persistence beyond
developmentally appropriate periods.
Trauma- and stressor-related disorders Exposure to a traumatic or stressful event, as in PTSD, is an explicit diagnostic criterion.
Dissociative disorders Disruption of and/or discontinuity of consciousness, memory, identity, emotion, perception, body
representation, motor control, and behavior, including dissociative identity disorder (multiple personality
disorder), dissociative amnesia.
Somatic symptom disorder and related dis- Physical symptoms apparently caused primarily by psychological rather than physiological factors; commonly
orders encountered in medical rather than mental health settings. Includes somatic symptom disorder, illness anxiety
disorder, conversion disorder.
Feeding and eating disorders Abnormal patterns of eating that significantly impair physical health and/or psychosocial functioning, including
pica, anorexia nervosa, bulimia nervosa, and binge-eating disorder.
Elimination disorders Inappropriate elimination of urine or feces, usually first diagnosed in childhood or adolescence.
Sleep–wake disorders Characterized by chronic sleep problems, including insomnia disorder, narcolepsy, sleep apneas, circadian
rhythm sleep–wake disorders, restless legs syndrome.
16-2 • Classifying and Treating Brain and Behavioral Disorders 569
The first set of criteria for diagnoses in psychiatry was developed in 1972. Since that time,
three parallel sets of criteria have gained prominence, and new versions appear periodically.
One is the most recent edition of the World Health Organization’s International Classification
of Diseases (ICD-10); another, the American Psychiatric Association’s Diagnostic and Statis- Diagnostic and Statistical Manual of Mental
tical Manual of Mental Disorders (DSM). The newest, launched by the National Institutes of Disorders (DsM) The American Psychiatric
Mental Health, is the Research Domain Criteria (RDoC). With this new classification system, Association’s classification system for
NIMH is looking to transform behavioral diagnoses by incorporating genetics, imaging, and psychiatric disorders.
cognitive science, among other levels of information.
In addition, the Society for Clinical Psychology provides a list of psychological disor-
ders, their symptoms, and a summary of psychological treatments. The National Institute of
Neurological Disorders and Stroke provides a list of neurological disorders, including their
symptoms, treatments, and any clinical trials that are investigating treatments. Classification
systems organize knowledge about disorders and their treatments and are useful for decision
making in such institutions as insurance companies, courts, and schools.
Table 16-3 summarizes the classification scheme used currently in the DSM-5. As with any
attempt to classify psychiatric disorders, the DSM is to some extent arbitrary and unavoidably
depends on prevailing cultural views. A good example is the social definition of sexual behav- Section 12-5 explores the relationship
ior viewed as abnormal. At its inception, the DSM listed homosexual behavior as pathological among sexual orientation, sexual identity,
but has omitted it since 1980. With evidence solidifying around a neural basis for the spec- and brain organization; and Section 15-5,
trum of gender identity, a similar fate will likely befall the DSM category gender dysphoria. sex differences in cognitive organization.
table 16-3 (continued)
Diagnostic category core features and examples of specific disorders
Sexual dysfunctions Characterized by a clinically significant disturbance in a person’s ability to respond sexually or to experience
sexual pleasure. Includes premature or delayed ejaculation and erectile disorder in males; female orgasmic or
sexual interest/arousal disorder.
Gender dysphoria Distress accompanying the incongruence between experienced or expressed gender and assigned gender.
Disruptive, impulse-control, and conduct Problems in self-control of emotions and behaviors, manifested in behaviors that violate others’ rights, such
disorders as aggression, and/or conflict with societal norms and authority figures. Includes oppositional defiant disorder,
intermittent explosive disorder, pyromania, kleptomania.
Substance-related and addictive disorders Encompasses 10 separate drug classes that affect the central nervous system, and gambling disorder.
Neurocognitive disorders Disorders dominated by impaired cognitive functioning of determinable underlying pathology and etiology,
including TBI and Alzheimer, Huntington, or Parkinson disease.
Personality disorders Enduring pattern of pervasive and inflexible inner experience and behavior that deviates markedly from cultural
expectations; onset occurs in adolescence or early adulthood and is stable over time. Includes paranoid
personality disorder, schizoid personality disorder, antisocial personality disorder, borderline personality
disorder, histrionic personality disorder, narcissistic personality disorder, dependent personality disorder,
obsessive-compulsive personality disorder.
Paraphilic disorders Disorders that cause distress or impairment to the individual; a paraphilia whose satisfaction entails harm
or risk of harm to others, including voyeuristic disorder, exhibitionistic disorder, frotteuristic disorder, sexual
masochism disorder, sexual sadism disorder, pedophilic disorder, fetishistic disorder.
Other mental disorders Symptoms characteristic of a mental disorder predominate but do not meet the full criteria for any other
DSM mental disorder.
Medication-induced movement disorders Determining causal relationships between medication exposure and development of movement disorders
and other adverse effects of medication is difficult. Some may occur in the absence of the medication. Notably, not categorized as mental disorders
are medication-induced parkinsonism, acute dystonia, acute akathisia, tardive dyskinesia, antidepressant
discontinuation syndrome.
Other conditions that may be a focus of Conditions or problems that cause significant impairment, including relational problems, problems related to
clinical attention abuse or neglect, educational and occupational problems, housing and economic problems, problems related
to crime or interaction with the legal system.
Source: Information from Diagnostic and Statistical Manual of Mental Disorders (5th ed.), 2013. Washington, DC: American Psychiatric Association.
570 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
Each revision of any classification system reflects new perspectives. For example, the
Focus 8-2 describes the autism spectrum. DSM-5 labels all forms of autism as autism spectrum disorder (ASD) and most forms of
schizophrenia as schizophrenia spectrum disorder. Classifying broad ranges of conditions as
one simplifies diagnosis but draws criticism for its associated loss of descriptive power and a
perceived difficulty in obtaining treatment sensitive to the severity of particular symptoms.
Among the continually emerging means of searching for indicators of behavioral disor-
ders, genetics and brain imaging, including MRI and PET, stand out. Although these tools
are not currently used clinically, they are increasingly used both to classify disorders and
to monitor treatment effectiveness. But to be useful, imaging test resolution, for example,
must be sensitive enough to detect unique features of brain disorders and specific enough to
rule out similar conditions. This sets a high bar, because many behavioral disorders display
similar abnormalities. Enlarged ventricles, indicating a loss of brain cells, may appear in
schizophrenia, Alzheimer disease, alcoholism, or head trauma, for example.
Nonetheless, imaging technology is shedding new light on behavioral
Average annual loss (%) disturbances. Imaging the brain structure, connections, and chemistry of
subjects with childhood-onset schizophrenia, for example, suggests that the
0 –1 –2 –3 –4 –5 condition begins in utero and is characterized by excessive pruning of short-
Typical adolescents Schizophrenic subjects distance cortical connections (Rao et al., 2015). Cortical maps derived by Ju-
dith Rapoport and coworkers (2012) reveal that between the ages of 13 and
18, children who developed schizophrenia showed a remarkable loss of gray
matter in the cerebral cortex (Figure 16-2). An earlier study by the same group
found changes in the quantity of growth factors that influence brain develop-
ment and a delayed growth rate in white matter—on the order of 2 percent per
year—in children with schizophrenia compared with healthy children (Gogtay
et al., 2008).
Figure 16-2 Early-Onset Abnormalities found throughout the brain vary by functional region and
Schizophrenia Comparison of three- correlate with the onset of behavioral disturbances characteristic of schizophrenia. Not all
dimensional maps derived from MRI disorders show such obvious loss of tissue but may show abnormal blood flow or metabolism
scans reveals that, compared with healthy
that can be detected by either fMRI or PET. The PET images in Figure 16-3 illustrate
teenagers aged 13 to 18 (left), patients with
childhood-onset schizophrenia (right) have metabolic changes in adult-onset schizophrenia. The scan on the left reveals an obvious
widespread loss of gray matter across abnormality in prefrontal cortex activity compared with the scan on the right, from an adult
the cerebral hemispheres. Courtesy of Paul who does not have schizophrenia. Note that the prefrontal area does not show loss of gray
Thompson and Arthur W. Toga, Laboratory of Neuro matter in the MRI study of early-onset schizophrenia reproduced in Figure 16-2. Therefore,
Imaging, Keck School of Medicine of USC and Judith L.
it is likely that the two diseases have different origins.
Rapoport, National Institute of Mental Health.
Combining behavioral diagnoses with genetic analysis and neuroimaging will move prac-
titioners beyond symptom checklists to objective medical diagnoses. Imaging analyses will
help target treatments to reduce the severity of such serious disorders as schizophrenia and
Alzheimer disease. Current imaging techniques do not detect all brain pathology. It is not
Figure 16-3 Adult-Onset
Schizophrenia Note the abnormally
low blood flow in the prefrontal cortex at
the top of the PET scan in the brain (left)
of an adult schizophrenia patient compared
(right) with that of an adult who does not
have schizophrenia.
Hank Morgan/Science Source
16-2 • Classifying and Treating Brain and Behavioral Disorders 571
whether a gene is present or absent but whether that gene is or is not expressed that is rel-
evant to its effects. The challenge lies in improving current techniques and in developing
others that can identify subtler nervous system abnormalities.
Classification systems such as taxonomy, the branch of biology that groups organisms The Basics in Section 1-3 overviews
according to their common characteristics and relationships, have advanced our knowledge taxonomy.
of brain structure and function. Likewise, classifications of behavioral disorders produced
by the behavioral sciences have advanced understanding. Yet classification systems have
their critics. One criticism is that “just because you name a disorder does not mean it exists.”
Another is that changing societal views result in the inclusion or exclusion of disorders, as
with sexual relationships other than heterosexuality.
Naming disorders becomes problematic as well. The term idiot once designated a per-
son with a low IQ score. When the term became pejorative, it was replaced with the term
retarded. That term then became pejorative, and the DSM-5 now uses the term intellectual
disability. Nevertheless, just as genetics has clarified taxonomic relationships among an-
imals, our growing understanding of brain function and genetics likely will clarify the
taxonomy of behavioral disorders. The NIMH’s Research Domain Criteria project, for
example, is one response to criticisms of broad behavioral classifications such as those used
in the DSM-5.
Treatments for Disorders
An inclusive list of brain and behavioral disorders would number in the thousands, includ-
ing, on the organic side, genetic and developmental disorders, infectious diseases, nervous The conditions listed in the Index of Disorders
system injuries, and degenerative dementias. Behavioral disorders would include PTSD constitute a mere fraction of the total.
among the anxiety-related disorders. Abnormalities may also appear via imbalances in bio-
chemical organization or nervous system operation. Biochemical abnormalities include dis-
ordered proteins in cell membrane channels, low or high neuroreceptor numbers, and low
or high numbers of molecules, especially neurotransmitters or hormones. Each disorder
may be associated with various structural changes, congenital abnormality of neurons or
glia, and neuronal death.
The ultimate goal for behavioral neuroscientists lies in applying their knowledge to gener-
ate treatments that can restore a disordered brain to a range of healthy functioning. This goal
is daunting because the first task is so difficult: learning what causes a particular behavioral
disturbance. Few behavioral disorders have a cause as simple as PKU does. Most, like schizo-
phrenia, are complex. A more achievable goal is to make small advances by improving current
treatments, to develop new treatments, and to analyze disease causes. Available treatments,
while extensive, fall into four general categories:
1. Neurosurgical. The skull is opened and some intervention is performed on the brain.
2. Electrophysiological. Brain function is modified by stimulation through the skull.
3. Pharmacological. A chemical that affects the brain is either ingested or injected.
4. Behavioral. Treatment manipulates the body or the experience, which in turn influences
the brain.
Neurosurgical Treatments
Neurosurgical manipulation of the nervous system is largely reparative, as when tumors Brain tumors are the topic of Focus 3-2.
are removed or arteriovenous (AV) malformations corrected. Typically, such neurosurgical AV malformation, or angioma, is imaged on
interventions are successful. Advances include improved imaging of a target for surgery—as page 582.
the surgery takes place—and methods that allow diseased tissue to be destroyed without
opening the skull. For example, radiosurgery uses energy, such as X-rays directed from dif-
ferent sources to converge on a target and destroy abnormal cells. The x-rays lack the energy
to damage healthy cells through which they pass: tissue is destroyed only where multiple
beams converge.
572 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
Treatment for Parkinson disease entails inactivating brain regions that produce tremors
and regions participating in the production of muscular rigidity that impairs movement. An
electrode is placed in the motor thalamus and an electric current used to damage neurons
responsible for producing the unwanted effects. Alternatively, in deep brain stimulation
(DBS), an electrode fixed in place in the globus pallidus or subthalamic nucleus is con-
nected to an external electrical stimulator that the patient can activate (Figure 16-4). The
stimulation can inactivate cells responsible for unwanted effects and so restore more normal
Zephyr/Science Source
movement (Knight et al., 2015).
DBS is also used experimentally to treat traumatic brain injury (TBI) and behavioral
dysfunctions such as obsessive-compulsive disorder (OCD) and major depression (Cleary
et al., 2015). Electrodes implanted in the brain are well tolerated and remain effective for
Figure 16-4 Deep Brain several years. Electrical stimulation can have an activating effect and so relieve depression
Stimulation X-ray of a human brain or compulsive behaviors. Stimulation may also make brain tissue more plastic and receptive
showing electrodes implanted in the to other treatments. During stimulation, patients can learn more effective thought and be-
thalamus for DBS. havioral patterns. For many conditions, DBS remains an experimental option of last resort.
It is not a permanent cure: when the stimulation stops, beneficial effects are reduced; hence
the importance of coupling DBS with cognitive-behavioral therapy.
deep brain stimulation (DBs) Neurosurgery Another highly experimental neurosurgical strategy draws on the fixed sequence of pre-
in which electrodes permanently implanted in natal brain development from cell division and cell differentiation to cell migration and
the brain stimulate a targeted area with a low- synaptogenesis. If a brain region is functioning abnormally or if it is diseased or dead, as
voltage electrical current to facilitate behavior.
occurs in TBI or after a stroke, it should be possible to return this region to the embryonic
state and regrow a healthy region. The use of so-called induced neurogenesis has a science
Figure 14-26 shows neurogenesis induced in fiction ring but may someday be feasible. In laboratory rats, for example, stem cells can be
a rat brain to repair a cortical stroke. induced by neurotrophic factors to generate new cells that can migrate to the site of an injury.
In the 1980s, neurosurgeons experimented with implanting fetal stem cells in adult
brains. Success was limited due to difficulties in cell placement and connections and rejec-
tion by the patient’s immune system. Another restorative idea comes from the discovery that
multipotent stem cells in other body regions, such as bone marrow and skin, appear capable
of manufacturing neural stem cells. Indeed, using appropriate manipulations, any cell can
Figure 8-8 diagrams the origins of specialized potentially be returned to a stem cell state. The advantage is that the patient’s own cells are
brain cells from multipotent neural stem cells. not rejected by the immune system.
If people’s own multipotent stem cells prove practical for generating neural stem cells, it
should be possible to extract stem cells, place them in a special culture medium to generate
thousands or millions of cells, and place these stem cells in the damaged brain. The cells
would be instructed to differentiate appropriately and develop the correct connections. Stem
cell transplantation is taken seriously today as a potential treatment for disorders such as TBI
and stroke, but it remains largely at an investigative stage (Savitz, 2015).
Electrophysiological Treatments
Treating the mind by treating the body is an ancient notion. In the 1930s, researchers used
insulin to lower blood sugar and produce seizures as a treatment for depression. By the 1950s,
insulin therapy had been replaced by electroconvulsive therapy (ECT), the first electrical
brain stimulation treatment.
ECT was developed as a treatment for otherwise untreatable depression, and although
its mode of action was not understood, it did prove useful. Although rarely used today, ECT
sometimes remains the only treatment that works for people with severe depression. One
Neurotrophic factors, nourishing chemical reason may be that it stimulates the production of a variety of neurotrophic factors, espe-
compounds, support neuronal growth, cially BDNF (brain-derived neurotrophic factor), that in turn restore inactive cells to a more
development, and viability. active mode.
Problems with ECT include the massive convulsions electrical stimulation causes. Large
doses of medication are normally required to prevent them. ECT also leads to memory loss,
a symptom that can be troublesome with repeated treatments. A noninvasive technique,
Figure 7-7 diagrams how TMS works. transcranial magnetic stimulation (TMS), uses magnetic rather than electrical stimulation.
16-2 • Classifying and Treating Brain and Behavioral Disorders 573
ReseaRch F cus 16-2
Treating Behavioral Disorders with Transcranial Magnetic Stimulation
In transcranial magnetic stimuation (TMS) a magnetic coil placed over the The primary clinical use of TMS, which the U.S. Food and Drug
scalp induces an electrical current in underlying brain regions. TMS can Administration formally approved in 2008, is for depression. Numerous
be applied to localized brain regions (focal areas) thought to be implicated studies report positive effects using TMS, but the required duration of treat-
in specific disorders. Manipulation of the magnetic field can stimulate an ment and the duration of beneficial effects remains under investigation.
area of cortex as small as a quarter—the cortical surface only or deeper The effects of brief pulses of TMS do not outlive the stimulation.
layers of brain tissue. Repetitive TMS (rTMS), however, which involves continuous stimulation
for up to several minutes, produces longer-lasting effects. What is
needed to fully evaluate TMS effects in alleviating depression is a dou-
ble-blind study, in which both therapists and patients are unaware of
whether real or sham stimulation is administered (Serafini et al., 2015).
In addition to treating depression, small but promising studies have
extended the possible benefits of TMS to schizophrenic auditory hallu-
cinations, anxiety disorders, neurodegenerative diseases, hemiparesis,
and pain syndrome (Wassermann & Zimmerman, 2012).
Among the problems in all studies of TMS are questions related
to the duration and intensity of stimulation and also to the area stim-
Marcello Massimini/University of Milan
ulated. Each person’s brain is slightly different, so to ensure that
appropriate structures are stimulated, MRI must be performed on
each subject.
Does TMS stimulation make the brain more plastic? If so, can
learning be enhanced? The idea is, when a train of TMS is delivered,
it produces a change in cortical excitability. This change in turn fa-
cilitates learning. Indeed, combined TMS and training can improve
In clinical therapy for depression, TMS influences neural activity the therapeutic effects of motor or cognitive training given alone
in a localized brain area. (Nevler & Ash, 2015).
Magnetic stimulation can be applied to a localized brain region. Anesthesia is not necessary.
TMS is an FDA-approved treatment for depression. Clinical applications, reviewed in Re-
search Focus 16-2, Treating Behavioral Disorders with Transcranial Magnetic Stimulation,
are growing.
Pharmacological Treatments
Several accidental discoveries, beginning in the 1950s, led to a pharmacological revolution
in the treatment of behavioral disorders:
1. The development of phenothiazines (neuroleptics) to treat schizophrenia stemmed from
a drug used to premedicate surgical patients. In the following decades, neuroleptic drugs
became increasingly more selective, and they remain effective.
2. A new class of antianxiety drugs was invented: the anxiolytics. Medications such as
Valium quickly became—and remain—the most widely prescribed drugs in the United
States.
3. l-Dopa provided the first drug treatment for serious motor dysfunction in Parkinson
disease. Once taken, l-dopa is converted into and replaces dopamine lost due to Parkinson
disease.
The power of psychoactive drugs to change disordered behavior revolutionized the phar-
maceutical industry. The central goal is developing drugs that can act as magic bullets to
correct the chemical imbalances found in various disorders. Research is directed toward
making drugs more selective in targeting specific disorders while producing fewer side ef-
fects. Both goals have proved difficult to achieve.
574 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
Pharmacological treatments have significant downsides. Acute and chronic side effects
top the list, and long-term use may cause new problems. Consider a person who receives anti-
depressant medication. The drug may ease the depression but it may also produce unwanted
side effects, including decreased sexual desire, fatigue, and sleep disturbance. The last two
effects may also interfere with cognitive functioning.
Thus, although a medication may be useful for getting a person out of a depressed state,
it may produce other symptoms that are themselves disturbing and may complicate recov-
ery. Furthermore, in depression related to a person’s life events, a drug does not provide the
Section 6-2 classifies psychoactive drugs and behavioral tools needed to cope with an adverse situation. Some psychologists say, “A pill is
their therapeutic effects. not a skill.”
Negative side effects of drug treatments are evident in many people whose schizophrenia
is being treated with neuroleptics. Antipsychotic drugs act on the mesolimbic dopamine sys-
Homing
Drug peptide tem, which affects motivation, among other functions. The side effect emerges because the
drugs also act on the nigrostriatal dopaminergic system, which controls movement. Patients
who take neuroleptics also eventually develop motor disturbances. Tardive dyskinesia, an
inability to stop the tongue, hands, or other body parts from moving, is a motor symptom of
long-term neuroleptic administration. Side effects of movement disorders can persist after
the psychoactive medication has been stopped. Taking drugs for behavioral disorders, then,
does carry risk. Rather than magic bullets, these medications often act like shotguns.
Despite their drawbacks, drugs do prove beneficial for many people. Improved drug chem-
istry will reduce side effects, as will improved delivery modes that bring a drug to a target sys-
tem with minimal effects on other systems. One improved delivery system uses nanoparticles
called liposomes, biosynthetic molecules 1 to 100 nm (nanometers, or billionths of a meter) in
Phospholipid size. One natural biological nanoparticle, with a radius of about 40 nm, is the synaptic vesicle
bilayer
that houses a neurotransmitter for delivery into the cell’s extracellular space. Liposomes
Liposome for Drug Delivery
Biosynthetic vesicles can deliver microscopic consisting of a synthetic vesicle with a homing peptide on the surface can, in principle, be
drugs or DNA to the body’s cells. Synthetic constructed to carry a drug across the blood–brain barrier and deliver it to specified types of
biology is a topic in Section 7-1. neuron or glial cells within the nervous system.
Behavioral Treatments
Treatments for behavioral disorders need not be direct biological or medical interventions.
Just as the brain can alter behavior, behavior can alter the brain. Behavioral treatments
focus on key environmental factors that influence how a person acts. As behavior changes
in response to treatment, the brain is affected as well.
An example is treatment for generalized anxiety disorders attributed to chronic stress.
People who endure a persistently high anxiety level often engage in maladaptive behaviors
to reduce it. While they require immediate treatment with antianxiety medication, long-term
treatment entails changing their behavior. Generalized anxiety disorder is not simply a prob-
Focus 12-3 recounts a case of generalized lem of abnormal brain activity but also of experiential and social factors that fundamentally
anxiety disorder. alter the person’s perception of the world.
Perhaps you are thinking that behavioral treatments may help somewhat in treating brain
dysfunction, but the real solution must lie in altering brain activity. Since every aspect of
behavior is the product of brain activity, behavioral treatments do act by changing brain
function. If people can change how they think and feel about themselves or some aspect of
their lives, this change has taken place because talking about their problems or resolving a
problem alters how their brain functions. In a sense then, a behavioral treatment is a biologi-
cal intervention. Behavioral treatments may sometimes be helped along by drug treatments
that make the brain more receptive to change through behavioral therapy. In this way, drug
treatments and behavioral treatments have synergistic effects, each helping the other to be
more effective.
Your behavior is a product of all your learning and social experiences. An obvious
approach to developing a treatment is to re-create a learning environment that replaces a
maladaptive behavior with an adaptive behavior. Thus, the various approaches to behavioral
16-2 • Classifying and Treating Brain and Behavioral Disorders 575
treatment use principles derived from experiment-based learning theory. Following is a sam-
pling of these approaches.
BehaviOr mOdifiCatiOn Behavioral therapies apply well-established learning principles
to eliminate unwanted behaviors. Therapists apply principles developed in studying learning
by reinforcement in laboratory settings, including operant and classical conditioning. For ex-
ample, if a person is debilitated by a fear of insects, rather than looking for inner causes, the
behavioral therapist tries to replace the maladaptive behaviors with more constructive ways
of behaving. These might include training the patient to relax while systematically exposing
him to unthreatening insects (butterflies) followed by gradual exposure to more threatening
insects (bees). This form of habituation (adaption to a repeatedly presented stimulus) is called
systematic desensitization.
COgnitive therapy Cognitive therapy operates from the perspective that thoughts
intervene between events and emotions. Consider responses to losing a job. One thought
could be, I’m a loser, life is hopeless. An alternative thought is, The job was a dead end. The
boss did me a favor. The former cognition might lead to depression, whereas the latter would
not. Cognitive therapies challenge a person’s self-defeating attitudes and assumptions and
are important for people with brain injury too, because it is easy for people to think that they
are crazy or stupid after brain injury. Equally if not more powerful is cognitive-behavioral
therapy, discussed in Section 16-4.
Lea Paterson/Science Source
neurOpSyChOlOgiCal therapy If a relative or friend had a stroke and became apha-
sic, you would expect him or her to attend speech therapy—a behavioral treatment for an
injured brain. The logic in speech therapy is that by practicing (relearning) the basic compo-
nents of speech and language, the patient should be able to regain at least some lost function.
The same logic can apply to other types of behavioral disorders, whether motor or cognitive.
Therapies for cognitive disorders resulting from brain trauma or dysfunction aim to retrain Systematic desensitization for a phobia,
people in the fundamental cognitive processes they have lost. Although cognitive therapy the most common among anxiety
seems as logical as speech therapy after a stroke, cognitive therapy assumes that we know disorders, as Focus 12-3 reports.
what fundamental elements of cognitive activity are meaningful to the brain. Cognitive sci-
entists are far from understanding these elements well enough to generate optimal therapies.
Still, neuropsychologists are developing neurocognitive programs that can improve func-
tional outcomes following TBI and stroke (Mateer & Sira, 2006; Sohlberg & Mateer, 1989).
Treatment effectiveness can be improved with computer-based tools and follow-up therapy.
emOtiOnal therapy In the 1920s, Sigmund Freud developed the idea that talking about
emotional problems enables people to gain insights into the causes of the problems and
serves as treatment too. Talk cures and other forms of psychological intervention may be
broadly categorized as psychotherapies.
Since Freud’s time, many ideas have been put forth about the best type of therapy for
emotional disorders. Key here is that for many disorders, whether neurological or psychiatric, tardive dyskinesia Inability to stop the
medical treatments are not effective unless patients also receive psychotherapy. Indeed, the tongue or other body parts from moving;
only effective treatment in many cases lies in addressing the unwanted behaviors directly— motor side effect of neuroleptic drugs.
in acquiring the skill rather than taking the pill. behavioral therapy Treatment that applies
Consider a 25-year-old woman pursuing a promising career as a musician who suffered learning principles, such as conditioning, to
a traumatic brain injury in an automobile accident. After the accident, she found that she eliminate unwanted behaviors.
was unable to read music. Not surprisingly, she soon became depressed. Part of her therapy cognitive therapy Psychotherapy based
required her to confront her disabling cognitive loss by talking about it rather than by simply on the perspective that thoughts intervene
stewing over it. Only when she pursued psychotherapy did she begin to recover from her between events and emotions, and thus the
intense depression. treatment of emotional disorders requires
For many people with emotional impairments resulting from brain disease or trauma, changing maladaptive patterns of thinking.
the most effective treatment for depression or anxiety is helping them adjust by encourag- psychotherapy Talk therapy derived
ing them to talk about their difficulties. Group therapy provides such encouragement and is from Freudian psychoanalysis and other
standard treatment in brain injury rehabilitation units. psychological interventions.
576 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
phySiCal aCtivit y and muSiC aS therapy Exercise and music
have positive effects on peoples’ attitudes, emotional well-being, and brain
function. Physical exercise demands visual control of movement. Music
affects arousal and activates the motor and premotor cortex. Listening to
music can improve gait in Parkinson and stroke patients and reduce pain
post surgery. Learning to play a musical instrument likewise is beneficial
therapy (François et al., 2015). Singing, a useful adjunct to rehabilitative
speech therapy, enhances the ability to enunciate. Physical activity, in-
cluding dancing and playing sports, combined with other therapies, im-
proves well-being and counteracts the effects of depression.
real-time fmri Using this behavior-modification technique, individu-
David Braun/Masterfile
als learn to change their behavior by controlling their own brain activation
patterns. Real-time fMRI was first used to treat intractable pain, which
produces a characteristic brain activity pattern (deCharms, 2008). The re-
searchers proposed that if subjects could see their brain activity via fMRI
Exercise boosts your mood because it in real time as they felt pain, they could be trained to reduce the neural ac-
boosts your dopamine levels. Section 10-4 tivity and lessen their pain. Real-time fMRI (rt-fMRI) uses a form of operant conditioning in
observes that practitioners have only begun
which the gradual modification of a participant’s behavior increases the probability of reward.
to tap music’s power as a therapeutic tool.
Think of rt-fMRI as a form of neural plasticity in which the individual learns new strate-
gies, guided by brain activation information. When subjects decrease brain activation in
Focus 11-5 describes an effective low-tech regions associated with pain, they report decreased pain perception. Conversely, through
strategy for controlling phantom limb pain. learning to increase brain activation in these regions, they would be able to increase their
pain—although it seems unlikely that this ability would be much cultivated! An actual po-
tential application of rt-fMRI is in monitoring brain activation when treatment for disorders
occurs in the context of behavioral therapy. Patients need not be consciously aware of the
therapy’s objectives: induced brain changes, whether conscious or unconscious, can prove
beneficial (Birbaumer et al., 2013).
virtual reality therapy The principle behind VR therapy is that patients enter or in-
teract with a virtual world displayed on a computer screen or through goggles. One example
is the Virtual Iraq and Afghanistan Simulation described in Research Focus 16-1. The par-
real-time fMRI (rt-fMRI) Behavior- ticipant can experience sights, sounds, even smells that mimic situations related to acquiring
modification technique in which individuals the behavioral disorder, in this case PTSD. In modified VR therapy a patient interacts as
learn to change their behavior by controlling a character in a computer game. Winning the game necessitates making adaptive choices;
their own patterns of brain activation. maladaptive choices result in losing the game (Shin et al., 2015).
16-2 review
Classifying and Treating Brain and Behavioral Disorders
Before you continue, check your understanding.
1. Three classifications of behavioral disorders are , , and .
2. is the study of the distribution and causes of diseases in human populations.
3. Developments in and have enabled their use in identifying
brain and behavior disorders.
4. Four treatment categories for behavioral disorders are , ,
, and .
5. A therapy in which an electrode delivers stimulation directly to the brain is called .
6. An effective replacement for electroconvulsive therapy (ECT) is .
7. Why are classification systems useful even though they are inexact?
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
16-3 • Understanding and Treating Neurological Disorders 577
16-3 Understanding and Treating
Neurological Disorders
In everyone’s lifetime, at least one close friend or relative will develop a neurological disor-
der, even if we ourselves escape them. Disorder causes are understood in a general sense,
and for most, rehabilitative treatment is emerging. In this section we review some common
neurological disorders: traumatic brain injury, stroke, epilepsy, multiple sclerosis, and neu-
rodegenerative disorders.
Traumatic Brain Injury
Traumatic brain injury (TBI), a wound to the brain that usually results from a blow to the
head, is the most common form of brain damage in people under age 40. TBI commonly
results from the head making impact with other objects—as can occur in automobile and
industrial accidents and in sports injuries. TBI can also follow blows to the chest that result
in a rapid increase in blood pressure, which can damage the brain indirectly. The incidence
of TBI is about eight times that of breast cancer, AIDS, spinal cord injury, and multiple
sclerosis combined.
The two most important factors in the incidence of head trauma are age and sex. Children Section 14-5 details a dancer’s recovery
and elderly people are more likely to injure their head in a fall than are others, and males from TBI.
between 15 and 30 incur brain injury especially in automobile and motorcycle accidents
(Figure 16-5). A child’s chance of having significant traumatic brain injury before he or she
is old enough to drive is 1 in 30.
1400 Figure 16-5 Incidence Rates of
1200 Head Trauma Based on combined
Rate per 100,000
1000 reports of emergency room visits,
Male hospitalizations, and deaths, this chart
800
graphs the estimated frequency of TBI in
600
males and females across the life span.
400
Information from the Centers for Disease Control.
200 Female
TBI in the United States: Emergency department visits,
0 hospitalizations, and deaths, 2004 (report).
0–4 5–9 10–14 15–19 20–24 25–34 35–44 45–54 55–64 65–74 75
Age group (years)
Concussion is a critical concern for both professional and amateur athletes, especially
those who play football, ice hockey, lacrosse, soccer, and no less for those on active military
duty. Sports account for about 20 percent of TBIs, and the U.S. Army Institute of Surgical
Research reports that traumatic brain injury affects more than 1 in 5 U.S. soldiers wounded
in war.
A large-scale longitudinal study is under way in cooperation with football and ice In longitudinal research, over time
hockey players who have a history of concussion and who have agreed to donate their investigators repeatedly observe or examine
brain for postmortem analysis. Preliminary examination of the brains of deceased pro- subjects with respect to the study’s
fessional football players who had a history of concussion and severe postconcussion variable(s).
symptoms, described in Clinical Focus 16-3, Concussion, reveal extensive, diffuse loss of
cerebral tissue.
Symptoms and Outcome of Brain Trauma
TBI can cause direct damage to the brain. Trauma can disrupt the brain’s blood supply,
induce bleeding (leading to increased intracranial pressure), cause swelling (leading to in-
creased intracranial pressure), expose the brain to infection, and scar brain tissue (the scar
578 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
clinical F cus 16-3
Concussion
Ann C McKee MD VA Boston/
Boston University School of Medicine
Early in 2011, 50-year-old former Chicago
Bears defensive back Dave Duerson shot
himself in the chest and died. He left a
note asking that his brain be studied. Du-
erson had played 11 years in the National
Football League, won two Super Bowls,
and received numerous awards.
As a pro player he endured at least
10 concussions, but they did not seem
serious enough to cause him to leave
the game. After retiring from football,
he went to Harvard and obtained a busi-
ness degree. He pursued a successful
business career until he began to have
Dave Duerson’s Brain Staining for tau protein highlights degenerating brain tissue (dark
trouble making decisions and controlling
brown areas) in the frontal cortex and medial temporal lobe of these coronal sections through
his temper. Duerson’s anterior right hemisphere. Damage to the subcortical basal ganglia in the sections’ central
Eventually, Duerson’s business and portions (yellowish areas) is sparse by comparison.
marriage failed. After his suicide, the
Center for the Study of Traumatic Encephalopathy in Boston did study The relationship between concussion in early life and later de-
his brain. The Center is conducting postmortem anatomical analyses generative brain disease suggests that concussion can initiate a cas-
of the brains of former athletes as part of a long-term longitudinal cade of pathological events that over years develop into CTE. CTE is
study. characterized by neurofibrillary tangles, plaques, and neuronal death.
Duerson’s diagnosis, chronic traumatic encephalopathy (CTE), is Cerebral atrophy and expanded ventricles due to cell loss are typical
a progressive degenerative disease found in individuals with a history in advanced cases. As shown in the illustration, researchers test for
of multiple concussions and other closed-head injuries. (A variant long cell death by staining for accumulation of the tau protein, which is
associated with boxing is dementia pugilistica, or DP.) associated with neuronal death and so is a sensitive marker for brain
Concussion, the common term for mild traumatic brain injury (MTBI), trauma.
is common in sports, especially contact sports, including American foot- The unknowns about CTE are many. Is just one or are many concus-
ball, ice hockey, and rugby. Concussion also results from falls in many sions required to initiate a cascade that results in CTE? Are individu-
other sports and from vehicular accidents. It is likely that the incidence als who get CTE especially susceptible? What constitutes a concussion?
of concussion is higher than 6 per 1000 individuals. Should blows to the head that result in no pronounced symptoms be
Concussion often goes unrecognized. For those that are diagnosed, distinguished from blows that result in loss of consciousness?
little apparent pathology appears after relatively short periods of rest, What we do know is that many well-known athletes, especially foot-
the usual treatment. Nevertheless, the relationship is well established ball and ice hockey players, have developed CTE. Clearly, much more
between concussion and a range of degenerative diseases that occur care needs to be taken, beginning in childhood, to prevent concussion
later in life—dementias, including Alzheimer disease, as well as Parkinson and to ensure that concussion is treated, even though what constitutes
disease, motor neuron disease, and CTE. adequate treatment remains uncertain (Rose et al., 2015).
being a focus for later epileptic seizures). The disruption in blood supply tends to be brief,
but a parallel disruption of energy production by neuronal mitochondria, which can persist
for weeks, is related to many postconcussion behavioral symptoms.
Traumatic brain injury is commonly accompanied by a loss of consciousness that may
be brief (minutes) or prolonged (coma). Duration of unconsciousness can serve as a measure
of the severity of damage, because it correlates directly with mortality, intellectual impair-
Section 1-2 presents a case study on ment, and deficits in social skills. The longer coma lasts, the greater the possibility of serious
recovering consciousness following TBI. impairment or death.
Two kinds of behavioral effects result from TBI: (1) impairment of specific functions
mediated by the cortex at the coup (the site of impact) or contrecoup (opposite side) lesion,
16-3 • Understanding and Treating Neurological Disorders 579
Figure 16-6 Mechanics of TBI Pink
A variety of mechanical and blue shading mark brain regions most
forces cause traumatic frequently damaged in closed-head injury.
brain injuries as a result A blow can produce a contusion both at
of a blow to the head.
the site of impact and on the opposite
side of the brain, owing to rebound
compression.
Damage at the site of impact is
called a coup (shown in pink).
Direction of blow Direction of blow
Pressure resulting from a coup
produces a contrecoup on the
opposite end or side of the brain
(shown in blue).
Movement of the brain may shear nerve fibers, causing microscopic
lesions, especially in frontal and temporal lobes. Blood trapped in the
skull (hematoma) and swelling (edema) cause pressure on the brain.
as illustrated in Figure 16-6, and (2) more generalized impairments from widespread trauma
chronic traumatic encephalopathy (cTE)
throughout the brain. Discrete impairment is most commonly associated with damage to
Progressive degenerative disease caused
the frontal and temporal lobes, the brain areas most susceptible to TBI. (See tissue samples by multiple concussions and other closed-
in Focus 16-3.) head injuries, characterized by neurofibrillary
More generalized impairment results from minute lesions and lacerations scattered tangles, plaques, cerebral atrophy, and
throughout the brain. Movement of the hemispheres in relation to one another causes tear- expanded ventricles due to cell loss.
ing characterized by a loss of complex cognitive functions, including mental speed, concen- magnetic resonance spectroscopy (MRs)
tration, and overall cognitive efficiency. Modification of MRI to identify changes
TBI patients generally complain of poor concentration or lack of ability. They fail to do in specific markers of neuronal function;
things as well as they could before the injury, even though their intelligence is unimpaired. promising for accurate diagnosis of traumatic
In fact, in our experience, people with high skill levels seem to be the most affected by TBI, brain injuries.
in large part because they are acutely aware of loss of a skill that prevents them from return-
ing to their former competence level.
Traumatic brain injury that damages the frontal and temporal lobes also tends to
significantly affect personality and social behavior. Few victims of traffic accidents
who have sustained severe head injuries ever resume their studies or return to gainful
employment. If they do reenter the work force, they do so at a lower level than before their
accident.
One frustrating problem with traumatic brain injury is misdiagnosis: chronic effects of
injuries often are unaccompanied by any obvious neurological signs or abnormalities in CT
or MRI scans. Patients may therefore be referred for psychiatric or neuropsychological evalu-
ation. MRI-based imaging techniques such as magnetic resonance spectroscopy (MRS),
however, are useful for accurate TBI diagnosis (Reis et al., 2015).
MRS, a modification of MRI, can identify changes in specific markers of neuronal func-
tion. One such marker is N-acetylaspartate (NAA), the second most abundant amino acid
in the human brain. Assessing the level of NAA expression provides a measure of neuronal
integrity, and deviations from normal levels (up or down) can be taken as a marker of abnor-
mal brain function. People with traumatic brain injury show a chronic decrease in NAA that
correlates with the severity of the injury. Although not yet in wide clinical use, MRS is a Section 7-3 introduces the MRS technique.
promising tool, not only for identifying brain abnormalities but also for monitoring cellular
response to therapeutic interventions.
580 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
Recovery from Traumatic Brain Injury
Recovery from head trauma may continue for 2 to 3 years and longer, but most cognitive
recovery occurs in the first 6 to 9 months. Recovery of memory functions appears to be
slower than recovery of general intelligence, and the final level of memory performance is
lower than for other cognitive functions. People with brainstem damage, as inferred from
oculomotor disturbance, have a poorer cognitive outcome, and a poorer outcome is probably
true of people with initial dysphasias or hemiparesis as well.
Although the prognosis for significant recovery of cognitive functions is good, optimism
about the recovery of social skills or personality traits, areas that often show significant
change, is less rosy. Findings from numerous studies support the conclusions that quality of
life—in social interactions, perceived stress levels, and enjoyment of leisure—is significantly
reduced after TBI and that this reduction is chronic. Attempts to develop tools to measure
changes in psychosocial adjustment in brain-injured people are few, so we must rely largely
on subjective descriptions and self-reports. Neither provides much information about the
specific causes of these problems (Block et al., 2015).
Stroke
Diagnosticians may be able to point to a specific immediate cause of stroke, an interruption
of blood flow from either blockage of a vessel or bleeding from a vessel. This initial event,
however, merely sets off a sequence of damage that progresses, even if the blood flow is
restored. Stroke results in a lack of blood, called ischemia, followed by a cascade of cellular
Focus 2-3 describes the symptoms and events that wreak the real damage. Changes at the cellular level can seriously compromise
aftereffects of stroke. not only the injured part of the brain but other brain regions as well.
Effects of Stroke
Consider what happens after a stroke interrupts the blood supply to a cerebral artery. In the
first seconds to minutes after ischemia, as illustrated in Figure 16-7, changes begin in the
affected regions’ ionic balance, including changes in pH and in the properties of the cell
membrane. These ionic changes result in several pathological events.
1. Release of massive amounts of glutamate results in prolonged opening of calcium
channels in cell membranes.
Figure 5-4 shows how calcium affects 2. Open calcium channels in turn allow toxic levels of calcium to enter the cell, not only
neurotransmitter release; Figure 5-15, how producing direct toxic effects but also instigating various second-messenger pathways that
metabotropic receptors can activate second can harm neurons. In the ensuing minutes to hours, mRNA is stimulated, altering protein
messengers. production in the neurons and possibly proving toxic to the cells.
3. Brain tissues become inflamed and swollen, threatening the integrity of cells that may
be far removed from the stroke site. As in TBI, an energy crisis ensues as mitochondria
reduce their production of ATP, resulting in less cerebral energy.
4. A form of neural shock occurs. During this diaschisis, areas distant from the damage are
functionally depressed. Thus, not only are local neural tissue and its function lost but areas
related to the damaged region also undergo a sudden withdrawal of excitation or inhibition.
5. Stroke may also be followed by changes in the injured hemisphere’s metabolism, its
ischemia Lack of blood to the brain, usually glucose utilization, or both. These changes may persist for days. As with diaschisis,
as a result of a stroke. the metabolic changes can severely affect the functioning of otherwise healthy tissue.
diaschisis Neural shock that follows brain For example, after a cortical stroke, metabolic rate has been shown to decrease about
damage in which areas connected to the 25 percent throughout the hemisphere.
site of damage show a temporary arrest of
function. Treatments for Stroke
neuroprotectant Drug used to try to block The ideal treatment is to restore blood flow in blocked vessels before the cascade of nasty
the cascade of poststroke neural events. events begins. One clot-busting drug is tissue plasminogen activator (t-PA), but t-PA must be
16-3 • Understanding and Treating Neurological Disorders 581
administered within 3 to 5 hours to be effective. Currently, only a small percentage of stroke use the f.a.s.t. test to spot stroke
patients arrive at the hospital soon enough, in large part because stroke is not quickly identi-
fied, transportation is slow, or the stroke is not considered an emergency. Face Ask for a smile to check both under-
standing and muscle control.
Other drugs called neuroprotectants can be used to try to block the cascade of postinjury
events, but to date we have no truly effective drugs. Clinical trials based on animal stud- Arms Check if one arm is weak by asking
ies have generally failed, in part because understanding what the appropriate brain targets the person to raise both arms.
should be is limited. speech Listen for slurred speech.
When the course of the stroke leads to dead brain tissue, the only treatments that can Time If you see any symptom, call 911 or the
be beneficial are those that facilitate plastic changes in the remaining brain. Examples are local emergency services number right away.
speech therapy and physical therapy. Revolutionary approaches to stroke rehabilitation use
virtual reality, computer games, and robotic machines (Laver et al., 2015).
Still, some simple treatments are surprisingly effective. One is constraint-induced therapy, Experiment 11-3 describes research with
pioneered by Edward Taub in the 1990s (Kawakkel et al., 2015). Its logic confronts a problem monkeys that contributed to developing
in poststroke recovery related to learned nonuse. Stroke patients with motor deficits in a limb constraint-induced therapy for people.
often compensate by overusing the intact limb, which in turn leads to increased loss of use
in the impaired limb.
In constraint-induced therapy, the intact limb is held in a sling for several
hours per day, forcing the patient to use the impaired limb. Nothing about the Ionic Second
changes messengers
procedure is magical: virtually any treatment that forces patients to practice be-
mRNA Proteins Inflammation Recovery
haviors extensively is successful. An important component of these treatments, 100
however, is a posttreatment contract in which the patients continue to practice
after the formal therapy is over. If they fail to do so, the chances for learned non-
Response (%)
use and a return of symptoms are high.
Another common effect of stroke is loss of speech. Specific speech therapy 50
programs can aid in the recovery of speech. Music and singing, mediated in part
by the right hemisphere, can augment speech therapy after left hemisphere
stroke.
Therapies using pharmacological interventions (e.g., noradrenergic, dopami- 0
Seconds Hours Weeks to
nergic, cholinergic agonists) combined with behavioral therapies provide equivo- to minutes to days months
cal gains in stroke patients. The bulk of evidence suggests that patients with
Figure 16-7 Results of Ischemia A
small gray matter strokes are most likely to show benefits from these treatments, cascade of events takes place after blood
whereas those with large strokes that include white matter show little benefit. flow is blocked as a result of stroke. Within
Finally, there have been many attempts to use either direct cortical stimulation or TMS in seconds, ionic changes at the cellular
combination with behavioral therapy as a stroke treatment. The idea is to induce plasticity in level spur changes in second-messenger
molecules and RNA production. Changes
regions adjacent to the dead tissue with the goal of enhancing the efficiency of the residual
in protein production and inflammation
parts of the neuronal networks. These treatments have proved beneficial in patients with follow and resolve slowly, in hours to days.
good residual motor control, but again, those with larger injuries show much less benefit, Recovery begins within hours to days and
presumably because the residual neuronal network is insufficient. continues for weeks to months or years.
Epilepsy
Epilepsy is characterized by recurrent seizures, which register on an electroencephalogram
(EEG) as highly synchronized neuronal firing indicated by a variety of abnormal waves. Focus 4-1 describes a diagnosis of epilepsy
About 1 person in 20 has at least one seizure in his or her lifetime, usually associated with an and shows an EEG being recorded.
infection, temperature, and hyperventilation during childhood (6 months to 5 years of age).
Most children who experience a seizure do not develop epilepsy, which affects between 0.2
percent and 4.1 percent of the population. Developed nations record a lower prevalence and
incidence of epilepsy compared with developing nations.
Classifying Seizures
Causes of epileptic seizures are categorized as genetic, structural/metabolic, or unknown.
Genetic epilepsy results directly from a known genetic defect. Causes of structural/metabolic
epilepsy include brain malformations and tumors, acquired disorders such as stroke and
582 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
Structural or metabolic epilepsy may result
from brain malformations such as angioma,
Simon Fraser/Royal Victoria Infirmary/Newcastle Upon Tyne/Science
or AV malformation, shown on this dorsal
view MRI. Abnormal cerebral blood vessels
(in white) form a balloonlike structure
(blue area at lower right) that caused the
death of brain tissue around it in the right
occipital cortex.
Photo Library/Science Source
trauma, and infections. The unknown category encompasses causes yet to be identified.
Table 16-4 summarizes the great variety of circumstances that appear to precipitate a
seizure. The range of circumstances is striking, but seizures do have a consistent feature:
table 16-4 factors that may they are most likely to occur when a person is sleeping.
Precipitate seizures in Seizures are classified by the way participating neural networks are distributed.
susceptible Persons Focal seizures arise from a synchronous, hyperactive local brain region. Thus, focal sei-
zures may have motor, sensory, autonomic, and/or psychogenic features. Focal seizures
Drugs are further classified as to whether awareness is retained or altered (dyscognitive seizure).
Alcohol
Generalized seizures may start at a focal location, then spread rapidly and bilaterally to
distributed networks in both hemispheres. In primary generalized epilepsy, seizures begin in
Analeptics
more widespread neural networks. Seizure diagnosis is improved by the use of a wearable
Excessive anticonvulsants device that records them (Gubbi et al., 2015).
Phenothiazines People having a seizure may cycle through the four stages charted in Figure 16-8: (1)
normal EEG record before onset; (2) onset and tonic phase, in which the body stiffens; (3)
Tricyclic antidepressants
clonic phase, in which the person makes rhythmic movements in time with the large, highly
Emotional stress synchronized discharges; and (4) a period of depressed EEG activity after the seizure ends.
Fever For the most part, seizures self-terminate. In some cases, termed status epilepticus, the
seizure’s driving force does not abate, often due to a brain insult or to drug withdrawal. In
Hormonal changes
this life-threatening condition, drug intervention with a fast-acting GABA agonist or gluta-
Adrenal steroids
mate antagonist is required to end the seizure. Death due to status epilepticus is much more
Adrenocorticotrophic hormone (ACTH) common in adults than in children (26 percent vs. 3 percent, respectively), and survivors
Menses often live with significant brain damage. The recommended time limit before intervention
is 5 minutes. Longer-lasting seizures are unlikely to self-terminate.
Puberty
People with epilepsy die unexpectedly at a rate 24 times that of the general population.
Hyperventilation Sudden unexpected death in epilepsy (SUDEP) has no identifiable cause (such as status epilep-
sensory stimuli ticus, drowning, or falling). Most evidence suggests that SUDEP occurs during or more often
after a seizure. Respiratory and cardiac failure may be common causes, but events leading
Flashing lights
up to SUDEP have yet to be characterized.
Laughing
Reading, speaking, coughing Treating Epilepsy
The first-line treatment for epilepsy is drugs to inhibit seizure development and propaga-
Sounds: music, bells
tion. Among the diverse range of mechanisms drugs employ to raise seizure thresholds are
sleep enhancing the action of the inhibitory neurotransmitter GABA and stabilizing the inac-
sleep deprivation tive state of sodium channels. Most people with epilepsy work with their physician to find
Trauma a drug and dosage that cause few side effects. In 30 percent to 40 percent of people with
epilepsy, however, antiseizure drugs fail to completely control the condition—intractable
Source: Information from J. H. Pincus & G. J. Tucker
(1974). Behavioral Neurobiology (p. 5). New York: Oxford
epilepsy. The most common treatment for intractable epilepsy in adults is surgical resection
University Press. of epileptogenic tissue, which has a success rate of about 70 percent. Deep-brain stimulation
16-3 • Understanding and Treating Neurological Disorders 583
1 2 3 4 Figure 16-8 Generalized Seizure Patterns Examples of EEG
patterns recorded during a generalized seizure. Dots on the hemispheres
LT below indicate the approximate recording sites. Column numbers mark
the seizure’s stages: (1) normal record before the attack; (2) onset of
RT
seizure and tonic phase; (3) clonic phase; and (4) a period of depressed
EEG activity after the seizure ends. Abbreviations: LT and RT, left and
right temporal; LF and RF, left and right frontal; LO and RO, left and right
LF occipital.
RF
LF RF
LO RO
LO
LT RT
RO
Left Right
may prove useful for intractable epilepsy: bilateral stimulation of the anterior thalamus has
focal seizure Seizure that arises at a
been successful in reducing seizure frequency. While DBS shows promise, more research is
synchronous, hyperactive, localized brain
needed (Ostergard & Miller, 2014).
region (at a focus).
Multiple Sclerosis generalized seizure Seizure that may start
at a focal location then spread rapidly and
In multiple sclerosis (MS), the myelin that encases axons is damaged and neuronal func- bilaterally to distributed networks in both
tions are disrupted. MS is characterized by myelin loss in both motor and sensory tracts and hemispheres.
nerves. The oligodendroglia that form the myelin sheath, and in some cases the axons, are
destroyed. Brain imaging with MRI, as shown in Figure 16-9, identifies areas of sclerosis in
the brain as well as in the spinal cord.
Remission followed by relapse is a striking feature of MS: in many cases, early symptoms
initially are followed by improvement. The course varies, running from a few years to as
long as 50 years. Paraplegia, the classic feature of MS, may eventually confine the affected
person to bed.
Worldwide, about 1 million people have MS; women outnumber men about two to one.
Multiple sclerosis is most prevalent in northern Europe and northern North America, rare
in Japan and in more southerly or tropical countries. Depending on region, incidence of
MS ranges from 2 to 150 per 100,000 people, making it one of the most common structural
nervous system diseases.
The cause or causes of MS are unknown. Proposed causes include bacterial infection, a
virus, environmental factors including pesticides, an immune response of the central ner-
vous system, misfolded proteins, and lack of vitamin D. Often, multiple cases occur in a
Plane of MRI section Lateral ventricles Figure 16-9 Diagnosing MS Imaged
by MRI, discrete multiple sclerosis lesions
appear as dark patches all around the
lateral ventricles and in the brain’s white
Living Art Enterprises, LLC/Science Source
matter.
White matter
Lesions
584 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
single family. Many genes have been associated with MS, but no clear evidence indicates as
yet that MS is inherited or transmitted from one person to another.
Research has focused on the immune system’s relation to MS and the possibility that
Section 4-4 describes another autoimmune MS is an autoimmune disease. The ability to discriminate between a foreign pathogen in
disease, myasthenia gravis. the body and the body itself is central to immune system functioning. If this discrimina-
tion fails, the immune system makes antibodies to a person’s own body, in this case, to
myelin.
As various organisms’ genomes have been sequenced, it has become apparent that all
have many genes in common. Thus the proteins found in different organisms are surpris-
ingly similar. And here is the problem for the human immune system: a foreign microbe may
contain proteins that are nearly identical to the body’s own proteins. If microbe and human
have a common gene sequence, the immune system can mistakenly attack itself, a process
Normal
myelinated known as horror autotoxicus.
nerve fiber Many microbial protein sequences are homologous with structures found in myelin,
which leads to an attack against the microbe and a person’s own myelin. Research showing
Exposed fiber the important role of the immune system in MS has intensified work on developing new
Damaged myelin
Nerve treatments (Kornek, 2015). One strategy is to build up immune system tolerance by inject-
affected ing DNA-encoding myelin antigens and DNA-encoding specific molecules in the cascade of
by MS
steps that leads to oligodendroglial cell death.
That MS is more common in extreme northern and southern latitudes has raised the
possibility that inadequate direct sunlight, which is necessary for the body to synthesize
MS destroys the myelin sheath. Sclerosis
vitamin D, factors into precipitating the condition (Sundström & Salzer, 2015). Lack of
comes from the Greek word for hardness.
understanding whether an acute or a longstanding deficiency is relevant complicates iden-
tifying a possible relationship. Possibly a vitamin D deficiency interacts with other factors
to increase susceptibility to MS. For example, a number of genes are involved in the trans-
port and absorption of vitamin D and variants of these genes are related to low levels of
vitamin D.
Some research has suggested that MS might originate from insufficient blood drainage
from the brain, which can be improved by cleaning or expanding veins from the brain,
including the jugular, to improve drainage. The treatment has been called liberation ther-
apy for its potential relief from a condition of chronic cerebrospinal venous insufficiency
(CCSVI). Internet discussion worldwide has led to Web sites advertising treatment using
vascular surgery for patients with MS. Numerous studies are examining a plethora of ques-
tions related to CCSVI. Primary among them: Is venous flow restricted in people with MS?
Optimism about an outcome has far outpaced the science, which questions the treatment
(Tsivgoulis et al., 2015).
Neurodegenerative Disorders
Human societies have never before undergone the age-related demographic shifts now de-
veloping in North America and Europe. Since 1900, the percentage of older people has in-
creased steadily. In 1900, about 4 percent of the population had attained 65 years of age. By
2030, about 20 percent will be older than 65—about 50 million people in the United States
alone.
autoimmune disease Illness resulting from Dementias affect 1 percent to 6 percent of the population older than age 65 and 10 per-
the loss of the immune system’s ability to cent to 20 percent of those older than age 80. For every person diagnosed with dementia, it
discriminate between foreign pathogens in the is estimated that several others endure undiagnosed cognitive impairments that affect their
body and the body itself. quality of life. Currently, more than 6 million people in the United States have a dementia
dementia Acquired and persistent syndrome diagnosis, a number projected to rise to about 15 million by 2050. By then, 1 million new U.S.
of intellectual impairment characterized cases per year will be emerging. Extending these projections across the rest of the developed
by memory and other cognitive deficits world portends staggering social and economic costs (Khachaturian & Khachaturian, 2015).
and impairment in social and occupational The World Health Organization estimates that by 2050, the incidence of dementia will bal-
functioning. loon to 135.5 million people worldwide.
16-3 • Understanding and Treating Neurological Disorders 585
Types of Dementia table 16-5 Degenerative and nondegenerative Dementias
Dementia is an acquired and persistent syndrome of intel- Degenerative Nondegenerative
lectual impairment. Its two essential features are (1) loss of Alzheimer disease Vascular dementias (e.g., multi-infarct
memory and other cognitive deficits and (2) impairment in Extrapyramidal syndromes dementia)
social and occupational functioning. Dementia is not a singu- (e.g., progressive supernuclear palsy) Infectious dementia (e.g., AIDS
lar disorder, but there is no clear agreement on how to split Wilson disease dementia)
up subtypes. Daniel Kaufer and Steven DeKosky (1999) divide Huntington disease Neurosyphilis
dementias into the broad categories of degenerative and non- Parkinson disease Posttraumatic dementia
degenerative (Table 16-5). Frontal temporal dementia Demyelinating dementia (e.g., multiple
sclerosis)
Nondegenerative dementias, a heterogeneous group of disor- Corticobasal degeneration
Toxic or metabolic disorders (e.g.,
ders with diverse causes, including diseases of the vascular or Leukodystrophies (e.g., vitamin B12 and niacin deficiencies)
endocrine systems, inflammation, nutritional deficiency, and adrenoleukodystrophy)
Chronic alcohol or drug abuse (e.g.,
toxins, are summarized on the right in Table 16-5. The most Prion-related dementias (e.g., Korsakoff syndrome)
prevalent cause is vascular. The most significant risk factors Creutzfeldt-Jakob disease)
for nondegenerative dementias are chronic hypertension, obe- Source: Information from D. I. Kaufer & S. T. DeKosky
(1999). Diagnostic Classifications: Relationship to the
sity, sedentary lifestyle, smoking, and diabetes. All are as well risk factors for cardiovascular Neurobiology of Dementia. In D. S. Charney, E. J. Nestler,
disease. Degenerative dementias, listed on the left in the table, presumably have a degree of & B. S. Bunney (eds). The Neurobiology of Mental Illness
(p. 642). New York: Oxford University Press
genetic transmission.
We now review two degenerative dementias, Parkinson and Alzheimer diseases. Both
pathological processes are primarily intrinsic to the nervous system, and both tend to affect
certain neural systems selectively.
Parkinson Disease
Parkinson disease is common. Estimates of its incidence vary up to 1.0 percent of the popula-
tion, rise sharply in old age, and are certain to grow in coming decades. The disease seems
related to degeneration of the substantia nigra and attendant loss of the neurotransmitter Figure 7-5 diagrams degeneration in the
dopamine produced there and released in the striatum. The disease therefore offers insight substantia nigra associated with Parkinson
into the roles played by the substantia nigra and dopamine in movement control. symptoms.
That Parkinson symptoms vary enormously illustrates the complexity inherent in under-
standing a neurological disorder. A well-defined set of cells degenerates, yet the symptoms
are not the same in every patient. Many symptoms strikingly resemble changes in motor
activity that occurs as a consequence of aging. Thus Parkinson disease offers indirect insight
into more general problems of neural changes in aging.
Symptoms begin insidiously, often with a tremor in one hand and slight stiffness in distal
parts of the limbs. Movements may become slower, the face becoming masklike with loss
of eye blinking and poverty of emotional expression. Thereafter the body may stoop and
the gait become a shuffle, with arms hanging motionless at the sides. Speech may slow and
become monotonous, and difficulty swallowing may cause drooling.
Although the disease is progressive, the rate at which symptoms worsen varies; only
rarely is progression so rapid that a person becomes disabled within 5 years. Usually 10 to
20 years elapse before symptoms cause incapacity. A distinctive aspect of Parkinson dis-
ease is its on-again–off-again quality: symptoms may appear suddenly and just as suddenly
disappear.
Partial remission may also occur in response to interesting or stimulating situations.
Neurologist Oliver Sacks (1998) recounted an incident in which a stationary Parkinson pa- Sacks, whose writings enriched the
tient leaped from his wheelchair at the seaside and rushed into the breakers to save a drown- neurological literature beyond measure, died
ing man, only to fall back into his chair immediately afterward and become inactive again. in 2015.
Remission of some symptoms in activating situations is common but usually not as dramatic
as this case. Simply listening to familiar music can help an otherwise inactive patient get up
and dance, for example. Or a patient who has difficulty walking may ride a bicycle or skate
effortlessly. Such activities can be used as physical therapy, and physical therapy is important
because it may slow disease progression.
586 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
The four major symptoms of Parkinson disease are tremor, rigidity, loss of spontaneous
Positive symptoms are behaviors not typically movement (hypokinesia), and postural disturbances. Each symptom may manifest in differ-
seen in people. Negative symptoms are the ent body parts in different combinations. Because some symptoms entail the appearance of
absence of typical behaviors or inability to abnormal behaviors (positive symptoms) and others the loss of normal behaviors (negative
engage in an activity. symptoms), we consider both major categories.
pOSitive SymptOmS Because positive symptoms are common in Parkinson disease, they
are thought to be inhibited, or held in check, in unaffected people but released from inhibi-
tion in the process of the disease. Following are the three most common:
1. Tremor at rest. Alternating movements of the limbs occur when they are at rest and stop
during voluntary movements or sleep. Hand tremors often have a pill-rolling quality, as if
a pill were being rolled between the thumb and forefinger.
2. Muscular rigidity. Increased muscle tone simultaneously in both extensor and flexor
muscles is particularly evident when the limbs are moved passively at a joint. Movement
is resisted, but with sufficient force the muscles yield for a short distance then resist
movement again. Thus, complete passive flexion or extension of a joint occurs in a series
of steps, giving rise to the term cogwheel rigidity. Rigidity may be severe enough to make
all movements difficult—like moving in slow motion and being unable to speed up the
process.
3. Involuntary movements. Small movements or changes in posture, sometimes referred to
as akathesia, or cruel restlessness, may accompany general inactivity to relieve tremor and
sometimes to relieve stiffness but often occurs for no apparent reason. Other involuntary
movements are distortions of posture, such as occur during oculogyric crisis (involuntary
turns of the head and eyes to one side), which last minutes to hours.
negative SymptOmS After detailed analysis of negative symptoms, Jean Prudin Martin
(1967) divided patients severely affected with Parkinson disease into five groups:
1. Disorders of posture. A disorder of fixation presents as an inability or difficulty in
maintaining a part of the body in its normal position in relation to other parts. A person’s
head may droop forward or a standing person may gradually bend forward, ending up on
the knees. Disorders of equilibrium. These disorders cause difficulties in standing or even
sitting unsupported. In less severe cases, people may have difficulty standing on one leg,
or if pushed lightly on the shoulders, they may fall passively without taking corrective
steps or attempting to catch themselves.
2. Disorders of righting. A person in a supine position has difficulty standing. Many advanced
patients have difficulty in even rolling over.
3. Disorders of locomotion. Normal locomotion requires support of the body against gravity,
stepping, balancing while the weight of the body is transferred from one leg to the other,
and pushing forward. Parkinson patients have difficulty initiating stepping. When they
do walk, they shuffle with short footsteps on a fairly wide base of support because they
have trouble maintaining equilibrium when shifting weight from one leg to the other. On
beginning to walk, Parkinson patients often demonstrate festination: they take faster and
faster steps and end up running forward.
4. Speech disturbances. One symptom most noticeable to relatives is the almost complete
absence of prosody (rhythm and pitch) in the speaker’s voice.
5. Hypokinesia. Poverty or slowness of movement may also manifest itself in a blankness
akathesia Small, involuntary movements or of facial expression, a lack of blinking or of swinging the arms when walking, a lack
changes in posture; motor restlessness. of spontaneous speech, or an absence of normal fidgeting. Akinesia also manifests in
festination Tendency to engage in a difficulty making repetitive movements, such as tapping, even in the absence of rigidity.
behavior, such as walking, faster and faster. People who sit motionless for hours show hypokinesia in its most striking manifestation.
16-3 • Understanding and Treating Neurological Disorders 587
COgnitive SymptOmS Although Parkinson disease is usually viewed as a motor disorder,
changes in cognition occur as well. Psychological symptoms in Parkinson patients are as vari-
able as the motor symptoms. Nonetheless, a significant percentage of patients show cognitive
symptoms that mirror their motor symptoms.
Oliver Sacks (1998) reported impoverishment of feeling, libido, motive, and attention: people
may sit for hours, apparently lacking the will to begin or continue any activity. Thinking seems
generally to be slowed and is easily confused with dementia because patients do not appear to Cognitive slowing in Parkinson patients has
be processing the content of conversations. In fact, they may be simply processing very slowly. some parallels to Alzheimer disease.
CauSeS Of parkinSOniSm The ultimate cause of Parkinson disease—loss of cells in the
substantia nigra—may result from disease, such as encephalitis or syphilis, from drugs such
as MPTP, or from unknown causes. Idiopathic causes—those related to the individual—may
include environmental pollutants, insecticides, and herbicides. Demographic studies of pa-
tient admissions in the cities of Vancouver, Canada, and Helsinki, Finland, show an in-
creased incidence of patients contracting the disease at ages younger than 40. This finding Actor Michael J. Fox, a native of Canada
has prompted the suggestion that water and air might contain environmental toxins that pictured in Focus 5-2, was diagnosed with
work in a fashion similar to MPTP (1-methyl-4-phenylpyridinium), a contaminant that has young-onset Parkinson disease at age 30.
been found in synthetic heroin and causes Parkinson disease.
treating parkinSOn diSeaSe The cure for Parkinson disease
is either to stop degeneration in the substantia nigra or to replace it.
Neither goal is achievable at present. Thus, current treatment is phar-
Copyright Katsuyoshi Tanaka, courtesy of the Mark Morris Dance Group
macological and directed toward support and comfort.
Psychological factors influence Parkinsonism’s major symptoms:
outcome is affected by how well a person copes. Patients should seek
behaviorally oriented treatment early—counseling on the meaning of
symptoms, the nature of the disease, and the potential for most pa-
tients to lead long, productive lives. Physical therapy consists of simple
measures, such as heat and massage, to alleviate painful muscle cramps
as well as training and exercise to cope with debilitating movement
changes. Used therapeutically, music and exercise can improve other
aspects of behavior, including balance and walking, and may actually
slow the course of the disease.
The prime objective of pharmacological treatment is increasing the
activity in whatever dopamine synapses remain. l-Dopa, a precursor of
Rhythmic movement helps Parkinson
dopamine, is converted into dopamine in the brain and enhances effective dopamine trans- patients restore the balance between
mission, as do drugs such as amantadine, amphetamine, monoamine oxidase inhibitors, and positive and negative symptoms. Patients
tricyclic antidepressants. Anticholinergic drugs, such as atropine, scopolamine, benztropine who participate in a specially designed
(Cogentin), and trihexyphenidyl (Artane), block the brain cholinergic systems that seem to Dance for PD (http://danceforparkinsons.
org/) class for people with Parkinson
show heightened activity in the absence of adequate dopamine activity. As the disease pro-
(PwP) like the one at the Mark Morris
gresses, drug therapies become less effective, and the incidence of side effects increases. Dance Center, pictured here, report that
Some drug treatments that directly stimulate dopamine receptors have been reported to moving to music helps them regain muscle
result in increased sexuality and an increased incidence of compulsive gambling. control. Exercise, including tai chi and
Two surgical treatments described in Section 16-2 are based on the idea that increased boxing, also reinforces treatments directed
activity of globus pallidus neurons inhibits motor function. A lesion of the internal part of the toward replacing depleted dopamine.
globus pallidus (GPi) can reduce rigidity and tremor. Hyperactivity of GPi neurons can also
be reduced neurosurgically by electrically stimulating the neurons via deep brain stimulation
(see Figure 16-4). A stimulating electrode is permanently implanted in the GPi or an adjacent Figure 11-13 charts how the GPi, a structure in
area, the subthalamic nucleus. Patients carry a small electric stimulator that they can turn on the basal ganglia, regulates movement force.
to induce DBS and so reduce rigidity and tremor. These two treatments may be used sequen-
tially: when DBS becomes less effective as the disease progresses, a GPi lesion may be induced.
A promising prospective Parkinson treatment involves increasing the population of
dopamine-producing cells. The simplest way is to transplant embryonic dopamine cells into
588 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
the basal ganglia. In the 1980s and 1990s, this treatment reported varying degrees of suc-
cess marked by poorly conducted studies with inadequate preassessment and postassessment
procedures. A newer treatment course proposes either transplanting stem cells that could
then be induced to take a dopaminergic phenotype or stimulating endogenous stem cells to
migrate to the basal ganglia. The advantage is that these stem cells need not be derived from
embryonic tissue but can come from a variety of sources, including the person’s own body.
All these treatments are experimental (Politis & Lindvall, 2012). Before cell replacement
will become a useful therapy, many questions must be resolved, including which cell source
is best, where in the brain to put grafts, and how new cells can be integrated into existing
brain circuits. Stem cells are not a quick fix for Parkinson disease, but the pioneering work
on this disease will be instrumental in applying such technology to other diseases.
Anatomical Correlates of Alzheimer Disease
Given the increasing population of elderly people and thus of Alzheimer disease, which ac-
counts for about 65 percent of all dementias, research is directed toward potential causes.
Personal lifestyle, environmental toxins, high levels of trace elements such as aluminum in
the blood, an autoimmune response, a slow-acting virus, reduced blood flow to the cerebral
hemispheres, and genetic predisposition are targets of ongoing research.
Incidence of Alzheimer disease is high in some families, making genetic causes pertinent
to understanding disease progression. Risk factors include the presence of the Apoe4 gene,
below-average IQ score, poor education, and TBI. Presumably, better educated and/or more
intelligent people and those who carry the Apoe2 gene are better able to compensate for cell
death in degenerative dementia.
A decade ago, the only way to identify and study Alzheimer disease was postmortem
pathology examination. This approach was less than ideal because determining which brain
changes came early in the disease and which resulted from those early changes was impos-
sible. Nonetheless, it became clear that widespread changes take place in neocortex and allo-
cortex and that associated changes take place in many neurotransmitter systems. Most of the
brainstem, cerebellum, and spinal cord are relatively spared from Alzheimer’s major ravages.
The principal neuroanatomical change in Alzheimer disease is the emergence of amyloid
plaques (clumps of protein from dead neurons and astrocytes), chiefly in allocortex and neo-
cortex. Increased plaque concentration in the cortex has been correlated with the magnitude
Focus 14-3, on Alzheimer etiology, includes a of cognitive deterioration. Plaques are generally considered nonspecific phenomena in that
micrograph of an amyloid plaque. they can be found in non-Alzheimer patients and in dementias caused by other known events.
Another anatomical correlate of Alzheimer disease is neurofibrillary tangles (accumula-
tions of microtubules from dead cells) found in both neocortex and allocortex, where the
Neurofilaments are a type of tubule that posterior half of the hippocampus is affected more severely than the anterior half. Neurofi-
reinforces cell structure, aids its movement, brillary tangles have been described mainly in human tissue and have also been observed in
and transports proteins. patients with Down syndrome and Parkinson disease and other dementias.
Finally, neocortical changes that correlate with Alzheimer disease are not uniform. As
Figure 16-10 shows plainly, the cortex atrophies and can lose as much as one-third of its
(A) Healthy brain (B) Brain characteristic of Alzheimer disease
Brain images were provided courtesy of
the Nun Study, University of Minnesota
Cortical Degeneration
Figure 16-10
in Alzheimer Disease Brain of (A) a
healthy elderly adult contrasted with (B) an
elderly adult’s brain that shows shriveling
due to cell shrinkage characteristic of
Alzheimer disease.
16-3 • Understanding and Treating Neurological Disorders 589
Figure 16-11 Stripped Branches
Alzheimer patients’ dendritic trees
degenerate and their neurons atrophy,
worsening their symptoms, including
memory loss and personality changes.
Science Source
Healthy adult Early Alzheimer Advanced Alzheimer Terminal Alzheimer
pattern disease disease disease
volume as the disease progresses. But cellular analyses at the microscopic level reveal that
some areas, including the primary sensory and motor cortices, especially the visual and
sensorimotor cortex, are relatively spared. The frontal lobes are less affected than is the
posterior cortex.
Areas of most extensive change are the neocortical association areas and the allocortex.
The entorhinal cortex is affected earliest and most severely. Entorhinal cortex is the major
information relay from the neocortex traveling to the hippocampus and related structures,
then back to the neocortex. Entorhinal damage is associated with memory loss, an early and
enduring symptom of Alzheimer disease, and is most likely caused by degenerative changes
that take place in this area.
Many studies describe cell loss in the cortices of Alzheimer patients, but this finding is
disputed. There seems to be a substantial reduction in large neurons, but these cells may
shrink rather than disappear. The more widespread cause of cortical atrophy appears to be
a loss of dendritic arborization (Figure 16-11).
In addition to cell loss and shrinkage, changes take place in the remaining cells’ neu-
rotransmitters. In the 1970s, researchers believed that a treatment paralleling l-dopa treat-
ment of Parkinson disease could be found for Alzheimer disease. The prime candidate
neurotransmitter was acetylcholine, and one treatment developed for Alzheimer disease is
medication that increases acetylcholine levels in the forebrain. An example, available both
orally and as a skin patch, is Exelon, the brand name for rivastigmine, a cholinergic agonist
that appears to provide temporary relief from disease progression. Unfortunately, Alzheimer
has proved far more complex, because transmitters other than ACh clearly are changed as Figure 14-17 shows how glutamate can affect
well. Noradrenaline, dopamine, and serotonin are reduced, as are the NMDA and AMPA NMDA and AMPA receptors to promote
receptors for glutamate. learning by association.
Are All Degenerative Dementias Aspects of
a Single Disease?
Neither Parkinson nor Alzheimer disease is related to a single brain structure or region, al-
though dopamine in the case of the former and acetylcholine in the case of the latter seem
more affected. Other similarities in their pathology suggest some common neurodegenera-
tive processes. Donald Calne (Calne & Mizuno, 2004) noted that when scientists traveled to
590 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
Guam at the end of World War II to investigate a reportedly widespread dementia described
Biophoto Associates/Science Source
as similar to Alzheimer disease, they did indeed report a high incidence of Alzheimer. Many
years later, Calne and his colleagues, also experts in Parkinson disease, examined the same
general group of people and found that they had Parkinson disease. Calne noted that, if
you look for Alzheimer symptoms in these people, you find them and miss the Parkinson
symptoms. And vice versa.
The best-studied similarity between the two diseases is the Lewy body (Figure 16-12), a
fibrous ring that forms within neuronal cytoplasm and is thought to correspond to abnormal
neurofilament metabolism. Until recently, the Lewy body was most often found in the region
Figure 16-12 Midbrain Lewy Body of the midbrain substantia nigra and believed to be a hallmark of Parkinson disease, as amy-
Lewy bodies (arrow) characteristic of loid plaques were viewed as a marker of Alzheimer disease. In fact, Lewy bodies appear in
Parkinson disease are found in the brain of several neurodegenerative disorders, including Alzheimer disease. There are even reports of
patients with other disorders as well. people with Alzheimerlike dementias who have no plaques and tangles but do have extensive
Lewy bodies in the cortex.
Alzheimer and Parkinson symptoms may be similar because both diseases have similar
origins. Indeed, the idea that several diseases marked by brain degeneration—including Hun-
tington disease, MS, and ALS—may have a similar origin is central to prion theory, advanced
in 1982 by Stanley B. Prusiner, who received the Noble Prize for his work in 1997. Its name
Infection as referred to in the definition is not derived from the terms protein and infection, a prion is an abnormally folded protein that
one caused by casual contact. causes progressive neurodegeneration.
Prions were identified during investigation of various degenerative brain diseases in hu-
mans and other animals. Creutzfeldt-Jakob disease, a rare human degenerative disease that
progresses rapidly, gained public prominence in the 1990s. People were contracting a similar
condition after eating beef from cattle that had displayed symptoms of bovine spongiform
Lewy body Circular fibrous structure found
encephalopathy (BSE), a degenerative brain condition accompanied by muscle wasting. BSE
in several neurodegenerative disorders;
in turn is similar to a condition in sheep called scrapies (the animals scrape or scratch them-
forms within the cytoplasm of neurons
selves) that also features wasting of brain and body. Chronic wasting disease is a similar condi-
and is thought to result from abnormal
neurofilament metabolism. tion found in deer and elk.
The infectious nature of such conditions was observed in the Fore tribe of Papua New
prion From protein and infection, an
Guinea in the 1950s. A large number of Fore were dying of a muscle-wasting condition called
abnormally folded protein that causes
kuru (meaning to shake in Fore). The Fore contracted kuru by practicing ritual cannibalism:
progressive neurodegenerative disorders.
they ate the brains of dead relatives, which the Fore believed preserves their spirits. In an
experiment to investigate the condition, body parts from kuru victims were fed to a chimp
that contracted the disease.
The infectious agent in these conditions is a prion. Prion proteins are found in healthy
cell membranes and may play a role in attaching one cell to another. Prion proteins also bind
to metallic ions, for example, copper. The proteins typically fold in a normal configuration
but can also misfold (Figure 16-13). The altered configuration causes disease.
A misfolded prion protein will attach to a healthy prion protein and cause it to misfold.
Misfolded prions tend to clump together, forming protein aggregates that eventually result
in cell death. Misfolded prions can also infect neighboring brain and body cells, resulting
in general brain degeneration
Figure 16-13 Disease Process Normal Diseased prion and muscle wasting. An in-
Left: Prion proteins typically fold into fectious prion can pass from
helixes and pleated sheets. Right: In Amino one individual to another,
misfolding, part of the protein helix acids in Amino acids
© Mayo Foundation for Medical Education
changes into a sheet. The result is an alpha helix in beta helix and even from one species to
infectious disease–causing prion. another, but only if the nor-
and Research. All rights reserved.
mal prion proteins in the two
individuals are similar. Inves-
tigations show that among
Amino acids several alleles of the gene
in sheet form
that produces normal prion
16-3 • Understanding and Treating Neurological Disorders 591
proteins, some are more susceptible to misfolding than are others. Individuals with alleles
that are not susceptible to misfolding, as are those Fore tribespeople who did not contract
kuru, are resistant to prion disease.
In Parkinson disease, the misfolded protein is proposed to be alpha synuclein. Its ac-
cumulation, largely in substantia nigra cells, is a Lewy body (Olanow & Brundin, 2013).
In Alzheimer disease, the accumulating protein forms amyloid plaques and mainly affects
cortical cells (Kumar et al., 2015). Misfolded proteins in oligodendroglia may be responsible
for the cell demyelination characteristic of MS and ALS (Shi et al., 2015).
The prion theory opens new avenues for investigating degenerative disease treatments,
including drugs that remove prions, block prion misfolding, or alter prion forms prone to
misfolding (Asante et al., 2015). Selective cattle breeding for prion alleles that do not produce
misfolding prevents BSE. Inserting a misfolding-resistant human prion allele into mice ren-
ders them resistant to prion disease. Any treatment developed for humans could potentially
treat BSE in cattle, scrapie in sheep, and wasting disease in deer and elk. Preventing prion
misfolding could even arrest, in part, degenerative consequences of traumatic brain injury
and concussion.
Age-Related Cognitive Loss
Most people who grow old do not become demented, but virtually every-
one acquires age-related cognitive loss, even while living an active, healthy,
productive life. Aging is associated with declines in perceptual functions,
Sandy Huffaker/The New York Times/Redux
especially vision, hearing, and olfaction, and declining motor, cognitive,
and executive (planning) functions as well. Older people tend to learn at a
slower pace and typically do not attain the same mastery of new skills as
do younger adults.
Noninvasive imaging studies reveal that aging is correlated with de-
creased white matter volume, probably related to myelin loss. This condi-
tion is reparable. There is little evidence of neuronal loss in typical aging,
although a reduction in neurogenesis in the hippocampus does occur.
Compared with younger people, older people tend to activate larger re- Brain Workout Engaging in cognitively
gions of their attentional and executive networks (parietal and prefrontal cortex) when stimulating activities can keep neural
they perform complex cognitive and executive tasks. This increased activation correlates networks and general cognitive function
from declining with age.
with reduced performance on tests of working memory as well as tests of attentional and
executive tasks.
Two lines of evidence suggest that that age-related declines in function can be slowed.
The first is aerobic exercise to enhance general health and improve the brain’s plasticity
via increased neurogenesis, gliogenesis, and trophic factor support. The second treatment
is brain exercise employing training strategies that enhance neural plasticity and reverse
learned nonuse. Most of us know the frustration of losing a skill—whether it’s trigonometry
or tennis—after getting out of practice. Skill loss does not reflect dementia but simply a
use-it-or-lose-it effect. Training programs designed to stimulate plasticity in the appropriate
cerebral circuitry include motor, auditory, or visual system–based cognitive and/or atten-
tional training. Brain training is designed to stimulate plasticity rather than to rehabilitate
specific losses.
William Milberg and his colleagues (e.g., Kuo et al., 2005; Leritz et al., 2011) have explored
the idea that aging changes in the brain take place in the context of the entire body’s aging.
For example, dementia may reflect a chronic cerebrovascular disorder, marginal high blood
pressure. Marginal elevations in blood pressure can lead to cerebral microbleeds, especially
in white matter. The cumulative effect of years or even decades of tiny bleeds would lead
eventually to increasingly disturbed cognition. The condition may first appear as a mild View the progression of these microbleeds, or
cognitive impairment (MCI) that slowly progresses, with cumulative microbleeds, toward silent strokes, at https://www.youtube.com/
dementia. watch?v=J3fb0CaDpEk.
592 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
16-3 review
Understanding and Treating Neurological Disorders
Before you continue, check your understanding.
1. As the developed world’s population ages, disease will become more common
than disease.
2. Even imaging techniques may miss pathology produced by .
3. Interruption of blood to the brain is called and if prolonged can result in
.
4. Although superficially appearing to be very different diseases, Parkinson and Alzheimer
have similarities such as and that suggest that they may be part of a
common disease spectrum.
5. Name two strategies that can reduce or reverse neurological and cognitive decline with
aging.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
16-4 Understanding and Treating
Psychiatric Disorders
40 The DSM-5 summarizes a wide range of mental disorders. We focus on the three general
behavioral categories—psychoses, mood disorders, and anxiety disorders—that are the best
35 studied and understood. Figure 16-14 summarizes their prevalence. Personal, family, and
social costs are not reflected in these statistics. Schizophrenia, bipolar disorder, and major
30
depression affect a smaller number of people, but their costs, in loss of social relationships,
Population, %
25 productivity, and medical care, are disproportionate.
Schizophrenia Spectrum and Other
37.5%
20
15
Psychotic Disorders
10 Psychoses are psychological disorders in which a person loses contact with reality, subject to
irrational ideas and distorted perceptions. Among the varieties of psychosis, schizophrenia
10.8%
5 is the most common and best understood. Although it takes many forms, whether schizo-
1.1%
0 phrenia is a single disorder or several disorders that share some symptoms is uncertain. The
Anxiety Mood Schizophrenia
diorders disorders spectrum complexity of behavioral and neurobiological factors that characterize schizophrenia makes
it especially difficult to diagnose and classify. Understanding schizophrenia is an evolving
Prevalence of Some
Figure 16-14
process and far from complete.
Psychiatric Illnesses Data from National
Institutes of Mental Health, http://www.nimh.nih.gov/
health/statistics/index.shtml
Diagnosing Schizophrenia
The DSM lists six diagnostic symptoms of schizophrenia:
1. Delusions—beliefs that distort reality
2. Hallucinations—distorted perceptions, such as hearing voices
3. Disorganized speech, such as incoherent statements or senselessly rhyming talk
4. Disorganized behavior or excessive agitation
5. The opposite extreme of agitation: catatonic behavior
6. Negative symptoms, such as blunted emotions or loss of interest and drive, all characterized
by the absence of some healthy response
The DSM criteria are subjective and more helpful in clinical diagnoses than in relating
schizophrenia to objective, measurable brain abnormalities.
16-4 • Understanding and Treating Psychiatric Disorders 593
Neurobiology of Schizophrenia
Although schizophrenia may produce a wide range of symptoms, individual differences in
behavioral effects exist as well. Voluminous research related to the origins and causes of
schizophrenia has emerged, but the three lines of research summarized in this section have
transformed ideas about its genetics, its development, and its associated brain correlates.
genetiCS It has long been recognized that genetics figures in schizophrenia, as does envi-
ronment. The more closely related an individual is to someone diagnosed with schizophre-
nia, the more likely he or she is to develop the condition. The concordance of schizophrenia
in identical twins is high: 50 percent is often cited. That the concordance for schizophrenia
is not 100 percent means that environmental factors also play a role (Shorter & Miller, 2015).
It is also likely that many genes are associated with schizophrenia. Mutations on a number
of chromosomes (candidates are 1, 6, 8, 13, and 22) predispose an individual to schizophrenia.
It is also likely that many mutations in candidate genes on those chromosomes are involved.
Genetic studies suggest that schizophrenia is probably a family of disorders and that the fam-
ily may include other conditions, such as major depression and bipolar disorder (Claes et al.,
2012). What may be common to the genes involved is that they contribute to brain develop-
ment and so may contribute to various abnormalities in brain development.
develOpment Typically, schizophrenia is diagnosed in young adulthood, but a body of
evidence suggests that it originates much earlier, even prenatally. Its expression in adulthood
must therefore await the conclusion of a host of developmental processes that ultimately shape
the adult human brain. That schizophrenia has developmental origins has many implications.
First, environmental factors acting through epigenetic mechanisms are likely to influence
brain development such that a subset of at-risk individuals develops adult schizophrenia.
Second, identifying developmental factors that contribute to schizophrenia provides the
best opportunity for intervention to reduce the risks of developing it. Any potential “cure”
for schizophrenia will depend on early detection and remediation through epigenetic mecha-
nisms (Gebicke-Haerter, 2012).
Brain COrrelateS Many studies show anatomical changes in the brain associated with
schizophrenia, especially in the temporal and frontal lobes.
1. Suggesting cell loss in these areas, the schizophrenic brain generally has large ventricles
and thinner cortex in the medial temporal regions and frontal cortex.
2. Some aspects of neuronal and fiber composition of the temporal lobes and the frontal lobes
are changed, as indicated by changes in their density imaged by MRI (Kong et al., 2012).
3. Alterations in neuronal structure show abnormal dendritic fields in cells in the dorsal
prefrontal regions; as shown in Figure 16-15, in the hippocampus (Cho et al., 2004); and
in the entorhinal cortex (Arnold et al., 1997).
In sum, this evidence seems almost definitive in identifying schizophrenia as a develop-
mental brain disorder associated in the main with alteration in the temporal and the frontal
cortex. These brain regions are associated with memory, language, and decision making.
(A) (B) Figure 16-15 Organic Dysfunction
(A) Rather than the consistently parallel
orientation of hippocampal neurons typical
in healthy brains, (B) the orientation of
hippocampal neurons in the brain of a
person with schizophrenia is haphazard.
Information from J. A. Kovelman & A. B. Scheibel (1984).
A neurohistologic correlate of schizophrenia. Biological
Hippocampus
Psychiatry, 19, p. 1613.
Organized (healthy) pyramidal Disorganized (schizophrenic)
neurons pyramidal neurons
594 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
Neurochemical Correlates of Schizophrenia
Neuroscientists also consider the neurochemical correlates of brain–behavior relations in
schizophrenia. Dopamine abnormalities were the first to be linked to schizophrenia, through
Neuroleptics are antipsychotic drugs two lines of evidence. First, most neuroleptic drugs act on the dopamine synapse was taken
described in Section 6-2. as evidence that schizophrenia is a disease of heightened activity in the ventral tegmental
dopamine system. Second, drugs that enhance dopaminergic activity, such as amphetamine,
can produce psychotic symptoms reminiscent of schizophrenia.
This dopamine theory of schizophrenia appears too simple, however, because many other
neurochemical abnormalities, summarized in Table 16-6, are also associated with schizo-
GABA is the brain’s main inhibitory phrenia—in particular, abnormalities in dopamine and dopamine receptors and in GABA
neurotransmitter. and GABA-binding sites. Recent evidence also suggests changes in the NMDA receptor in
schizophrenia, a finding that is leading to the development of new classes of glutamate drug
therapy (Pannese et al., 2012). Patients vary widely in the extent of each abnormality, how-
ever. How these neurochemical variations might relate to the presence or absence of specific
symptoms is not yet known.
To summarize, schizophrenia is a complex disorder associated with
table 16-6 Biochemical changes associated with schizophrenia
abnormalities in brain structure and metabolism, especially in prefron-
Decreased dopamine metabolites in cerebrospinal fluid tal and temporal cortex, and with neurochemical abnormalities in dopa-
Increased striatal D2 receptors mine, glutamate, and GABA. Given the complexity of all these factors,
Decreased expression of D3 and D4 mRNA in specific cortical regions it comes as no surprise that schizophrenia is so difficult to characterize
and to treat.
Decreased cortical glutamate
Increased cortical glutamate receptors
Decreased glutamate uptake sites in cingulate cortex
Mood Disorders
The DSM-5 identifies a continuum of affective disorders, separating
Decreased mRNA for synthesizing GABA in prefrontal cortex bipolar and related disorders from depressive disorders (see Table 16-3).
Increased GABA A-binding sites in cingulate cortex The bipolar category is positioned between schizophrenia and depres-
Source: Information from W. Byne, E. Kemegther, L. Jones, V. Harouthunian, and K. L. sive disorders, forming a bridge between the diagnostic classes that
Davis (1999). The neurochemistry of schizophrenia. In D. S. Charney, E. J. Nestler, & B. S. takes into account symptoms, family history, and genetics. Depression
Bunney. The Neurobiology of Mental Illness (p. 242). New York: Oxford University Press.
and mania—our principal interests here—represent the extremes of
affect. The main symptoms of major depression are prolonged feelings
Focus 6-3 explains the threat of suicide of worthlessness and guilt, disruption of normal eating habits, sleep disturbances, a general
attendant to untreated major depression. slowing of behavior, and frequent thoughts of suicide.
Mania, the opposite affective extreme from depression, is characterized by excessive
euphoria, which the subject perceives as typical. The affected person often formulates gran-
diose plans and is uncontrollably hyperactive. Periods of mania often change, sometimes
abruptly, to depression and back again to mania, a condition designated as bipolar disorder.
Neurobiology of Depression
Brain and environment both contribute to the complex neurobiology of depression. Predis-
posing factors related to brain anatomy and chemistry thus may contribute more to affective
changes in some people, whereas life experiences contribute mainly to affective changes in
other people. As a result, a bewildering number of life, health, and brain factors have been
related to depression. These factors include economic or social failure, circadian rhythm
disruption, vitamin D and other nutrient deficiency, pregnancy, brain injury, diabetes, car-
diovascular events, and childhood abuse, among many others.
A major approach in neurobiological studies of depression is to ask whether a common
brain substrate exists for depression. Antidepressant drugs acutely increase the synaptic
levels of norepinephrine and serotonin, a finding that led to the idea that depression results
from decreased availability of one or both neurotransmitters. Lowering their levels in healthy
participants does not produce depression, however. And while antidepressant medications
increase the level of norepinephrine and serotonin within days, it takes weeks for drugs to
start relieving depression.
16-4 • Understanding and Treating Psychiatric Disorders 595
Among the various explanations suggested for these confounding results, none is com-
pletely satisfactory. Ronald Duman (2004) reviewed evidence to suggest that antidepressants
act, at least in part, on signaling pathways, such as on cAMP, in the postsynaptic cell. Neuro-
trophic factors appear to affect antidepressant action and may underlie the neurobiology of Section 14-4 explores the relation of
depression. Investigators know, for example, that brain-derived neurotrophic factor (BDNF) hormones, trophic factors, and psychoactive
is down-regulated by stress and up-regulated by antidepressant medication (Wang et al., 2012). drugs to neuroplasticity.
Given that BDNF acts to enhance the growth and survival of cortical neurons and syn-
apses, BDNF dysfunction may adversely affect norepinephrine and serotonin systems through
the loss of either neurons or synapses. Antidepressant medication may increase BDNF release
through its actions on cAMP. Key here is that the cause of depression probably is not merely a
simple decrease in transmitter levels. Many brain changes are related to depression.
Mood and Reactivity to Stress
A significant psychological factor in understanding depression is reactivity to stress. Section 6-5 explains the neurobiology of the
Monoamines—the noradrenergic and serotoninergic activating systems diagrammed in stress response—how it begins and ends.
Figure 16-16A—modulate hormone secretion by the hypothalamic–pituitary–adrenal sys-
tem—the HPA axis—illustrated in Figure 16-16B. When we are stressed, the HPA axis is
stimulated to secrete corticotropin-releasing hormone, which stimulates the pituitary to
produce adrenocorticotropic hormone (ACTH). ACTH circulates through the blood and
stimulates the adrenal medulla to produce cortisol. Normally, cortisol helps us deal with
stress. If we cannot cope, or if stress is intense, excessive cortisol can wield a negative influ- mania Disordered mental state of extreme
ence on the brain, damaging the feedback loops the brain uses to turn off the stress response. excitement.
Excessive stress early in life may be especially detrimental. During critical periods in early bipolar disorder Mood disorder
childhood, abuse or other severe environmental stress can permanently disrupt HPA axis characterized by periods of depression
reactivity: it becomes constantly overactive. Overactivity in the HPA axis results in overse- alternating with normal periods and periods
cretion of cortisol, an imbalance associated with depression in adulthood. Patrick McGowan of intense excitation, or mania.
and colleagues (2010) wondered if early experiences could alter gene expression related to HPA axis Hypothalamic–pituitary–adrenal
cortisol activity in the HPA axis. They compared, postmortem, hippocampi obtained from circuit that controls the production and
suicide victims with a history of childhood abuse and hippocampi from other suicide victims release of hormones related to stress.
(A) (B)
Stress
Hypothalamus –
feedback loop
Deactivation
Corticotrophin-
Locus coeruleus releasing
homone
Noradrenergic system
In depression this
shutdown fails,
Hypo- producing chronic
thalamus activation, which
Anterior is experienced as Figure 16-16 Stress-Activating
pituitary chronic stress. System (A) Medial view showing that in
the brainstem, cell bodies of noradrenergic
(norepinephrine) neurons emanate from
ACTH the locus coeruleus (top) and cell bodies
of the serotonergic activating system
Raphe nuclei Adrenal emanate from the raphe nuclei (bottom).
Serotonergic system gland Cortisol (B) When activated, the HPA axis affects
mood, thinking, and indirectly, cortisol
Kidney
secretion by the adrenal glands. HPA
deactivation begins when cortisol binds to
hypothalamic receptors.
596 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
This research confirms studies on the effects with no childhood abuse or from controls. Abused suicide victims showed decreased gene
of stress on hippocampal function reported in expression for cortisol receptors relative to the controls. These results, derived from epi-
Sections 6-5, 7-5, and 8-4. genetics, confirm that early neglect or abuse alters the HPA axis for life.
To summarize, the diffuse distribution of the norepinephrine- and serotonin-activating
systems makes relating depression to a single brain structure impossible. Findings from neuro-
imaging studies show that depression is accompanied by increased blood flow and glucose me-
tabolism in the orbitofrontal cortex, anterior cingulate cortex, and amygdala. Blood flow drops
as the symptoms of depression remit when a patient takes antidepressant medication (Drevets,
Kishore, & Krishman, 2004). Antidepressants effectively increase the amount of serotonin in
the cortex and may also stimulate brain repair. For example, fluoxetine (Prozac) stimulates
both BDNF production and neurogenesis in the hippocampus, resulting in a net increase
cognitive-behavioral therapy (cBT) in granule cells, described in Research Focus 16-4, Antidepressant Action and Brain Repair.
Problem-focused, action-oriented, structured Although we have emphasized biological correlates of depression, the best treatment
treatment for eliminating dysfunctional need not be a direct biological intervention. Cognitive-behavioral therapy (CBT) is an ex-
thoughts and maladaptive behaviors. cellent—arguably the best—therapy for depression. It focuses on challenging the patient’s
beliefs and perceptions. The objective is to identify dysfunctional thoughts and beliefs that
accompany negative emotions and to replace them with more realistic ones.
Simply pointing out that a person’s beliefs are faulty is not likely to be effective, however,
because it probably took months or years to develop those beliefs. The neural circuits under-
lying faulty beliefs must change, just as the strategies for developing new ones must change.
In a real sense then, CBT is effective if it induces neural plasticity and changes brain activity.
ReseaRch F cus 16-4
Antidepressant Action and Brain Repair
Excessive stress, poor coping skills, or both contribute to excessive cortisol Luca Santarelli and colleagues (2003) used knockout mice that
levels in the brain and to depression and anxiety. Granule cells in the hip- lacked a specific serotonin receptor (5-HT-1A) sensitive to fluoxetine.
pocampus, which are especially sensitive to cortisol, can die when cortisol They exposed these mice along with mice with intact 5-HT-1A recep-
levels either are reduced, as shown in the figure, or increased excessively. tors to chronic, unpredictable stress. Both groups developed a general
These hippocampal cells may play a role in regulating cortisol levels deterioration in their fur coat.
and switching off the brain’s stress response. Their absence leaves the Chronic antidepressant treatment affected only the mice with intact
HPA axis unchecked. Then increased cortisol levels contribute to more serotonin receptors, and only these mice displayed enhanced neuro-
neuron death and to depression and anxiety. It’s a vicious circle. genesis. Thus, because antidepressants activate serotonin receptors,
A remarkable finding emerged from studying how antidepressants serotonin must participate in enhancing neurogenesis.
such as fluoxetine (Prozac) and other selective serotonin reuptake inhibi- The literature on hippocampal neurogenesis is the most prolific in
tors affect the hippocampus. The SSRIs increased neurogenesis in the neuroscience, represented by over 3000 papers reporting mainly on
subgranular zone, cell migration into the dentate gyrus, and the number animal models. To summarize their findings, phenomena we perceive
of functioning cells there (Malberg et al., 2000). as bad (deprivation in infancy, conflict, stress, poor diet, most drugs)
That antidepressants take some weeks to produce their positive ef- depress neurogenesis, and phenomena we perceive as good (exercise,
fects on behavior and that new neurons take some weeks to migrate enriched environment, sufficient sleep, good diet) enhance neurogen-
and incorporate into the hippocampus suggest that the antidepressants’ esis. Finding the signaling pathways that enhance neurogenesis may
mechanism of action is to enhance hippocampal function—in essence, to reveal the relationships among altered cognition, memory, depression,
replace the neural switch that turns off the stress response. and the effects of antidepressant drugs (Costa et al., 2015).
Healthy rat hippocampus Neuronal degeneration
Hippocampus
Images from S. C. Spanswick and R. J. Sutherland (2010). Object-context specific memory deficits associated
with loss of hippocampal granule cells after adrenalectomy in rats. Learning and Memory, 17:241-245. Figure 2
16-5 • Is Misbehavior Always Bad? 597
Anxiety Disorders
We are all subject to anxiety, usually acutely in response to stress or less commonly as chronic
reactivity—an increased anxiety response—even to seemingly minor stressors. Anxiety reac-
tions certainly are not pathological; they are likely an evolutionary adaptation for coping with
adverse conditions. But anxiety can become pathological and make life miserable. Anxiety
disorders are among the most common psychiatric conditions. The DSM-5 lists 10 classes
Focus 12-3 describes symptoms of anxiety
of anxiety disorders that together affect 15 percent to 35 percent of the population at some
disorders; Section 6-5, how stress-induced
point in their life lives (see Figure 16-14). damage contributes to PTSD.
Imaging studies of people with anxiety disorders record increased baseline activity in
the cingulate cortex and parahippocampal gyrus and enhanced responsiveness to anxiety-
provoking stimuli in the amygdala and prefrontal cortex. This finding suggests excessive
excitatory neurotransmission in a circuit involving cingulate cortex, amygdala, and the
parahippocampal region. Because drugs that enhance the inhibitory transmitter GABA are Figure 12-18 diagrams these limbic
particularly effective in reducing anxiety, researchers hypothesize that excessive excitatory system structures and charts their major
neurotransmission in this circuit is anxiety. But what causes it? connections.
Considerable interest has developed in investigating why some people show pathological
anxiety to stimuli to which others have a milder response. One hypothesis, covered earlier,
in the section on depression, is that stressful experiences early in life increase susceptibility
to a variety of behavioral disorders, especially anxiety disorders.
Although anxiety disorders used to be treated primarily with benzodiazepines, such as
Valium, now they are also treated with SSRIs, such as Prozac, Paxil, Celexa, and Zoloft.
Antidepressant drugs do not act immediately, however, suggesting that the treatments
must stimulate some gradual change in brain structure, much as these drugs act in treating
depression.
Cognitive-behavioral therapy is as effective as drugs in treating anxiety. The most effec- One more time: a pill is not a skill.
tive behavioral therapies expose and re-expose patients to their fears. For example, treating
a phobic fear of germs requires exposing the patient repeatedly to potentially germy environ-
ments, such as public washrooms, until the discomfort abates.
16-4 review
Understanding and Treating Behavioral Disorders
Before you continue, check your understanding.
1. Schizophrenia is a complex disorder associated with neurochemical abnormalities in
, , and .
2. Schizophrenia is associated with pronounced anatomical changes in the
and cortices.
3. The monoamine-activating systems that have received the most investigation related to
understanding depression are and .
4. The most effective treatment for depression and anxiety disorders is .
5. Describe the main difficulty in linking genes to schizophrenia.
Answers appear at the back of the book.
For additional study tools, visit :
www.macmillanhighered.com/launchpad/kolb5e
16-5 Is Misbehavior Always Bad?
You know this movie plot: a person sustains a blow to the head, then becomes a better
person. Do pathological changes in brain and behavior sometimes lead to behavioral im-
provement in real life? A report by Jim Giles (2004) on Tommy McHugh’s case is thought
provoking.
598 Chapter 16 • WHAT HAPPENS WHEN THE BRAIN MISBEHAVES?
McHugh (1949–2012), a heroin addict, committed multiple serious crimes and spent a
great deal of time in jail. Later he had a cerebral hemorrhage (bleeding into the brain) from
an aneurysm. The bleeding was repaired surgically with a metal clip on the leaking artery.
To learn more and view McHugh’s art, go to After he recovered from the injury, McHugh’s personality changed dramatically. He took up
http://www.tommymchugh.co.uk. painting, which he had never done before, and became a successful artist.
McHugh’s injury-induced brain changes appear to have been beneficial, but the exact na-
ture of his brain injury has not been identified. The metal clip in his brain precluded the use
of MRI. Aspects of his cognitive behavior suggest that he may have had frontal lobe damage.
The phenomenon in which an individual acquires a new skill after an injury is called
acquired savant syndrome. There are other reports of people who have developed new musi-
cal or artistic talents after their injuries (Miller et al., 2000). Corrigan and colleagues (2012)
propose that allied savant skills can be acquired by depressing inhibitory systems in the
brain so that new skill strategies can be activated. In experiments, for example, depressing
participants’ left hemispheres with TMS briefly improved mathematical skills, which are
subserved by the right hemisphere.
The general idea of artificially manipulating the brain for the better is controversial
cognitive enhancement Brain function (Heinz et al., 2012). Influencing brain function through a strategy loosely described as
enhancement by pharmacological, cognitive enhancement enlists current knowledge of pharmacology, brain plasticity, brain
physiological, or surgical manipulation. stimulation, neurogenetics, and other specialties to boost brain functioning. Of course,
people already use drugs to alter brain function, and the basis of many therapies is to en-
In Focus 6-1, a brief history of cognitive hance brain function. Psychosurgical techniques such as frontal lobotomy were based on
enhancers is context for a trend: procuring the general idea that brain function could be improved. As yet, however, evidence is lacking
medication prescribed for ADHD as a study that cognitive enhancement for the average person is better than old-fashioned but readily
aid. available methods: learning, practice, and a healthy lifestyle.
Summary
Contemporary understanding of brain and behavior is providing of disorders will lead to better classification systems. Advances in
new insights, explanations, and treatments for brain disorders. genetics and brain imaging will aid this effort. The table summarizes
Neurologists, who treat organic disorders, and psychiatrists, who the range of available treatments, from highly invasive neurosurgery
treat behavioral disorders, are forging a unified understanding of mind to noninvasive electrophysiology, from moderately invasive
and brain: neuropsychoanalysis. pharmacology to behavioral treatments.
16-1Multidisciplinary Research on
Brain and Behavioral Disorders general treatment categories
Most behavioral disorders have multiple causes—genetic, epigenetic,
Neurosurgical Behavioral
biochemical, anatomical, social–environmental variables—all of them
interacting. Research methods directed toward these causes include Direct intervention Manipulation of experience
family studies designed to find a genetic abnormality that might be DBS Behavior modification
corrected, biochemical anomalies that might be reversed by drug Stem cell transplantation Cognitive, cognitive-behavioral
or hormone therapy, anatomical pathologies that might account for therapy
Tissue removal or repair
behavioral changes, and social–environmental variables. Neuropsychological
Electrophysiological
Investigators rely increasingly on neuroimaging (fMRI, PET,
Emotional therapy, psychotherapy
TMS, ERP) to examine brain–behavior relations in vivo in healthy Noninvasive manipulation
participants as well as in people with disorders. Interest in more Physical activity, music
ECT
refined behavioral measurements is growing, especially for cognitive rt-fMRI
TMS, rTMS
behavior, the better to understand behavioral symptoms. VR exposure and other
Pharmacological
computer-based simulations
Classifying and Treating Brain
16-2 Chemical administration
and Behavioral Disorders Antibiotics or antivirals
Disorders can be classified according to presumed etiology (cause), Psychoactive drugs
symptomatology, or pathology. The classification systems developed
Neurotrophic factors
by psychologists, psychiatrists, and neurologists overlap, and each is
revised from time to time. Clearly, better understanding the causes Nutrition
Key Terms 599
Understanding and Treating
16-3 the population of the developed world ages. Like other plagues in
Neurological Disorders human history, dementias affect not only the person with the disease
If a disorder, such as depression, is presumably caused primarily by but also the caregivers, about half of whom seek psychiatric care
a biochemical imbalance, treatment is likely to be pharmacological, themselves.
although brain activation with TMS also is effective and is noninvasive. 16-5 Is Misbehavior Always Bad?
If the disorder has a suspected anatomical cause, treatment may
In rare cases, people with a behavioral disorder also have some
include removal of pathological tissue (as in epilepsy) or implanted
benefit. An individual who has a brain injury, for example, may
electrodes to activate underactive regions (as in Parkinson disease
suddenly display an artistic talent. The explanation for this acquired
and stroke). Many disorders require medical treatment concurrent with
savant syndrome is that depressing the brain’s inhibitory systems can
behavioral therapy, including physiotherapy or cognitive rehabilitation
activate new skill strategies. Artificially manipulating the brain with
in patients with stroke and TBI, and cognitive-behavioral therapies for
cognitive enhancers is a controversial approach to improving brain
patients with depression and anxiety disorders.
function.
Understanding and Treating
16-4
Behavioral Disorders
The number of people who endure hidden diseases of behavior,
especially neurodegenerative disorders and stroke, is increasing as
key termS
akathesia, p. 586 cognitive-behavioral therapy focal seizure, p. 583 neuropsychoanalysis, p. 565
autoimmune disease, p. 584 (CBT), p. 596 generalized seizure, p. 583 phenylketonuria (PKU), p. 565
behavioral therapy, p. 575 deep brain stimulation (DBS), HPA axis, p. 595 posttraumatic stress disorder
p. 572 (PTSD), p. 562
bipolar disorder, p. 595 ischemia, p. 580
dementia, p. 584 prion, p. 590
chronic traumatic Lewy body, p. 590
encephalopathy (CTE), diaschisis, p. 580 psychotherapy, p. 575
magnetic resonance
p. 579 Diagnostic and Statistical spectroscopy (MRS), p. 579 real-time fMRI (rt-fMRI), p. 576
cognitive enhancement, p. 598 Manual of Mental Disorders
mania, p. 595 tardive dyskinesia, p. 575
(DSM), p. 569
cognitive therapy, p. 575 neuroprotectant, p. 580 virtual reality (VR) exposure
festination, p. 586
therapy, p. 562
Visit to access the e-Book, videos, adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
this page left intentionally blank
answer s to sec tion re view self-t est s
Chapter 1 5. Changes in climate may have driven many Review 2-3
What Are the Origins of Brain and physical changes in hominids, including The Central Nervous System:
the nearly threefold increase in brain size
Behavior? from apes to modern humans. Evidence Mediating Behavior
suggests that each new hominid species 1. levels of function
Review 1-1
appeared after climate changes devas- 2. spinal cord
Neuroscience in the tated old environments and produced 3. hindbrain; midbrain; diencephalon
Twenty-First Century new ones. Eventually, modern humans
1. Traumatic brain injury (TBI) evolved adaptability sufficient to allow us 4. cerebellum
2. central nervous system (CNS); peripheral to populate almost every climatic region 5. basal ganglia; limbic system
nervous system (PNS) on earth. 6. allocortex; neocortex; sensory; motor;
3. cerebrum; forebrain; hemispheres; integrative
Review 1-5
brainstem 7. The forebrain regulates cognitive activ-
Modern Human Brain Size ity, including thought and memory, and
4. inherited; learning and Intelligence holds ultimate control over movement
5. Research on embodied behavior proposes 1. species-typical behavior (behavior).
that we understand each other not only by
listening to words but also by observing 2. culture; memes
Review 2-4
gestures and other body language and that 3. g; multiple intelligences
we think not only with silent language but 4. In comparing different species, a larger
Somatic Nervous System:
also with overt gestures and body language. brain correlates with more complex Transmitting Information
behavior. In comparing individuals within a 1. cranial nerves; spinal (peripheral) nerves
Review 1-2 species, brain size and intelligence are only 2. same
Perspectives on Brain and remotely related. Rather, the complexity of
3. head; internal organs and glands
Behavior different brain regions is related to behav-
ioral abilities. Humans, for example, vary 4. The law of Bell and Magendie states that
1. mentalism; dualism; Materialism widely in body size and in brain size as sensory (afferent) spinal nerve fibers are
2. natural selection; Charles Darwin well as in having different kinds of intelli- dorsal (in humans, posterior) and motor
3. minimally conscious state or MCS; persis- gence. All of these factors make any simple (efferent) spinal fibers are ventral (in
tent vegetative state or PVS comparison of individuals’ brain sizes and humans, anterior). This law is important
intelligence impossible. because it allows neurologists to predict
4. In formulating the theory of natural the location of spinal cord damage accu-
selection, Darwin relied on observation to rately according to changes in sensation or
conclude that living organisms are related Chapter 2
movement.
and pass traits from parents to offspring. What Is the Nervous System’s Functional
Mendel used experimentation to show
that heritable factors underlie phenotypic
Anatomy? Review 2-5
variation among species. Review 2-1 Autonomic and Enteric
Overview of Brain Function Nervous Systems: Visceral
Review 1-3
and Structure Relations
Evolution of Brains and of 1. behavior; brain 1. ganglia
Behavior 2. in any order: frontal; temporal; parietal; 2. sympathetic; parasympathetic; in
1. nervous systems occipital opposition
2. nerve net; bilaterally symmetrical; ganglia; 3. neuroplasticity 3. The ANS operates largely outside our
chordate conscious awareness, whether we are
4. white matter; gray matter awake or asleep, to regulate the vegetative
3. cladogram
5. tracts; nerves functions essential to life.
4. Humans possess the largest brain of all
6. Compare your diagram with Figure 2-2B. 4. numbers and types of neurons and glia and
animals relative to body size and the most
complex brain structure. of chemical transmitters
Review 2-2
5. microbiome; nutrients; chemicals
Review 1-4 The Nervous System’s 6. Psychobiotics are live organisms that,
Evolution of the Human Brain Evolutionary Development when ingested in adequate amounts, can
1. forebrain; midbrain; hindbrain benefit people with psychiatric illness.
and Behavior
1. common ancestor; chimpanzee 2. behavior
Review 2-6
2. hominid; Australopithecus; Homo habilis; 3. The forebrain has grown dramatically over
Homo erectus the course of vertebrate evolution. But Ten Principles of Nervous
3. encephalization quotient (EQ); counting
primitive forms have not been discarded System Function
and replaced as more complex nervous 1. in any order: olfactory system; somatic
brain cells (neurons) systems emerged. The forebrain’s growth nervous system; ANS; ENS
4. in any order: climate changes; changes thus is an elaboration of functions already
in lifestyle skills; physiological changes; present in the other brain regions and 2. multiple levels of functioning
delayed maturation or neoteny leads to its functioning on multiple levels. 3. excitation; inhibition
A-1
A-2 answers
4. Any individual’s perceived reality is only Chapter 4 Chapter 5
a rough approximation of what is actually
present. An animal’s representation of the
How Do Neurons Use Electrical Signals How Do Neurons Communicate and Adapt?
world depends on the nature of the infor- to Transmit Information? Review 5-1
mation sent to the animal’s brain. Review 4-1 A Chemical Message
Searching for Electrical 1. chemical synapses; gap junction
Chapter 3 Activity in the Nervous System 2. experience; learning
What Are the Nervous System’s Functional 1. René Descartes 3. axodendritic; axosomatic; axomuscular;
Units? 2. stimulation; recording axoaxonic; axosynaptic; axoextracellular;
axosecretory; dendrodendritic
Review 3-1 3. in any order: how to record from the
giant axons of the North Atlantic squid; 4. dendrite; cell body or soma
Cells of the Nervous System how to use an oscilloscope to measure 5. When an action potential reaches an axon
1. in either order: neurons; 86 billion; glia; small changes in voltage; how to craft terminal, (1) a chemical transmitter that has
87 billion microelectrodes small enough to place been synthesized and stored in the axon
2. in either order: exciting; inhibiting on or in an axon terminal (2) is released from the presyn-
3. in any order: sensory neurons; detect and 4. in either order: concentration gradient, from aptic membrane into the synaptic cleft.
convey incoming stimuli into the CNS; an area of relatively high concentration to The transmitter (3) diffuses across the
interneurons; form links between sensory an area of lower concentration; voltage cleft and binds to receptors on the post-
and motor neurons; motor neurons; make gradient, from an area of relatively high synaptic membrane. (4) The transmitter is
muscles move charge to an area of lower charge deactivated.
4. in any order: ependymal cells; astrocytes; 5. Ion channels in cell membranes may open Review 5-2
microglia; oligodendroglia; Schwann cells; to facilitate ion movement, close to impede
nourishing; removing waste; insulating; ion movement, or pump ions across the
Varieties of Neurotransmitters
supporting; repairing membrane. and Receptors
5. The main obstacle is duplicating the 1. synthesis; release; receptor action;
Review 4-2 inactivation
complexity of a mammalian brain and its
ability to change (plasticity). Advances in Electrical Activity of a 2. in any order: small-molecule transmitters;
artificial intelligence are bringing increas- Membrane peptide transmitters; gaseous transmitters;
ingly sophisticated robotic technology to 1. resting potential; ions lipid transmitters
fruition. 3. in either order: acetate, choline; acetylcho-
2. semipermeable; negative
linesterase or AChE
Review 3-2 3. hyperpolarization; depolarization
4. lipid; postsynaptic
Internal Structure of a Cell 4. action potential; nerve impulse
5. An ionotropic receptor’s pore or channel
1. in any order: cell membrane; nucleus; 5. Nerve impulses travel more rapidly on can be opened or closed to regulate the
endoplasmic reticulum (or ER); Golgi myelinated axons because of saltatory flow-through of ions, directly effecting rapid
bodies; microtubules (or tubules); vesicles conduction: action potentials leap between and usually excitatory voltage changes on
2. proteins; in any order: channels; gates; the nodes separating the glial cells that the cell membrane. Metabotropic receptors,
pumps form the axon’s myelin sheath. which are generally inhibitory and slow
3. DNA; RNA; protein Review 4-3
acting, activate second messengers to indi-
4. endoplasmic reticulum (or ER); Golgi rectly produce changes in cell function and
How Neurons Integrate structure.
bodies; microtubules; exocytosis
Information
5. By using most of the proteins that it makes, Review 5-3
1. excitatory postsynaptic potentials (EPSPs);
a cell enables itself to interact with other
cells and to modify their behavior. The col-
inhibitory postsynaptic potentials (IPSPs) Neurotransmitter Systems
lective action of cells mediates behavior. 2. time; space; integrates and Behavior
3. cell body; initial segment; axon 1. neurotransmitter; neurotransmitter
Review 3-3 2. acetylcholine or ACh; acetylcholine or ACh;
4. Some neurons have voltage-sensitive
Genes, Cells, and Behavior channels on their dendrites that allow the acetylcholine or ACh; norepinephrine or NE
1. 23; protein reverse movement of an action potential 3. in either order: serotonin or 5-HT; dopamine
2. alleles; proteins into the neurons’ dendritic fields. or DA
3. mutation; Down syndrome; trisomy Review 4-4 4. in any order: cholinergic; dopaminergic;
noradrenergic; serotonergic
4. recessive; dominant Into the Nervous System
5. This idea has been attractive for a long
5. Selective breeding; Cloning; transgenic and Back Out time, because a clear relationship exists
6. Gene methylation or DNA methylation 1. sensory system or sense between DA loss in the substantia nigra
7. Mendelian genetics concentrates on 2. sensory receptor cell; voltage-sensitive and Parkinson disease and because
inheritance patterns—on which genes 3. motor; muscles acetylcholine and norepinephrine are
parents pass to their offspring and off- clearly related to somatic and autonomic
spring pass to succeeding generations. 4. autoimmune; acetylcholine behaviors. But for other neurotransmit-
Epigenetics is the study of how the 5. The varieties of membrane channels generate ter systems in the brain, establishing
environment and experience can affect the transmembrane charge, mediate graded clear one-to-one relationships has proved
the inherited genome. potentials, and trigger the action potential. difficult.
answers A-3
Review 5-4 5. Behavioral myopia theory suggests that Review 7-2
Adaptive Role of Synapses intoxicated individuals are unusually re- Measuring the Brain’s
sponsive to local and immediate cues, so
in Learning and Memory the environment excessively influences Electrical Activity
1. synapse; learning their behavior, while consequences go 1. in any order: single-cell recording; EEG;
2. in either order: habituation; sensitization ignored. ERP; MEG
3. presynaptic axon terminal; sensory; 2. action potentials
Review 6-4
calcium; less 3. graded potentials
4. interneurons; potassium or K; calcium ions
Explaining and Treating Drug 4. magnetic activity of many neurons;
or Ca2+ Abuse three-dimensional localization of the cell
5. posttraumatic stress disorder or PTSD; 1. liking (pleasure); tolerance; wanting groups generating the measured field
sensitization (craving); sensitization 5. EEG is much less expensive than MEG.
6. Permanent responses to frequently 2. frontal cortex; brainstem; mesolimbic
dopamine system (pathways); basal Review 7-3
occurring stimuli are biologically (or be-
haviorally and/or metabolically) efficient, ganglia Anatomical Imaging
but if stimuli change suddenly, a lack of 3. inheritance; epigenetics Techniques: CT and MRI
flexibility becomes maladaptive. 4. drugs; other life experiences 1. in either order: computed tomography or CT
5. A reasonable approach to treatment views scan; magnetic resonance imaging or MRI
Chapter 6 2. neural connections or fiber pathways;
drug addiction in the same way as chronic
How Do Drugs and Hormones Influence the behavioral addictions and medical prob- concentrations of brain metabolites
Brain and Behavior? lems are viewed: as a lifelong challenge for 3. brain injury or brain damage
most people.
Review 6-1 4. CT produces X-ray images of one object
from many angles, then uses scan-
Principles of Review 6-5
ning software to combine them into a
Psychopharmacology Hormones three-dimensional image of the brain.
1. psychoactive drugs; psychopharmacology 1. neurohormones; pituitary gland; releasing
hormones; brain Review 7-4
2. blood–brain barrier; brain
3. synapses; agonists; antagonists
2. in either order: steroids; peptides Functional Brain Imaging
3. homeostatic; gonadal; glucocorticoids 1. in any order: functional magnetic reso-
4. tolerance; sensitization nance imaging or fMRI; optical tomography
4. anabolic (or anabolic–androgenic) steroids;
5. in any order: feces; urine; sweat; breath; or fNIRS; functional positron emission
muscle mass; masculinizing
breast milk tomography or PET
5. epinephrine; cortisol
6. (a) Drug use at home is unlikely to con- 2. radioactively labeled molecules;
dition drug-taking behavior to familiar 6. The hippocampus is important in ending neurochemical
home cues, so tolerance is likely to occur. the stress response by regulating cortisol
levels. If cortisol remains elevated by pro- 3. cerebral blood flow
(b) Novel cues in a work setting may
enhance conditioning and so sensitize longed stress, eventually it damages the 4. Resting-state images in PET and rs-fMRI
the occasional drug user. hippocampus. can identify abnormalities in brain func-
tion. rs-fMRI can also identify functional
Review 6-2 connections in the resting brain.
Chapter 7
Grouping Psychoactive Drugs
1. in either order: behavioral; psychoactive
How Do We Study the Brain’s Structures Review 7-5
and Functions? Chemical and Genetic
2. GABA A; Cl– or chloride ion
Review 7-1
Measures of Brain and Behavior
3. MAO inhibitors; SSRIs
1. biochemical; in either order: microdialysis;
4. endorphins Measuring and Manipulating voltammetry
5. release; reuptake; D2 Brain and Behavior 2. concordance rates
6. Psychotropic drugs act on many 1. in either order: brain function; behavior;
any one from among: place learning, 3. DNA; gene expression
neurotransmitters, including acetylcho-
matching to place, landmark learning 4. Epigenetic studies show that life experi-
line, anandamide, dopamine, epinephrine,
2. sectioning and staining; multiphoton ence can alter gene expression and that
glutamate, norepinephrine, and serotonin.
microscope these changes are associated with changes
Review 6-3 in neuronal structure and connectivity.
3. in any order: brain lesions; brain Altered neuronal organization in turn is
Factors Influencing Individual stimulation; drugs; optogenetics; associated with changes in behavior.
Responses to Drugs chemogenetics
1. disinhibition theory (also, impulse control); 4. Brain stimulation methods include using Review 7-6
learning; behavioral myopia theory electrical pulses, as in DBS; magnetic Comparing Neuroscience
fields, as in TMS; chemicals, by administer-
2. Substance abuse; addiction or substance
ing drugs; or in the transgenic techniques
Research Methods
dependence 1. in any order: temporal resolution; spatial
of optogenetics, which employs light, and
3. psychomotor activation; mesolimbic chemogenetics, which employs synthetic resolution; degree of invasiveness
dopamine system drugs to interact exclusively with designer 2. any one or more: EEG, ERP, and/or fNIRS;
4. females; males receptors. inexpensive
A-4 answers
3. The fundamental goal of neuroscience 3. testosterone Review 9-5
research is to gain an understanding of 4. critical periods or sensitive periods The Visual Brain in Action
brain–behavior relationships.
5. Adolescence is a time of rapid brain 1. hemianopia
Review 7-7 change related to pubertal hormones and 2. scotomas
psychosocial stressors, both of which
Using Animals in make the brain vulnerable to disorders.
3. monocular blindness
Brain–Behavior Research 4. optic ataxia
1. any two in any order: stroke; ADHD; Chapter 9 5. Damage to the dorsal stream produces
Parkinson disease; schizophrenia deficits in visually guided movements.
How Do We Sense, Perceive, and See the Damage to the ventral stream produces
2. whether laboratory animals have the same
symptoms that humans do World? deficits in object recognition.
3. neural bases; treatments Review 9-1
4. Using laboratory animals in research Nature of Sensation and Chapter 10
leads to concerns about animal welfare Perception How Do We Hear, Speak, and Make Music?
and raises ethical issues about whether 1. Sensory receptors Review 10-1
animals should be used in research and,
if so, in what types of research. 2. Receptive; density Sound Waves: Stimulus for
3. target in the brain Audition
Chapter 8 4. subjective experience of sensation 1. air pressure waves or compression waves
5. Each modality has many receptors and or sound waves
How Does the Nervous System Develop sends information to the cortex to form 2. in any order: frequency; amplitude;
and Adapt? topographic maps. complexity
Review 8-1 3. in any order: loudness; pitch; prosody,
Review 9-2
Three Perspectives on Brain quality or timbre
The Visual System’s Functional
Development 4. temporal
1. behavior
Anatomy 5. Delivery speed, or the number of sound
1. retinal ganglion cells or RGCs segments that can be analyzed per second,
2. neural circuits
2. P or parvocellular; M or magnocellular distinguishes speech and musical sounds
3. any three in any order: hormones; sensory from other auditory inputs. Nonlanguage
experience; injuries; genes 3. geniculostriate; tectopulvinar
sounds faster than 5 segments per second
4. Behaviors cannot emerge until the req- 4. facial agnosia or prosopagnosia
are heard as a buzz, yet we are capable of
uisite neural structures are sufficiently 5. The dorsal stream to the parietal lobe understanding speech delivered at nearly
mature. processes the visual guidance of move- 30 segments per second. Random or
ments (the how). The ventral stream to the aperiodic sounds are noise.
Review 8-2 temporal lobe processes the visual percep-
Neurobiology of Development tion of objects (the what).
Review 10-2
1. neural tube Functional Anatomy of the
Review 9-3
2. neurogenesis; gliogenesis Auditory System
Location in the Visual World
3. in either order: cell adhesion molecules or 1. ossicles or, in any order, hammer, anvil, and
1. small size
CAMs; tropic factors stirrup
2. photoreceptors; retinal ganglion cells,
4. in either order: myelination; synaptic 2. inner hair cells; cochlea
lateral geniculate neurons, cortical
pruning
neurons 3. in either order: basilar; tectorial
5. Dynamic changes in frontal lobe structure
3. topographic map 4. auditory or cochlear; auditory vestibular or
(morphology) are related to the develop-
ment of intelligence. 4. corpus callosum eighth
5. The fovea is represented by a larger area 5. inferior colliculus; medial geniculate
Review 8-3 in the cortex than the visual field’s periph- nucleus
Using Emerging Behaviors to ery, and thus there is more processing 6. The planum temporale is larger in the left
Infer Neural Maturation of foveal information in region V1 than of hemisphere, and Heschl’s gyrus is larger
peripheral information. in the right. In most people, this anatomi-
1. independent finger movements or the
cal asymmetry correlates to a functional
pincer grasp
Review 9-4 asymmetry: the left temporal cortex ana-
2. vocabulary; sound processing
Neuronal Activity lyzes language-related sounds, whereas
3. Piaget’s stages of cognitive development the right temporal cortex analyzes music-
1. bars of light
4. temporal lobe; basal ganglia related ones.
2. temporal
5. Correlation does not prove causation. 3. trichromatic theory Review 10-3
Review 8-4 4. opponent Neural Activity and Hearing
Brain Development and the 5. RGCs are excited by one wavelength of 1. tonotopic
light and inhibited by another, producing
Environment two pairs of what seem to be color
2. cochlea
1. chemoaffinity hypothesis opposites—red versus green and blue 3. superior olive; trapezoid body
2. amblyopia versus yellow. 4. audition for action
answers A-5
5. The brain detects a sound’s location via 6. The motor cortex, M1, is organized into a 5. Any given odorant stimulates a unique
two mechanisms. Neurons in the brain- set of functional categories that encode a pattern of receptors, and the summed
stem (hindbrain) compute the ITD, the time movement lexicon, or dictionary. Used in activity, or pattern of activity, produces our
difference in a sound wave’s arrival at each different combinations, these few move- perception of a particular odor.
ear. Other neurons in the brainstem com- ments enable more complex movements.
pute IID, the difference in sound amplitude Review 12-3
Review 11-3
(loudness) in each ear. Evolution, Environment,
Basal Ganglia, Cerebellum, and Behavior
Review 10-4 and Movement 1. rewards or reinforcers
Anatomy of Language 1. basal ganglia; force 2. taste aversion learning
and Music 2. hyperkinetic; hypokinetic 3. innate releasing mechanisms or IRMs
1. language; music 3. accuracy; skills 4. tasting
2. in any order: Broca’s area; supplementary 4. The cerebellum compares an intended
speech area; face area of motor cortex 5. When two unrelated events are experi-
movement with the actual movement, cal- enced together, they may inadvertently
3. Wernicke’s culates any necessary corrections, and become associated. For example, unex-
4. Broca’s informs the cortex to correct the movement. pected pain in the presence of a stranger
5. in either order: perfect (or absolute) pitch; Review 11-4
may lead to a faulty association between
amusic or tone deaf the person and the pain.
Somatosensory System
6. Three lines of evidence support the idea
that language is innate: the universality Receptors and Pathways Review 12-4
of language, the natural acquisition by 1. hapsis; proprioception; nociception Neuroanatomy of Motivated
children, and the presence of syntax in all 2. posterior; anterior and Emotional Behavior
languages. 3. pain gate 1. regulatory; nonregulatory
Review 10-5 4. periaqueductal gray matter or PAG 2. hypothalamus
Auditory Communication 5. vestibular; balance 3. in any order: hypothalamus; limbic system;
frontal lobes
in Nonhuman Species 6. Without proprioception, sensory information
about body location and movement is lost 4. in any order: dorsolateral; orbitofrontal;
1. epigenetic mechanisms
and can be regained by only using vision. ventromedial
2. left
5. amygdala
3. echolocation; sonar Review 11-5
6. hormones
4. Birdsong dialects demonstrate that the songs Exploring the Somatosensory
7. The limbic system stimulates emotional
young birds hear influence how they sing. Cortex reactions and species-typical behaviors,
1. primary; secondary whereas the frontal lobes generate the
Chapter 11 2. apraxia rationale for behavior at the right time and
context, taking into account factors such
How Does the Nervous System Respond to 3. dorsal visual; ventral visual
as external events and internal information.
Stimulation and Produce Movement? 4. Pain perception does not depend simply on
pain sensations but is a construct of the Review 12-5
Review 11-1 brain.
A Hierarchy of Movement Control of Regulatory and
Control Chapter 12 Nonregulatory Behavior
1. in any order: lateral hypothalamus; ventrome-
1. hierarchy What Causes Emotional and Motivated dial hypothalamus; paraventricular nucleus
2. prefrontal; premotor; motor cortex or M1 Behavior? 2. in either order: hypothalamus; amygdala
3. brainstem Review 12-1 3. in either order: organizing; activating
4. spinal cord Identifying the Causes 4. osmotic; hypovolemic
5. Lower-level functions in the motor of Behavior 5. Variations in epigenetic effects could lead
hierarchy can continue in the absence of
1. rewarding to different architecture and function of
higher-level ones, but the higher levels
2. minimum level of sensory stimulation the hypothalamus among heterosexuals,
provide voluntary control over movements.
homosexuals, and transgender individuals.
When the brain is disconnected from the 3. smell and taste or chemical senses
spinal cord then, movement can no longer
4. In general, behavior is controlled by neural Review 12-6
be controlled at will.
circuits that are modulated by a wide range Reward
of factors.
Review 11-2 1. rewarding
Motor System Organization Review 12-2 2. wanting; liking
1. topographic; homunculus; larger The Chemical Senses 3. in any order: dopamine; opioid;
2. motor map 1. olfactory epithelium benzodiazepine–GABA
3. corticospinal; lateral corticospinal; anterior 2. flavor 4. Intracranial self-stimulation is a phenom-
corticospinal enon whereby animals learn to turn on a
3. pheromones stimulating electric current to their brain,
4. trunk; arm; finger 4. allele of the taste receptor gene TAS2R38; presumably because it activates the neural
5. muscles; in either order: flexes, extends number of taste buds system that underlies reward.
A-6 answers
Chapter 13 Review 13-6 4. hippocampus
Why Do We Sleep and Dream? Sleep Disorders 5. behavioral sensitization
1. insomnia; narcolepsy 6. Plastic changes in neural networks can
Review 13-1
2. drug-dependent insomnia interfere with behavior, essentially by
A Clock for All Seasons learning behaviors that interfere with
3. sleep paralysis; cataplexy
1. circannual; circadian healthy function. Examples are addiction
4. REM sleep behavioral disorder or REM and PTSD.
2. free-running; Zeitgebers
without atonia; subcoerulear
3. any 2: light pollution; jet lag; working swing 5. Orexin is probably only one of many Review 14-5
shifts; working night shifts factors related to waking behavior, as
4. Circadian rhythm allows us to synchronize animals with narcolepsy can be awake
Recovery from Brain Injury
our behavior with our body’s metabolic but then collapse into sleep. 1. in any order: learn new ways to solve
processes—so that we are hungry at problems; reorganize the brain to do more
optimal times for eating, for example, with less; replace the lost neurons
Chapter 14
and tired at optimal sleep times. 2. in either order: direct cortical stimulation;
How Do We Learn and Remember? deep brain stimulation or DBS
Review 13-2 Review 14-1 3. neurotrophic
Neural Basis of the Biological Connecting Learning and 4. Functional improvement after brain
Clock Memory injury reflects compensation rather than
1. superchiasmatic nucleus or SCN recovery.
1. Pavlovian or classical
2. retinohypothalamic; melanopsin ganglion 2. operant or instrumental
or photosensitive retinal ganglion Chapter 15
3. implicit; explicit
3. shell; chemical; anatomical
4. Episodic How Does the Brain Think?
4. Experimental evidence suggests that the
5. Memory is not localized to any particular Review 15-1
circadian rhythm can put a time stamp on a
brain circuit or region. Rather, multiple
behavioral event, rendering it easier to re-
memory circuits vary with the require- The Nature of Thought
call at the same time in the circadian cycle 1. in order: attending to; identifying; making
ments of the memory task.
that it occurred in previously. meaningful responses to
Review 14-2
Review 13-3 2. language; flexibility
Dissociating Memory Circuits
Sleep Stages and Dreaming 1. in either order: hippocampus; amygdala
3. neuron
1. in either order: REM, rapid eye movement; 4. Much of human thought is verbal.
NREM, non–rapid eye movement 2. basal ganglia Language allows us to categorize informa-
3. Lashley searched for explicit memory tion and provides a way to organize our
2. EOG or electrooculogram; EMG or electro-
in the perceptual and motor systems of behavior around time.
myogram; EEG or electroencephalogram
his animal subjects using invasive tests
3. five; lengthening designed mostly for implicit memory. Review 15-2
4. everyone; real time Milner studied a patient with medial Cognition and the Association
temporal removal and used behavioral
5. Interpreting dreams is difficult because it
tests of both explicit and implicit memory.
Cortex
is always possible that the interpreter will 1. knowledge; cognition
impose his or her own explanation, or spin,
Review 14-3 2. temporal; parietal
on the dreams.
Neural Systems Underlying 3. in either order: plan movements; organize
Review 13-4 Explicit and Implicit Memories behavior over time
What Does Sleep Accomplish? 1. in either order: hippocampus; neocortex 4. Mirror
1. biological; restorative; memories (or cortex) 5. Multimodal cortex allows the brain to
2. Explicit; implicit 2. implicit combine characteristics of stimuli across
3. place cell; NREM 3. amygdala different sensory modalities, whether we
4. consolidation encounter them together or separately.
4. microsleep
5. If a memory can be stored during waking, 5. Emotional experiences stimulate hormonal Review 15-3
sleep may not be essential for its storage. and neurochemical activating systems that
stimulate the amygdala. The amygdala in Expanding Frontiers of
Review 13-5 turn modulates the laying down of memory Cognitive Neuroscience
circuits in the rest of the brain. 1. cognitive neuroscience
Neural Bases of Sleep
1. reticular activating system or RAS; NREM Review 14-4 2. brain connectome
2. coma Structural Basis of Brain 3. cerebellum
3. REM sleep Plasticity 4. social interactions
4. subcoerulear 1. long-term potentiation or LTP; long-term 5. theory of mind
5. We have separate neural systems for depression or LTD 6. decision making
keeping us awake while we are still 2. GABAergic or inhibitory 7. in any order: understanding others;
(cholinergic) and awake when we move 3. in either order: synapse number; neuron understanding oneself; self-regulation;
(serotinergic). number social living
answers A-7
Review 15-4 Review 15-7 7. Classification systems can be revised
Cerebral Asymmetry in Consciousness using new information such as that
obtained from genetics and brain imaging.
Thinking 1. complex
1. in either order: spatial behavior; music 2. Consciousness Review 16-3
2. in either order: controlling voluntary 3. consciousness Understanding and Treating
movement sequences; language 4. Movements in which speed is critical, Neurological Disorders
3. corpus callosum such as hitting a pitched ball, cannot be 1. Alzheimer; Parkinson
4. Because the hemispheres process controlled consciously.
2. TBI or traumatic brain injury
information differently, they think differ-
Chapter 16 3. ischemia; stroke
ently. And the existence of language in the
left hemisphere allows it to label computa- 4. loss of cells from the substantia nigra;
What Happens When The Brain accumulation of Lewy bodies
tions and thus make inferences that the
right cannot. Misbehaves? 5. Aerobic exercise and brain training are
Review 16-1 strategies for enhancing or stimulating
Review 15-5 neuroplasticity as we age.
Multidisciplinary Research on
Variations in Cognitive Brain and Behavioral Disorders Review 16-4
Organization
1. in either order: sex; handedness
1. brainstem and limbic system; neocortex; Understanding and Treating
dorsal frontal cortex
2. neural circuits
Psychiatric Disorders
2. in any order: genetic errors; epigenetic 1. in any order: dopamine, glutamate, GABA
3. synesthesia mechanisms; progressive cell death; rapid
cell death; loss of neural connections 2. in either order: temporal; frontal
4. Gonadal hormones influence brain
development and shape neural circuits in 3. PKU or phenylketonuria 3. in either order: norepinephrine; serotonin
adulthood. 4. subjective 4. cognitive-behavioral therapy or CBT
5. Brain pathology can exist without obvious 5. Many genetic and epigenetic influences
Review 15-6 contribute to every behavior, including
clinical symptoms and clinical symptoms
Intelligence without obvious pathology. schizophrenia.
1. g factor or general intelligence; multiple
intelligences; convergent and divergent; Review 16-2
intelligence A; intelligence B Classifying and Treating Brain
2. structural; functional and Behavioral Disorders
3. any 3, in any order: gyral patterns; 1. any 3 in any order: social, psychological,
cytoarchitectonics; vascular patterns; psychiatric, neurological
neurochemistry 2. Epidemiology
4. epigenetic 3. genetics, neuroimaging
5. Both fMRI and ERP studies show that the 4. in any order: neurosurgical, electrophysi-
efficiency of prefrontal–parietal circuits is ological, pharmacological, behavioral
related to standard intelligence measures.
“Executive” function is related to gray 5. deep brain stimulation or DBS
matter volume in the frontal lobe. 6. transcranial magnetic stimulation or TMS
this page left intentionally blank
glossary
A aphagia Failure to eat; may be due to an unwilling- behavioral neuroscience Study of the biological bases of
absolutely refractory The state of an axon in the repolar- ness to eat or to motor difficulties, especially with behavior in humans and other animals.
izing period, during which a new action potential swallowing. behavioral sensitization Escalating behavioral response
cannot be elicited (with some exceptions), because aphasia Inability to speak or comprehend language to the repeated administration of a psychomotor
gate 2 of sodium channels, which are not voltage despite the presence of normal comprehension stimulant such as amphetamine, cocaine, or nicotine;
sensitive, are closed. and intact vocal mechanisms. Broca’s aphasia is the also called drug-induced behavioral sensitization.
acetylcholine (ACh) First neurotransmitter discovered inability to speak fluently despite the presence of behavioral therapy Treatment that applies learning prin-
in the PNS and CNS; activates skeletal muscles in the normal comprehension and intact vocal mechanisms. ciples, such as conditioning, to eliminate unwanted
SNS; may either excite or inhibit internal organs in Wernicke’s aphasia is the inability to understand or behaviors.
to produce meaningful language even though word
the ANS.
production remains intact.
beta (β) rhythm Fast brain wave activity pattern associ-
action potential Large, brief reversal in the polarity of an ated with a waking EEG.
axon membrane. apoptosis Genetically programmed cell death. bilateral symmetry Body plan in which organs or parts
activating system Neural pathways that coordinate apraxia Inability to make voluntary movements in the present on both sides of the body are mirror images
brain activity through a single neurotransmitter; absence of paralysis or other motor or sensory impair- in appearance. For example, the hands are bilaterally
its cell bodies lie in a brainstem nucleus; axons are ment, especially an inability to make proper use of symmetrical, whereas the heart is not.
an object.
distributed through a wide CNS region. binding problem Philosophical question focused on
addiction Desire for a drug; manifested by frequent use, association cortex Neocortex outside primary how the brain ties single and varied sensory and
leading to physical dependence in addition to abuse; sensory and motor cortices; functions to produce motor events together into a unified perception or
often associated with tolerance and unpleasant, some- cognition. behavior.
times dangerous, withdrawal symptoms on cessation. associative learning Linkage of two or more unrelated biological clock Neural system that times behavior.
Per the DSM-5, called substance use disorder. stimuli to elicit a behavioral response. biorhythm Inherent timing mechanism that controls or
afferent Conducting toward a CNS structure. astrocyte Star-shaped glial cell that provides structural initiates biological processes.
agonist Substance that enhances synapse function. support to CNS neurons and transports substances bipolar disorder Mood disorder characterized by periods
between neurons and blood vessels.
akathesia Small, involuntary movements or changes in of depression alternating with normal periods and
posture; motor restlessness. atonia Lacking tone; condition of complete muscle periods of intense excitation, or mania.
inactivity produced by motor neuron inhibition. bipolar neuron Sensory neuron with one axon and one
allele Alternative form of a gene; a gene pair contains
two alleles. attention Narrowing or focusing awareness to a part of dendrite.
the sensory environment or to a class of stimuli. blind spot Retinal region where axons forming the optic
alpha rhythm Regular wave pattern in an electroenceph-
alogram; found in most people when they are relaxed attention-deficit/hyperactivity disorder (ADHD) Devel- nerve leave the eye and blood vessels enter and leave;
with eyes closed. opmental disorder characterized by core behavioral has no photoreceptors and is thus said to be blind.
symptoms, including impulsivity, hyperactivity, and/ blob Region in V1 that contains color-sensitive neurons,
Alzheimer disease Degenerative brain disorder related
or inattention. as revealed by staining for cytochrome oxidase.
to aging that first appears as progressive memory loss
and later develops into generalized dementia. auditory flow Change heard as a person and a source of blood–brain barrier Tight junctions between the cells
sound move relative to one another.
amblyopia Condition in which vision in one eye is re- that compose blood vessels in the brain, providing a
duced as a result of disuse; usually caused by a failure autism spectrum disorder (ASD) Range of cognitive barrier to the entry of an array of substances, includ-
of the two eyes to look in the same direction. symptoms from mild to severe that characterize au- ing toxins, into the brain.
tism; severe symptoms include greatly impaired social brain connectome Map of the complete structural
amnesia Partial or total loss of memory.
interaction, a bizarre and narrow range of interests, and functional fiber pathways of the human brain
amphetamine Drug that releases the neurotransmitter marked abnormalities in language and communica- in vivo.
dopamine into its synapse and like cocaine, blocks tion, and fixed, repetitive movements.
dopamine reuptake. brainstem Central structure of the brain; responsible for
autoimmune disease Illness resulting from an abnormal most unconscious behavior.
amplitude Stimulus intensity; in audition, roughly immune response by the body against substances and
equivalent to loudness, graphed by the increasing tissues normally present in the body.
Broca’s area Anterior left hemisphere speech area that
height of a sound wave. functions with the motor cortex to produce move-
autonomic nervous system (ANS) Part of the PNS that ments needed for speaking.
amusia Tone deafness—inability to distinguish between regulates the functioning of internal organs and
musical notes. glands.
amygdala Almond-shaped collection of nuclei in the autoreceptor Self-receptor in a neuronal membrane; C
limbic system; plays a role in emotional and species- that is, it responds to the same transmitter released by carbon monoxide (CO) Gaseous neurotransmitter;
typical behaviors. the neuron. activates cellular metabolism.
anabolic steroid Class of synthetic hormones related to axon Root, or single fiber, of a neuron that carries mes- cataplexy State of atonia, as in REM sleep, occurring
testosterone that have both muscle-building (anabolic) sages to other neurons. while a person is awake and active; linked to strong
and masculinizing (androgenic) effects; also called emotional stimulation.
anabolic–androgenic steroid.
axon collateral Branch of an axon.
axon hillock Juncture of soma and axon. cell adhesion molecule (CAM) A chemical molecule
androgen Class of hormones that stimulates or controls to which specific cells can adhere, thus aiding in
masculine characteristics and level of sexual interest. migration.
anencephaly Failure of the forebrain to develop. B cell assembly Hypothetical group of neurons that
anomalous speech representation Condition in which a back propagation Reverse movement of an action become functionally connected via common sensory
person’s speech zones are located in the right hemi- potential into the soma and dendritic field of a neu- inputs; proposed by Hebb as the basis of perception,
sphere or in both hemispheres. ron; postulated to play a role in plastic changes that memory, and thought.
anorexia nervosa Exaggerated concern with being underlie learning. cell body (soma) Core region of the cell containing the
overweight that leads to inadequate food intake and barbiturate Drug that produces sedation and sleep. nucleus and other organelles for making proteins.
often excessive exercising; can lead to severe weight basal ganglia Subcortical forebrain nuclei that coor- central nervous system (CNS) The brain and spinal cord,
loss and even starvation. dinate voluntary movements of the limbs and body; which together mediate behavior.
antagonist Substance that blocks synapse function. connected to the thalamus and to the midbrain. cerebellum Major brainstem structure specialized for
anterior spinothalamic tract Pathway from the spinal basic rest–activity cycle (BRAC) Recurring cycle of tem- learning and coordinating movements; assists the
cord to the thalamus that carries information about poral packets, about 90-minute periods in humans, cerebrum in generating many behaviors.
pain and temperature. during which an animal’s level of arousal waxes and cerebral cortex Thin, heavily folded film of nerve tissue
anterograde amnesia Inability to remember events wanes. composed of neurons that is the outer layer of the
subsequent to a disturbance of the brain such as head basilar membrane Receptor surface in the cochlea that forebrain. Also called neocortex.
trauma, electroconvulsive shock, or neurodegenera- transduces sound waves into neural activity. cerebral palsy Group of disorders that result from brain
tive disease. behavioral myopia “Nearsighted” behavior displayed damage acquired perinatally (at or near birth).
antianxiety agent Drug that reduces anxiety, including under the influence of alcohol: local and immediate cerebral voltammetry Technique used to identify the
minor tranquilizers such as benzodiazepines and cues become prominent; remote cues and conse- concentration of specific chemicals in the brain as
sedative-hypnotic agents. quences are ignored. animals behave freely.
G-1
G-2 glossary
cerebrospinal fluid (CSF) Clear solution of sodium chlo- conditioned stimulus (CS) In Pavlovian conditioning, depolarization Decrease in electrical charge across a
ride and other salts that fills the ventricles inside the an originally neutral stimulus that after association membrane, usually due to the inward flow of sodium
brain and circulates around the brain and spinal cord with an unconditioned stimulus (UCS) triggers a ions.
beneath the arachnoid layer in the subarachnoid space. conditioned response (CR). dermatome Body segment corresponding to a segment
cerebrum (forebrain) Major structure of the forebrain cone Photoreceptor specialized for color and high of the spinal cord.
that consists of two mirror image hemispheres (left visual acuity. Diagnostic and Statistical Manual of Mental Disorders
and right) and is responsible for most conscious connectome Comprehensive map of all structural (DSM) The American Psychiatric Association’s clas-
behavior. connectivity (the physical wiring) in an organism’s sification system for psychiatric disorders.
channel Opening in a protein embedded in the cell nervous system. diaschisis Neural shock that follows brain damage in
membrane that allows the passage of ions. consciousness The mind’s level of responsiveness to which areas connected to the site of damage show a
chemical synapse Junction at which messenger impressions made by the senses. temporary arrest of function.
molecules are released when stimulated by an action consolidation Process of stabilizing a memory trace dichotic listening Experimental procedure for simulta-
potential. after learning. neously presenting a different auditory input to each
chemoaffinity hypothesis Proposal that neurons or their constraint-induced therapy Procedure in which restraint ear through stereophonic earphones.
axons and dendrites are drawn toward a signaling of a healthy limb forces a patient to use an impaired diencephalon The between brain, which integrates
chemical that indicates the correct pathway. limb to enhance recovery of function. sensory and motor information on its way to the
chemogenetics Transgenic technique that combines contralateral neglect Ignoring a part of the body or cerebral cortex.
genetics and synthetic drugs to activate targeted cells world on the side diffusion Movement of ions from an area of higher con-
in living tissue. opposite (contralateral to) that of a brain injury. centration to an area of lower concentration through
cholinergic neuron Neuron that uses acetylcholine as convergent thinking Form of thinking that searches random motion.
its main neurotransmitter; cholinergic applies to any for a single answer to a question (such as 2 + 2 = ?); diffusion tensor imaging (DTI) Magnetic resonance
neuron that uses ACh as its main transmitter. contrasts with divergent thinking. imaging method that can image fiber pathways in the
chordate Animal that has both a brain and a spinal cord. corpus callosum Band of white matter containing about brain by detecting the directional movements of water
chronic traumatic encephalopathy (CTE) Progressive 200 million nerve fibers that connects the two cerebral molecules.
degenerative disease caused by multiple concussions hemispheres to provide a route for direct communica- dimer Two proteins combined into one.
and other closed-head injuries, characterized by tion between them. disinhibition theory Explanation holding that alcohol
neurofibrillary tangles, plaques, cerebral atrophy, and cortical column Anatomic organization that represents a has a selective depressant effect on the brain’s frontal
expanded ventricles due to cell loss. functional unit six cortical layers deep and approxi- cortex, which controls judgment, while sparing
chronotype Individual differences in circadian activity. mately 0.5 mm square, perpendicular to the cortical subcortical structures responsible for more instinctual
circadian rhythm Day–night rhythm. surface. behaviors, such as desire.
cladogram Phylogenetic tree that branches repeatedly, corticospinal tract Bundle of nerve fibers directly con- diurnal animal Organism that is active chiefly during
suggesting a taxonomy of organisms based on the necting the cerebral cortex to the spinal cord, branch- daylight.
time sequence in which evolutionary branches arise. ing at the brainstem into an opposite-side lateral tract divergent thinking Form of thinking that searches for
clinical trial Consensual experiment directed toward that informs movement of limbs and digits and a multiple solutions to a problem (how many ways can a
developing a treatment. same side anterior tract that informs movement of the pen be used?); contrasts with convergent thinking.
trunk; also called pyramidal tract.
cochlea Inner ear structure containing the auditory dopamine (DA) Amine neurotransmitter involved in
receptor cells. cranial nerve One of a set of 12 nerve pairs that control coordinating movement, attention, learning, and in
sensory and
cochlear implant Electronic device implanted surgically motor functions of the head, neck, and internal
reinforcing behaviors.
into the inner ear to transduce sound waves to neural organs. dopamine hypothesis of schizophrenia Idea that
activity and allow a deaf person to hear. excess dopamine activity causes symptoms of
critical period Developmental window during which
cognition Act or process of knowing or coming to know; some event has a long-lasting influence on the brain;
schizophrenia.
in psychology, refers to thought processes. also, sensitive period. dorsal stream Visual processing pathway from V1 to the
cognitive-behavioral therapy (CBT) Problem-focused, cross-tolerance Reduction of response to a novel
parietal lobe; guides movements relative to objects.
action-oriented, structured treatment for eliminating drug because of tolerance to a chemically related dorsolateral prefrontal cortex (DLPFC) Brodmann areas 9
dysfunctional thoughts and maladaptive behaviors. drug. and 46; makes reciprocal connections with posterior
cognitive enhancement Brain function enhancement culture Learned behaviors that are passed on from
parietal cortex and the superior temporal sulcus;
by pharmacological, physiological, or surgical responsible for selecting behavior and movement with
one generation to the next through teaching and respect to temporal memory.
manipulation.
imitation.
cognitive neuroscience Study of the neural bases of Down syndrome Chromosomal abnormality resulting
cytoarchitectonic map Map of the neocortex based on in intellecutal impairment and other abnormalities,
cognition.
the organization, structure, and distribution of the usually caused by an extra chromosome 21.
cognitive therapy Psychotherapy based on the perspec- cells.
tive that thoughts intervene between events and emo- drug dependence insomnia Condition resulting from
tions, and thus the treatment of emotional disorders continuous use of sleeping pills; drug tolerance also
requires changing maladaptive patterns of thinking. D results in deprivation of either REM or NREM sleep,
color constancy Phenomenon whereby an object’s per- deafferentation Loss of incoming sensory input, usually leading the user to increase the drug dosage.
ceived color tends to remain constant relative to other due to damage to sensory fibers; also loss of any affer- dualism Philosophical position that both a nonmaterial
colors, regardless of changes in illumination. ent input to a structure. mind and a material body contribute to behavior.
coma Prolonged state of deep unconsciousness resem- decibel (dB) Measure of the relative physical intensity dyslexia Impairment in learning to read and write;
bling sleep. of sounds. probably the most common learning disability.
common ancestor Forebear of two or more lineages or declarative memory Ability to recount what one knows,
family groups; ancestral to both groups. to detail the time, place, and circumstances of events; E
compensation Following brain damage, neuroplastic often lost in amnesia.
echolocation Identifying and locating an object by
ability to modify behavior from that used prior to the deep brain stimulation (DBS) Neurosurgery in which bouncing sound waves off it.
damage. electrodes implanted in the brain stimulate a targeted
area with a low-voltage electrical current to facilitate efferent Conducting away from a CNS structure.
competitive inhibitor Drug, such as nalorphine and
naloxone, that acts quickly to block opioid action by behavior. electrical stimulation Passage of an electrical current
competing with the opioid for binding sites; used to delta (δ) rhythm Slow brain wave activity pattern associ- from the uninsulated tip of an electrode through
treat opioid addiction. ated with deep sleep. tissue, resulting in changes in the electrical activity of
the tissue.
computed tomography (CT) X-ray technique that pro- dementia Acquired and persistent syndrome of intel-
duces a static three-dimensional image of the brain in lectual impairment characterized by memory and electrical synapse See gap junction.
cross section—a CT scan. other cognitive deficits and impairment in social and electrocorticography (ECoG) Graded potentials recorded
concentration gradient Difference in the relative abun- occupational functioning. with electrodes placed directly on the brain’s surface.
dance of a substance among regions of a container; dendrite Branching extension of a neuron’s cell mem- electroencephalogram (EEG) Graph that records electri-
allows the substance to diffuse from an area of higher brane; greatly increases the cell’s surface area; collects cal activity from the brain and mainly indicates
concentration to an area of lower concentration. information from other cells. graded potentials of many neurons.
conditioned response (CR) In Pavlovian conditioning, dendritic spine Protrusion that greatly increases the electrographic seizures Abnormal rhythmic neuronal
the learned response to a formerly neutral condi- dendrite’s surface area; typical point of dendritic discharges; may be recorded by an electroencephalo-
tioned stimulus (CS). contact with the axons of other cells. gram.
glossary G-3
embodied behavior Theory that the movements we festination Tendency to engage in a behavior, such as glutamate (Glu) Amino acid neurotransmitter; typically
make and the movements we perceive in others are walking, faster and faster. excites neurons.
central to communication with others. fetal alcohol spectrum disorder (FASD) Range of physi- gonadal (sex) hormone One of a group of hormones,
emotion Cognitive interpretation of subjective feelings. cal and intellectual impairments observed in some such as testosterone, that control reproductive func-
emotional memory Memory for the affective properties children born to alcoholic parents. tions and bestow sexual appearance and identity as
of stimuli or events. filopod (pl. filopodia) Process at the end of a developing male or female.
encephalization quotient (EQ) Jerison’s quantitative axon that reaches out to search for a potential target graded potential Small voltage fluctuation across the
measure of brain size obtained from the ratio of ac- or to sample the intercellular environment. cell membrane.
tual brain size to expected brain size, according to the focal seizure Seizure that arises at a synchronous, gray matter Areas of the nervous system composed pre-
principle of proper mass, for an animal of a particular hyperactive, localized brain region (at a focus). dominantly of cell bodies and capillary blood vessels
body size. forebrain Evolutionarily the newest part of the brain; that either collect and modify information or support
end plate On a muscle, the receptor–ion complex that coordinates advanced cognitive functions such as this activity.
is activated by the release of the neurotransmitter thinking, planning, and language; contains the limbic growth cone Growing tip of an axon.
acetylcholine from the terminal of a motor neuron. system, basal ganglia, and neocortex. growth spurt Sporadic period of sudden growth that
endocannabinoid Class of lipid neurotransmitters, fovea Central region of the retina specialized for high lasts for a finite time.
including anandamide and 2-AG, synthesized at the visual acuity; its receptive fields are at the center of gyrus (pl. gyri) A small protrusion or bump formed by
postsynaptic membrane to act on receptors at the the eye’s visual field. the folding of the cerebral cortex.
presynaptic membrane; affects appetite, pain, sleep, free-running rhythm Rhythm of the body’s own devising
mood, memory, anxiety, and the stress response. in the absence of all external cues.
endorphin Opioid peptide that acts as a neurotransmit- frequency Number of cycles a wave completes in a H
ter and may be associated with feelings of pain or given time. habituation Learned behavior in which the response to
pleasure; mimicked by opioid drugs such as morphine, a stimulus weakens with repeated presentations.
frontal lobe Part of the cerebral cortex often generally
heroin, opium, and codeine. hair cell Specialized neurons in the cochlea tipped by
characterized as performing the brain’s executive
enteric nervous system (ENS) Mesh of neurons embed- functions, such as decision making; lies anterior to cilia; when stimulated by waves in the cochlear fluid,
ded in the lining of the gut, running from the esopha- the central sulcus and beneath the frontal bone of the cilia bend and generate graded potentials in inner
gus through the colon; controls the gut. the skull. hair cells, the auditory receptor cells.
entorhinal cortex Located on the medial temporal lobe functional magnetic resonance imaging (fMRI) Magnetic hapsis Perceptual ability to discriminate objects on the
surface; provides a major route for neocortical input resonance imaging in which changes in elements basis of touch.
to the hippocampal formation; often degenerates in such as iron or oxygen are measured during the hemisphere Literally, half a sphere, referring to one side
Alzheimer disease. performance of a specific behavior; used to measure of the cerebrum.
entrain Determine or modify the period of a biorhythm. cerebral blood flow during behavior or resting.
hertz (Hz) Measure of sound wave frequency (repetition
ependymal cell Glial cell that makes and secretes CSF; functional near-infrared spectroscopy (fNIRS) Noninva- rate); 1 hertz equals 1 cycle per second.
found on the walls of the brain’s ventricles. sive technique that gathers light transmitted through
heterozygous Having two different alleles for the same
epidermal growth factor (EGF) Neurotrophic factor; stim- cortical tissue to image oxygen consumption; form of
trait.
ulates the subventricular zone to generate cells that optical tomography.
hindbrain Evolutionarily the oldest part of the
migrate into the striatum and eventually differentiate brain; contains the pons, medulla, reticular formation,
into neurons and glia. G and cerebellum, structures that coordinate and
epigenetics Differences in gene expression related to G protein Guanyl nucleotide–binding protein coupled control most voluntary and involuntary
environment and experience. to a metabotropic receptor; when activated, binds to movements.
epinephrine (EP, or adrenaline) Chemical messenger other proteins. hippocampus From the Greek word for seahorse; distinc-
that acts as a neurotransmitter in the CNS and as a gamma-aminobutyric acid (GABA) Amino acid neu- tive allocortical structure lying in the medial temporal
hormone to mobilize the body for fight or flight dur- rotransmitter; typically inhibits neurons. lobe; participates in species-specific behaviors,
ing times of stress. memory, and spatial navigation and is vulnerable to
ganglia Collection of nerve cells that function some-
episodic memory Autobiographical memory for events what like a brain. the effects of stress.
pegged to specific place and time contexts.
gap junction (electrical synapse) Area of contact histamine (H) Neurotransmitter that controls arousal
estrogens Variety of sex hormones responsible for the between adjacent cells in which ion channels form a and waking; can cause the constriction of smooth
distinguishing characteristics of the female. pore that allows ions to pass directly from one cell to muscles; when activated in allergic reactions, con-
event-related potentials (ERPs) Complex electroen- the next. stricts airway and contributes to asthma.
cephalographic waveform related in time to a specific gate Protein embedded in a cell membrane that allows homeostatic hormone One of a group of hormones that
sensory event. substances to pass through the membrane on some maintain internal metabolic balance and regulate
evolutionary psychology Discipline that seeks to apply occasions but not on others. physiological systems in an organism.
principles of natural selection to understand the gender identity The degree to which a person feels male homeostatic mechanism Process that maintains critical
causes of human behavior. or female. body functions within a narrow, fixed range.
excitation Increase in the activity of a neuron or brain gene DNA segment that encodes the synthesis of a hominid General term referring to primates that walk
area. particular protein. upright, including all forms of humans, living and
excitatory postsynaptic potential (EPSP) Brief depolar- extinct.
gene (DNA) methylation Epigenetic process in which
ization of a neuron membrane in response to stimula- a methyl group attaches to the DNA sequence, sup- homonymous hemianopia Blindness of an entire left or
tion, making the neuron more likely to produce an pressing or enabling gene expression. right visual field.
action potential.
generalized anxiety disorder Persistently high levels of homozygous Having two identical alleles for a trait.
explicit memory Conscious memory: subjects can anxiety often accompanied by maladaptive behaviors to homunculus Representation of the human body in
retrieve an item and indicate that they know the reduce anxiety; thought to be caused by chronic stress. the sensory or motor cortex; also any topographical
retrieved item is the correct one. generalized seizure Seizure that may start at a focal representation of the body by a neural area.
extinction In neurology, neglect of information on one location then spread rapidly and bilaterally to distrib- HPA axis Hypothalamic–pituitary–adrenal circuit that
side of the body when presented simultaneously with uted networks in both hemispheres. controls the production and release of hormones
similar information on the other side of the body. geniculostriate system Projections from the retina to the related to stress.
extrastriate (secondary visual) cortex (V2–V5) Visual lateral geniculate nucleus to the visual cortex. Huntington disease Hereditary disease characterized by
cortical areas in the occipital lobe outside the striate genotype Particular genetic makeup of an individual. chorea (ceaseless involuntary jerky movements) and
cortex. progressive dementia, ending in death.
glabrous skin Skin that does not have hair follicles but
eyeblink conditioning Experimental technique in which contains larger numbers of sensory receptors than do hydrocephalus Buildup of fluid pressure in the brain
subjects learn to pair a formerly neutral stimulus with hairy skin areas. and, in infants, swelling of the head, if the flow
a defensive blinking response. of CSF is blocked; can result in intellectual
glial cell Nervous system cell that provides insulation,
nutrients, and support and that aids in repairing impairment.
F neurons and eliminating waste products. hydrogen sulfide (H2S) Gaseous neurotransmitter;
facial agnosia Face blindness—the inability to recog- glioblast Product of a progenitor cell that gives rise to slows cellular metabolism.
nize faces; also called prosopagnosia. different types of glial cells. hyperconnectivity Increased local connections between
fear conditioning Conditioned emotional response glucocorticoid One of a group of steroid hormones, such two related brain regions.
between a neutral stimulus and an unpleasant event, as cortisol, secreted in times of stress; important in hyperkinetic symptom Excessive involuntary movement,
such as a shock, that results in a learned association. protein and carbohydrate metabolism. as seen in Tourette syndrome.
G-4 glossary
hyperphagia Overeating that leads to significant weight learned taste aversion Acquired association between a metabolic syndrome Combinations of medical disorders,
gain. specific taste or odor and illness; leads to an aversion including obesity and insulin abnormalities, that col-
hyperpolarization Increase in electrical charge across a to foods that have the taste or odor. lectively increase the risk of developing cardiovascular
membrane, usually due to the inward flow of chloride learning Relatively permanent change in behavior that disease and diabetes.
or sodium ions or the outward flow of potassium ions. results from experience. metabotropic receptor Embedded membrane protein
hypnogogic hallucination Dreamlike event as sleep learning set Rules of the game; implicit understanding with a binding site for a neurotransmitter linked to
begins or while a person is in a state of cataplexy. of how a problem can be solved with a rule that can a G protein; can affect other receptors or act with
be applied in many different situations. second messengers to affect other cellular processes,
hypokinesia Slowness or absence of movement. including opening a pore.
hypokinetic symptom Paucity of movement, as seen in Lewy body Circular fibrous structure found in several
neurodegenerative disorders; forms within the cy- metaplasticity Interaction among different plastic
Parkinson disease. changes in the brain.
toplasm of neurons and is thought to result from
hypothalamus Diencephalon structure that contains abnormal neurofilament metabolism. microdialysis Technique used to determine the chemi-
many nuclei associated with temperature regulation,
eating, drinking, and sexual behavior. light pollution Exposure to artificial light that changes cal constituents of extracellular fluid in freely moving
activity patterns and so disrupts circadian rhythms. animals.
hypovolemic thirst Thirst produced by a loss of overall microelectrode A microscopic insulated wire or a
fluid volume from the body. limbic system Disparate forebrain structures lying
between the neocortex and the brainstem that form a saltwater-filled glass tube whose uninsulated tip is
functional system controlling affective and motivated used to stimulate or record from neurons.
I behaviors and certain forms of memory; includes microglia Glial cells that originate in the blood, aid in cell
implicit memory Unconscious memory: subjects can cingulate cortex, amygdala, and hippocampus, among repair, and scavenge debris in the nervous system.
demonstrate knowledge, such as a skill, conditioned other structures. microsleep Brief sleep period lasting a second or so.
response, or recall of events on prompting but cannot locked-in syndrome Condition in which a patient is midbrain Central part of the brain; contains neural
explicitly retrieve the information. aware and awake but cannot move or communicate circuits for hearing and seeing as well as orienting
imprinting Formation of an attachment by an animal to verbally because of complete paralysis of nearly all movements.
voluntary muscles except the eyes.
one or more objects or animals at a critical period in mind Proposed nonmaterial entity responsible for intel-
development. long-term depression (LTD) Long-lasting decrease in ligence, attention, awareness, and consciousness.
inhibition Decrease in the activity of a neuron or brain synaptic effectiveness after low-frequency electrical
stimulation.
mind–body problem Difficulty of explaining how a
area. nonmaterial mind and a material body interact.
inhibitory postsynaptic potential (IPSP) Brief hyper- long-term potentiation (LTP) Long-lasting increase in
synaptic effectiveness after high-frequency stimula-
minimally conscious state (MCS) Condition in which a
polarization of a neuron membrane in response to person can display some rudimentary behaviors, such
stimulation, making the neuron less likely to produce tion.
as smiling or uttering a few words, but is otherwise
an action potential. luminance contrast Amount of light an object reflects not conscious.
initial segment Area near or overlapping the axon relative to its surroundings.
mirror neuron Cell in the primate premotor and parietal
hillock where the action potential begins. cortex that fires when an individual observes an ac-
innate releasing mechanism (IRM) Hypothetical mecha- M tion taken by another individual.
nism that detects specific sensory stimuli and directs magnetic resonance imaging (MRI) Technique that monoamine oxidase (MAO) inhibitor Antidepressant
an organism to take a particular action. produces a static three-dimensional brain image by drug that blocks the enzyme monoamine oxidase
insomnia Disorder of slow-wave sleep resulting in passing a strong magnetic field through the brain, from degrading such neurotransmitters as DA, NE,
prolonged inability to sleep. followed by a radio wave, then measuring a radio and 5-HT.
insula Multifunctional cortical tissue located within the frequency signal emitted from hydrogen atoms. monosynaptic reflex Reflex requiring one synapse
lateral fissure; contains language and taste percep- magnetic resonance spectroscopy (MRS) Magnetic between sensory input and movement.
tion–related regions and neural structures underlying resonance imaging method that uses the hydrogen mood stabilizer Drug for treating bipolar disorder;
social cognition. proton signal to determine the concentration of brain mutes the intensity of one pole of the disorder, thus
intelligence A Hebb’s term for innate intellectual metabolites. making the other pole less likely to recur.
potential, which is highly heritable and cannot be magnetoencephalogram (MEG) Magnetic potentials motivation Behavior that seems purposeful and goal-
measured directly. recorded from detectors placed outside the skull. directed.
intelligence B Hebb’s term for observed intelligence, in- magnocellular (M) cell Large visual system neuron sensi- motor neuron Cell that carries efferent information
fluenced by experience and other factors in the course tive to moving stimuli and black-white vision. from the brain and spinal cord to make muscles
of development; measured by intelligence tests. major depression Mood disorder characterized by pro- contract.
interneuron Association cell interposed between a longed feelings of worthlessness and guilt, disruption motor sequence Movement modules preprogrammed by
sensory neuron and a motor neuron; in mammals, of normal eating habits, sleep disturbances, a general the brain and produced as a unit.
interneurons constitute most of the brain’s neurons. slowing of behavior, and frequent thoughts of suicide. multiple sclerosis (MS) Nervous system disorder resulting
ionotropic receptor Embedded membrane protein; acts mania Disordered mental state of extreme excitement. from the loss of myelin around axons in the CNS.
as (1) a binding site for a neurotransmitter and (2) a masculinization Process by which exposure to andro- mutation Alteration of an allele that yields a different
pore that regulates ion flow to directly and rapidly gens (male sex hormones) alters the brain, rendering it version of its protein.
change membrane voltage. identifiably male. myelin Glial coating that surrounds axons in the central
ischemia Lack of blood to the brain, usually as a result materialism Philosophical position that behavior can be and peripheral nervous systems; prevents adjacent
of a stroke. explained as a function of the nervous system without neurons from short circuiting.
recourse to the mind.
J medial forebrain bundle (MFB) Tract that connects
brainstem structures with various parts of the limbic
N
jet lag Fatigue and disorientation resulting from rapid system; forms the activating projections that run from narcolepsy Slow-wave sleep disorder in which a person
travel through time zones and exposure to a changed the brainstem to basal ganglia and frontal cortex. uncontrollably falls asleep at inappropriate times.
light–dark cycle. natural selection Darwin’s theory for explaining how
medial geniculate nucleus Major thalamic region con-
cerned with audition. new species evolve and how existing species change
K medial pontine reticular formation (MPRF) Nucleus in over time. Differential success in the reproduction of
different characteristics (phenotypes) results from the
Klüver-Bucy syndrome Behavioral syndrome, character- the pons participating in REM sleep.
interaction of organisms with their environment.
ized especially by hypersexuality, that results from melatonin Hormone secreted by the pineal gland during
bilateral injury to the temporal lobe. the dark phase of the day–night cycle; influences daily
neocortex (cerebral cortex) Most recently evolved outer
layer (new bark) of the forebrain, composed of about
Korsakoff syndrome Permanent loss of the ability to learn and seasonal biorhythms.
six layers of gray matter; constructs our reality.
new information (anterograde amnesia) and to retrieve meme An idea, behavior, or style that spreads from
old information (retrograde amnesia) caused by dien- person to person within a culture.
neoteny Process in which juvenile stages of predeces-
cephalic damage resulting from chronic alcoholism or sors become adult features of descendants; idea
memory Ability to recall or recognize previous experience. derived from the observation that more recently
malnutrition that produces a vitamin B1 deficiency.
Ménière disease Disorder of the middle ear resulting in evolved species resemble the young of their common
vertigo and loss of balance. ancestors.
L meninges Three layers of protective tissue—dura mater, nerve Large collection of axons coursing together
lateralization Localization of function primarily on one arachnoid, and pia mater—that encase the brain and outside the CNS.
side of the brain. spinal cord. nerve growth factor (NGF) Neurotrophic factor that
law of Bell and Magendie The principle that sensory mentalism Explanation of behavior as a function of the stimulates neurons to grow dendrites and synapses
fibers are dorsal and motor fibers are ventral. nonmaterial mind. and in some cases promotes the survival of neurons.
glossary G-5
nerve impulse Propagation of an action potential on the occipital lobe Part of the cerebral cortex where visual Pavlovian conditioning Learning achieved when neutral
membrane of an axon. processing begins; lies at the back of the brain and stimulus (such as a tone) comes to elicit a response
nerve net Simple nervous system that has no center but beneath the occipital bone. after its repeated pairing with some event (such as
consists of neurons that receive sensory information ocular dominance column Functional column in the delivery of food); also called classical conditioning or
and connect directly to other neurons that move visual cortex maximally responsive to information respondent conditioning.
muscles. coming from one eye. peptide hormone Chemical messenger synthesized by cel-
netrin Member of the only class of tropic molecules yet oligodendroglia Glial cells in the CNS that myelinate lular DNA that acts to affect the target cell’s physiology.
isolated. axons. perception Subjective interpretation of sensations by
neural Darwinism Hypothesis that the processes of cell operant conditioning Learning procedure in which the brain.
death and synaptic pruning are, like natural selec- the consequences (such as obtaining a reward) of a periaqueductal gray matter (PAG) Nuclei in the mid-
tion in species, the outcome of competition among particular behavior (such as pressing a bar) increase brain that surround the cerebral aqueduct joining
neurons for connections and metabolic resources in a or decrease the probability of the behavior occurring the third and fourth ventricles; PAG neurons contain
neural environment. again; also called instrumental conditioning. circuits for species-typical behaviors (e.g., female
neural network Functional group of neurons that con- opioid analgesic Drug such as morphine, with sleep- sexual behavior) and play an important role in the
nects wide areas of the brain and spinal cord. inducing (narcotic) and pain-relieving (analgesic) modulation of pain.
neural plate Primitive neural tissue that gives rise to the properties; originally called narcotic analgesic. peribrachial area Cholinergic nucleus in the dorsal
neural tube. opponent process Explanation of color vision that em- brainstem having a role in REM sleep behaviors;
projects to medial pontine reticular formation.
neural stem cell Self-renewing multipotential cell that phasizes the importance of the apparently opposing
gives rise to any of the different types of neurons and color pairs: red versus green and blue versus yellow. period Time required to complete an activity cycle.
glia in the nervous system. optic ataxia Deficit in the visual control of reaching and peripheral nervous system (PNS) All of the neurons in
neural tube Structure in the early stage of brain devel- other movements. the body outside the brain and spinal cord; provides
opment from which the brain and spinal cord develop. optic chiasm Junction of the optic nerves, one from sensory and motor connections to and from the
neuritic plaque Area of incomplete necrosis (dead each eye, at which the axons from the nasal halves of central nervous system.
tissue) consisting of a central protein core (amyloid) the retinas cross to the brain’s opposite side. perirhinal cortex Cortex lying next to the rhinal fissure
surrounded by degenerative cellular fragments; often optic flow Streaming of visual stimuli that accompanies on the ventral surface of the brain.
seen in the cortex of people with dementias such as an observer’s movement through space. perseveration Tendency to emit repeatedly the same
Alzheimer disease. optogenetics Transgenic technique that combines verbal or motor response to varied stimuli.
neuroblast Product of a progenitor cell that gives rise to genetics and light to excite or inhibit targeted cells in persistent vegetative state (PVS) Condition in which a
any of the different types of neurons. living tissue. person is alive but unaware, unable to communicate or
neuroeconomics Interdisciplinary field that seeks to orbitofrontal cortex (OFC) Prefrontal cortex behind the to function independently at even the most basic level.
understand how the brain makes decisions. eye sockets (the orbits); receives projections from the phenotype Set of individual characteristics that can be
neuron Specialized nerve cell engaged in information dorsomedial nucleus of the thalamus; central to a seen or measured.
processing. variety of emotional and social behaviors, including phenotypic plasticity An individual’s capacity to develop
eating; also called orbital frontal cortex.
neuropeptide Short (fewer than 100), multifunctional into more than one phenotype.
amino acid chain; acts as a neurotransmitter and can organizational hypothesis Proposal that hormonal action phenylketonuria (PKU) Behavioral disorder caused by
act as a hormone; may contribute to learning. during development alters tissue differentiation; for
elevated levels of the amino acid phenylalanine in
example, testosterone masculinizes the brain.
neuroplasticity The nervous system’s potential for the blood and resulting from a defect in the gene for
physical or chemical change to adapt to environmen- orienting movement Movement related to sensory the enzyme phenylalanine hydroxylase; the major
tal change and to compensate for injury. inputs, such as turning the head to see the source of symptom is severe developmental disability.
a sound.
neuroprosthetics Field that develops computer-assisted pheromone Odorant biochemical released by one animal
devices to replace lost biological function. oscilloscope Device that serves as a sensitive voltmeter that acts as a chemosignal and can affect the physiol-
by registering changes in voltage over time. ogy or behavior of another animal.
neuroprotectant Drug used to try to block the cascade of
poststroke neural events. osmotic thirst Thirst that results from a high concen- phobia Fear of a clearly defined object or situation.
tration of dissolved chemicals, or solutes, in body
neuropsychoanalysis Movement within neuroscience photoreceptor Specialized retinal neuron that trans-
fluids.
and psychoanalysis to combine the insights of both to duces light into neural activity.
yield a unified understanding of mind and brain. ossicle Bone of the middle ear; includes malleus (ham- pituitary gland Endocrine gland attached to the bottom
mer), incus (anvil), and stapes (stirrup).
neuropsychology Study of the relations between brain of the hypothalamus; its secretions control the activi-
function and behavior, especially in humans. otoacousitic emissions Spontaneous or evoked sound ties of many other endocrine glands; associated with
waves produced within the ear by the cochlea and
neurotransmitter Chemical with an excitatory or inhibi- biological rhythms.
escape from the ear.
tory effect when released by a neuron onto a target. place cell Hippocampal neuron maximally responsive to
neurotrophic factor A chemical compound that supports specific locations in the world.
growth and differentiation in developing neurons and P plasticity The nervous system’s potential for physical
may act to keep certain neurons alive in adulthood. pain gate Hypothetical neural circuit in which activity or chemical change; enhances its adaptability to
nitric oxide (NO) Gaseous neurotransmitter; acts, for in fine-touch and pressure pathways diminishes the environmental change and its ability to compensate
example, to dilate blood vessels, aid digestion, and activity in pain and temperature pathways. for injury. (Also called neuroplasticity.)
activate cellular metabolism. panic disorder Recurrent attacks of intense terror that positron emission tomography (PET) Imaging technique
nocioception Perception of pain, temperature, and itch. come on without warning and without any apparent that detects changes in blood flow by measuring
relation to external circumstances. changes in the uptake of compounds such as oxygen
node of Ranvier The part of an axon that is not covered
parahippocampal cortex Cortex located along the dorsal or glucose; used to analyze the metabolic activity of
by myelin.
medial temporal lobe surface. neurons.
nonregulatory behavior Behavior unnecessary to the
animal’s basic survival needs. paralysis Loss of sensation and movement due to posterior spinothalamic tract Pathway that carries fine-
nervous system injury. touch and pressure fibers.
noradrenergic neuron From adrenaline, Latin for epi-
nephrine; a neuron containing norepinephrine. paraplegia Paralysis of the legs due to spinal cord injury. postsynaptic membrane Membrane on the transmitter,
or input, side of a synapse.
norepinephrine (NE, or noradrenaline) Neurotransmitter parasympathetic division Part of the autonomic nervous
that accelerates heart rate in mammals; found in the system; acts in opposition to the sympathetic divi- posttraumatic stress disorder (PTSD) Syndrome charac-
brain and in the sympathetic division of the ANS. sion—for example, preparing the body to rest and terized by physiological arousal associated with recur-
digest by reversing the alarm response or stimulating rent memories and dreams arising from a traumatic
NREM (non-REM) sleep Slow-wave sleep associated with event that occurred months or years earlier.
delta rhythms. digestion.
parietal lobe Part of the cerebral cortex that directs prefrontal cortex (PFC) Extensive frontal lobe area
nuclei (sing. nucleus) A group of cells forming a cluster anterior to the motor and premotor cortex; key to
that can be identified with special stains to form a movements toward a goal or to perform a task, such
as grasping an object; lies posterior to the central controlling executive functions such as planning.
functional grouping.
sulcus and beneath the parietal bone at the top of preparedness Predisposition to respond to certain
the skull. stimuli differently from other stimuli.
O Parkinson disease Disorder of the motor system cor- presynaptic membrane Axon terminal membrane on the
obesity Excessive accumulation of body fat. related with a loss of dopamine from the substantia transmitter, or output, side of a synapse.
obsessive-compulsive disorder (OCD) Behavior charac- nigra and characterized by tremors, muscular rigidity, primary auditory cortex (area A1) Asymmetrical struc-
terized by compulsively repeated acts (such as hand and a reduction in voluntary movement. tures within Heschl’s gyrus in the temporal lobes;
washing) and repetitive, often unpleasant, thoughts parvocellular (P) cell Small visual system neuron sensi- receive input from the ventral region of the medial
(obsessions). tive to differences in form and color. geniculate nucleus.
G-6 glossary
primary visual cortex (V1) Striate cortex in the occipital relatively refractory The state of an axon in the later sensory deprivation Experimental setup in which a
lobe that receives input from the lateral geniculate phase of an action potential during which increased participant is allowed only restricted sensory input;
nucleus. electrical current is required to produce another participants generally have a low tolerance for depri-
priming Using a stimulus to sensitize the nervous action potential; a phase during which potassium vation and may even hallucinate.
system to a later presentation of the same or a similar channels are still open. sensory neuron Cell that detects or carries sensory
stimulus. releasing hormone Peptide released by the hypothala- information into the spinal cord and brain.
prion From protein and infection, an abnormally folded mus that increases or decreases hormone release from serotonin (5-HT) Amine neurotransmitter; helps to
protein that causes progressive neurodegenerative the anterior pituitary. regulate mood and aggression, appetite and arousal,
disorders. REM sleep Fast brain wave pattern displayed by the perception of pain, and respiration.
procedural memory Ability to recall a movement neocortical EEG record during sleep. sexual dimorphism Differential development of brain
sequence or how to perform some act or behavior. resting potential Electrical charge across the insulating areas in the two sexes.
progenitor cell (precursor cell) Derived from a stem cell; cell membrane in the absence of stimulation; a store sexual orientation A person’s pattern of sexual attrac-
it migrates and produces a neuron or a glial cell. of potential energy produced by a greater negative tion—to the opposite sex or to the same sex or to
charge on the intracellular side relative to the extracel- both sexes.
proprioception Perception of the position and move-
lular side. sleep apnea Inability to breathe during sleep, causing a
ment of the body, limbs, and head.
prosody Melodic tone of the speaking voice. resting-state fMRI (rs-fMRI) Magnetic resonance imag- sleeper to wake up to breathe.
ing method that measures changes in elements such sleep paralysis Atonia and dreaming occurring when
protein Folded-up polypeptide chain that serves a as iron or oxygen when the individual is resting (not
particular function in the body. a person is awake, usually just falling asleep or
engaged in a specific task). waking up.
psyche Synonym for mind, an entity once proposed to reticular activating system (RAS) Large reticulum (mix-
be the source of human behavior. slow-wave sleep NREM sleep.
ture of cell nuclei and nerve fibers) that runs through
psychedelic drug Drug that can alter sensation and the center of the brainstem; associated with sleep–
slowly adapting receptor Body sensory receptor that
perception; examples are lysergic acid diethylamide responds as long as a sensory stimulus is on the body.
wake behavior and behavioral arousal; also called the
(LSD), mescaline, and psilocybin. reticular formation. small-molecule transmitter Quick-acting neurotransmit-
psychoactive drug Substance that acts to alter mood, ter synthesized in the axon terminal from products
reticular formation Midbrain area in which nuclei and derived from the diet.
thought, or behavior; is used to manage neuropsycho- fiber pathways are mixed, producing a netlike ap-
logical illness; or is abused. pearance; associated with sleep–wake behavior and social neuroscience Interdisciplinary field that seeks
psychological construct Idea or set of impressions that behavioral arousal. to understand how the brain mediates social
interactions.
some mental ability exists as an entity; memory, retina Light-sensitive surface at the back of the eye
language, and emotion are examples. consisting of neurons and photoreceptor cells. somatic marker hypothesis Proposal that marker signals
psychomotor activation Increased behavioral and cogni- arising from emotions and feelings act to guide behav-
retinal ganglion cell (RGC) One of a group of retinal ior and decision making, usually in an unconscious
tive activity: at certain levels of consumption, the neurons with axons that give rise to the optic nerve.
drug user feels energetic and in control. process.
retinohypothalamic tract Neural route formed by axons somatic nervous system (SNS) Part of the PNS that
psychopharmacology Study of how drugs affect the of photosensitive retinal ganglion cells (pRGCs) from includes the cranial and spinal nerves to and from
nervous system and behavior. the retina to the suprachiasmatic nucleus; allows light the muscles, joints, and skin, which produce move-
psychosurgery Any neurosurgical technique intended to to entrain the SCN’s rhythmic activity. ment, transmit incoming sensory input, and inform
alter behavior. retrograde amnesia Inability to remember events that the CNS about the position and movement of body
psychotherapy Talk therapy derived from Freudian took place before the onset of amnesia. parts.
psychoanalysis and other psychological interventions. reuptake Deactivation of a neurotransmitter when somatosensory neuron Brain cell that brings sensory
pump Protein in the cell membrane that actively trans- membrane transporter proteins bring the transmitter information from the body into the spinal cord.
ports a substance across the membrane. back into the presynaptic axon terminal for reuse. sound wave Mechanical displacement of molecules
Purkinje cell Distinctively shaped interneuron found in rod Photoreceptor specialized for functioning at low caused by changing pressure that possesses the physi-
the cerebellum. light levels. cal properties of frequency, amplitude, and complex-
pyramidal cell Distinctively shaped interneuron found ity. Also compression wave.
in the cerebral cortex. spatial summation Addition of one graded potential to
S another that occur close in space.
Q saltatory conduction Fast propagation of an action species Group of organisms that can interbreed.
quadrantanopia Blindness of one quadrant of the visual potential at successive nodes of Ranvier; saltatory species-typical behavior Behavior that is characteris-
means leaping. tic of all members of a species, such as walking in
field.
schizophrenia Behavioral disorder characterized by delu- amphibians.
quadriplegia Paralysis of the legs and arms due to spinal
cord injury. sions, hallucinations, disorganized speech, blunted spinal cord Part of the central nervous system encased
emotion, agitation or immobility, and a host of associ- within the vertebrae (spinal column); provides most
quantum (pl. quanta) Amount of neurotransmitter, ated symptoms. of the connections between the brain and the rest of
equivalent to the content of a single synaptic vesicle, the body.
that produces a just-observable change in postsynap- Schwann cell Glial cell in the PNS that myelinates
tic electric potential. sensory and motor axons. split brain Surgical disconnection of the hemispheres
scotoma Small blind spot in the visual field caused by by severing the corpus callosum.
migraine or by a small lesion of the visual cortex. stereotaxic apparatus Surgical instrument that permits
R the researcher to target a specific part of the brain.
scratch reflex Automatic response in which an animal’s
radial glial cell Path-making cell that a migrating neu- hind limb reaches to remove a stimulus from the steroid hormone Fat-soluble chemical messenger synthe-
ron follows to its appropriate destination. surface of its body. sized from cholesterol.
rapidly adapting receptor Body sensory receptor that re- second-generation antidepressant Drug that acts storage granule Membranous compartment that holds
sponds briefly to the onset of a stimulus on the body. similarly to tricyclics (first-generation antidepressants) several vesicles containing a neurotransmitter.
rate-limiting factor Any chemical in limited supply that but more selectively on 5-HT reuptake transporter stretch-sensitive channel Ion channel on a tactile sen-
restricts the pace at which another chemical can be proteins; also called atypical antidepressant. sory neuron that activates in response to stretching of
synthesized. second messenger Chemical that initiates a biochemi- the membrane, initiating a nerve impulse.
real-time fMRI (rt-fMRI) Behavior-modification technique cal process when activated by a neurotransmitter (the striate cortex Primary visual cortex (V1) in the occipital
in which individuals learn to change their behavior by first messenger). lobe; shows stripes (striations) on staining.
controlling their own patterns of brain activation. striatum Caudate nucleus and putamen of the basal
segmentation Division into a number of parts that are
receptive field Sensory region that stimulates a receptor similar; refers to the idea that many animals, includ- ganglia.
cell or neuron. ing vertebrates, are composed of similarly organized stroke Sudden appearance of neurological symptoms as
reconsolidation Process of restabilizing a memory trace body segments. a result of severely interrupted blood flow.
after the memory is revisited. selective serotonin reuptake inhibitor (SSRI) Tricyclic substance abuse A pattern of drug use in which people
referred pain Pain that arises in one of the internal antidepressant drug that blocks 5-HT reuptake into rely on a drug chronically and excessively, allowing it
organs but is felt on the surface of the body. the presynaptic terminal. to occupy a central place in their life.
regulatory behavior Behavior motivated to meet the sensation Registration by the sensory organs of physical subunit Protein molecule that assembles with other
animal’s survival needs. stimuli from the environment. protein molecules.
reinforcer In operant conditioning, any event that sensitization Learned behavior in which the response to subventricular zone Lining of neural stem cells sur-
strengthens the behavior it follows. a stimulus strengthens with repeated presentations. rounding the ventricles in adults.
glossary G-7
sudden infant death syndrome (SIDS) Unexplained death testosterone Sex hormone secreted by the testes and U
while asleep of a seemingly healthy infant less than responsible for the distinguishing characteristics of
1 year old. the male.
unconditioned response (UCR) Unlearned, naturally
occurring response to the unconditioned stimulus
sulcus (pl. sulci) A groove in brain matter; most are in thalamus Diencephalon structure through which (UCS), such as salivation when food is in the
the neocortex or cerebellum. information from all sensory systems is integrated mouth.
supplementary speech area Speech production region and projected into the appropriate region of the
unconditioned stimulus (UCS) A stimulus that naturally
on the left frontal lobe dorsal surface. neocortex.
and automatically (unconditionally) triggers an uncon-
suprachiasmatic nucleus (SCN) Master biological clock theory of mind Ability to attribute mental states to ditioned response (UCR).
located in the hypothalamus just above the optic others.
chiasm. threshold potential Voltage on a neural membrane at
V
sympathetic division Part of the autonomic nervous which an action potential is triggered by the opening
system; arouses the body for action, such as mediating of sodium and potassium voltage-sensitive channels; ventral stream Visual processing pathway from V1
the involuntary fight-or-flight response to alarm by about −50 mV relative to extracellular surround. Also to the temporal lobe for object identification and
increasing heart rate and blood pressure. called threshold limit. perceiving related movements.
symptomatic seizure Identified with a specific cause, tolerance Decrease in response to a drug with the pas- ventricle One of four cavities in the brain that contain
such as infection, trauma, tumor, vascular malfor- sage of time. CSF to cushion the brain; may play a role in maintain-
mation, toxic chemicals, very high fever, or other tonotopic representation In audition, structural organiza- ing brain metabolism.
neurological disorders. tion for processing of sound waves from lower to ventrolateral thalamus Part of the thalamus that carries
synapse Spatial junction between one neuron and higher frequencies. information about body senses to the somatosensory
another; forms the information transfer site between topographic map Spatially organized neural representa- cortex.
neurons. tion of the external world. vertebrae (sing. vertebra) The bones that form the
synaptic cleft Gap separating the neuronal presynaptic topographic organization Neural spatial representation spinal column.
membrane from the postsynaptic membrane. of the body or areas of the sensory world perceived by vestibular system Somatosensory system comprising a
synaptic vesicle Membranous compartment that a sensory organ. set of receptors in each inner ear that respond to body
encloses a quantum of neurotransmitter. Tourette syndrome Disorder of the basal ganglia char- position and to movement of the head.
synesthesia Ability to perceive a stimulus of one acterized by tics, involuntary vocalizations (including virtual-reality (VR) exposure therapy Controlled virtual
sense as the sensation of a different sense, as when curse words and animal sounds), and odd, involuntary immersion environment that, by allowing individuals
sound produces a sensation of color; literally, feeling movements of the body, especially of the face and to relive traumatic events, gradually desensitizes them
together. head. to stress.
syntax Ways in which words are put together; proposed tract Large collection of axons coursing together in the visual field Region of the visual world seen by the eyes.
to be unique to human language. CNS. visual-form agnosia Inability to recognize objects or
synthetic biology Design and construction of bio- transcranial magnetic stimulation (TMS) Procedure drawings of objects.
logical devices, systems, and machines not found in in which a magnetic coil is placed over the skull to visuospatial memory Use of visual information to recall
nature. stimulate the underlying brain; used either to induce an object’s location in space.
behavior or to disrupt ongoing behavior. voltage gradient Difference in charge between two
T transgender Possessing personal characteristics that regions that allows a flow of current if the two regions
transcend traditional gender boundaries and cor- are connected.
tardive dyskinesia Inability to stop the tongue or other
responding sexual norms; a person’s belief that he or voltage-sensitive channel Gated protein channel that
body parts from moving; motor side effect of neuro-
she was born the wrong sex. opens or closes only at specific membrane voltages.
leptic drugs.
transgenic animal Product of technology in which one voltmeter Device that measures the flow and the
Tay-Sachs disease Inherited birth defect caused by the
or more genes from one species is introduced into the strength of electrical voltage by recording the
loss of genes that encode the enzyme necessary for
genome of another species to be passed along and difference in electrical potential between two bodies.
breaking down certain fatty substances; appears 4 to 6
expressed in subsequent generations.
months after birth and results in intellectual disability,
physical changes, and death by about age 5. transmitter-activated receptor Protein that has a binding
site for a specific neurotransmitter and is embedded W
tectopulvinar system Projections from the retina to the wanting-and-liking theory Explanation holding that
in the membrane of a cell.
superior colliculus to the pulvinar (thalamus) to the when a drug is associated with certain cues, the cues
parietal and temporal visual areas. transmitter-sensitive channel Receptor complex that has
both a receptor site for a chemical and a pore through themselves elicit desire for the drug; also called incen-
tectum Roof (area above the ventricle) of the midbrain; tive sensitization theory.
which ions can flow.
its functions are sensory processing, particularly Wernicke’s area Secondary auditory cortex (planum
visual and auditory, and the production of orienting transporter Protein molecule that pumps substances
across a membrane. temporale) lying behind Heschl’s gyrus at the rear of
movements. the left temporal lobe; regulates language comprehen-
tegmentum Floor (area below the ventricle) of the traumatic brain injury (TBI) Wound to the brain that sion. Also posterior speech zone.
midbrain; a collection of nuclei with movement- results from a blow to the head.
white matter Areas of the nervous system rich in fat-
related, species-specific, and pain perception func- trichromatic theory Explanation of color vision based sheathed neural axons that form the connections
tions. on the coding of three primary colors: red, green, and between brain cells.
temporal lobe Part of the cerebral cortex that functions blue.
wild type Typical allele (most common in a population).
in connection with hearing, language, and musical tricyclic antidepressant First-generation antidepressant;
abilities; lies below the lateral fissure, beneath the its chemical structure, characterized by three rings, withdrawal symptom Physical and psychological behav-
temporal bone at the side of the skull. blocks 5-HT reuptake transporter proteins. ior displayed by an addict when drug use ends.
temporal summation Addition of one graded potential to tropic molecule Signaling molecule that attracts or
another that occur close in time. repels growth cones. Z
terminal button (end foot) Knob at the tip of an axon tumor Mass of new tissue that grows uncontrolled and Zeitgeber Environmental event that entrains biological
that conveys information to other neurons. independent of surrounding structures. rhythms: German for time giver.
references
Chapter 1 Gould, S. J. (1981). The Mismeasure of a man. Milton, K. (2003). The critical role played by
Antón, S. C., Potts, R., & Aiello, L. C. New York: Norton. animal source foods in human (Homo)
(2014). Human evolution. Evolution of Gross, C. G. (1995). Aristotle on the brain. evolution. Journal of Nutrition, 133
early Homo: An integrated biological The Neuroscientist, 1,4, 245–250. (Suppl. 2), 3886S–3892S.
perspective. Science, 45, 1236828. Hampshire, A., Highfield, R. R., Parkin, B. Owen, A. M. (2015). Using functional
Darwin, C. (1871). The Descent of Man, L., & Owen, A. M. (2012). Fractionating magnetic resonance imaging and
and Selection in Relation to Sex. London: human intelligence. Neuron, 76, electroencephalography to detect
J. Murray. 1225–1237. consciousness after severe brain injury.
Darwin, C. (1963). On the origin of species Hebb, D. O. (1949). The organization of Handbook of Clinical Neurology, 127,
by means of natural selection, or the behavior: A neuropsychological theory. 277–293.
preservation of favored races in the struggle New York: Wiley. Pickering, R., Dirks, P. H., Jinnah, Z., de
for life. New York: New American Library. Herculano-Houzel. S., Avelino-de-Souza, K., Ruiter, D. J., Churchill, S. E., et al. (2011).
(Original work published 1859.) Neves, K., Porfirio, J., Messeder, D., Australopithecus sediba at 1.977 Ma and
Darwin, C. (1965). The expression of the Mattos Feijo, L., Maldonado, J., & implications for the origins of the genus
emotions in man and animals. Chicago: Manger, P. R. (2014). The elephant brain Homo. Science, 333, 1421–1423.
University of Chicago Press. (Original in numbers. Frontiers in Neuroanatomy. Potts, R., & Sloan, C. (2010). What does it
work published 1872.) 12, 8–46. mean to be human? Companion volume
Deary, I. J. (2000). Looking down on human Heron, W. (1957). The pathology of boredom. to the Smithsonian National Museum
intelligence: From psychometrics to the Scientific American, 196(1), 52–56. of Natural History’s David H. Koch Hall
brain. Oxford Psychology Series, No. 34. Herringa, R. J., Birn, R. M., Ruttle, P. L., of Human Origins. Washington, DC:
New York: Oxford University Press. Burghy, C. A., Stodola, D.E., Davidson, National Geographic Society.
Dennett, D. (1978). The intentional stance. R. J., & Essex, M. J. (2013). Childhood Prinz, J. (2008). Is consciousness embodied?
Cambridge, MA: MIT Press. maltreatment is associated with altered In P. Robbins and. M. Aydede (Eds.),
Descartes, R. (1972). Treatise on man (T. S. fear circuitry and increased internalizing Cambridge Handbook of Situated Cognition.
Hall, Trans.). Cambridge, MA: Harvard symptoms by late adolescence. Proceedings Cambridge: Cambridge University Press.
University Press. (Original work published of the National Academy of Sciences Sankararaman, S., Mallick S., Dannemann, M.,
1664.) of the United States of America, 110, Prüfer, K., Kelso, J., Pääbo, S., Patterson, N.,
Dunbar, R. (1998). Grooming, gossip, and the 19119–19124. Reich, D. (2014). The genomic landscape
evolution of language. Cambridge, MA: Jacobson, E. (1932). Electrophysiology of of Neanderthal ancestry in present-day
Harvard University Press. mental activities. American Journal of humans. Nature, 507, 354–357.
Eibl-Eibesfeldt, I. (1970). Ethology: The Psychology, 44, 677–694. Savage-Rumbaugh, S. (1999). Ape
biology of behavior. New York: Holt, Jerison, H. J. (1973). The evolution of the brain communication: Between a rock and a
Rinehart and Winston. and intelligence. New York: Academic hard place in origins of language—What
Flynn, J. R. (2012). Are we getting smarter? Press. non-human primates can tell us. School of
Rising IQ in the twenty-first century. Johanson, D., & Edey, M. (1981). Lucy: The American Research Press.
Cambridge: Cambridge University Press. beginnings of humankind. New York: Schiff, N. D., & Fins, J. J. (2007). Deep brain
Fonseca-Azevedo K., & Herculano-Houzel, S. Warner Books. stimulation and cognition: Moving from
(2012). Metabolic constraint imposes Kunz, A. R., & Iliadis, C. (2007). Hominid animal to patient. Current Opinion in
tradeoff between body size and number evolution of the arteriovenous system Neurology, 20, 638–642.
of brain neurons in human evolution. through the cranial base and its relevance Stedman, H. H., Kozyak, B. W., Nelson, A.,
Proceedings of the National Academy for craniosynostosis. Child’s Nervous Thesier, D. M., Su, L. T., Low, D. W.,
of Sciences United States of America, System, 23, 1367–1377. Bridges, C. R., Shrager, J. B., Minugh-
109:18571–18576. Lewin, R. (1998). The Origin of Modern Purvis, N., & Mitchell, M. A. (2004).
Gardner, H. (2006). Multiple intelligences: Humans. New York: Scientific American Myosin gene mutation correlates with
New horizons. New York: Basic Books. Library. anatomical changes in the human lineage.
Gardner R. A., & Gardner B. T. (1969). Linge, F. R. (1990). Faith, hope, and love: Nature, 428, 415–418.
Teaching sign language to a chimpanzee. Nontraditional therapy in recovery from Tagliatela, J. P., Russell, J. L., Schaeffer, J.
Science, 165, 664–672. serious head injury, a personal account. A., & Hopkins, W. D. (2011). Chimpanzee
Gillespie-Lynch, K., Greenfield, P. M., Canadian Journal of Psychology, 44, vocal signaling points to a multimodal
Lyn, H., & Savage-Rumbaugh, S. (2014). 116–129. origin of human language. PLoS One, 6,
Gestural and symbolic development Maslin, M. A., Shultz, S., & Trauth, M. H. e18852.
among apes and humans: Support for a (2015). A synthesis of the theories and Terkel, J. (1995). Cultural transmission in the
multimodal theory of language evolution. concepts of early human evolution. black rat: Pinecone feeding. Advances in
Frontiers in Psychology, 30, 1228. Philosophical Transaction of the Royal the Study of Behavior, 24, 119–154.
Gordon, A. D., Nevell, L., & Wood, B. (2008). Society of London, B Biological Sciences, Villmoare, B., Kimbel, W. H., Seyoum, C.,
The Homo floresiensis cranium (LB1): 370, 20140064. Campisano, C. J., DiMaggio, E. J., Rowan,
Size, scaling, and early Homo affinities. Mesoudi, A., Whiten, A., & Laland, K. N. J., Braun, D. R., Arrowsmith, J. R., &
Proceedings of the National Academy of (2006). Towards a unified science of Reed, K. E., (2015). Early Homo at 2.8
Sciences of the United States of America, cultural evolution. Behavioural and Brain Ma from Ledi-Geraru, Afar, Ethiopia.
105, 4650–4655. Sciences 29, 329–347. Science, 20, 1352–1355.
R-0
References R-1
Watson, S. K., Townsend, S. W., Schel, A. Schmahmann, J. D. (2010). The role of the Herculano-Houzel, S., Manger, P. R., & Kaas,
M., Wilke, C., Wallace, E. K., Cheng, L., cerebellum in cognition and emotion: J. H. (2014). Brain scaling in mammalian
West, V., & Slocombe, K. E. (2015). Vocal Personal reflections since 1982 on the evolution as a consequence of concerted
learning in the functionally referential dysmetria of thought hypothesis, and and mosaic changes in numbers of
food grunts of chimpanzees. Current its historical evolution from theory to neurons and average neuronal cell size.
Biology, 5, 495–499. therapy. Neuropsychology Reviews, 20, Frontiers in Neuroanatomy, 8:77.
Weiner, J. (1995). The beak of the finch. 236–260. Kaati, G., Bygren, L. O., Pembrey, M., &
New York: Vintage. Sjöström, M. (2007). Transgenerational
Workman, A. D., Charvet, C. J., Clancy, B., Chapter 3 response to nutrition, early life
Darlington, R. B., & Finlay, B. L. Bainbridge, M. N., Wiszniewski, W., circumstances and longevity. European
(2013). Modeling transformations Murdock, D. R., Friedman, J., Gonzaga- Journal of Human Genetics, 15, 784–790.
of neurodevelopmental sequences Jauregui, C., et al. (2011). Whole-genome Kusakari, S., Saitow, F., Ago, Y., Shibasaki, K.,
across mammalian species. Journal of sequencing for optimized patient Sato-Hashimoto, M., Matsuzaki, Y.,
Neuroscience, 33, 7368–7380. management. Science Translational et al. (2015). Shp2 in forebrain neurons
Zollikofer, C. P. (2012). Evolution of hominid Medicine, 3, 87re3. regulates synaptic plasticity, locomotion,
cranial ontogeny. Progress in Brain Balaban, E. (2005). Brain switching: Studying and memory formation in mice.
Research, 195, 273–292. evolutionary behavioral changes in the Molecular and Cell Biology, MCB, 35,
context of individual brain development. 1557–1572.
Chapter 2 International Journal of Developmental Livet, J., Weissman, T. A., Kang, H., Draft,
Appireddy, R. M. R., Demchuk, A. M., Biology, 49, 117–124. R. W., Lu, J., Bennis, R. A., et al. (2007).
Goyal, M., Menon, B. K., Eesa, M., Bertram, R., Daou, A., Hyson, R. L., Transgenic strategies for combinatorial
Choi, P., et al. (2015). Endovascular Johnson, F., & Wu, W. (2014). Two neural expression of fluorescent proteins in the
therapy for ischemic stroke. Journal of streams, one voice: Pathways for theme nervous system. Nature, 450, 56–62.
Clinical Neurology, 11, 1–8. and variation in the songbird brain. Mimori, T., Nariai, N., Kojima, K., Sato, Y.,
Avetisyan, M., Schill, E. M., & Heuchkeroth, Neuroscience, 26, 806–817. Kawai, Y., Yamaguchi-Kabata, Y., et al.
R. O. (2015). Building a second brain Butte, P. V., Mamelak, A., Parrish-Novak, J., (2015). Estimating copy numbers of alleles
in the bowel. Journal of Clinical Drazin, D., Shweikeh, F., Gangalum, from population-scale high-throughput
Investigation, 125, 899–907. P. R., et al. (2014). Near-infrared imaging sequencing data. BMC Bioinformatics,
Barton, R. A. (2012). Embodied cognitive of brain tumors using the Tumor Paint 16(Suppl. 1), S4.
evolution and the cerebellum. BLZ-100 to achieve near-complete Ostrom, Q. T., Gittelman, H., Liao, P.,
Philosophical Transactions of the Royal resection of brain tumors. Neurosurgery Rouse, C., Chen, Y., Dowling, J., et
Society B, 367, 2097–2107. Focus, 36(2), E1. al. (2014). CBTRUS statistical report:
Baumann, O., Borra, R. J., Bower, J. M., Casano, A. M., & Peri, F. (2015). Microglia: Primary brain and central nervous system
Cullen, K. E., Habas, C., Ivry, R. B., et al. Multitasking specialists of the brain. tumors diagnosed in the United States in
(2015). Consensus paper: The role of Developmental Cell, 23, 469–477. 2007–2011. Neuro-oncology, 16 (Suppl. 4),
the cerebellum in perceptual processes. Charney, E. (2012). Behavior genetics and iv1–iv63.
Cerebellum, 14, 197–220. postgenomics. Behavioral Brain Sciences, Persson, M. E., Roth, L. S., Johnsson, M.,
Brodmann, K. (1909). Vergleichende 35(5), 331–358. Wright, D., & Jensen, P. (2015).
Lokalisationlehr der Grosshirnrinde Chen, J. L., Andermann, M. L., Keck, T., Xu, Humandirected social behaviour in dogs
in ihren Prinzipien dargestellt auf N. L., & Ziv, Y. (2013). Imaging neuronal shows significant heritability. Genes, Brain
Grund des Zellenbaues. Leipzig: populations in behaving rodents: Paradigms and Behavior, 14, 337–344.
J. A. Barth. for studying neural circuits underlying Ramón y Cajal, S. (1909–1911). Histologie
Farmer, A. D., Randall, H. A., & Aziz, Q. behavior in the mammalian cortex. Journal du systeme nerveux de l’homme et des
(2014). It’s a gut feeling: How the gut of Neuroscience, 33, 17631–17640. vertebres. Paris: Maloine.
microbiota affects the state of mind. Eddy, C. M., & Rickards, H. E. (2015). Reeve, R., van Schaik, A., Jin, C., Hamilton,
Journal of Physiology, 592(14), Theory of mind can be impaired prior T., Torben-Neilsen, B., & Webb, B. (2007).
2981–2988. to motor onset in Huntington’s disease. Directional hearing in a silicon cricket.
Fiorito, G., & Scotto, P. (1992). Observational Neuropsychology, 29, 792–798. Biosystems, 87, 307–313.
learning in Octopus vulgaris. Science, 256, Gill, J. M., & Rego, A. C. (2009). The R6 lines Rojczyk-Gołębiewska, E., Palasz, A.,
545–547. of transgenic mice: A model for screening Worthington, J. J., Markowski, G., &
Gilbert, S. F., & Epel, D. (2009). Ecological new therapies for Huntington’s disease. Wiaderkiewicz, R. (2015). Neurolight:
developmental biology: Integrating Brain Research Reviews, 59, 410–431. Astonishing advances in brain imaging.
epigenetics, medicine, and evolution. Giorgi, E. E. (2015, April). From many, one. International Journal of Neuroscience, 125,
New York: Sinauer. The Scientist. 91–99.
Hatcher, M. A., & Starr, J. A. (2011). Role of Gu, X., Cantle, J. P., Greiner, E. R., Lee, Rosenegger, D. G., & Gordon, G. R. (2015).
tissue plasminogen activator in ischemic C. Y., Barth, A. M., Gao, F., et al. (2015). A slow or modulatory role of astrocytes in
stroke. Annals of Pharmacotherapy, 45, N17 modifies mutant huntingtin nuclear neurovascular coupling. Microcirculation,
364–371. pathogenesis and severity of disease in HD 22, 197–203.
Langhorne, P., Bernhardt, J., & Kwakkel, G. BAC transgenic mice. Neuron, 85, 726–741. Rusielewicz, T., Nam, J., Damanakis, E.,
(2011). Stroke rehabilitation. Lancet, 277, Guerrero-Bosagna, C., & Jensen, P. (2015). John, G. R., Raine, C. S., & Melendez-
1693–1702. Globalization, climate change, and Vasquez, C. V. (2014). Accelerated repair
Papez, J. W. (1937). A proposed mechanism transgenerational epigenetic inheritance: of demyelinated CNS lesions in the
of emotion. Archives of Neurology and Will our descendants be at risk? Clinical absence of non-muscle myosin IIB. Glia,
Psychiatry, 38, 724–744. Epigenetics, 7, 8. 62, 580–591.
R-2 References
Wahlsten, D., & Ozaki, H. S. (1994). Defects Eccles, J. (1965). The synapse. Scientific Bosch, M., & Hayashi, Y. (2012). Structural
of the fetal forebrain in acallosal mice. American, 21(1), 56–66. plasticity of dendritic spines. Current
In M. Lassonde & M. A. Jeeves (Eds.), Fenno, L., Yizhar, O., & Deisseroth, K. Opinion in Neurobiology, 22, 383–388.
Callosal agenesis (pp. 125–132). New York: (2011). The development and application Dere, E., & Zlomuzica, A. (2012). The role of
Plenum. of optogenetics. Annual Review of gap junctions in the brain in health and
Wang, X., & Guo, Z. (2015). Chlorotoxin- Neuroscience, 34, 389–412. disease. Neuroscience and Biobehavioral
conjugated onconase as a potential Hodgkin, A. L., & Huxley, A. F. (1939). Action Reviews, 36, 206–217.
anti-glioma drug. Oncology Letters, 9, potentials recorded from inside nerve Ehringer, H., & Hornykiewicz, O.
1337–1342. fiber. Nature, 144, 710–711. (1960/1974). Distribution of noradrenaline
Webb, B. (1996). A cricket robot. Scientific Legenstein, R., & Maass, W. (2011). Branch- and dopamine (3-hydroxytyramine) in
American, 275(6), 94–99. specific plasticity enables self-organization the human brain and their behavior in
Wittmeier, S., Alessandro, C., Bascarevic, N., of nonlinear computation in single neurons. the presence of disease affecting the
Dalamagkidis, K., Devereux, D., Diamond, Journal of Neuroscience, 31, 10787–10802. extrapyramidal system. In J. Marks (Ed.),
A., et al. (2013). Toward anthropomimetic Liewald, J. F., Brauner, M., Stephens, G. The treatment of Parkinsonism with L-
robotics: Development, simulation, J., Bouhours, M., Schultheis, C., Xhen, dopa (pp. 45–56). Lancaster, UK: MTP
and control of a musculoskeletal torso. M., et al. (2008). Optogenetic analysis of Medical and Technical Publishing.
Artificial Life, 19, 171–193. synaptic function. Nature Methods, 10, Hamilton, T. J., Wheatley, B. M., Sinclair,
Wu, H., Wang, Y., Zhang, Y., Yang, M., Lv, J., 895–902. D. B., Bachmann, M., Larkum, M. E.,
Liu, J., et al. (2015). TALE nickase- Mohajerani, M. H., & Cherubini, E. (2006). & Colmers, W. F. (2010). Dopamine
mediated SP110 knockin endows cattle Role of giant depolarizing potentials modulates synaptic plasticity in dendrites
with increased resistance to tuberculosis. in shaping synaptic currents in the of rat and human dentate granule cells.
Proceedings of the National Academy of developing hippocampus. Critical Reviews Proceedings of the National Academy of
Sciences United States of America, 112, in Neurobiology, 18, 13–23. Sciences United States of America, 107(42):
E1530–E1539. Rezania, K., Soliven, B., Baron, J., Lin, H., 18185–18190.
Penumalli, V., & van Besien, K. (2012). Hebb, D. O. (1949). The organization of
Chapter 4 Myasthenia gravis, an autoimmune behavior. New York: Wiley.
Allen, M. J., Lacroix, J. J., Ramachandran, S., manifestation of lymphoma and Herrmann, N., Chau, S. A., Kircanski, I.,
Capone, R., Whitlock, J. L., et al. (2011). lymphoproliferative disorders: Case & Lanctôt, K. L. (2011). Current and
Mutant SOD1 forms ion channel: reports and review of literature. Leukemia emerging drug treatment options for
Implications for ALS pathophysiology. and Lymphoma, 53, 371–380. Alzheimer’s disease: A systematic review.
Neurobiology of Diseases, 45, 831–838. Valdueza, J. M., Doepp, F., Schreiber, S. J., Drugs, 71, 2031–2065.
Bano, S., Yadav, S. N., Chaudhary, V., van Oosten, B. W., Schmierer, K., Paul, F., Lane, E. L., Björklund, A., Dunnett, S. B.,
& Garga, U. C. (2011). Neuroimaging et al. (2013). What went wrong? The & Winkler, C. (2010). Neural grafting
in epilepsy. Journal of Pediatrics and flawed concept of cerebrospinal venous in Parkinson’s disease unraveling the
Neuroscience, 6, 19–26. insufficiency. Journal of Cerebral Blood mechanisms underlying graft-induced
Bartholow, R. (1874). Experimental Flow and Metabolism, 33, 657–668. dyskinesia. Progress in Brain Research, 184,
investigation into the functions of the Zhang, F., Aravanis, A. M., Adamantidis, A., 295–309.
human brain. American Journal of Medical de Lecea, L., & Deisseroth, K. (2007). Langston, J. W. (2008). The case of the frozen
Sciences, 67, 305–313. Circuit-breakers: Optical technologies for addicts. Pantheon Books, 1995. Original
Bender, K. J., & Trussell, L. O. (2012). The probing neural signals and systems. Nature from the University of Michigan, digitized
physiology of the axon initial segment. Reviews Neuroscience, 8, 577–581. August 5, 2008.
Annual Review of Neuroscience, 35, Magee, J. C., & Cook, E. P. (2000). Somatic
249–265. Chapter 5 EPSP amplitude is independent of
Bhalla, D., Druet-Cabanac, M., Godet, B., & Bailey, C. H., Kandel, E. R., & Harris, K. M. synapse location in hippocampal
Preux, P.-M. (2011). Etiologies of epilepsy: (2015). Structural components of synaptic pyramidal neurons. Nature Neuroscience,
A comprehensive review. Expert Review of plasticity and memory consolidation. Cold 3, 895–903.
Neurotherapeutics, 11, 861–876. Spring Harbor Perspectives in Biology. doi: Mechoulam, R., Hanus, L. O., Pertwee, R.,
Cao, Z. F., Burdakov, D., & Sarnyai, Z. (2011). 10.1101/cshperspect.a021758. & Howlett, A. C. (2014). Early
Optogenetics: Potentials for addiction Ballard, A., Tetrud, J. W., & Langston, J. W. phytocannabinoid chemistry to
research. Addiction Biology, 16, 519–531. (1985). Permanent human parkinsonism endocannabinoids and beyond. Nature
Crotty, P., Sangrey, T., & Levy, W. B. (2006). due to 1-methyl-4-phenyl-1, 2, 3, Neuroscience Reviews 15, 757–764.
Metabolic energy cost of action potential 6-tetrahydropyridine (MPTP). Neurology, Moore, T. J., Glenmullen, J., & Mattison,
velocity. Journal of Neurophysiology, 96, 35, 949–956. D. R. (2014). Reports of pathological
1237–1246. Barbeau, A., Murphy, G. F., & Sourkes, T. L. gambling, hypersexuality and compulsive
Debanne, D. (2011). The nodal origin of (1962). Les catecholamines dans la maladie shopping associated with dopamine
intrinsic bursting. Neuron, 25, 569–570. de Parkinson. In J. de Ajuriaguerva (Ed.), receptor agonist drugs. JAMA Internal
Descartes, R. (1972). Treatise on man (T. S. Monoamines et système nerveux central. Medicine, 174, 1930–1933.
Hall, Trans.). Cambridge, MA: Harvard pp. 247–262. Symposium Bel-Air, Geneva, Parkinson, J. (1817/1989). An essay on the
University Press. (Original work published 1961. Geneva: Georg et Ci. shaking palsy. In A. D. Morris & F. C.
1664.) Birkmayer, W., & Hornykiewicz, O. (1961). Rose (Eds.), James Parkinson: His life and
Duncan, J. S., Sander, J. W., Sisodiya, S. M., Der L-3, 4-Dioxyphenylalanin (L-DOPA) times (pp. 151–175). Boston: Birkhauser.
& Walker, M. C. (2006). Adult epilepsy. Effekt bei der Parkinson A Kinase. Wiener Sacks, O. (1976). Awakenings. New York:
Lancet, 367, 1087–1100. Klinische, 73, 787–789. Doubleday.
References R-3
Tréatikoff, C. (1974). Thesis for doctorate Brown, A. R., Owen, S. F., Peters, J., Zhang, Griffin, J. A., Umstattd, M. R., & Usdan,
in medicine, 1919. In J. Marks (Ed.), The Y., Soffker, M., Paull, G.C., et al. S. L. (2010). Alcohol use and high-risk
treatment of Parkinsonism with L-dopa (2015). Climate change and pollution sexual behavior among collegiate women:
(pp. 29–38). Lancaster, UK: MTP Medical speed declines in zebrafish populations. A review of research on alcohol myopia
and Technical Publishing. Proceedings of the National Academy of theory. Journal of American College
Ungerstedt, U. (1971). Adipsia and aphagia Science United States of America, 112, Health, 58, 523–532.
after 6-hydroxydopamine induced 1237–1246. Hampson, E., & Kimura, D. (2005). Sex
degeneration of the nigrostriatal dopamine Büttner, A. (2011). Review: The neuro- differences and hormonal influences
system in the rat brain. Acta Physiologica pathology of drug abuse. Neuropathology on cognitive function in humans. In
(Scandinavia), 82 (Suppl. 367), 95–122. and Applied Neurobiology, 37, 118–134. J. B. Becker, S. M. Breedlove, & D. Crews
Widner, H., Tetrud, J., Rehngrona, S., Snow, B., Clauss, J. A., Avery, S. N., & Blackford, J. U. (Eds.), Behavioral endocrinology
Brundin, P., Gustavii, B., et al. (1992). (2015, March 14). The nature of individual (pp. 357–398). Cambridge, MA: MIT Press.
Bilateral fetal mesencephalic grafting differences in inhibited temperament and Hardee, J. E., Weiland, B. J., Nichols, T. E.,
in two patients with Parkinsonism risk for psychiatric disease: A review and Welsh, R. C., Soules, M. E., Steinberg, D. B.,
induced by 1-methyl-4-phenyl-1, 2, 3, meta-analysis. Progress in Neurobiology, et al. (2014). Development of impulse
6-tetrahydropyridine (MPTP). New England 127–128, 23–45. control circuitry in children of alcoholics.
Journal of Medicine, 327, 1556–1563. Comer, R. J. (2011). Fundamentals of abnormal Biological Psychiatry, 76, 708–716.
psychology (7th ed.). New York: Worth. Hill, A. S., Sahay, A., & Hen, R. (2015,
Chapter 6 Cowan, R. L., Roberts, D. M., & Joers, J. M. April 2). Increasing adult hippocampal
Aagaard, L., & Hansen, E. H. (2011). The (2008). Neuroimaging in human MDMA neurogenesis is sufficient to reduce
occurrence of adverse drug reactions (Ecstasy) users. Annals of the New York anxiety and depression-like behaviors.
reported for attention deficit hyperactivity Academy of Sciences, 1139, 291–298. Neuropsychopharmacology, 40, 2368–2378.
disorder (ADHD) medications in the Czoli, C. D., Hammond, D., Reid, J. L., Hillemacher, T., Weinland, C., Lenz, B.,
pediatric population: A qualitative review Cole. A. G., & Leatherdale. S. T. (2015). Kraus, T., Heberlein, A., Glahn, A., et al.
of empirical studies. Neuropsychiatric Use of conventional and alternative tobacco (2015). DNA methylation of the LEP gene
Disorders and Treatments, 7, 729–744. and nicotine products among a sample is associated with craving during alcohol
Advokat, C. D., Comaty, J. E., & Julien, R. M. of Canadian youth. Journal of Adolescent withdrawal. Psychoneuroendocrinology, 51,
(2014). A primer of drug action (13th ed.). Health, 57, 123–125. [Epub ahead of print.] 371–377.
New York: Worth. Di Forti, M., Sallis, H., Allegri, F., Trotta, A., Isacsson, G., & Rich C. L. (2014).
Asarnow, J. R., Porta, G., Spirito, A., Emslie, Ferraro, L., Stilo, S. A., et al. (2014). Daily Antidepressant drugs and the risk of
G., Clarke, G., et al. (2011). Suicide attempts use, especially of high-potency cannabis, suicide in children and adolescents.
and nonsuicidal self-injury in the treatment drives the earlier onset of psychosis in Paediatric Drugs, 16, 115–122.
of resistant depression in adolescents: cannabis users. Schizophrenia Bulletin, 40, Isbell, H., Fraser, H. F., Wikler, R. E.,
Findings from the TORDIA study. Journal 1509–1517. Belleville, R. E., & Eisenman, A. J. (1955).
of the American Academy of Child and Durell, T. M., Kroutil, L. A., Crits-Christoph, An experimental study of the etiology of
Adolescent Psychiatry, 50, 772–781. P., Barchha, N., & Van Brunt, D. E. “rum fits” and delirium tremens. Quarterly
Barth, C., Villringer, A., & Sacher, J. (2015). (2008). Prevalence of nonmedical Journal of Studies on Alcohol, 16, 1–35.
Sex hormones affect neurotransmitters methamphetamine use in the United Kerr, D. C., Zava, D. T., Piper, W. T., Saturn,
and shape the adult female brain during States. Substance Abuse Treatment, S. R., Frei, B., & Gombart, A. F. (2015).
hormonal transition periods. Frontiers in Prevention, and Policy, 3, 19. Associations between vitamin D levels and
Neuroscience, 20, 9–37. Everitt, B. J. (2014). Neural and psychological depressive symptoms in healthy young adult
Becker, J. B., Breedlove, S. M., Crews, D., mechanisms underlying compulsive women. Psychiatry Research, 227, 46–51.
& McCarthy, M. M. (2002). Behavioral drug seeking habits and drug memories: Lajud, N., & Torner, L. (2015). Early life stress
endocrinology (2nd ed.). Cambridge, MA: Indications for novel treatments and hippocampal neurogenesis in the
Bradford. of addiction. European Journal of neonate: Sexual dimorphism, long-term
Becker, J. B., & Hu, M. (2008). Sex Neuroscience, 40, 2163–2182. consequences and possible mediators.
differences in drug abuse. Frontiers in Fraioli, S., Crombag, H. S., Badiani, A., Frontiers in Molecular Neuroscience,
Neuroendocrinology, 29(1), 36–47. & Robinson, T. E. (1999). 8, 3. doi: 10.3389/fnmol.2015.00003.
Berninger, J. P., LaLone, C. A., Villeneuve, Susceptibility to amphetamine- eCollection 2015.
D. L., & Ankley, G. T. (2015). induced locomotor sensitization is Landré, L., Destrieux, C., Baudry, M.,
Prioritization of pharmaceuticals for modulated by environmental stimuli. Barantin, L., Cottier, J. P., et al. (2010).
potential environmental hazard through Neuropsychopharmacology, 20, 533–541. Preserved subcortical volumes and
leveraging a large scale mammalian Freud, S. (1974). Cocaine papers (R. Byck, cortical thickness in women with sexual
pharmacological dataset. Environment Ed.). New York: Penguin. abuse-related PTSD. Psychiatry Research,
and Toxicological Chemistry. doi: 10.1002/ Grande, I., & Vieta, E. (2015). 183, 181–186.
etc.2965. [Epub ahead of print.] Pharmacotherapy of acute mania: Lee, B. Y., Park, S. Y., Ryu, H. M., Shin,
Bourgin, J., Cachia, A., Boumezbeur, F., Monotherapy or combination therapy C. Y., Ko, K. N., Han, J. Y., et al. (2015).
Djemaï, B., Bottlaender, M., Duchesnay, with mood stabilizers and antipsychotics? Changes in the methylation status of
E., et al. (2015, March 11). Hyper-responsivity CNS Drugs, 29, 221–227. DAT, SERT, and MeCP2 gene promoters
to stress in rats is associated with a large Greely, H., Sahakian, B., Harris, J., Kessler, R. in the blood cell in families exposed
increase in amygdala volume: A 7T MRI C., Gazzaniga, M., et al. (2008). Towards to alcohol during the periconceptional
study. European Journal of Neuropsy- responsible use of cognitive-enhancing period. Alcohol and Clinical and
chopharmacology. [Epub ahead of print.] drugs by the healthy. Nature, 456, 702–705. Experimental Research, 39, 239–250.
R-4 References
Liu, P., Lu, H., Filbey, F. M., Tamminga, Reinstatler, L., & Youssef, N. A. (2015). Whishaw, I. Q., Mittleman, G., & Evenden,
C. A., Cao, Y., & Adinoff, B. (2014). MRI Ketamine as a potential treatment for J. L. (1989). Training-dependent decay in
assessment of cerebral oxygen metabolism suicidal ideation: A systematic review of performance produced by the neuroleptic
in cocaine-addicted individuals: the literature. Drugs, 15, 37–43. cis(Z)-flupentixol on spatial navigation by
Hypoactivity and dose dependence. NMR Roberts, N. P., Roberts, P. A., Jones, N., rats in a swimming pool. Pharmacology,
Biomedicine, 27, 726–732. & Bisson, J. I. (2015). Psychological Biochemistry, and Behavior, 32, 211–220.
Lubman, D. I., Cheetham, A., & Yücel, interventions for post-traumatic stress Wilkinson, S. T., Radhakrishnan R., &
M. (2015). Cannabis and adolescent disorder and comorbid substance use D’Souza, D. C. (2014). Impact of cannabis
brain development. Pharmacology and disorder: A systematic review and meta- use on the development of psychotic
Therapeutics, 148C, 1–16. analysis. Clinical Psychological Reviews, disorders. Current Addiction Reports, 1(2),
MacAndrew, C., & Edgerton, R. B. 38, 25–38. 115–128.
(1969). Drunken comportment: A social Robinson, T. E., & Becker, J. B. (1986). Yager, L. M., Pitchers, K. K., Flagel, S. B.,
explanation. Chicago: Aldine. Enduring changes in brain and behavior & Robinson, T. E. (2015). Individual
MacDonald, T. K., MacDonald, G., Zanna, produced by chronic amphetamine variation in the motivational and
M. P., & Fong, G. T. (2000). Alcohol, administration: A review and evaluation of neurobiological effects of an opioid cue.
sexual arousal, and intentions to use animal models of amphetamine psychosis. Neuropsychopharmacology, 40, 1269–1277.
condoms in young men: Applying alcohol Brain Research Reviews, 11, 157–198.
myopia theory to risky sexual behavior. Robinson, T. E., & Berridge, K. C. Chapter 7
Health Psychology, 19, 290–298. (2008). Incentive sensitization theory. Brown, A. R., Antle, M. C., Hu, B., & Teskey,
McCann, U. D., Lowe, K. A., & Ricaurte, Philosophical Transactions of the Royal G. C. (2011). High frequency stimulation
G. A. (1997). Long-lasting effects of Society of London, 363, 3137–3146. of the subthalamic nucleus acutely rescues
recreational drugs of abuse on the central Roitman, P., Mechoulam, R., Cooper-Kazaz, neocortical movement representations and
nervous system. The Neurologist, 3, R., & Shalev, A. (2014). Preliminary, motor deficits following 6-hydroxydopamine
399–411. open-label, pilot study of add-on oral administration in rats. Experimental
McGowan, P. O., Sasaki, A., D’Alessio, A. C., Δ9-tetrahydrocannabinol in chronic post- Neurology, 231, 82–90.
Dymov, S., Labonté, B., Szyf, M., traumatic stress disorder. Clinical Drug Bueller, J. A., Aftab, M., Sen, S., Gomez-
et al. (2009). Epigenetic regulation of the Investigations, 34, 587–591. Hassan, D. Burmeister, M., & Zubieta,
glucocorticoid receptor in human brain Sapolsky, R. M. (2004). Why zebras don’t get J.-K. (2006). BDNF Val66Met allele is
associates with childhood abuse. Nature ulcers (3rd ed.). New York: Henry Holt. associated with reduced hippocampal
Neurosciences, 12, 342–348. Sapolsky, R. M. (2005). The influence of volume in healthy subjects. Biological
Mead, E. A., & Sarkar, D. K. (2014). Fetal social hierarchy on primate health. Psychiatry, 59, 812–815.
alcohol spectrum disorders and their Science, 308(5722), 648–652. Cacucci, F., Yi, M., Wills, T. J., Chapmans,
transmission through genetic and Sevincer, A. T., & Oettingen, G. (2014). P., & O’Keefe, J. (2008). Place cell firing
epigenetic mechanisms. Frontiers in Alcohol myopia and goal commitment. correlates with memory deficits and
Genetics, 5, 154–159. Frontiers in Psychology, 4, 169–175. amyloid plaque burden in Tg2576
Nguyen, B. M., Kim, D., Bricker, S., Bongard, Smith, A. D., Smith, S. M., de Jager, C. A., Alzheimer mouse model. Proceedings
F., Neville, A., Putnam, B., et al. (2014). Whitbread, P., Johnston, C., et al. (2010). of the National Academy of Sciences
Effect of marijuana use on outcomes in Homocysteine-lowering by B vitamins slows United States of America, 105, 7863–7868.
traumatic brain injury. American Surgery, the rate of accelerated brain atrophy in Caspi, A., Moffitt, T. E., Cannon, M.,
80, 979–983. mild cognitive impairment: A randomized McClay, J., Murray, R., et al. (2005).
Nugent, B. M., Tobet, S. A., Lara, H. controlled trial. PLoS One, 8, e12244. Moderation of the effect of adolescent-
E., Lucion, A. B., Wilson, M. E., Steen, E., Terry, B. M., Rivera, E. J., Cannon, onset cannabis use on adult psychosis by a
Recabarren, S. E., et al. (2012). Hormonal J. L., Neely, T. R., Tavares, R., et al. functional polymorphism in the catechol-
programming across the lifespan. (2005). Impaired insulin and insulin-like O-methyltransferase gene: Longitudinal
Hormone and Metabolic Research, 44, growth factor expression and signaling evidence of a gene X environment
577–586. mechanisms in Alzheimer’s disease: Is this interaction. Biological Psychiatry, 57,
Nugent, B. M., Wright, C. L., Shetty, A. C., type 3 diabetes? Journal of Alzheimer’s 1117–1127.
Hodes, G. E., Lenz, K. M., Mahurkar, A., Disease, 7, 63–80. Damasio, H., & Damasio, A. R. (1989). Lesion
et al. (2015). Brain feminization requires Teixeira-Gomes, A., Costa, V. M., Feio- analysis in neuropsychology. New York:
active repression of masculinization via Azevedo, R., Bastos, M. L., Carvalho, F., Oxford University Press.
DNA methylation. Nature Neuroscience, & Capela, J. P. (2015). The neurotoxicity Fox, P. T., & Raichle, M. E. (1986). Focal
18(5), 690–697. of amphetamines during the adolescent physiological uncoupling of cerebral blood
Popova, S., Lange, S., Bekmuradov, D., period. International Journal of flow and oxidative metabolism during
Mihic, A., & Rehm, J. (2011). Fetal alcohol Developmental Neuroscience, 41, 44–62. somatosensory stimulation in human
spectrum disorder prevalence estimates Vevelstad, M., Oiestad, E. L., Middelkoop, G., subjects. Proceedings of the National
in correctional systems: A systematic Hasvold, I., Lilleng, P., et al. (2012). The Academy of Sciences United States of
literature review. Canadian Journal of PMMA epidemic in Norway: Comparison America, 83, 1140–1144.
Public Health, 102, 336–340. of fatal and non-fatal intoxications. Forensic Fraga, M. F., Ballestar, E., Paz, M. F., Ropero,
Pouget, J. G., Shams, T. A., Tiwari, A. K., Science International, 219, 151–157. S., Setien, F., Ballestar, M. L., et al. (2005).
& Müller, D. J. (2014). Pharmacogenetics Wenger, J. R., Tiffany, T. M., Bombardier, C., Epigenetic differences arise during the
and outcome with antipsychotic drugs. Nicholls, K., & Woods, S. C. (1981). lifetime of monozygotic twins. Proceedings
Dialogues in Clinical Neuroscience, 16, Ethanol tolerance in the rat is learned. of the National Academy of Sciences United
555–566. Science, 213, 575–577. States of America, 102, 10604–10609.
References R-5
Gonzalez, C. L. R., Gharbawie, O. A., National Research Council (1996). The guide Whishaw, I. Q. (1989). Dissociating
& Kolb, B. (2006). Chronic low-dose for the care and use of laboratory animals. performance and learning deficits in
administration of nicotine facilitates Washington, DC: National Academy spatial navigation tasks in rats subjected
recovery and synaptic change after focal Press. to cholinergic muscarinic blockade. Brain
ischemia in rats. Neuropharmacology, 50, Ogawa, S., Lee, T. M., Kay, A. R., & Tank, Research Bulletin, 23, 347–358.
777–787. D. W. (1990). Brain magnetic resonance Whishaw, I. Q., & Kolb, B. (2005). The
Haubensak, W., Kunwar, P. S., Cai, H., imaging with contrast dependent on blood behavior of the laboratory rat. New York:
Ciocchi, S., Wall, N. R., Ponnusamy, R., et oxygenation. Proceedings of the National Oxford University Press.
al. (2010). Genetic dissection of an amygdala Academy of Sciences United States of
microcircuit that gates conditioned fear. America, 87, 9868–9872. Chapter 8
Nature, 468, 270–276. O’Keefe, J. (2006). Hippocampal Agate, R. J., Grisham, W., Wade, J., Mann,
Kolb, B., & Walkey, J. (1987). Behavioural neurophysiology in the behaving S., Wingfield, J., Schanen, C., et al. (2003).
and anatomical studies of the posterior animal. In P. Andersen, R. Morris, D. Neural, but not gonadal, origin of brain
parietal cortex of the rat. Behavioural Amaral, T. Bliss, & J. O’Keefe (Eds.), The sex differences in a gynandromorphic
Brain Research, 23, 127–145. Hippocampus Book. (pp. 475–548). New finch. Proceedings of the National
Kut, C., Chaichana, K. L., Xi, J., Raza, York: Oxford University Press. Academy of Sciences United States of
S. M., Ye, X., McVeigh, E. R., et al. O’Keefe, J., & Dostrovsky, J. (1971). The America, 100, 4873–4878.
(2015). Detection of human brain hippocampus as a spatial map. Brain Ames, E. W. (1997). The development of
cancer infiltration ex vivo and in vivo Research, 34, 171–175. Romanian orphanage children adopted to
using quantitative optical coherence Penfield, W., & Jasper, H. H. (1954). Epilepsy Canada. Final report to Human Resources
tomography. Science Translational and the functional anatomy of the human Development, Canada.
Medicine 17, 292ra100. doi: 10.1126/ brain. Boston: Little, Brown. Anda, R. F., Felitti, V. J., Bremner, J. D.,
scitranslmed.3010611. Posner, M. I., & Raichle, M. E. (1997). Images Walker, J. D., Whitfield, C., et al. (2006).
Kwong, K. K., Belliveau, J. W., Chesler, D. A., of mind. New York: W. H. Freeman. The enduring effects of abuse and
Goldberg, I. E., Weisskoff, R. M., Reza, M. F., Ikoma, K., Ito, T., Ogawa, T., & related adverse experiences in childhood:
Poncelet, B. P., et al. (1992). Dynamic Mano, Y. (2007). N200 latency and P300 A convergence of evidence from
magnetic resonance imaging of human amplitude in depressed mood post-traumatic neurobiology and epidemiology. European
brain activity during primary sensory brain injury patients. Neuropsychological Archives of Psychiatry and Clinical
stimulation. Proceedings of the National Rehabilitation, 17, 723–734. Neuroscience, 256, 174–186.
Academy of Sciences United States of Schallert, T., Whishaw, I. Q., Ramirez, Berens, A. E., & Nelson, C. A. (2015). The
America, 89, 5678. V. D., & Teitelbaum, P. (1978). science of early adversity: Is there a
Lecendreux, M., Konofal, E., Cortese, S., & Compulsive, abnormal walking role for large institutions in the care
Faraone, S. V. (2015). A 4-year follow-up of caused by anticholinergics in akinetic, of vulnerable children? Lancet, S0140-
attention-deficit/hyperactivity disorder in 6-hydroxydopamine-treated rats. Science, 6736(14), 61131–61134.
a population sample. Journal of Clinical 199, 1461–1463. Blumberg, S. J., Bramlett, M. D., Kogan, M. D.,
Psychiatry, 76, 712–719. Schlaepfer, T. E., Bewernick, B. H., Kayser, Schieve, L. A., Jones, J. R., et al. (2013).
Lomber, S. G., & Payne, B. R. (1996). S., Mädler, B., & Coenen, V. A. (2013). Changes in prevalence of parent-reported
Removal of two halves restores the whole: Rapid effects of deep brain stimulation autism spectrum disorder in school-aged
Reversal of visual hemineglect during for treatment-resistant major depression. US children: 2007 to 2011–2012. National
bilateral cortical or collicular inactivation Biological Psychiatry, 73 (12), 1204–1212. Health Statistics Reports, 65, 1–11.
in the cat. Visual Neuroscience, 13, Scoville, W. B., & Milner, B. (1957). Bock, J., Rether, K., Grogerr, N., Xie, L., &
1143–1156. Loss of recent memory after bilateral Braun, K. (2014). Perinatal programming
May, L., Byers-Heinlein, K., Gervain, J., hippocampal lesions. Journal of Neurology, of emotional brain circuits: An integrative
& Werker, J. F. (2011). Language and Neurosurgery, and Psychiatry, 20, 11–21. view from systems to molecules. Frontiers
the newborn brain: Does prenatal Spinney, L. (2005). Optical topography and of Neuroscience, 11, 1–15. doi: 10. 3389/
language experience shape the neonate the color of blood. The Scientist, 19, 25–27. fnins. 2014. 00011.
neural response to speech? Frontiers in Szyf, M., McGowan, P., & Meaney, M. J. Bourgeois, J.-P. (2001). Synaptogenesis in the
Psychology, 2, 1–9. (2008). The social environment and the neocortex of the newborn: The ultimate
McGowan, P. O., Sasaki, A., D’Alessio, A. C., epigenome. Environmental Molecular frontier for individuation? In C. A.
Dymov, S., Labonté, B., Szyf, M., et al. Mutagenetics, 49, 46–60. Nelson & M. Luciana (Eds.), Handbook of
(2009). Epigenetic regulation of the Tisdall, M. M., & Smith, M. (2006). Cerebral Developmental Cognitive Neuroscience.
glucocorticoid receptor in human brain microdialysis: Research technique Cambridge, MA: MIT Press.
associates with childhood abuse. Nature or clinical tool. British Journal of Bunney, B. G., Potkin, S. G., & Bunney, W. E.
Neuroscience, 12, 342–348. Anaesthesia, 97, 18–25. (1997). Neuropathological studies of
Morris, R. G. M. (1981) Spatial localization Van den Heuvel, M. P., & Hulshoff Pol, brain tissue in schizophrenia. Journal of
does not require the presence of local cues. H. E. (2010). Exploring the brain Psychiatric Research, 31, 159–173.
Learning and Motivation, 12, 239–260. network: A review on resting-state fMRI Changeux, J.-P., & Danchin, A. (1976). Selective
Mychasiuk, R., Schmold, N., Ilnytskyy, S., functional connectivity. European stabilization of developing synapses as a
Kovalchuk, O., Kolb, B., & Gibb, R. Neuropsychopharmcology, 20, 519–534. mechanism for the specification of neuronal
(2011). Prenatal bystander stress alters Wess, J., Nakajima, K., Jain, S. (2013). Novel networks. Nature, 264, 705–712.
brain, behavior, and the epigenome of designer receptors to probe GPCR Chen, R., Jiao, Y., & Herskovits, E. H. (2011).
developing rat offspring. Developmental signaling and physiology. Trends in Structural MRI in autism spectrum
Neuroscience, 33, 159–169. Pharmacological Sciences, 34, 385–392. disorder. Pediatric Research, 69, 63R–68R.
R-6 References
Clarke, R. S., Heron, W., Fetherstonhaugh, Horn, G., Bradley, P., & McCabe, B. J. (1985). Malanga, C. J., & Kosofsky, B. E. (2003).
M. L., Forgays, D. G., & Hebb, D. O. Changes in the structure of synapses Does drug abuse beget drug abuse?
(1951). Individual differences in dogs: associated with learning. Journal of Behavioral analysis of addiction liability in
Preliminary report on the effects of Neuroscience, 5, 3161–3168. animal models of prenatal drug exposure.
early experience. Canadian Journal of Hsiao E. Y., McBride, S. W., Hsien, S., Developmental Brain Research, 147, 47–57.
Psychology, 5(4), 150–156. Sharon, G., Hyde, E. R., McCue, T., et al. Marin-Padilla, M. (1993). Pathogenesis of
Cowan, W. M. (1979). The development of (2013). Microbiota modulate behavioral late-acquired leptomeningeal heterotopias
the brain. Scientific American, 241(3), 116. and physiological abnormalities associated and secondary cortical alterations: A
Epstein, H. T. (1979). Correlated brain and with neurodevelopmental disorders. Cell, Golgi study. In A. M. Galaburda (Ed.),
intelligence development in humans. In 155, 1451–1463. Dyslexia and development: Neurobiological
M. E. Hahn, C. Jensen, & B. C. Dudek Huttenlocher, P. R. (1994). Synaptogenesis in aspects of extraordinary brains (pp. 64–88).
(Eds.), Development and evolution of brain human cerebral cortex. In G. Dawson & Cambridge, MA: Harvard University
size: Behavioral implications (pp. 111–131). K. W. Fischer (Eds.), Human behavior and Press.
New York: Academic Press. the developing brain (pp. 137–152). New Minnes, S., Singer, L. T., Min, M. O., Wu,
Finegold, S. M., Molitoris, D., Song, Y., Liu, York: Guilford Press. M., Lang, A., & Yoon, S. (2014). Effects
C., Vaisanen, M. L., Bolte, E., et al. (2002). Juraska, J. M. (1990). The structure of the of prenatal cocaine/polydrug exposure
Gastrointestinal microflora studies in late- cerebral cortex: Effects of gender and the on substance abuse by age 15. Drug and
onset autism. Clinical Infective Diseases, environment. In B. Kolb & R. Tees (Eds.), Alcohol Dependence, 134, 201–210.
35, S6–S16. The cerebral cortex of the rat (pp. 483–506). Moore, K. L. (1988). The developing human:
Gershon, E. S., & Rieder, R. O. (1992). Major Cambridge, MA: MIT Press. Clinically oriented embryology (4th ed.).
disorders of mind and brain. Scientific Kinney, H. C. (2009). Brainstem mechanisms Philadelphia: Saunders.
American, 267(3), 126–133. underlying the sudden infant death Mychasiuk, R., Gibb, R., & Kolb, B. (2011).
Geschwind, D. H., & Rakic, P. (2013). syndrome: Evidence from human Prenatal stress produces sexually
Cortical evolution: Judge the brain by its pathologic studies. Developmental dimorphic and regionally specific changes
cover. Neuron, 80, 633–647. Psychobiology, 51, 223–233. in gene expression in hippocampus and
Gibb, R., Gonzalez, C., & Kolb, B. (2014). Klein, D., Watkins, K. E., Zatorre, R. J., & frontal cortex of developing rat offspring.
Prenatal enrichment and recovery from Milner, B. (2006). Word and nonword Developmental Neuroscience, 33, 531–538.
perinatal cortical damage: Effects of repetition in bilingual subjects: A PET Mychasiuk, R., Muhammad, A., & Kolb, B.
maternal complex housing. Frontiers study. Human Brain Mapping, 27, 153–161. (2014). Environmental enrichment alters
in Behavioral Neuroscience, 8, 223. doi: Kolb, B., & Gibb, R. (1993). Possible structural plasticity of the adolescent
10.3389/fnbeh.2014.00223. anatomical basis of recovery of function brain but does not remediate the effects
Giussani, C., Roux, F. E., Lubrano, V., after neonatal frontal lesions in rats. of prenatal nicotine exposure. Synapse,
Gaini, S. M., & Bello, L. (2007). Review Behavioral Neuroscience, 107, 799–811. 68, 293–305.
of language organization in bilingual Kolb, B., Mychasiuk, R., Muhammad, A., National Institute on Drug Abuse (2012).
patients: What can we learn from direct Li, Y., Frost, D. O., & Gibb, R. (2012). http://www.drugabuse.gov/publications/
brain mapping? Acta Neurochir (Wien), Experience and the developing prefrontal research-reports/tobacco/smoking-
149, 1109–1116. cortex. Proceedings of the National Academy pregnancy—what-are-risks
Goldstein, J. M., Seidman, L. J., Horton, N. J., of Sciences United States of America. Nelson, C. A., & Luciana, M. (Eds.) (2008).
Makris, N., Kennedy, D. N., Caviness, V. S., Kovelman, J. A., & Scheibel, A. B. (1984). A Handbook of developmental cognitive
Jr., et al. (2001). Normal sexual dimorphism neurohistologic correlate of schizophrenia. neuroscience, 2nd ed. Cambridge, MA:
of the adult human brain assessed by in Biological Psychiatry, 19, 1601–1621. MIT Press.
vivo magnetic resonance imaging. Cerebral Kuhl, P. K. (2011). Early language learning Nelson, C. A., Zeanah, C. H., Fox, N. A.,
Cortex, 11, 490–497. and literacy: Neuroscience implications Marshall, P. J., Smyke, A. T., & Guthrie,
Guerrini, R., Dobyns, W. B., & Barkovich, for education. Mind, Brain and Education, D. (2007). Cognitive recovery in socially
A. J. (2007). Abnormal development of 5, 128–142. deprived young children: The Bucharest
the human cerebral cortex: Genetics, Lenneberg, E. H. (1967). Biological Early Intervention Project. Science, 318,
functional consequences and treatment foundations of language. New York: Wiley. 1937–1940.
options. Trends in Neurosciences, 31, Lenroot, R. K., Gogtay, N., Greenstein, D. K., Noble, K. G., Houston, S. M., Brito, N. H.,
154–162. Wells, E. M., Wallace, G. L., Clasen, L. S., Bartsch, H., Kan, E., Kuperman, J. M.,
Halliwell, C., Comeau, W., Gibb, R., Frost, et al. (2007). Sexual dimorphism of brain et al. (2015). Family income, parental
D. O., & Kolb, B. (2009). Factors influencing development trajectories during childhood education and brain structure in children
frontal cortex development and recovery and adolescence. NeuroImage, 36, 1065–1073. and adolescents. Nature Neuroscience, 18,
from early frontal injury. Developmental Levitin, D. J., & Rogers, S. E. (2005). Absolute 773–778.
Neurorehabilitation, 12, 269–278. pitch: Perception, coding, and controversies. Nordahl, C. W., Scholz, R., Yang, X.,
Harker, A., Raza, S., Williamson, K., Kolb, Trends in Cognitive Science, 9, 26–33. Buonocore, M. H., Simon, T., Rogers S.,
B., & Gibb, R. (2015). Preconception Lorenz, K. (1970). Studies on animal et al. (2012). Increased rate of amygdala
paternal stress in rats alters dendritic and human behavior (Vols. 1 and 2). growth in children aged 2 to 4 years with
morphology and connectivity in the brain Cambridge, MA: Harvard University Press. autism spectrum disorders: A longitudinal
of developing male and female offspring. Lu, L. H., Leonard, C. M., Thompson, P. M., study. Archives of General Psychiatry, 69,
Neuroscience, 303, 200–210. Kan, E., Jolley, J., Welcome, S. E., et al. 53–61.
Harlow, H. F. (1971). Learning to love. San (2007). Normal developmental changes in Nyagu, A. I., Loganovsky, K. N.,
Francisco: Albion. inferior frontal gray matter are associated & Loganovskaja, T. K. (1998).
Hebb, D. O. (1947). The effects of early with improvement in phonological Psychophysiological aftereffects of
experience on problem solving at maturity. processing: A longitudinal MRI analysis. prenatal irradiation. International Journal
American Psychologist, 2, 737–745. Cerebral Cortex, 17, 1092–1099. of Psychophysiology, 30, 303–311.
References R-7
O’Hare, E. D., & Sowell, E. R. (2008). Rutter, M. (1998). Developmental catch-up, Weiss, S., Reynolds, B. A., Vescovi, A. L.,
Imaging developmental changes in gray and deficit, following adoption after severe Morshead, C., Craig, C. G., & van der
and white matter in the human brain. global early privation. Journal of Child Kooy, D. (1996). Is there a neural stem cell
In C. A. Nelson and M. Luciana (Eds.), Psychology and Psychiatry, 39, 465–476. in the mammalian forebrain? Trends in
Handbook of developmental cognitive Salm, A. K., Pavelko, M., Drouse, E. M., Neurosciences, 19(9), 387–393.
neuroscience (pp. 23–38), Cambridge, MA: Webster, W., Kraszpulski, M., & Birkle, Werker, J. F., & Tees, R. C. (1992). The
MIT Press. D. L. (2004). Lateral amygdala nucleus organization and reorganization of human
Overman, W., Bachevalier, J., Schuhmann, expansion in adult rats is associated with speech perception. Annual Review of
E., & Ryan, P. (1996). Cognitive gender exposure to prenatal stress. Developmental Neuroscience, 15, 377–402.
differences in very young children Brain Research, 148, 159–167. Yakovlev, P. E., & Lecours, A.-R. (1967).
parallel biologically based cognitive Schnack, H. G., van Haren, N. E., Brouwer, The myelogenetic cycles of regional
gender differences in monkeys. Behavioral R. M., Evans, A., Durston, S., Boomsma, maturation of the brain. In A. Minkowski
Neuroscience, 110, 673–684. D. I., et al. (2014). Changes in thickness (Ed.), Regional development of the brain in
Overman, W., Bachevalier, J., Turner, M., and surface area of the human cortex early life. Oxford: Blackwell.
& Peuster, A. (1992). Object recognition and their relationship with intelligence.
versus object discrimination: Comparison Cerebral Cortex, 25, 1608–1617. Chapter 9
between human infants and infant Shaw, P., Greenstein, D., Lerch, J., Clasen, L., Bálint, R. (1909). Seelenlähmung des
monkeys. Behavioral Neuroscience, 106, Lenroot, R., et al. (2006). Intellectual “Schauens,” optische Ataxie, räumliche
15–29. ability and cortical development in children Störung der Aufmerksamkeit.
Paterson, D. S., Trachtenberg, F. L., and adolescents. Nature, 440, 666–679. Monatschrift für Psychiatrie und
Thompson, E. G., Belliveau, R. A., Beggs, Shingo, T., Gregg, C., Enwere, E., Fujikawa, H., Neurologie, 25, 51–81.
A. H., Dranall, et al. (2006). Multiple Hassam, R., Greary, C., et al. (2003). Farah, M. J. (1990). Visual agnosia.
serotonergic brainstem abnormalities in Pregnancy-stimulated neurogenesis in Cambridge, MA: MIT Press.
sudden infant death syndrome. Journal of the adult female forebrain mediated by Geschwind, N. (1972). Language and the
the American Medical Association, 296, prolactin. Science, 299, 117–120. brain. Scientific American, 226(4), 78–83.
2124–2132. Smyke, A. T., Zeanah, C. H., Gleason, M. M., Goodale, M. A., Milner, D. A., Jakobson, L. S.,
Paus, T., Keshavan, M., & Giedd, J. N. (2008). Drury, S. S., Fox, N. A., et al. (2012). A & Carey, J. D. P. (1991). A kinematic
Why do so many psychiatric disorders randomized controlled trial comparing analysis of reaching and grasping
emerge during adolescence? Nature foster care and institutional care for movements in a patient recovering from
Reviews Neuroscience, 9, 947–957. children with signs of reactive attachment optic ataxia. Nature, 349, 154–156.
Payne, B. R., & Lomber, S. G. (2001). disorder. American Journal of Psychiatry, Hamilton, R. H., Shenton, J. T., & Coslett,
Reconstructing functional systems after 169, 508–514. H. B. (2006). An acquired deficit of
lesions of cerebral cortex. Nature Reviews Sodhi, M. S., & Sanders-Bush, E. (2004). audiovisual speech processing. Brain and
Neuroscience, 2, 911–919. Serotonin and brain development. Language, 98, 66–73.
Petanjek, Z., Judas, M., Simic, G., Rasin, International Review of Neurobiology, 59, Hasson, U., Nir, Y., Levy, I., Fuhrmann, G.,
M. R., Uylings, H. B. M., et al. (2011). 111–174. & Malach, R. (2004). Intersubject
Extraordinary neoteny of synaptic Sowell, E. R., Thompson, P. M., Leonard, synchronization of cortical activity during
spines in the human prefrontal cortex. C. M., Welcome, S. E., Kan, E., & Toga, natural vision. Science, 303, 1634–1640.
Proceedings of the National Academy of A. W. (2004). Longitudinal mapping of Held, R. (1968). Dissociation of visual
Sciences U S A, 108, 13281–13286. cortical thickness and brain growth in function by deprivation and
Piaget, J. (1952). The origins of intelligence in normal children. Journal of Neuroscience, rearrangement. Psychologische Forschung,
children. New York: Norton. 24, 8223–8231. 31, 338–348.
Purpura, D. P. (1974). Dendritic spine Sowell, E. R., Thompson, P. M., & Toga, A. W. Hubel, D. H., & Weisel, T. N. (1977).
“dysgenesis” and mental retardation. (2004). Mapping changes in the human Functional architecture of macaque
Science, 186, 1126–1127. cortex throughout the span of life. The monkey visual cortex. Proceedings of the
Raizada, R. D. S., Richards, T. L., Meltzoff, Neuroscientist, 10, 372–392. Royal Society of London B, 198, Figure 23.
A., & Kuhl, P. K. (2008). Socioeconomic Sperry, R. W. (1963). Chemoaffinity in the Jerison, H. J. (1973). The evolution of the brain
status predicts hemispheric specialization orderly growth of nerve fiber patterns and and intelligence. New York: Academic Press.
of the left inferior frontal gyrus in young connections. Proceedings of the National Kline, D. W. (1994). Optimizing the
children. NeuroImage, 40, 1392–1401. Academy of Sciences United States of visibility of displays for older observers.
Rakic, P. (1974). Neurons in rhesus monkey America, 50, 703–710. Experimental Aging Research, 20, 11–23.
cerebral cortex: Systematic relation Suomi, S. J. (2011). Risk, resilience, and Kuffler, S. W. (1952). Neurons in the retina:
between time of origin and eventual gene-environment interplay in primates. Organization, inhibition and excitatory
disposition. Science, 183, 425. Journal of the Canadian Academy of Child problems. Cold Spring Harbor Symposia
Raza, S., Harker, A., Richards, S., Kolb, B., and Adolescent Psychiatry, 20, 289–297. on Quantitative Biology, 17, 281–292.
& Gibb, R. (2015). Tactile stimulation Twitchell, T. E. (1965). The automatic Milner, A. D., & Goodale, M. A. (2006). The
improves neuroanatomical pathology but grasping response of infants. visual brain in action (2nd ed.). Oxford:
not behaviour in rats prenatally exposed Neuropsychologia, 3, 247–259. Oxford University Press.
to valproic acid. Behavioural Brain Wallace, P. S., & Whishaw, I. Q. (2003). Sacks, O., & Wasserman, R. (1987). The case
Research, 282, 25–36. Independent digit movements and of the colorblind painter. The New York
Riesen, A. H. (1982). Effects of environments precision grip patterns in 1–5-month-old Review of Books, 34, 25–33.
on development in sensory systems. In human infants: Hand-babbling, including Snowden, R., Thompson, P., & Troscianko, T.
W. D. Neff (Ed.), Contributions to sensory vacuous then self-directed hand and digit (2008). Basic vision: An introduction
physiology (Vol. 6, pp. 45–77). New York: movements, precedes targeted reaching. to visual perception. Oxford: Oxford
Academic Press. Neuropsychologia, 41, 1912–1918. University Press.
R-8 References
Szentagothai, J. (1975). The “module- Johansson, B. B. (2012). Multisensory Trehub, S., Schellenberg, E. G., &
concept” in cerebral cortex architecture. stimulation in stroke rehabilitation. Ramenetsky, G. B. (1999). Infants’ and
Brain Research, 95, 475–496. Frontiers in Human Neuroscience, 6, 60. adults’ perception of scale structures.
Tanaka, K. (1993). Neuronal mechanisms of Kim, K. H. S., Relkin, N. R., Young-Min Journal of Experimental Psychology: Human
object recognition. Science, 262, 685–688. Lee, K., and Hirsch, J. (1997). Distinct Perception and Performance, 25, 965–975.
Weizkrantz, L. (1986). Blindsight: A case cortical areas associated with native and Zatorre, R. J., Evans, A. C., & Meyer, E.
study and implications. Oxford: Oxford second languages. Nature 388, 171–174. (1994). Neural mechanisms underlying
University Press. Knudsen, E. I. (1981). The hearing of the barn melodic perception and memory for pitch.
Wong-Riley, M. T. T., Hevner, R. F., Cutlan, owl. Scientific American, 245(6), 113–125. Journal of Neuroscience, 14, 1908–1919.
R., Earnest, M., Egan, R., Frost, J., & Loeb, G. E. (1990). Cochlear prosthetics. Zatorre, R. J., Evans, A. C., Meyer, E.,
Nguyen, T. (1993). Cytochrome oxidase in Annual Review of Neuroscience, 13, & Gjedde, A. (1992). Lateralization of
the human visual cortex: Distribution in 357–371. phonetic and pitch discrimination in
the developing and the adult brain. Visual Marler, P. (1991). The instinct to learn. In speech processing. Science, 256,
Neuroscience, 10, 41–58. S. Carey and R. German (Eds.), The 846–849.
Zaidi, F. H., Hull, J. T., Peirson, S. N., Wulff, epigenesis of mind: Essays on biology and Zatorre, R. J., Meyer, E., Gjedde, A., &
K., Aeschbach, D., et al. (2007). Short- cognition (p. 39). Hillsdale, NJ: Erlbaum. Evans, A. C. (1996). PET studies of
wavelength light sensitivity of circadian, Nottebohm, F., & Arnold, A. P. (1976). Sexual phonetic processing of speech: Review,
pupillary, and visual awareness in humans dimorphism in vocal control areas of the replication, and reanalysis. Cerebral
lacking an outer retina. Current Biology, songbird brain. Science, 194, 211–213. Cortex, 6, 21–30.
17, 2122–2128. Penfield, W., & Roberts, L. (1956). Speech
Zihl, J., von Cramon, D., & Mai, N. (1983). and brain mechanisms. Oxford, London: Chapter 11
Selective disturbance of movement vision Oxford University Press. Aflalo, T. N., & Graziano, M. S. (2007).
after bilateral brain damage. Brain, 106, Peretz, I., Kolinsky, R., Tramo, M., Labrecque, Relationship between unconstrained
313–340. R., Hublet, C., Demeurisse, G., et al. arm movements and single-neuron firing
(1994). Functional dissociations following in the macaque motor cortex. Journal of
Chapter 10 bilateral lesions of auditory cortex. Brain, Neuroscience, 127, 2760–2780.
Bermudez, P., Lerch, J. P., Evans, A. C., & 117, 1283–1301. Alessandria, M., Vetrugno, R., Cortelli, P., &
Zatorre, R. J. (2009). Neuroanatomical Pinker, S. (1997). How the mind works. Montagna, P. (2011). Normal body scheme
correlates of musicianship as revealed New York: Norton. and absent phantom limb experience in
by cortical thickness and voxel-based Rauschecker, J. P. (2012). Ventral and dorsal amputees while dreaming. Consciousness
morphometry. Cerebral Cortex, 19, streams in the evolution of speech and and Cognition, 20, 831–834.
1583–1596. language. Frontiers in Evolutionary Alexander, R. E., & Critcher, M. D. (1990).
Boonman, A., Bumrungsri, S., & Yovel, Y. Neuroscience, 4:7. doi: 10.3389/ Functional architecture of basal ganglia
(2014). Nonecholocating fruit bats produce fnevo.2012.00007. circuits: Neural substrates of parallel
biosonar clicks with their wings. Current Romanski, L. M., Tian, B., Fritz, J., Mishkin, processing. Trends in Neuroscience, 13, 269.
Biology, 24, 2962–2967. M., Goldman-Rakic, P. S., & Rauschecker, Asanuma, H. (1989). The motor cortex.
Bregman, A. S. (2005). Auditory scene J. P. (1999). Dual streams of auditory New York: Raven Press.
analysis and the role of phenomenology afferents target multiple domains in Blakemore, S. J., Wolpert, D. M., & Frith,
in experimental psychology. Canadian the primate prefrontal cortex. Nature C. D. (1998). Central cancellation of
Psychology, 46, 1, 32–40. Neuroscience, 2, 1131–1136. self-produced tickle sensation. Nature
Chomsky, N. (1965). Aspects of the theory of Sunitha Suresh, B. S., De Oliveira, G. S. Jr., Neuroscience, 1, 635–640.
syntax. Cambridge, MA: MIT Press. & Suresh, S. (2015). The effect of audio Bleton, J. P., Teremetz, M., Vidailhet, M.,
Clarke, G. M. (2015). The multi-channel therapy to treat postoperative pain in Mesure, S., Maier, M. A., Lindberg,
cochlear implant: Multi-disciplinary children undergoing major surgery: A P. G. (2014). Impaired force control in
development of electrical stimulation randomized controlled trial. Pediatric writer’s cramp showing a bilateral deficit
of the cochlea and the resulting clinical Surgical International, 31, 197–201. in sensorimotor integration. Movement
benefit. Hearing Research, 322, 4–13. Teie, P. U. (1998). Noise-induced hearing Disorders, 29, 130–134.
Daniel, E. (2007). Noise and hearing loss: A loss and symphony orchestra musicians: Brinkman, C. (1984). Supplementary motor
review. The Journal of School Health, 77, Risk factors, effects, and management. area of the monkey’s cerebral cortex:
225–231. Maryland Medical Journal, 47, 13–18. Short- and long-term deficits after
Drake-Lee, A. B. (1992). Beyond music: Teng, S., & Whitney, D. (2011). The acuity unilateral ablation and the effects of
Auditory temporary threshold shift in rock of echolocation: Spatial resolution in the subsequent callosal section. Journal of
musicians after a heavy metal concert. sighted compared to expert performance. Neuroscience, 4, 918–992.
Journal of the Royal Society of Medicine, Journal of Visual Impairment & Blindness, Casile, A., Caggiano, V., & Ferrari, P. F.
85, 617–619. 105, 20–32. (2011). The mirror neuron system: A fresh
Geissmann, T. (2001). Gibbon songs and Thaler, L., Arnott, S. R., & Goodale, M. A. view. Neuroscientist, 17, 524–538.
human music from an evolutionary (2011). Neural correlates of natural human Castellanos, F. X., Cortese, S., & Proal, E.
perspective. In N. L. Wallin, B. Merker, & echolocation in early and late blind (2014). Connectivity. Current Topics in
S. Brown (Eds.), The origins of music echolocation experts. PLoS ONE, 6, Behavioral Neuroscience, 16, 49–77.
(pp. 103–124). Cambridge, MA: MIT Press. e20162. Church, J. A., Fair, D. A., Dosenbach, N. U.,
Hyde, K. L., Lerch, J. P., Zatorre, R. J., Thompson, C. K., Meitzen, J., Replogle, K., Cohen, A. L., Miezin, F. M., Petersen,
Griffiths, T. D., Evans, A. C., & Peretz, Drnevich, J., Lent, K. L., et al. (2012). S. E., & Schlaggar, B. L. (2009). Control
I. (2007). Cortical thickness in congenital Seasonal changes in patterns of gene networks in paediatric Tourette syndrome
amusia: When less is better than more. expression in avian song control brain show immature and anomalous patterns of
Journal of Neuroscience, 27, 13028–13032. regions. PLoS One, 7, e35119. functional connectivity. Brain, 32, 225–238.
References R-9
Cole, J. (1995). Pride and a daily marathon. Kaas, J. H., Stepniewska, I., & Gharbawie, O. Penfield, W., & Boldrey, E. (1958). Somatic
Cambridge, MA: MIT Press. (2012). Cortical networks subserving upper motor and sensory representation in the
Corkin, S., Milner, B., & Rasmussen, T. limb movements in primates. European cerebral cortex as studied by electrical
(1970). Somatosensory thresholds. Archives Journal of Physical and Rehabilitation stimulation. Brain, 60, 389–443.
of Neurology, 23, 41–58. Medicine, 48, 299–306. Pons, T. P., Garraghty, P. E., Ommaya, A. K.,
Critchley, M. (1953). The parietal lobes. Kalueff, A. V., Aldridge, J. W., LaPorte, J. L., Kaas, J. H., Taum, E., & Mishkin, M.
London: Arnold. Murphy D. L., & Tuohimaa, P. (2007). (1991). Massive cortical reorganization
Daly, J. J., & Huggins, J. E. (2015). Brain- Analyzing grooming microstructure in after sensory deafferentation in adult
computer interface: Current and emerging neurobehavioral experiments. Nature macaques. Science, 252, 1857–1860.
rehabilitation applications. Archives of Protocols, 25, 38–44. Roland, P. E. (1993). Brain activation.
Physical and Medical Rehabilitation, 96 Kambi, N., Halder, P., Rajan, R., Arora, V., New York: Wiley-Liss.
(3 Suppl.), S1–S7. Chand, P., et al. (2014). Large-scale Rothwell, J. C., Taube, M. M., Day, B. L.,
Davarpanah Jazi, S., Yau, M., Westwood, reorganization of the somatosensory Obeso, J. A., Thomas, P. K., & Marsden,
D. A., & Heath, M. (2015). Pantomime- cortex following spinal cord injuries C. D. (1982). Manual motor performance
grasping: The ‘return’ of haptic feedback is due to brainstem plasticity. Nature in a deafferented man. Brain, 105, 515–542.
supports the absolute specification of Communications, 8:5, 3602. Sacks, O. W. (1998). The man who mistook his
object size. Experimental Brain Research, Kern, U., Busch, V., Rockland, M., Kohl, M., wife for a hat: And other clinical tales.
233, 2029–2040. & Birklein, F. (2009). Prevalence and New York: Touchstone Books.
Evarts, E. V. (1968). Relation of pyramidal risk factors of phantom limb pain and Thach, W. T. (2007). On the mechanism of
tract activity to force exerted during phantom limb sensations in Germany: cerebellar contributions to cognition.
voluntary movement. Journal of A nationwide field survey. Schmerz, 23, Cerebellum, 6, 163–167.
Neurophysiology, 31, 14–27. 479–488. Therrien, A. S., Bastian, A. J. (2015).
Foster, E., Wildner, H., Tudeau, L., Haueter, Lang, C. E., & Schieber, M. H. (2004). Cerebellar damage impairs internal
S., Ralvenius, W. T., Jegen, M., et al. Reduced muscle selectivity during predictions for sensory and motor
(2015). Targeted ablation, silencing, and individuated finger movements in function. Current Opinion in
activation establish glycinergic dorsal humans after damage to the motor Neurobiology, 33, 127–133.
horn neurons as key components of a cortex or corticospinal tract. Tinaz, S., Malone, P., Hallett, M., Horovitz,
spinal gate for pain and itch. Neuron, 85, Journal of Neurophysiology, 91, S. G. (2015). Role of the right dorsal
1289–1304. 1722–1733. anterior insula in the urge to tic in
Friedhoff, A. J., & Chase, T. N. (1982). Gilles Lashley, K. S. (1951). The problem of serial Tourette syndrome. Movement Disorders,
de la Tourette syndrome. Advances in order in behavior. In L. A. Jeffress (Ed.), doi: 10.1002/mds.26230.
Neurology, 35, 1–17. Cerebral mechanisms and behavior von Holst, E. (1973). The collected papers of
Friend, D. M., & Kravitz, A. V. (2014). (pp. 112–136). New York: Wiley. Erich von Holst (R. Martin, Trans.). Coral
Working together: Basal ganglia Leonard, C. M., Glendinning, D. S., Wilfong, Gables, FL: University of Miami Press.
pathways in action selection. Trends in T., Cooper, B. Y., & Vierck, C. J., Jr. (1991). Williams, T. H., Gluhbegovic, N., & Jew, J.
Neuroscience, 37, 301–303. Alterations of natural hand movements (2000). The human brain: Dissections
Hashimoto, Y., Honda, T., Matsumura, after interruption of fasciculus cuneatus of the real brain (CD-ROM). Brain
K., Nakao, M., Soga, K., Katano, K., in the macaque. Somatosensory and Motor University: brain-university.com.
et al. (2015). Quantitative evaluation of Research, 9, 61–75. Windt, J. M., Harkness, D. L., &
human cerebellum-dependent motor Lopez-Escamez. J. A., Carey, J., Chung, Lenggenhager, B. (2015). Tickle me,
learning through prism adaptation of W. H., Goebel, J. A., Magnusson, M., I think I might be dreaming! Sensory
hand-reaching movement. PLoS One. Mandalà, M., et al. (2015). Diagnostic attenuation, self-other distinction, and
(3):e0119376. criteria for Ménière’s disease. Journal of predictive processing in lucid dreams.
Hellman, R. B., Chang, E., Tanner, J., Vestibular Research, 25, 1–7. Frontiers in Human Neuroscience, 8, 717.
Helms Tillery, S. I., & Santos, V. J. Melzack, R. (1973). The puzzle of pain.
(2015). A robot hand testbed designed for New York: Basic Books. Chapter 12
enhancing embodiment and functional Melzack, R., & Wall, P. D. (1965). Pain Ackerly, S. S. (1964). A case of paranatal
neurorehabilitation of body schema in mechanisms: A new theory. Science, 150, bilateral frontal lobe defect observed
subjects with upper limb impairment or 971–979. for thirty years. In J. M. Warren &
loss. Frontiers in Human Neuroscience, 9, Mountcastle, V. B. (1978). An organizing K. Akert (Eds.), The frontal granular cortex
1–26. principle for cerebral function: The unit and behavior (pp. 192–218). New York:
Hess, W. R. (1957). The functional module and the distributed system. In McGraw-Hill.
organization of the diencephalon. London: G. M. Edelman & V. B. Mountcastle Adelmann, P. K., & Zajonc, R. B. (1989). Facial
Grune & Stratton. (Eds.), The mindful brain (pp. 7–50). efferents and the experience of emotion.
Imani, S., Zagari, Z., Rezaei Zarchi, S., Cambridge, MA: MIT Press. Annual Review of Psychology, 40, 249–280.
Jorjani, M., Nasri, S. (2015). Functional Nudo, R. J., Wise, B. M., SiFuentes, F., & Bao, A.-M., & Swaab, D. F. (2011). Sexual
recovery of carbon nanotube/ Milliken, G. W. (1996). Neural substrates differentiation of the human brain: Relation
nafion nanocomposite in rat model for the effects of rehabilitative training to gender identity, sexual orientation and
of spinal cord injury. Artificial Cells on motor recovery after ischemic infarct. neuropsychiatric disorders. Frontiers in
Nanomedicine and Biotechnology, 10, Science, 272, 1791–1794. Neuroendocrinology, 32, 214–226.
1–6. Panksepp, J. (2007). Neuroevolutionary Bartoshuk, L. M. (2000). Comparing sensory
Kaas, J. H. (1987). The organization and sources of laughter and social joy: experiences across individuals: Recent
evolution of neocortex. In S. P. Wise (Ed.), Modeling primal human laughter psychophysical advances illuminate
Higher brain functions (pp. 237–298). New in laboratory rats. Behavioural Brain genetic variation in taste perception.
York: Wiley. Research, 4, 231–244. Chemical Senses, 25, 447–460.
R-10 References
Beatty, J. (1995). Principles of behavioral Fung, T. T., van Dam, R. M., Hankinson Lundstrom, J. N., Boyle, J. A., Zatorre, R. J.,
neuroscience (p. 339). Dubuque, IA: Brown S. E., Stampfer, M., Willett, W. C., & Hu, & Jones-Gotman, M. (2008). Functional
& Benchmark. F. B. (2010). Low-carbohydrate diets and neuronal processing of body odors differs
Becker, J. B., Berkley, K. J., Geary, N., all-cause and cause-specific mortality: from that of similar common odors.
Hampson, E., Herman, J. P., & Young, Two cohort studies. Annals of Internal Cerebral Cortex, 18, 1466–1474.
E. A. (2008). Sex differences in the brain: Medicine, 153, 289–298. MacLean, P. D. (1949). Psychosomatic
From genes to behavior. New York: Oxford Garcia, J., & Koelling, R. A. (1966). Relation disease and the “visceral brain”: Recent
University Press. of cue to consequences in avoidance developments bearing on the Papez
Berridge, K. C. (1996). Food reward: learning. Psychonomic Science, 4, 123–124. theory of emotion. Psychosomatic
Brain substrates of wanting and liking. Garrison, K. A., Zeffiro, T. A., Scheinost, D., Medicine, 11, 338–353.
Neuroscience and Biobehavioral Reviews, Constable, R. T., & Brewer, J. A. (2015, McCarthy, M. M., Auger, A. P., Bale, T. L.,
20, 6. Apr 23). Meditation leads to reduced De Vries, G. J., Dunn, G. A., et al. (2009).
Brunetti, M., Babiloni, C., Ferretti, A., default mode network activity beyond an The epigenetics of sex differences in
Del Gratta, C., Merla, A., et al. (2008). active task. Cognitive Affective Behavioral the brain. Journal of Neuroscience, 29,
European Journal of Neuroscience, 27, Neuroscience, 15, 712–720. 12815–12823.
2922–2927. Gerkin, R.C., & Castro, J. B. (2015). The Money, J., & Ehrhardt, A. A. (1972). Man and
Buss, D. (2014). Evolutionary psychology: The number of olfactory stimuli that humans woman, boy and girl. Baltimore: Johns
new science of the mind (5th ed.). New can discriminate is still unknown. eLife Hopkins University Press.
York: Taylor & Francis. 4:e08127. Mozaffarinan, D., Tao Hao, M. P. H., Rimm,
Butler, R. A., & Harlow, H. F. (1954). Glickman, S. E., & Schiff, B. B. (1967). E. B., Willett, W. C., & Hu, F. B. (2011).
Persistence of visual exploration in A biological theory of reinforcement. Changes in diet and lifestyle and long-
monkeys. Journal of Comparative and Psychological Review, 74, 81–109. term weight gain in women and men.
Physiological Psychology, 47, 257–263. Gorski, R. A. (1984). Critical role for the New England Journal of Medicine, 364,
Daly, M., & Wilson, M. (1988). Homicide. medial preoptic area in the sexual 2392–2404.
New York: Aldine. differentiation of the brain. Progress in Olds, J., & Milner, P. (1954). Positive
Damasio, A. R. (1999). The feeling of what Brain Research, 61, 129–146. reinforcement produced by electrical
happens: Body and emotion in the making Heron, W. (1957). The pathology of boredom. stimulation of septal area and other
of consciousness. New York: Harcourt Scientific American, 196(1), 52–56. regions of rat brain. Journal of
Brace. Insel, T. R., & Fernald, R. D. (2004). How Comparative and Physiological Psychology,
Davis, M., Walker, D. L., & Myers, K. M. the brain processes social information: 47, 419–427.
(2003). Role of the amygdala in fear Searching for the social brain. Annual Olsson, S. B., Barnard, J., & Turri, L.
extinction measured with potentiated Review of Neuroscience, 27, 697–722. (2006). Olfaction and identification of
startle. Annals of the New York Academy Jacob, S., Kinnunen, L. H., Metz, J., unrelated individuals: Examination of
of Sciences, 985, 218–232. Cooper, M., & McClintock, M. K. the mysteries of human odor recognition.
Day, J. J., & Sweatt, J. D. (2011). Cognitive (2001). Sustained human chemosignal Journal of Chemical Ecology, 32,
neuroepigenetics: A role for epigenetic unconsciously alters brain function. 1635–1645.
mechanisms in learning and memory. Neuroreport, 12, 2391–2394. Panagiotakos, D. B., Pitsavos, C.,
Neurobiology of Learning and Memory, 96, Jacobsen, C. F. (1936). Studies of cerebral Polychronopoulos, E., Chrysohoou, C.,
2–12. function in primates. Comparative Zampelas, A., & Trichopoulou, A. (2004).
Dethier, V. G. (1962). To know a fly. San Psychology Monographs, 13, 1–68. Can a Mediterranean diet moderate the
Francisco: Holden-Day. Janes, A. C., Farmer, S., Frederick, B. deB., development and clinical progression
Duffy, V. B., Hayes, J. E., Davidson, A. C., Nickerson, L. D., & Lucas, S. E. (2014). An of coronary heart disease? A systematic
Kidd, J. R., Kidd, K. K., & Bartoshuk, increase in tobacco craving is associated review. Medical Science Monitor, 10,
L. M. (2010). Vegetable intake in college- with enhanced medial prefreontal cortex RA193–RA198.
aged adults is explained by oral sensory network coupling. PLoS One, 9, e88228. Robinson, T. E., & Berridge, K. C.
phenotypes and TAS2R38 genotype. Janes, A. C., Nickerson, L. D., Frederick, B. (2008). Incentive sensitization theory.
Chemosensory Perception, 3, 137–148. deB., & Kaufman, M. H. (2012). Prefrontal Philosophical Transactions of the Royal
Eisenberger, N. I., Jarcho, J. M., Lieberman, and limbic resting state brain network Society of London, 363, 3137–3146.
M. D., & Naliboff, B. D. (2006). An functional connectivity differs between Schroeder, M., Krebs, M. O., Bleich, S.,
experimental study of shared sensitivity biotine-dependent smokers and non- & Frieling, H. (2010). Epigenetics and
to physical pain and social rejection. Pain, smoking controls. Drug and Alcohol depression. Current Opinion in Psychiatry,
126, 132–138. Dependence, 125, 252–259. 23, 588–592.
Eisenberger, N. I., Lieberman, M. D., & Klüver, H., & Bucy, P. C. (1939). Preliminary Seeley, R. J., & Woods, S. C. (2003).
Williams, K. D. (2003). Does rejection analysis of the temporal lobes in monkeys. Monitoring of stored and available fuel by
hurt? An fMRI study of social exclusion. Archives of Neurology and Psychiatry, 42, the CNS: Implications for obesity. Nature
Science, 302, 290–292. 979–1000. Reviews Neuroscience, 4, 885–909.
Everitt, B. J. (1990). Sexual motivation: A neural Kross, E., Berman, M. G., Mischel, W., Shai, I., Schwarzfuchs, D., Henkin, Y.,
and behavioral analysis of the mechanisms Smith, E. E., & Water, T. D. (2011). Shahar, D. R., Witkow, S., et al. (2008).
underlying appetitive and copulatory Social rejection shares somatosensory Weight loss with a low-carbohydrate,
responses of male rats. Neuroscience and representations with physical pain. Mediterranean, or low-fat diet. New
Biobehavioral Reviews, 14, 217–232. Proceedings of the National Academy of England Journal of Medicine, 359,
Field, T. M., Woodson, R., Greenberg, R., Sciences United States of America, 108, 229–241.
& Cohen, D. (1982), Discrimination and 6270–6275. Skinner, B. F. (1938). The behavior of
imitation of facial expression by neonates. LeDoux, J. (1996). The emotional brain. New organisms. New York: Appleton-Century-
Science, 218, 179–181. York: Simon & Schuster. Crofts.
References R-11
Smith, D. V., & Shepherd, G. M. (2003). Cain, S. W., Verwey, M., Szybowska, Freud, S. (1990). The interpretation of dreams.
Chemical senses: Taste and olfaction. M., Ralph, M. R., & Yeomans, J. S. Leipzig and Vienna: Franz Deuticke.
In L. R. Squiare, F. E. Bloom, S. K. (2007). Carbachol injections into the Gangwisch, J. E. (2014). Invited commentary:
McConnell, J. L. Roberts, N. C. Spitzer, intergeniculate leaflet induce nonphotic Nighttime light exposure as a risk
& M. J. Zigmond (Eds.), Fundamental phase shifts. Brain Research, 1177, 59–65. factor for obesity through disruption
Neuroscience (2nd ed., pp. 631–667). New Carter, K. A., Hathaway, N. E., & Lettieri, of circadian and circannual rhythms.
York: Academic Press. C. F. (2014). Common sleep disorders in American Journal of Epidemiology, 180,
Stern, K., & McClintock, M. K. (1998). children. American Family Physician, 89, 251–253.
Regulation of ovulation by human 368–377. Gerhart-Hines, Z., Lazar, M. A. (2015).
pheromones. Nature, 392, 177–179. Chang, A. M., Aeschbach, D., Duffy, J. F., Circadian metabolism in the light of
Veldhuizen, M. G., Albrecht, J., Zelano, C., Czeisler, C. A. (2015). Evening use of evolution. Endocrinology Reviews, 36(3),
Boesveldt, S., Breeslin, P., & Lundstrom, light-emitting eReaders negatively affects 289–304. er20151007.
J. N. (2011). Identification of human sleep, circadian timing, and next-morning Gerrard, J. L., Burke, S. N., McNaughton,
gustatory cortex by activation likelihood alertness. Proceedings of the National B. L., & Barnes, C. A. (2008). Sequence
estimation. Human Brain Mapping, 32, Academy of Sciences United States of reactivation in the hippocampus
2256–2266. America, 112, 232–237. is impaired in aged rats. Journal of
Wise, R. A. (1996). Addictive drugs and brain Claustrat, B., Leston, J. (2015). Melatonin: Neuroscience, 30, 7883–7890.
stimulation reward. Annual Review of Physiological effects in humans. Hall, C. S., Domhoff, G. W., Blick, K. A.,
Neuroscience, 19, 319–340. Neurochirurgie, 61(2–3), 77–84. & Weesner, K. E. (1982). The dreams of
Woo, C.-W., Koban, L., Kross, E., Lindquist, Corrêa Cde, C., Blasca, W. Q., & college men and women in 1950 and 1980:
M. A., Banich, M. T., Ruzic, L., et al. Berretin-Felix, G. (2015). Health A comparison of dream contents and sex
(2014). Separate neural representations for promotion in obstructive sleep apnea differences. Sleep, 5, 188–194.
physical pain and social rejection. Nature syndrome. International Archives of Hobson, J. A. (2002). Sleep and dream
Communications, 5, 5380. doi: 10.1038/ Otorhinolaryngology, 19, 166–170. suppression following a lateral medullary
ncomms6380 de Lavilléon, G., Lacroix, M. M., Rondi-Reig, infarct: A first-person account.
Woolley, C. S., Gould, E., Frankfurt, M., & L., & Benchenane, K. (2015). Explicit Consciousness and Cognition, 11, 377–390.
McEwen, B. (1990). Naturally occurring memory creation during sleep demonstrates Hobson, J. A. (2004). 13 dreams Freud never
fluctuation in dendritic spine density on a causal role of place cells in navigation. had: A new mind science. New York: Pi
adult hippocampal pyramidal neurons. Nature Neuroscience, 18, 493–495. Press.
Journal of Neuroscience, 10, 4035–4039. Dement, W. C. (1972). Some must watch while Hughes, S., Jagannath, A., Hankins, M. W.,
World Health Organization (2000). Obesity: some must sleep. Stanford, CA: Stanford Foster, R. G., & Peirson, S. N. (2015).
Preventing and managing the global Alumni Association. Photic regulation of clock systems.
epidemic. WHO Technical Report Series, Dissel, S., Angadi, V., Kirszenblat, L., Suzuki, Methods in Enzymology, 552, 125–143.
No. 894, 1–253. Y., Donlea, J., Klose, M., et al. (2015). Jones, B. E. (1993). The organization of
Sleep restores behavioral plasticity to central cholinergic systems and their
Chapter 13 Drosophila mutants. Current Biology, 25, functional importance in sleep–waking
Amariei, C., Tomita, M., & Murray, D. B. 1270–1280. states. Progress in Brain Research, 98,
(2014). Quantifying periodicity in omics Dubey, A. K., Handu, S. S., & Mediratta, 61–71.
data. Frontiers in Cellular Developmental P. K. (2015). Suvorexant: The first Jouvet, M. (1972). The role of monoamines
Biology, 19, 2:40. orexin receptor antagonist to treat and acetylcholine-containing neurons in
Batterink, L. J., Oudiette, D., Reber, insomnia. Journal of Pharmacology and the regulation of the sleep–waking cycle.
P. J., & Paller, K. A. (2014). Sleep Pharmacothereputics, 6, 118–121. Ergebnisse der Physiologie, 64, 166–307.
facilitates learning a new linguistic rule. Edwards, C. L., Ruby, P. M., Malinowski, Kang, J. I., Park, C. I., Namkoong, K., &
Neuropsychologia, 65, 169–179. J. E., Bennett, P. D., & Blagrove, M. T. Kim, S. J. (2015). Associations between
Bendix, C., Marshall, C. M., & Harmon, (2013). Dreaming and insight. Frontiers in polymorphisms in the NR1D1 gene
F. G. (2015). Circadian clock genes Psychology, 24, 974–979. encoding for nuclear receptor REV-ERBα
universally control key agricultural traits. Elliott, A. S., Huber, J. D., O’Callaghan, J. P., and circadian typologies. Chronobiology
Molecular Plant, S1674-2052(15), 171–179. Rosen, C. L., & Miller, D. B. (2014). International, 32, 568–572.
Binkley, S. (1990). The clockwork sparrow. A review of sleep deprivation studies Kerr, D. C., Zava, D. T., Piper, W. T., Saturn,
Englewood Cliffs, NJ: Prentice Hall. evaluating the brain transcriptome. S. R., Frei, B., & Gombart, A. F. (2015).
Blumberg, M. S. (2015). Developing Springerplus, 3:728. Associations between vitamin D levels
sensorimotor systems in our sleep. Current Filevich, E., Dresler, M., Brick, T. R., and depressive symptoms in healthy
Directions in Psychological Science, 24, & Kühn, S. (2015). Metacognitive young adult women. Psychiatry Research,
32–37. mechanisms underlying lucid dreaming. 227, 46–51.
Bosler, O., Girardet, C., Franc, J. L., Becquet, Journal of Neuroscience, 35, 1082–1088. Klinger, E. (1990). Daydreaming. Los Angeles,
D., François-Bellan, A. M. (2015). Forloni, G., Tettamanti, M., Lucca, U., CA: Tarcher (Putnam).
Structural plasticity of the circadian Albanese, Y., Quaglio, E., Chiesa, R., Kreutzmann, J., Havekes, R., Abel, T., &
timing system: An overview from flies to et al. (2015). Preventive study in subjects at Meerlo, P. (2015). Sleep deprivation and
mammals. Frontiers in Neuroendocrinology, risk of fatal familial insomnia: Innovative hippocampal vulnerability: Changes in
S0091-3022(15)00014-X. approach to rare diseases. Prion, 9, 75–79. neuronal plasticity, neurogenesis and
Cain, S. W., McDonald, R. J., & Ralph, M. R. Foulkes, D., & Domhoff, G. W. (2014). cognitive function. Neuroscience.
(2008). Time stamp in conditioned place Bottom-up or top-down in dream Labrecque, N., & Cermakian N. (2015).
avoidance can be set to different circadian neuroscience? A top-down critique of two Circadian clocks in the immune system.
phases. Neurobiology of Learning and bottom-up studies. Conscious Cognition, Journal of Biological Rhythms, 30 (4),
Memory, 89, 591–594. 27, 168–171. 277–290.
R-12 References
Lajoie, P., Aronson, K. J., Day, A., & Nelini, C., Bobbo, D., & Mascetti, G. G. Siegel, J. (2004). Brain mechanisms
Tranmer, J. (2015). A cross-sectional (2012). Monocular learning of a spatial task that control sleep and waking.
study of shift work, sleep quality and enhances sleep in the right hemisphere Naturwissenschaften, 91, 355–365.
cardiometabolic risk in female hospital of domestic chicks (Gallus gallus). Silver, R., LeSauter, J., Tresco, P. A., &
employees. BMJ Open, 10;5(3):e007327. Experimental Brain Research, 18, 381–388. Lehman, M. N. (1996). A diffusible
Lamberg, L. (2003). Scientists never dreamed Nir, Y., & Tononi, G. (2010). Dreaming coupling signal from the transplanted
finding would shape half-century of sleep and the brain: From phenomenology to suprachiasmatic nucleus controlling
research. Journal of the American Medical neurophysiology. Trends in Cognitive circadian locomotor rhythms. Nature, 382,
Association, 290, 2652–2654. Science, 14, 88–100. 810–813.
Lan, K. C., Chang, D. W., Kuo, C. E., Nobunaga, M., Obukuro, K., Kurauchi, Y., Smarr, B. L. (2015). Digital sleep logs
Wei, M. Z., Li, Y. H., Shaw, F. Z., Hisatsune, A., Seki, T., Tsutsui, M., reveal potential impacts of modern
et al. (2015). Using off-the-shelf lossy et al. (2014). High fat diet induces specific temporal structure on class performance
compression for wireless home sleep pathological changes in hypothalamic in different chronotypes. Journal of
staging. Journal of Neuroscience Methods, orexin neurons in mice. Neurochemistry Biological Rhythms, 30, 61–67.
246, 142–152. International, 78, 61–66. Valli, K., & Revonsuo, A. (2009). The threat
Landgraf, D., Tsang, A. H., Leliavski, A., Osorio, I., & Daroff, R. B. (1980). Absence of simulation theory in light of recent
Koch, C. E., Barclay, J. L., Drucker, REM and altered NREM sleep in patients empirical evidence: A review. American
D. J., et al. (2015). Oxyntomodulin with spinocerebellar degeneration and slow Journal of Psychology, 122, 17–38.
regulates resetting of the liver circadian saccades. Annals of Neurology, 7, 277–280. Vanderwolf, C. H. (2002). An odyssey
clock by food. eLife 4, e06253. Pellegrino, R., Kavakli, I. H., Goel, N., through the brain, behavior and the mind.
Li, Y., Ma, W., Kang, Q., Qiao, L., Tang, D., Cardinale, C. J., Dinges, D. F., Kuna, Amsterdam: Kluwer Academic.
Qiu, J., et al. (2015). Night or darkness, S. T., et al. (2015). A novel BHLHE41 Webb, I. C., Antle, M. C., & Mistlberger, R. E.
which intensifies the feeling of fear? variant is associated with short sleep and (2014). Regulation of circadian rhythms in
International Journal of Psychophysiology, resistance to sleep deprivation in humans. mammals by behavioral arousal. Behavioral
97 (1), 46–57. Sleep, 37, 1327–1336. Neuroscience, 128, 304–325.
Lungato, L., Gazarini, M. L, Paredes- Postuma, R. B., Gagnon, J. F., Tuineaig, M., Weingarten, J. A., & Collop, N. A. (2013). Air
Gamero, E. J., Tufik, S., & D’Almeida, Bertrand, J. A., Latreille, V., Desjardins, travel: Effects of sleep deprivation and jet
V. (2015). Paradoxical sleep deprivation C., et al. (2013). Antidepressants and REM lag. Chest, 144, 1394–1401.
impairs mouse survival after infection with sleep behavior disorder: Isolated side Wijemanne, S., & Jankovic, J. (2015). Restless
malaria parasites. Malaria Journal, 14, 183. effect or neurodegenerative signal? Sleep, legs syndrome: Clinical presentation
Mahowald, M. W., & Schenck, C. H. 36, 1579–1585. diagnosis and treatment. Sleep Medicine,
(2015). REM sleep behaviour disorder: A Quinlan, J., & Quinlan, J. (1977). Karen Ann: 16, (6), 678–690.
window on the sleeping brain. Brain, 138, The Quinlans tell their story. Toronto: Wilson, M. A., & McNaughton, B. L. (1994).
1131–1133. Doubleday. Reactivation of hippocampal ensemble
Malcolm-Smith, S., Koopowitz, S., Pantelis, Ralph, M. R., & Lehman, M. N. (1991). memories during sleep. Science, 265,
E., & Solms, M. (2012). Approach/ Transplantation: A new tool in the 676–679.
avoidance in dreams. Consciousness and analysis of the mammalian hypothalamic Wilson, S., & Argyropoulos, S. (2005).
Cognition, 21, 408–412. circadian pacemaker. Trends in Antidepressants and sleep: A qualitative
Maquet, P., Laureys, S., Peigneux, P., Fuchs, Neurosciences, 14, 363–366. review of the literature. Drugs, 65,
S., Petiau, C., et al. (2000). Experience- Rasch, B., & Born, J. (2013). About sleep’s 927–947.
dependent changes in cerebral activation role in memory. Physiological Reviews, 93, Zaidi, F. H., Hull, J. T., Peirson, S. N., Wulff,
during human REM sleep. Nature 681–766. K., Aeschbach, D., et al. (2007). Short-
Neuroscience, 3, 831–836. Raven, P. H., Evert, R. F., & Eichorn, S. E. wavelength light sensitivity of circadian,
Mårtensson, B., Pettersson, A., Berglund, L., (1992). Biology of plants. New York: Worth pupillary, and visual awareness in humans
& Ekselius, L. (2015). Bright white light Publishers. lacking an outer retina. Current Biology,
therapy in depression: A critical review Reiter, R. J. (1980). The pineal and its 17, 2122–2128.
of the evidence. Journal of Affective hormones in the control of reproduction Zhang, R., Lahens, N. F., Balance, H. I.,
Disorders, 182, 1–7. in mammals. Endocrinology Review, 1, Hughes, M. E., & Hogenesch, J. B. (2014).
Mistlberger, R. E., & Antle, M. C. (2011). 120. A circadian gene expression atlas in
Entrainment of circadian clocks in Richter, C. P. (1965). Biological clocks in mammals: Implications for biology and
mammals by arousal and food. Essays in medicine and psychiatry. Springfield, IL: medicine. Proceedings of the National
Biochemistry, 49, 119–136. Charles C Thomas. Academy of Sciences United States of
Monecke, S., Brewer, J. M., Krug, S., & Roffward, H. P., Muzio, J., & Dement, W. C. America, 111 (45), 16219–16224.
Bittman, E. L. (2011). Duper: A mutation (1966). Ontogenetic development of the
that shortens hamster circadian period. human sleep–dream cycle. Science, 152, Chapter 14
Biological Rhythms, 26, 283–292. 604–619. Bliss, T. V., & Lomo, T. (1973). Long-lasting
Moruzzi, G., & Magoun, H .W. (1949). Brain Schenck, C. H., Bundlie, S. R., Ettinger, potentiation of synaptic transmission
stem reticular formation and activation M. G., & Mahowald, M. W. (1986). in the dentate are of the anaesthetized
of the EEG. Electroencephalography and Chronic behavioral disorders of rabbit following stimulation of the
Clinical Neurophysiology, 1, 455–473. human REM sleep: A new category of perforant path. Journal of Physiology, 232,
Mulder, C. K., Reckman, G. A., Gerkema, parasomnia. Sleep, 25, 293–308. 331–356.
M. P., & Van der Zee, E. A. (2015). Time- Schmal, C., Myung, J., Herzel, H., & Cahill, L., Babinsky, R., Markowitsch, H. J.,
place learning over a lifetime: Absence of Bordyugov, G. (2015). A theoretical study & McGaugh, J. L. (1995). The amygdala
memory loss in trained old mice. Learning on seasonality. Frontiers in Neurology, and emotional memory. Nature, 377,
and Memory, 22, 278–288. 7(6), 94. 295–296.
References R-13
Candia, V., Wienbruch, C., Elbert, T., Hampson, E., & Kimura, D. (1988). Lashley, K. S. (1960). In search of the engram.
Rockstroh, B., & Ray, W. (2003). Reciprocal effects of hormonal Symposium No. 4 of the Society of
Effective behavioral treatment of fluctuations on human motor and Experimental Biology. In F. A. Beach,
focal hand dystonia in musicians alters perceptual-spatial skills. Behavioral D. O. Hebb, C. T. Morgan, & H. T. Nissen
somatosensory cortical organization. Neuroscience, 102, 456–459. (Eds.), The neuropsychology of Lashley
Proceedings of the National Academy of Hebb, D. O. (1947). The effects of early (pp. 478–505). New York: McGraw-
Sciences United States of America, 100, experience on problem solving at maturity. Hill. (Reprinted from R. Sutton (Ed.),
7942–7946. American Psychologist, 2, 737–745. Physiological mechanisms of animal
Chang, F.-L. F., & Greenough, W. T. ( 1982). Hebb, D. O. (1949). The organization of behavior, pp. 454–482, 1951. Cambridge:
Lateralized effects of monocular training behavior: A neuropsychological theory. Cambridge University Press.)
on dendritic branching in adult split-brain New York: Wiley. LeDoux, J. E. (1995). In search of an
rats. Brain Research, 232, 283–292. Jacobs, B., Schall, M., & Scheibel, A. B. emotional system in the brain: Leaping
Corkin, S. (2002). What’s new with the (1993). A quantitative dendritic analysis from fear to emotion and consciousness.
amnesic patient H. M.? Nature Reviews of Wernicke’s area in humans: II. Gender, In M. S. Gazzaniga (Ed.), The cognitive
Neuroscience, 3, 153–160. hemispheric, and environmental factors. neurosciences (pp. 1047–1061). Cambridge,
Corkin, S., Amaral, D. G., Gonzalez, R. G., Journal of Comparative Neurololgy, 327, MA: MIT Press.
Johnson, K. A., & Hyman, B. T. (1997). 97–111. Lepage, M., McIntosh, A. R., & Tulving, E.
H. M.’s medial temporal lobe lesion: Jacobs, B., & Scheibel, A. B. (1993). A (2001). Transperceptual encoding and
Findings from magnetic resonance quantitative dendritic analysis of retrieval process in memory: A PET study
imaging. Journal of Neuroscience, 17, Wernicke’s area in humans: I. Lifespan of visual and haptic objects. Neuroimage,
3964–3979. changes. Journal of Comparative 14, 572–584.
Damasio, A. R., Tranel, D., & Damasio, Neurology, 327, 83–96. LePort, A. K., Mattfeld, A. T., Dickinson-
H. (1989). Amnesia caused by herpes Kaas, J. (2000). The reorganization of sensory Anson, H., Falon, J. H., Stark, C. E.,
simplex encephalitis, infarctions in basal and motor maps after injury in adult Kruggle, F., et al. (2012). Behavioral and
forebrain, Alzheimer’s disease and anoxia/ mammals. In M. S. Gazzaniga (Ed.), The neuroanatomical investigation of Highly
ischemia. In F. Boller & J. Grafman (Eds.), cognitive neurosciences (pp. 223–236). Superior Autobiographical Memory
Handbook of neuropsychology (Vol. 3, Cambridge, MA: MIT Press. (HSAM). Neurobiology of Learning and
pp. 149–166). New York: Elsevier. Kempermann, G., Kuhn, H. G., & Gage, Memory, 98, 78–92.
Davis, M. (1992). The role of the amygdala F. H. (1998). Experience-induced Loftus, E. F. (1997). Creating false memories.
in fear and anxiety. Annual Review of neurogenesis in the senescent dentate Scientific American, 277(3), 70–75.
Neuroscience, 15, 353–375. gyrus. Journal of Neuroscience, 18, MacDougall, M., & Fine, A. (2014). The
Day, J. J., Kennedy, A. J., & Sweatt, J. D. 3206–3212. expression of long-term potentiation:
(2015). DNA methylation and its Kolb, B., Cote, S., Ribeiro-da-Silva, A., & reconciling the preists and the postivists.
implications and accessibility for Cuello, A. C. (1997). Nerve growth factor Philosophic Transactions of the Royal
neuropsychiatric therapeutics. Annual treatment prevents dendritic atrophy Society B Biological Science, 269,
Review of Pharmacology and Toxicology, and promotes recovery of function after 20130135. doi: 10.1098/rstb.
55, 591–611. cortical injury. Neuroscience, 76, 1146. Maguire, E. A., Gadian, D. G., Johnsrude,
Eriksson, P. S., Perfilieva, E., Bjork-Eriksson, Kolb, B., & Gibb, R. (2014). Searching for I. S., Good, C. D., Ashburner, J.,
T., Alborn, A. M., Nordborg, C., Peterson, principles of brain plasticity and behavior. Frackowiak, R. S., et al. (2000). Navigation-
D. A., et al. (1998). Neurogenesis in Cortex, 58, 251–260. related structural change in the
the adult human hippocampus. Nature Kolb, B., Gibb, R., & Gorny, G. (2003). hippocampi of taxi drivers. Proceedings of
Medicine, 4, 1313–1317. Experience-dependent changes in dendritic the National Academy of Sciences United
Fuster, J. M. (1995). Memory in the cerebral arbor and spine density in neocortex vary States of America, 97, 4398–4403.
cortex. Cambridge, MA: MIT Press. with age and sex. Neurobiology of Learning Mahncke, H. W., Bronstone, A., &
Fuster, J. M., Bodner, M., & Kroger, J. K. and Memory, 79, 1–10. Merzenich, M. M. (2006). Brain plasticity
(2000). Cross-modal and cross-temporal Kolb, B., Gorny, G., Cote, S., Ribeiro-da- and functional losses in the aged:
association in neurons of frontal cortex. Silva, A., & Cuello, A. C. (1997). Nerve Scientific bases for a novel intervention.
Nature, 405, 347–351. growth factor stimulates growth of Progress in Brain Research, 157, 81–109.
Gazzaniga, M. S. (Ed.). (2000). The new cortical pyramidal neurons in young adult Markowitsch, H. J., & Staniloiu, A. (2013).
cognitive neurosciences. Cambridge, MA: rats. Brain Research, 751, 289–294. The impairment of recollection in
MIT Press. Kolb, B., Gorny, G., Li, Y., Samaha, A. N., functional amnesic states. Cortex, 49,
Geschwind, N., & Galaburda, A. M. (1985). & Robinson, T. E. (2003). Amphetamine 1494–1510.
Cerebral lateralization. Cambridge, MA: or cocaine limits the ability of later Markowitsch, H. J. (2003). Psychogenic amnesia.
MIT Press. experience to promote structural plasticity Neuroimage, 20 (Suppl. 1), S132–S138.
Gould, E., Tanapat, P., Hastings, N. B., in the neocortex and nucleus accumbens. Martin, A., Haxby, J. V., Lalonde, F. M.,
& Shors, T. J. (1999). Neurogenesis in Proceedings of the National Academy of Wiggs, C. L., & Ungerleider, L. G. (1995).
adulthood: A possible role in learning. Science United States of America, 100, Discrete cortical regions associated with
Trends in Cognitive Sciences, 3, 186–191. 10523–10528. knowledge of color and knowledge of
Gould, E., Tanapat, P., McEwen, B. Kolb, B., Morshead, C., Gonzalez, C., Kim, action. Science, 270, 102–105.
S., Flugge, G., & Fuchs, E. (1998). N., Shingo, T., & Weiss, S. (2007). Growth Martin, P. R. (1985). Cover, Alcohol Health &
Proliferation of granule cell precursors factor–stimulated generation of new Research World, 9 (Spring 1985).
in the dentate gyrus of adult monkeys is cortical tissue and functional recovery McGaugh, J. (2004). The amygdala modulates
diminished by stress. Proceedings of the after stroke damage to the motor cortex the consolidation of memories of
National Academy of Sciences United of rats. Journal of Cerebral Blood Flow and emotionally arousing experiences. Annual
States of America, 95, 3168–3171. Metabolism, 27, 983–397. Review of Neuroscience, 27, 1–28.
R-14 References
McKenzie, S., & Eichenbaum, H. (2011). Purves, D., & Voyvodic, J. T. (1987). Imaging Stewart, J., & Kolb, B. (1994). Dendritic
Consolidation and reconsolidation: Two mammalian nerve cells and their branching in cortical pyramidal cells in
lives of memories? Neuron, 71, 224–233. connections over time in living animals. response to ovariectomy in adult female
Meloni, E. G., Gillis, T. E., Manoukian, J., Trends in Neurosciences, 10, 398–404. rats: Suppression by neonatal exposure to
& Kaufman, M. J. (2014). Xenon impairs Ragert, P., Schmidt, A., Altenmuller, E., testosterone. Brain Research, 654, 149–154.
reconsolidation of fear memories in a rat & Dinse, H. R. (2003). Superior tactile Sutherland, R. J., Sparks, F. T., &
model of post-traumatic stress disorder performance and learning in professional Lehmann, H. (2010). Hippocampus and
(PTSD). PLoS ONE, 9(8): e106189. pianists: Evidence for meta-plasticity retrograde amnesia in the rat model:
doi:10.1371 /journal.pone.0106189. in musicians. European Journal of A modest proposal for the situation of
Miller, C. A., Gavin, C. F., White, J. A., Neuroscience, 19, 473–478. systems consolidation. Neuropsychologia,
Parrish, R. R., Honasoge, A., Yancey, Ramachandran, V. S. (1993). Behavioral 48, 2357–2369.
C. R., et al. (2010). Cortical DNA and magnetoencephalographic correlates Temple, E., Deutsch, G. K., Poldrack, R. A.,
methylation maintains remote memory. of plasticity in the adult human brain. Miller, S. L., Tallal, P., Merzenich, M. M.,
Nature Neuroscience, 13, 664–666. Proceedings of the National Academy et al. (2003). Neural deficits in children
Milner, B., Corkin, S., & Teuber, H. (1968). of Sciences United States of America, 90, with dyslexia ameliorated by behavioral
Further analysis of the hippocampal 10413–10420. remediation: Evidence from functional
amnesic syndrome: 14-year follow-up study Ramón y Cajal, S. (1928). Degeneration MRI. Proceedings of the National
of HM. Neuropsychologia, 6, 215–234. and regeneration of the nervous system. Academy of Sciences United States of
Mishkin, M. (1982). A memory system in London: Oxford University Press. America, 100, 2860–2865.
the brain. Philosophical Transactions of Reynolds, B., & Weiss, S. (1992). Generation Thorndike, E. L. (1898). Animal intelligence:
the Royal Society of London, Biological of neurons and astrocytes from isolated An experimental study of the associative
Sciences, 298, 83–95. cells of the adult mammalian central processes in animals. Psychological Review
Mishkin, M., Suzuki, W. A., Gadian, D. G., nervous system. Science, 255, 1707–1710. Monograph Supplements, 2, 1–109.
& Vargha-Khadem, F. (1997). Hierarchical Robinson, T. E., & Kolb, B. (1997). Persistent Tulving, E. (2002). Episodic memory:
organization of cognitive memory. structural adaptations in nucleus accumbens From mind to brain. Annual Review of
Philosophical Transactions of the Royal and prefrontal cortex neurons produced by Psychology, 53, 1–25.
Society of London, Biological Sciences, prior experience with amphetamine. Journal Turner, A., & Greenough, W. T. (1985).
352, 1461–1467. of Neuroscience, 17, 8491–8498. Differential rearing effects on rat visual
Murray, E. (2000). Memory for objects in Robinson, T. E., & Kolb, B. (2004). Structural cortex synapses: I. Synaptic and neuronal
nonhuman primates. In M. S. Gazzaniga plasticity associated with drugs of abuse. density and synapses per neuron. Brain
(Ed.), The new cognitive neurosciences Neuropharmacology, 47(Suppl. 1), 33–46. Research, 329, 195–203.
(pp. 753–763). Cambridge, MA: MIT Press. Sainsbury, R. S., & Coristine, M. (1986). Walker, L. C., & Jucker, M. (2015).
Mychasiuk, R., Muhammad, A., Ilnystskyy, Affective discrimination in moderately Neurodegenerative diseases: Expanding
S., & Kolb, B. (2013). Persistent gene to severely demented patients. Canadian the prion concept. Annual Review of
expression changes in NAc, mPFC, and Journal on Aging, 5, 99–104. Neuroscience, 38, 87–103.
OFC associated with previous nicotine or Sapolsky, R. M. (1992). Stress, the aging brain, Wise, R. A. (2004). Dopamine, learning and
amphetamine exposure. Behavioural Brain and the mechanisms of neuron death. motivation. Nature Neuroscience Reviews,
Research, 256, 655–661. Cambridge, MA: MIT Press. 5, 483–494.
Mychasiuk, R., Muhammad, A., Ilnystskyy, S., Schacter, D. L. (1983). Amnesia observed: Wisniewski, T., & Goni, F. (2015).
Kovalchuk, O., & Kolb, B. (2015). Persistent Remembering and forgetting in a natural Immunotherapeutic approaches for
gene expression changes in mPFC, OFC, environment. Journal of Abnormal Alzheimer’s disease. Neuron, 85,
and hippocampus associated with adult Psychology, 92, 236–242. 1162–1176.
stress. Manuscript in submission. Sherry, D. F., Jacobs, L. F., & Gaulin, S. J. Woollett, K., & Maguire, E. A. (2011).
Nudo, R. J., Plautz, E. J., & Milliken, G. W. C. (1992). Spatial memory and adaptive Acquiring “the Knowledge” of London’s
(1997). Adaptive plasticity in primate specialization of the hippocampus. Trends layout drives structural brain changes.
motor cortex as a consequence of in Neuroscience, 15, 298–303. Current Biology, 21, 2109–2014.
behavioral experience and neuronal Sirevaag, A. M., & Greenough, W. T. (1987). Woolley, C. S., Gould, E., Frankfurt, M.,
injury. Seminars in Neuroscience, 9, 13–23. Differential rearing effects on rat visual & McEwen, B. S. (1990). Naturally
O’Keefe, J. (2006). Hippocampal cortex synapses: III. Neuronal and glial occurring fluctuation in dendritic spine
neurophysiology in the behaving animal. nuclei, boutons, dendrites, and capillaries. density on adult hippocampal pyramidal
In P. Andersen, R. Morris, D. Amaral, Brain Research, 424, 320–332. neurons. Journal of Neuroscience, 10,
T. Bliss, & J. O’Keefe (Eds.), The Sirevaag, A. M., & Greenough, W. T. (1988). 4035–4039.
Hippocampus Book (pp. 475–548). New A multivariate statistical summary of
York: Oxford University Press. synaptic plasticity measures in rats Chapter 15
O’Keefe, J., & Nadel, L. (1978). The exposed to complex, social and individual Adolphs, R., Gosselin, F., Buchanan, T. W.,
hippocampus as a spatial map. New York: environments. Brain Research, 441, Tranel, D., Schyns, P., & Damasio, A. R.
Oxford University Press. 386–392. (2005). A mechanism for impaired fear
Patihis, L., Frenda, S. J., LePort, A. K. R., Skinner, B. F. (1938). The behavior of organisms. recognition after amygdala damage.
Petersen, N., Nichols, R. M., Stark, C. New York: Appleton-Century-Crofts. Nature, 433, 68–72.
E. L., et al. (2013). False memories in Squire, L. R., Genzel, L., Wixted, J. T., Baumann, O., Borra, B. J., Bower, J. M.,
highly superior autobiographical memory & Morris, R. G. (2015). Memory Cullen, K. E., Habas, C., Ivry, R. B., et al.
individuals. Proceedings of the National consolidation. Cold Spring Harbor (2015) Consensus paper: The role of
Academy of Sciences United States of Perspectives in Biology, 7. pii: a021766. doi: the cerebellum in perceptual processes.
America, 110, 20947–20952. 10.1101/cshperspect.a021766 Cerebellum, 14, 197–220.
References R-15
Barton, R. A. (2012). Embodied cognitive Gray, J. R., & Thompson, P. M. (2004). Lieberman, M. D., Berkman, E. T., &
evolution and the cerebellum. Neurobiology of intelligence: Science and Wager, T. D. (2012). Correlations in
Philosophical Transactions of the Royal ethics. Nature Reviews Neuroscience, 5, social neuroscience aren’t voodoo.
Society B, 367, 2097–2107. 471–482. Perspectives on Psychological Science, 33,
Boria, S., Fabbri-Destro, M., Cattaneo, L., Guilford, J. P. (1967). The nature of human 1393–1406.
Sparaci, L., Sinigaglia, C., Santelli, E., intelligence. New York: McGraw-Hill. Loui, P., Li, H. C., Hohmann, A., & Schlaug,
et al. (2009). Intention understanding in Hebb, D. O. (1949). The Organization of G. (2011). Enhanced cortical connectivity
autism. PLoS ONE, 4, e5596. Behavior. New York: McGraw-Hill. in absolute pitch musicians: A model
Calvin, W. H. (1996). How brains think. New Hebb, D. O. (1980). Essay on mind. Hillsdale, for local hyperconnectivity. Journal of
York: Basic Books. NJ: Lawrence Erlbaum. Cognitive Neuroscience, 23, 1015–1026.
Carr, L., Iacoboni, M., Dubeau, M. C., Hickok, G. (2013). Do mirror neurons McClure, S. M., Li, J., Tomlin, D., Cypert,
Mazziotta, J. C., & Lenzi, G. L. (2003). subserve action understanding? K. S., Montague, L. M., & Montague,
Neural mechanisms of empathy in Neuroscience Letters, 540, 56–58. P. R. (2004). Neural correlates of
humans: A relay from neural systems for Hickok, G. (2014). The myth of motor neurons. behavioral preferences for culturally
imitation to limbic areas. Proceedings of New York: Norton. familiar drinks. Neuron, 44, 379–387.
the National Academy of Sciences United Hubbard, E. W. (2007). Neurophysiology of Mlodinow, L. (2009). The drunkard’s walk:
States of America, 100, 5497–5502. synesthesia. Current Psychiatry Reports, 9, How randomness rules our lives. New York:
Castiello, U., Paulignan, Y., & Jeannerod, M. 193–199. Vintage Books.
(1991). Temporal dissociation of motor Iacoboni, M., & Dapretto, M. (2006). Moran, J., & Desimone, R. (1985). Selective
responses and subjective awareness. Brain, The mirror neuron system and the attention gates visual processing in the
114, 2639–2655. consequences of its dysfunction. Nature extrastriate cortex. Science, 229, 782–784.
Chalmers, D. J. (1995). The conscious mind: Neuroscience Reviews, 7, 942–951. Mukerjee, M. (1996). Interview with a parrot
In search of a fundamental theory. Oxford: Ingalhalikar, M., Smith, A., Parker, D., [field note]. Scientific American, 274(4), 24.
Oxford University Press. Satterthwaite, P. D., Elliott, M. A., Newsome, W. T., Shadlen, M. N., Zohary,
Crick, F., & Koch, C. (1998). Consciousness and Ruparel, K., et al. (2013). Sex differences E., Britten, K. H., & Movshon, J. A.
neuroscience. Cerebral Cortex, 8, 97–107. in the structural connectome of the (1995). Visual motion: Linking neuronal
Csibra, G. (2007). Action mirroring and human brain. Proceedings of the National activity to psychophysical performance.
action understanding: An alternative Academy of Sciences United States of In M. Gazzaniga (Ed.), The cognitive
account. In P. Haggard, Y. Rosetti, & M. America, 111, 823–828. neurosciences (pp. 401–414). Cambridge,
Kawato (Eds). Sensorimotor foundations James, W. (1890). Principles of psychology. MA: MIT Press.
of higher cognition: Attention and New York: Henry Holt. Olulade, O. A., Jamal, N. I., Koo, D. S.,
Performance XII (pp. 453–459). Oxford: Kelly, C., Biswal, B. B., Craddock, R. C., Perfetti, C. A., LaSasso, C., & Eden, G. F.
Oxford University Press. Castellanos, F. X., & Milham, M. P. (2015). Neuroanatomical evidence in
Cytowic, R. E. (1998). The man who tasted (2012). Characterizing variation in the support of the bilingual advantage theory.
shapes. Cambridge, MA: MIT Press. functional connectome: Promise and Cerebral Cortex, Jul 16. pii: bhv152. [Epub
Diamond, M. C., Scheibel, A. B., Murphy, pitfalls. Trends in Cognitive Science, 16, ahead of print.]
G. M., Jr., & Harvey, T. (1985). On the 181–188. Pepperberg, I. M. (1990). Some cognitive
brain of a scientist: Albert Einstein. Kimura, D. (1967). Functional asymmetry of capacities of an African grey parrot
Experimental Neurology, 88, 198–204. the brain in dichotic listening. Cortex, 3, (Psittacus erithacus). In P. J. B. Slater, J. S.
Duncan, J., Seitz, R. J., Kolodny, J., Bor, D., 163–178. Rosenblatt, & C. Beer (Eds.), Advances in
Herzog, H., Ahmed, A., Newell, F. N., Kimura, D. (1973). The asymmetry of the the study of behavior (Vol. 19, pp. 357–409).
& Emslie, H. (2000). A neural basis for human brain. Scientific American, 228(3), New York: Academic Press.
general intelligence. Science, 289, 457–459. 70–78. Pepperberg, I. M. (1999). The Alex studies.
Gardner, H. (1983). Frames of mind. New Kimura, D. (1999). Sex and cognition. Cambridge, MA: Harvard University
York: Basic Books. Cambridge, MA: MIT Press. Press.
Gaulin, S. J. (1992). Evolution of sex Kolb, B., & Stewart, J. (1991). Sex-related Pepperberg, I. M. (2006). Ordinality and
differences in spatial ability. Yearbook of differences in dendritic branching of cells inferential ability of a grey parrot
Physical Anthropology, 35, 125–131. in the prefrontal cortex of rats. Journal of (Psittacus erithacus). Journal of
Gazzaniga, M. S. (1970). The bisected brain. Neuroendocrinology, 3, 95–99. Comparative Psychology, 120, 205–216.
New York: Appleton-Century-Crofts. Kranz, G. S., Hahn, A., Kaufmann, U., Ramachandran, V. S., & Oberman, L. M.
Gazzaniga, M. S. (1992). Nature’s mind. New Kublbock, M., Hummer, A., Ganger S., (2006). Broken mirrors: A theory of
York: Basic Books. et al. (2014). White matter microstructure autism. Scientific American, 295,
Gazzaniga, M. S., Ivry, R. B., & Mangun, G. R. in transsexuals and controls investigated 62–69.
(1999). Cognitive science: The biology of the by diffusion tensor imaging. Journal of Rameson, L. T., Morellis, S. A., &
mind. New York: Norton. Neuroscience, 34, 15466–15474. Lieberman, M. D. (2012). The neural
Ghanzanfar, A. A., & Schroeder, C. E. (2006). Langer, N., Pedroni, A., Gianotti, L. R., correlates of empathy: Experience,
Is neocortex essentially multisensory? Hanggi, J., Knoch D., & Jancke, L. (2009). automaticity, and prosocial behavior.
Trends in Cognitive Science, 10, 278–285. Functional brain network efficiency Journal of Cognitive Neuroscience, 24,
Goldstein, J. M., Seidman, J. L., Horton, N. J., predicts intelligence. Human Brain 235–245.
Makris, N., Kennedy, D. N., et al. (2001). Mapping, 4, 299–307. Rasmussen, T., & Milner, B. (1977). The role
Normal sexual dimorphism of the adult Lieberman, M. D. (2007). Social cognitive of early left brain injury in determining
human brain assessed by in vivo magnetic neuroscience: A review of core processes. lateralization of cerebral speech functions.
resonance imaging. Cerebral Cortex, 11, Annual Review of Psychology, 58, Annals of the New York Academy of
490–497. 259–289. Sciences, 299, 355–369.
R-16 References
Rizzolatti, G. (2007). Mirrors on the mind. Witelson, S. F., & Goldsmith, C. H. (1991). Corrigan, N. M., Richards, T. L., Treffert,
New York: Oxford University Press. The relationship of hand preference to D. A., & Dager, S. R. (2012). Toward a
Rizzolatti, G., & Craighero, L. (2004). The anatomy of the corpus callosum in men. better understanding of the savant brain.
mirror-neuron system. Annual Review of Brain Research, 545, 175–182. Comprehensive Psychiatry, 53, 706–717.
Neuroscience, 27, 169–192. Witelson, S. F., Kigar, D. L., & Harvey, T. Costa, V., Lugert, S., & Jagasia, R. (2015).
Rizzolatti, G., & Fabbri-Destro, M. (2010). (1999). The exceptional brain of Albert Role of adult hippocampal neurogenesis
Mirror neurons: From discovery to Einstein. Lancet, 353, 2149–2153. in cognition in physiology and disease:
autism. Experimental Brain Research, 200, Yeo, B. T. T., Fienen, F. M., Sepulcre, J., Pharmacological targets and biomarkers.
223–237. Sabuncu, M. R., Lashkari, D., Handbook of Experimental Pharmacology,
Sacks, O. (1989). Seeing voices. Los Angeles: Hollinshead, M., et al. (2011). The 228, 99–155.
University of California Press. organization of the human cerebral Costanzo, M. E., Chou, Y. Y., Leaman, S.,
Sala-Llonch, R., Bartres-Faz, D., & cortex estimated by intrinsic functional Pham, D. L., Keyser, D., Nathan, D. E.,
Junque, C. (2015). Reorganization connectivity. Journal of Neurophysiology, et al. (2014). Connecting combat-related mild
of brain networks in aging: A review 106, 1125–1165. traumatic brain injury with posttraumatic
of functional connectivity studies. stress disorder symptoms through brain
Frontiers in Psychology. doi: 10.3389/ Chapter 16 imaging. Neuroscience Letters, 577, 11–15.
fpsyg.2015.00663. American Psychiatric Association. (2013). deCharms, R. C. (2008). Applications of real-
Sawamoto, N., Honda, M., Okada, T., Diagnostic and Statistical Manual of time fMRI. Nature Reviews Neuroscience,
Hanakawa, T., Kanda, M., et al. (2000). Mental Disorders (5th ed.). Washington, 9, 720–729.
Expectation of pain enhances responses DC: American Psychiatric Association. Drevets, W. C., Kishore, M. G., & Krishman,
to nonpainful somatosensory stimulation Arnold, S. E., Rushinsky, D. D., & Han, L. Y. K. R. R. (2004). Neuroimaging studies of
in the anterior cingulate cortex and (1997). Further evidence of abnormal mood disorders. In D. S. Charney & E. J.
parietal operculum/posterior insula: cytoarchitecture in the entorhinal cortex Nestler (Eds.), The Neurobiology of Mental
An event-related functional magnetic in schizophrenia using spatial point Illness (2nd ed., pp. 461–490). New York:
resonance imaging study. Journal of analyses. Biological Psychiatry, 142, Oxford University Press.
Neuroscience, 20, 7438–7445. 639–647. Duman, R. S. (2004). The neurochemistry of
Sperry, R. (1968). Mental unity following Asante, E. A., Smidak, M., Grimshaw, A., depressive disorders. In D. S. Charney &
surgical disconnection of the cerebral Houghton R., Tomlinson A., Jeelani, A., E. J. Nestler (Eds.), The Neurobiology of
hemispheres. Harvey Lectures, 62, et al. (2015). A naturally occurring variant Mental Illness (2nd ed., pp. 421–439). New
293–323. of the human prion protein completely York: Oxford University Press.
Stein, B. E., & Rowland, B. A. (2011). prevents prion disease. Nature, 522(7557), Fereshtehnejad, S. M., Romenets, S. R.,
Organization and plasticity in 478–481. Anang, J. B., Latreille, V., Gagnon, J. F.,
multisensory integration: Early and late Birbaumer, N., Ruiz, S., & Sitaram, R. (2013). & Postuma, R. B. (2015). New clinical
experience affects its governing principles. Learned regulation of brain metabolism. subtypes of Parkinson disease and their
Progress in Brain Research, 191, 145–163. Trends in Cognitive Science, 17, 295–302. longitudinal progression: A prospective
Stewart, J., & Kolb, B. (1994). Dendritic Block, C., West, S., & Goldin, Y. (2015). cohort comparison with other phenotypes.
branching in cortical pyramidal cells in Misconceptions and misattributions about JAMA Neurology, 72(8), 863–873.
response to ovariectomy in adult female traumatic brain injury: An integrated Foroozani, H., Abiri, M., Salehpour, S.,
rats: Suppression by neonatal exposure to conceptual framework. PM&R, Bagherian, H., Sharifi, Z., Alaei, M. R., et
testosterone. Brain Research, 654, 149–154. S1934-1482(15)00279-8. al. (2015). Molecular characterization of
Takeuchi, H., Sugiura, M., Sassa, Y., Calne, D. B., & Mizuno, Y. (2004). The QDPR gene in Iranian families with BH4
Sekiguchi, A., Yomogida, Y., et al. (2012). neuromythology of Parkinson’s disease. deficiency: Reporting novel and recurrent
Neural correlates of the differences Parkinsonism and Related Disorders, 10, mutations. JIMD Reports, 21, 123–128.
between working memory speed and 319–322. François, C., Grau-Sánchez, J., Duarte, E.,
simple sensorimotor speed: An fMRI Charney, D. S., Nestler, E. J., & Bunney, B. S. & Rodriguez-Fornells, A. (2015). Musical
study. PLoS One, 7, e30579. (Eds.). (1999). The Neurobiology of Mental training as an alternative and effective
Vul, E., Harris, C., Winkielman, P., & Illness. New York: Oxford University method for neuro-education and neuro-
Pashler, H. (2009). Puzzlingly high Press. rehabilitation. Frontiers in Psychology, 6,
correlations in f MRI studies of emotion, Cho, R. Y., Gilbert, H., & Lewis, D. A. (2004). 475–485.
personality, and social cognition. The neurobiology of schizophrenia. In Gebicke-Haerter, P. J. (2012). Epigenetics of
Perspectives on Psychological Science, 4, D. S. Charney & F. J. Nestler (Eds.), The schizophrenia. Pharmacopsychiatry, 45,
274–290. Neurobiology of Mental Illness (2nd ed., Suppl. 1, S42–S48.
Vul, E., & Pashler, H. (2012). Voodoo and pp. 299–310). New York: Oxford University Giles J. (2004). Neuroscience: Change of
circularity errors. Neuroimage, 62, Press. mind. Nature, 430, 14.
945–948. Claes, S., Tang, Y. L., Gillespie, C. F., & Gogtay, N., Lu, A., Leow, A. D., Klunder, A. D.,
Wada, J., & Rasmussen, T. (1960). Cubells, J. F. (2012). Human genetics Lee, A. D., Chavez, A., et al. (2008). Three-
Intracarotid injection of sodium amytal of schizophrenia. Handbook of Clinical dimensional brain growth abnormalities in
for the lateralization of cerebral speech Neurology, 106, 37–52. childhood-onset schizophrenia visualized
dominance: Experimental and clinical Cleary, D. R., Ozpinar, A., Raslan, A. M., & by using tensor-based morphometry.
observations. Journal of Neurosurgery, 17, Ko, A. L. (2015). e Neurosurgical Focus, Proceedings of the National Academy of
266–282. 38, E2. Sciences U S A, 105, 15979–15984.
References R-17
Gonçalves, R., Pedrozo, A.L., Coutinho, E.S., Kumar, J., Namsechi, R., & Sim, V. L. Ostergard, T., & Miller, J. P. (2014). Deep
Figueira, I., & Ventura, P. (2012). Efficacy (2015). Structure-based peptide design to brain stimulation: New directions. Journal
of virtual reality exposure therapy in the modulate amyloid beta aggregation and of Neurosurgical Science, 58, 191–198.
treatment of PTSD: A systematic review. reduce cytotoxicity. PLoS One, 12;10(6). Pannese, R., Minichino, A., Pignatelli, M.,
PLoS One, 7(12), e48469. Kuo, H.-K., Jones, R. N., Milberg, W. P., Delle Chiaie, R., Biondi, M., & Nicoletti, F.
Gross, C., & Hen, R. (2004). The Tennstedt, S., Talbot, L., et al. (2005). Effect (2012). Evidences on the key role of the
developmental origins of anxiety. Nature of blood pressure and diabetes mellitus metabotropic glutamatergic receptors
Reviews Neuroscience, 5, 545–552. on cognitive and physical functions in in the pathogenesis of schizophrenia:
Gubbi, J., Kusmakar, S., Rao, A., Yan, B., older adults: A longitudinal analysis of the A “breakthrough” in pharmacological
O’Brien, T., & Palaniswami, M. (2015). advanced cognitive training for independent treatment. Reviews in Psychiatry, 47, 149–169.
Automatic detection and classification and vital elderly cohort. Journal of the Politis, M., & Lindvall, O. (2012). Clinical
of convulsive psychogenic non-epileptic American Geriatrics Society, 53, 1154–1161. application of stem cell therapy in
seizures using a wearable device. IEEE Kwakkel, G., Veerbeek, J. M., van Wegen, Parkinson’s disease. BMC Medicine, 10, 1.
Journal of Biomedical and Health E. E., & Wolf, S. L. (2015). Constraint- Rao, J., Chiappelli, J., Kochunov, P., Regenold,
Information. [Epub ahead of print.] induced movement therapy after stroke. W. T., Rapoport, S. I., & Hong, L. E. (2015).
Heinz, A., Kipke, R., Heimann, H., Lancet Neurology, 14, 224–234. Is schizophrenia a neurodegenerative
& Wiesing, U. (2012). Cognitive Laver, K. E., George, S., Thomas, S., Deutsch, disease? Evidence from age-related decline
neuroenhancement: False assumptions J. E., & Crotty, M. (2015). Virtual reality for of brain-derived neurotrophic factor
in the ethical debate. Journal of Medical stroke rehabilitation. Cochrane Database in the brains of schizophrenia patients
Ethics, 38, 372–375. Systems Review, Sep 7;(9):CD008349. and matched nonpsychiatric controls.
Heninger, G. R. (1999). Special challenges in Leritz, E. C., Salat, D. H., Williams, V. J., Neurodegenerative Diseases, 15, 38–44.
the investigation of the neurobiology of Schnyer, D. M., Rudolph, J. L., et al. Rapoport, J. L., Giedd, J. N., & Gogtay, N.
mental illness. In D. S. Charney, E. J. (2011). Thickness of the human cerebral (2012). Neurodevelopmental model of
Nestler, & B. S. Bunney (Eds.), The cortex is associated with metrics of schizophrenia: Update 2012. Molecular
Neurobiology of Mental Illness (pp. 89–98). cerebrovascular health in a normative Psychiatry, 17, 1228–1238.
New York: Oxford University Press. sample of community dwelling older Reis, C., Wang, Y., Akyol, O., Ho, W. M.,
Holmstrom, L. L., & Burgess, A. W. The adults. Neuroimage, 54, 2659–2671. Ii, R. A., Stier, G., et al. (2015). What’s
victim of rape: Institutional reactions. Malberg, J. E., Eisch, A. J., Nestler, E. J., new in traumatic brain injury: Update
Wiley-Interscience, 1978. & Duman, R. S. (2000). Chronic on tracking, monitoring and treatment.
Jorge, R. E. (2015). Posttraumatic stress antidepressant treatment increases International Journal of Molecular Science,
disorder. Behavioral Neurology and neurogenesis in adult rat hippocampus. 16, 11903–11965.
Neuropsychiatry, 21, 789–805. Journal of Neuroscience, 20, 9104–9110. Rizzo, A., Buckwalter, J. G., John, B.,
Kaufer, D. I., & DeKosky, S. T. (1999). Martin, J. P. (1967). The basal ganglia and Newman, B., Parsons, T., Kenny, P.,
Diagnostic classifications: Relationship posture. London: Ritman Medical. et al. (2012). STRIVE: Stress Resilience in
to the neurobiology of dementia. In D. S. Mateer, C. A., & Sira, C. S. (2006). Cognitive Virtual Environments: A pre-deployment
Charney, E. J. Nestler, & B. S. Bunney and emotional consequences of TBI: VR system for training emotional coping
(Eds.), The Neurobiology of Mental Illness Intervention strategies for vocational skills and assessing chronic and acute
(p. 642). New York: Oxford University Press. rehabilitation. NeuroRehabilitation, 21, stress responses. Studies in Health and
Khachaturian, Z. S., & Khachaturian, 315–326. Technology Information, 173, 379–385.
A. S. (2015, June 5). Politics of science: McGowan, P. O., & Szyf, M. (2010). Rose, S. C., Weber, K. D., Collen, J. B., &
Progress toward prevention of the Environmental epigenomics: Heyer, G. L. (2015). The diagnosis and
dementia-Alzheimer’s syndrome (review). Understanding the effects of parental care management of concussion in children
Molecular Aspects of Medicine, 43-44, 3-15. on the epigenome. Essays in Biochemistry, and adolescents. Pediatric Neurology, 53,
Knight, E. J., Testini, P., Min, H. K., Gibson, 48, 275–287. 108–118.
W. S., Gorny, K. R., Favazza, C. P., et al. Miller, B. L., Boone, K., Cummings, J. L., Sacks, O. (1998). The man who mistook his
(2015). Motor and nonmotor circuitry Read, S. L., & Mishkin, F. (2000). wife for a hat: And other clinical tales.
activation induced by subthalamic Functional correlates of musical and New York: Touchstone.
nucleus deep brain stimulation in patients visual ability in frontotemporal dementia. Santarelli, L., Saxe, M., Gross, C., Surget, A.,
with Parkinson disease: Intraoperative British Journal of Psychiatry, 176, 458–463. Battaglia, F., et al. (2003). Requirement
functional magnetic resonance imaging National Institute of Mental Health Web of hippocampal neurogenesis for the
for deep brain stimulation. Mayo Clinic site: http://www.nimh.nih.gov/health/ behavioral effects of antidepressants.
Proceedings, 90, 773–785. publications/the-numbers-count-mental- Science, 301, 805–809.
Kong, L., Herold, C., Stieltjes, B., Essig, M., disorders-in-america/index.shtml Savitz, S. I. (2015). Developing cellular
Seidl, U., et al. (2012). Reduced gray to Nevler, N., Ash, E.L. (2015). TMS as a tool for therapies for stroke. Stroke, 46, 2026–2031.
white matter tissue intensity contrast in examining cognitive processing. Current Serafini, G., Pompili, M., Belvederi, M. M.,
schizophrenia. PLoS One, 7, e37016. Neurological and Neuroscience Reports, Respino, M., Ghio, L., Girardi, P.,
Kornek, B. (2015). An update on the use of 15, 575. et al. (2015). The effects of repetitive
natalizumab in the treatment of multiple Olanow, C. W., & Brundin, P. (2013). transcranial magnetic stimulation on
sclerosis: Appropriate patient selection Parkinson’s disease and alpha synuclein: Is cognitive performance in treatment-
and special considerations. Patient Parkinson’s disease a prion-like disorder? resistant depression. A systematic review.
Preference and Adherence, 9, 675–684. Movement Disorders, 28, 31–40. Neuropsychobiology, 71, 125–139.
R-18 References
Shi, Q., Chen, L. N., Zhang, B. Y., Xiao, Sohlberg, M. M., & Mateer, C. (1989). Wang, J., Zhao, X., & He, M. (2012). Is BDNF
K., Zhou, W., Chen, C., et al. (2015). Introduction to Cognitive Rehabilitation. a biological link between depression
Proteomics analyses for the global New York: Guilford. and type 2 diabetes mellitus? Medical
proteins in the brain tissues of different Sundström, P., & Salzer, J. (2015). Vitamin Hypotheses, 79, 255–258.
human prion diseases. Molecular Cell D and multiple sclerosis: From Wassermann, E. M., & Zimmermann, T.
Proteomics, 14, 854–869. epidemiology to prevention. Acta (2012). Transcranial magnetic brain
Shin, J. H., Bog, G., Park, S., Ho, G., & Jang, S. Neurology Scandanavia Supplement, 132, stimulation: Therapeutic promises
(2015). Effects of game-based virtual 56–61. and scientific gaps. Pharmacology and
reality on health-related quality of life in Tsivgoulis, G., Faissner, S., Voumvourakis, Therapeutics, 133(1), 9.
chronic stroke patients: A randomized, K., Katsanos, A. H., Triantafyllou, N., Wingenfeld, K., & Wolf, O. T. (2014).
controlled study. Computational Grigoriadis, N., et al. (2015). “Liberation Stress, memory, and the hippocampus.
Biological Medicine, 63, 92–98. treatment” for chronic cerebrospinal Frontiers in Neurological Neuroscience.
Shorter, K. R., & Miller, B. H. ( 2015). Epigenetic venous insufficiency in multiple 34, 109–120.
mechanisms in schizophrenia. Progress in sclerosis: The truth will set you free.
Biophysics and Molecular Biology, 118, 1–7. Brain and Behavior, 5, 3–12.
Na me Inde x
Aagaard, L., 172 Battaglia, F., 596 Bramlett, M. D., 255 Chang, E., 386 Czeisler, C. A., 455
Abel, T., 467 Batterink, L. J., 469 Braun, K., 266 Chang, Fen-Lei, 505 Czoli, C. D., 193
Abiri, M., 565 Baudry, M., 206 Brauner, M., 131 Changeux, Jean-Pierre, 257
Ackerly, Stafford, 420 Bauman, O., 34, 536 Breeslin, P., 405 Chapmans, P., 223 Dager, S. R., 598
Adelmann, Pamela, 424 Beatty, J., 421 Bregman, Albert, Charcot, Jean-Martin, 134, 140 D’Alessio, A. C., 206
Adinoff, B., 198 Becker, J. B., 178, 179, 194, 435 Bremner, J. D., 258 Charney, E., 98, 104 D’Almeida, V., 467
Adolphs, Ralph, 530 Becquet, D., 443 Brewer, J. A., 425 Charvet, C. J., 26 Daly, Martin, 407
Aeschbach, D., 296, 451, 455 Beery, Alexis, 74, 96 Brewer, J. M., 452 Chau, S. A., 160 Damanakis, E., 86
Aflalo, T. N., 367, 368 Beery, Joe, 74 Brick, T. R., 476 Chaudhary, V., 108 Damasio, A. R., 227, 421,
Aftab, M., 236 Beery, Noah, 74, 96 Bricker, S., 198 Cheetham, A., 199 422, 490
Agate, Robert, 275 Beery, Retta, 74 Brinkman, C., 359 Chen, C., 591 Damasio, H., 227
Ago, Y., 102 Beggs, A. H., 277 Brito, N. H., 246 Chen, J. L., 75 Danchin, A., 257
Aiello, L. C., 25 Bekmuradov, D., 183 Britten, K. H., 522 Chen, L. N., 591 Daniel, E., 326
Akyol, O., 579 Belleville, R. E., 177, 178 Broca, Paul, 211, 217, 342, Chen, Y., 83 Dannemann, M., 22
Alaei, M. R., 565 Belliveau, J. W., 230 416, 417, 539 Cherubini, E., 130 Daou, A., 76
Albanese, Y., 472 Belliveau, R. A., 277 Brodmann, Korbinian, 56, Chesler, D. A., 230 Darlington, R. B., 26
Alborn, A. M., 503 Bello, L., 268 211, 390 Chiapelli, J., 570 Daroff, R. B., 467
Albrecht, J., 405 Belvederi, M. M., 573 Bronstone, A., 513 Chiesa, R., 472 Darwin, Charles, 8, 9, 10, 11, 13,
Aldridge, J. W., 362 Benchenane, K., 468 Brouwer, R. M., 246 Cho, R. Y., 593 27, 257, 350, 410
Alessandria, M., 386 Bender, K. J., 128 Brown, A. R., 219 Chomsky, Noam, 341 Davarpanah Jazi, S., 358
Allegri, F., 199 Bendix, C., 444 Brundin, P., 161 Chou, Y. Y., 562 Davidson, A. C., 404
Altenmuller, E., 507 Berens, A. E., 272 Brunetti, M., 434 Chrétien, Jean, 63 Davis, K. L., 594
Alzheimer, Alois, 492 Berger, Hans, 210, 223 Buchanan, T. W., 530 Christine, J., 26 Davis, M., 422, 498
Amaral, D. G., 488 Berglund, L., 448 Buckwalter, J. G., 562 Chung, W. H., 389 Day, B. L., 382
Amariei, C., 444 Berman, M. G., 394 Bucy, Paul, 422, 423 Church, J. A., 374 Day, J. J., 408, 509
Ames, Elenor, 272 Bermudez, P., 347 Bueller, Joshua, 236 Churchill, S. E., 21 Daynes, Elisabeth, 22
Anang, J. B., 567 Bernhardt, J., 45 Bumrungsri, S., 351 Ciocchi, S., 221 de Jager, C. A., 185
Anda, Robert, 258 Bernstein, Julius, 111 Bundlie, S. R., 475 Claes, S., 593 de la Tourette, Gilles, 374
Andermann, M. L., 75 Berretin-Felix, G., 474 Bunney, B. G., 278 Clancy, B., 26 de Lavilléon, G., 468
Angadi, V., 469 Berridge, Kent, 194, 437, 438 Bunney, William, 278 Clark, Graeme, 338 de Mairan, Jean Jacques
Antle, M. C., 219, 450, 451 Berry, Chuck, 140 Buonocore, M. H., 255 Clarke, G., 186 d’Ortous, 444
Antón, S. C., 25 Berthold, A. A., 200, 203 Burdakov, D., 131 Clarke, R. S., 270 De Oliviera, G. S., Jr., 347
Appireddy, R. M. R., 45 Bertram, R., 76 Burgess, Ann, 562 Clasen, L., 259, 260 de Ruiter, D. J., 21
Argyropoulos, S., 467 Bertrand, J. A., 467 Burghy, C. A., 28 Clauss, J. A., 206 De Vries, G. J., 432, 435
Aristotle, 7 Bewernick, B. H., 219 Burke, Chris, 101 Claustrat, B., 454 Debanne, D., 130
Arnold, A. P., 350 Bhalla, D., 108 Burmeister, M., 236 Cleary, D. R., 572 deCharms, R. C., 576
Arnold, S. E., 593 Binkley, S., 446 Busch, V., 386 Coenen, V. A., 219 Deisseroth, K., 131
Arnott, S. R., 336 Biondo, M., 594 Buss, David, 407 Cohen, D., 406 DeKosky, Steven, 585
Arora, V., 393 Birbaumer, N., 576 Butler, Robert, 400 Cohen, M., 407 Del Gratta, C., 434
Asante, E. A., 591 Birkle, D. L., 271 Butte, P. V., 83 Cole, A. G., 193 Delle Chiaie, R., 594
Asanuma, Hiroshi, 391 Birklein, F., 386 Büttner, A., 198 Cole, Jonathan, 382 Demchuk, A. M., 45
Asarnow, J. R., 186 Birkmayer, W., 152 Byers-Heinlein, K., 210 Collen, K. D., 578 Dement, W. C., 458, 459, 461,
Aschoff, Jurgen, 445 Birn, R. M., 28 Bygren, L. O., 105 Collop, N. A., 448 465, 474, 475
Aserinsky, Eugene, 458 Biswal, B. B., 535 Bygren, Lars Olov, 105 Comeau, W., 276 Dere, E., 142
Ash, E. L., 573 Bittman, E. L., 452 Byne, W., 594 Comer, R. J., 185 Descartes, René, 7, 8, 46,
Asperger, Hans, 255 Bjork-Eriksson, T., 503 Byron, Don, 326 Constable, R. T., 425 108, 476
Auburtin, Ernest, 211 Bjorklund, A., 161 Cook, E. P., 146 Desimone, Robert, 529
Auger, A. P., 432, 435 Blaise deB., Frederick, 439 Cacucci, F., 223 Cooper, B. Y., 392 Desjardins, C., 467
Blakemore, Sarah, 392 Cahill, L., 499 Cooper, M., 403 Destrieux, C., 206
Babiloni, C., 434 Blasca, W. Q., 474 Cai, H., 221 Cooper-Kazaz, R., 190 Dethier, Vincent, 409
Babinsky, R., 499 Bleich, S., 424 Cain, Donald, 455 Coristine, Marjorie, 499 Deutsch, G. K., 480
Bachevalier, Jocelyne, 264, 274 Blick, K. A., 462 Cain, S. W., 451 Corkin, Suzanne, 392, 488, 489 Deutsch, J. E., 581
Badiani, A., 180 Bliss, Timothy, 500 Calne, Donald, 589, 590 Cormack, Allan, 226 Di Forti, M., 199
Bagherian, H., 565 Block, C., 580 Calvin, William, 522 Corrêa Cde, C., 474 Dickinson-Anson, H., 487
Bailey, C. H., 163, 166 Blumberg, M. S., 461 Campbell, Jeeves, 15 Corrigan, N. M., 598 DiMaggio, E. J., 21
Balaban, E., 102 Blumberg, S. J., 255 Campbell, Joan, 15 Cortelli, P., 386 Dinges, D. F., 452
Balance, H. I., 444 Bobbo, D., 469 Campbell, Matthew, 15 Cortese, S., 363 Dinse, H. R., 507
Bale, T. L., 432, 435 Bock, J., 266 Campisano, C. J., 21 Coslett, H. B., 287 Dirks, P. H., 21
Bálint, R., 316 Bodner, M., 495 Candia, Victor, 507 Costa, V., 596 Dissel, S., 469
Ballard, A., 161 Boehner, John, 2 Cannon, J. L., 202 Costanzo, M. E., 562 Dobyns, W. B., 277
Ballestar, E., 237 Boesveldt, S., 405 Cannon, M., 236 Cote, S., 515 Doepp, F., 126
Ballestar, M. L., 237 Bog, G., 576 Cantle, J. P., 100 Cottier, J. P., 206 Domhoff, G. W., 462
Banich, M. T., 394 Boldrey, E., 366 Cao, Y., 198 Cowan, R. L., 198 Donlea, J., 469
Bano, S., 108 Bolte, E., 275 Cao, Z. F., 131 Cowan, W. M., 250 Dosenbach, N. U., 374
Bao, A. M., 435 Bongard, F., 198 Cardinale, C. J., 452 Craddock, R. C., 535 Dostrovsky, J., 222
Barantin, L., 206 Boone, K., 598 Carey, J., 389 Craighero, L., 531 Dowling, J., 83
Barbeau, A., 152 Boonman, A., 351 Carter, K. A., 464 Crick, Francis, 556 Drake-Lee, A. B., 325
Barchha, N., 186 Bor, D., 553 Casano, A. M., 85 Critchley, M., 394 Drazin, D., 83
Barclay, J. L., 450 Bordyugov, G., 447 Caspi, A., 236 Crits-Christoph, P., 186 Dressler, M., 476
Barkovich, A. J., 277 Born, J., 467 Castellanos, F. X., 363, 535 Crombag, H. S., 180 Drevets, W. C., 596
Barnard, J., 404 Borra, R. J., 34, 536 Castiello, U., 557 Crotty, M., 581 Drnevich, J., 349
Baron, J., 126 Bosch, M., 167 Castro, J. B., 403 Crotty, P., 125 Droiuse, E. M., 271
Barth, A. M., 100 Bosler, O., 443 Caton, Richard, 111 Crutcher, M. D., 375 Drucker, D. J., 450
Barth, C., 200 Boswell, (Patient), 489, 490 Cermakian, N., 448 Csibra, G., 531 Druet-Cabanac, M., 108
Bartholow, Roberts, 109, 111 Bouhours, M., 131 Chaichana, K. L., 232 Cubells, J. F., 593 Drury, S. S., 272
Barton, R. A., 52, 536 Bourgeois, J. P., 257 Chalfie, Martin, 75 Cuello, A. C., 515 Duarte, E., 576
Bartoshuk, Linda, 404 Bourgin, J., 206 Chalmers, David, 557 Cullen, K. E., 34, 536 Duerson, Dave, 578
Bartres-Faz, D., 534 Bower, J. M., 34, 536 Chand, P., 393 Cummings, J. L., 598 Duffy, J. F., 455
Bartsch, H., 246 Boyle, J. A., 404 Chang, A. M., 455 Cutlan, R., 299 Duffy, Valerie, 404
Bastian, A. J., 378 Bradley, P., 270 Chang, D. W., 457 Cytowic, Richard, 551 Duman, R. S., 596
N-1
N-2 Name Index
Dunbar, Robin, 25 Franklin, Benjamin, 456 Goldstein, Jill, 273, 546, 547 Hasvold, I., 198 Imani, S., 365
Duncan, J., 553 Fraser, H. F., 177, 178 Golgi, Camillo, 75, 76 Hathaway, N. E., 464 Ingalhalikar, M., 548, 549
Duncan, J. S., 108 Frederick, B. deB., 438 Gombart, A. F., 185 Haubensak, W., 221 Insel, T., 413
Dunn, G. A., 432, 435 Frei, B., 185 Gomez-Hassan, D., 236 Haueter, S., 387 Isacsson, G., 186
Durell, T. M., 186 Freud, Sigmund, 57, 172, 189, Gonçalves, R., 562 Havekes, R., 467 Isbell, H., 177, 178
Durston, S., 246 432, 462, 563, 564, 575 Goni, F., 492 Hawking, Stephen, 134 Ivry, R. B., 520
Dylan, Bob, 100 Frieling, H., 424 Gonzalez, C., 270, 517 Haxby, J. V., 486
Dymoy, S., 206 Friend, D. M., 375 Gonzalez, Claudia, 220 Hayashi, Y., 167 Jacob, S., 403
Frith, C. D., 392, 557 Gonzalez, R. G., 488 Hayes, J. E., 404 Jacobs, B., 508
Earnest, M., 299 Fritsch, Gustav, 109, 366 Goodale, M. A., 336 He, M., 595 Jacobs, L. F., 493, 494
Eccles, John C., 127, 128 Fritz, J., 333 Goodale, Mel, 297, 313, 316, 317 Heath, M., 358 Jacobsen, Carlyle, 423
Eddy, C. M., 100 Frost, D., 258, 276 Goodkin, H. P., 377 Hebb, Donald O., 11, 163, 266, Jacobson, Edmond, 5
Eden, G. F., 555 Fuchs, E., 510 Gordon, A. D., 21 267, 270, 276, 400, 401, 504, Jagannath, A., 451
Edey, M., 21 Fuchs, S., 468 Gordon, G. R., 84 522, 524, 525, 555 Jagasia, R., 596
Edgerton, Robert, 192 Fuhrmann, R., 300 Gorny, G., 505 Heberlein, A., 196 Jain, S., 221
Eesa, M., 45 Fujikawa, H., 251 Gorny, K. R., 572 Heckman, James, 246, 267 Jamal, N. I., 555
Egan, J., 299 Fung, Teresa, 428 Gorski, Roger, 432 Heimann, H., 598 James, William, 528
Ehrhardt, Anke, 432 Fuster, Joaquin, 495 Gosselin, F., 530 Heinz, A., 598 Jancke, L., 555
Ehringer, H., 140 Gould, E., 434, 509 Held, R., 289 Janes, Amy, 438, 439
Eibl-Eibesfeldt, Irenäus, 5 Gabrieli, J. D. E., 480 Gould, Elizabeth, 503, 510 Hellman, R. B., 386 Jang, S., 576
Eichenbaum, H., 497 Gadian, W. A., 495, 498 Gould, Stephen Jay, 27 Helms Tillery, S. I., 386 Jankovic, J., 460
Einstein, Albert, 29, 553 Gage, F. H., 504 Goyal, M., 45 Hen, R., 185 Jasper, H. H., 223
Eisenman, A. J., 177, 178 Gagnon, J. F., 467, 567 Grau-Sánchez, J., 576 Heninger, G. R., 566 Jeannerod, M., 557
Ekselius, L., 448 Gaini, S. M., 268 Gray, J. R., 553 Henkin, Y., 428 Jeannerod, Marc, 557
Elbert, T., 507 Galaburda, Albert, 253, 480 Gray, Stephen, 109 Herculano-Houzel, S., 23, 24, Jegen, M., 387
Ellington, Duke, 552 Galvani, Luigi, 109 Graziano, M. S. A., 367, 368 25, 76, 82 Jenner, Bruce, 435
Elliott, A. S., 466 Gangwisch, J. E., 455 Greary, C., 251 Herold, C., 593 Jenner, Caitlyn, 435
Elliott, M. A., 548, 549 Gao, F., 100 Greely, H., 172 Heron, W., 270 Jensen, P., 101, 105
Emslie, G., 186 Garcia, John, 409 Greenberg, D., 407 Heron, Woodburn, 5, 400 Jerison, Harry, 22, 23, 303
Enswere, E., 251 Gardner, Alan, 9 Greenberg, R., 406 Herringa, R. J., 28 Jin, C., 80
Epel, D., 36 Gardner, Beatrice, 9 Greenfield, P. M., 9 Herrmann, N., 160 Jinnah, Z., 21
Epstein, Herman, 264 Gardner, Howard, 29, 553, Greenough, W. T., 504, 505 Hertz, Heinrich Rudolph, 323 Joers, J. M., 198
Eriksson, P. S., 503 554, 555 Greenstein, D. K., 259, 260 Herzel, H., 447 Johanson, D., 21
Essig, M., 593 Gardner, Randy, 466 Gregg, C., 251 Herzog, H., 553 John, B., 562
Ettinger, M., 475 Garga, U. C., 108 Greiner, E. R., 100 Hess, Walter, 361, 362 John, G. R., 86
Evans, A. C., 246, 345, 347 Garraghty, P. E., 393 Griffin, J. A., 192 Hevner, R. F., 299 Johnson, F., 76
Evarts, Edward, 368 Garrison, K. A., 425 Griffiths, T. D., 347 Heyer, J. B., 578 Johnson, K. A., 488
Evenden, J. L., 179 Gaulin, S. J., 493, 494, 549 Grigoriadis, N., 584 Hickok, Gregory, 531 Johnsson, M., 101
Everitt, Barry, 195, 434 Gavin, C. F., 509 Grimshaw, A., 591 Highfield, R. R., 29 Johnston, C., 185
Gazarini, M. L., 467 Grisham, W., 275 Hill, A. S., 185 Jolley, J., 261
Fair, D. A., 374 Gazzaniga, Michael, 172, 520, Grogerr, N., 266 Hillemacher, T., 196 Jones, Barbara, 471
Faissner, S., 584 545, 558 Gross, C., 596 Hinshelwood, James, 480 Jones, J. R., 255
Falk, Dean, 26 Gebicke-Haerter, P. J., 593 Gross, C. G., 7 Hirsch, J., 341 Jones, L., 594
Falon, J. H., 487 Gehrig, Lou, 134 Gu, X., 100 Hisatsune, A., 475 Jones, R. N., 591
Farmer, Stacey, 439 Geissmann, Thomas, 322 Gubbi, J., 582 Hitzig, Eduard, 109, 366 Jones-Gotman, M., 404
Favazza, C. P., 572 Genzel, L., 497 Guerrero-Bosagna, C., 105 Ho, G., 576 Jorgani, M., 365
Felitti, V. J., 258 George, S., 581 Guerrini, R., 277 Ho, W. M., 579 Jorge, R. E., 562
Fenno, L., 131 Gérard, François, 7 Guilford, J. P., 554, 555 Hobson, J. Allan, 446, 462, 463, Jouvet, Michel, 472, 475
Fereshtehnejad, S. M., 567 Gerhart-Hines, Z., 447 Guo, Z., 83 476, 477 Jucker, M., 492
Fernald, R. D., 413 Gerkema, M. P., 456 Gustavii, B., 161 Hodes, G. E., 203 Jung, Carl, 462
Ferraro, L., 199 Gerkin, R. C., 403 Guthrie, D., 272 Hodgkin, Alan, 112, 113, 114 Junque, C., 534
Ferretti, A., 434 Gershon, E. S., 278 Guthrie, Marjorie, 100 Hodler, Ferdinand, 463 Juraska, J. M., 274
Fetherstonhaugh, M. L., 270 Gervain, J., 210 Guthrie, Woody, 100 Hogenesch, J. B., 444
Feynman, Richard, 552 Geschwind, Norman, 315, 480 Hohmann, A., 535 Kaas, J. H., 24, 25, 76, 82, 390,
Field, M., 407 Ghanzanfar, A. A., 527 Habas, C., 34, 536 Holmstrom, Lynda, 562 393, 394, 506
Field, Tiffany, 406 Gharbawie, O., 220, 390, 506 Halder, P., 393 Honasage, A., 509 Kaati, G., 105
Fienen, F. M., 534 Ghio, L., 573 Hall, Calvin, 462 Honda, T., 378 Kalueff, A. V., 362
Filbey, F. M., 198 Gianotti, L. R., 555 Hall, Stuart, 460 Hong, L. E., 570 Kambi, N., 393
Filevich, E., 476 Gibb, Robbin, 258, 266, 270, Hallett, M., 374 Horn, Gabriel, 270 Kan, Eric, 246, 261
Fine, A., 502 276, 505, 511 Halliwell, C., 276 Hornykiewicz, O., 140, 152 Kandel, Eric, 163, 164, 166
Finegold, S. M., 275 Gibson, W. S., 572 Hamilton, Roy, 287 Horovitz, S. G., 374 Kang, J. L., 452
Fink, Bob, 322 Giedd, J. N., 275, 570 Hamilton, T., 80 Horton, N. J., 273, 546, 547 Kang, Q., 456
Fins, J. J., 13 Giedde, A., 345, 347 Hammond, D., 193 Houghton, R, 591 Kanner, Leo, 255
Fiorito, Graziano, 49 Giffords, Gabrielle, 2 Hampshire, A., 29 Hounsfield, Godfrey, 226 Katano, K., 378
Fisch, A. J., 596 Gilbert, H., 593 Hampson, Elizabeth, 203, 509 Houston, S. M., 246 Katsanos, A. H., 584
Flagel, S. B., 196 Gilbert, S. F., 36 Han, J. Y., 183 Houston, Whitney, 182 Katz, Bernard, 144
Flechsig, Paul, 259, 260 Giles, Jim, 597 Han, L. Y., 593 Howlett, A. C., 153 Kaufer, Daniel, 585
Flugge, G., 510 Gill, J. M., 102 Hanggi, J., 555 Hsiao, Elaine, 275 Kaufman, M. H., 438
Flynn, J. R., 29 Gillespie, C. F., 593 Hankins, M. W., 451 Hsien, S., 275 Kaufman, M. J., 498
Fong, G. T., 191 Gillespie-Lynch, K., 9 Hankinson, S. E., 428 Hu, B., 219 Kavakli, I. H., 452
Fonseca-Azevedo, Karina, Gillis, T. E., 498 Hansen, E.H., 172 Hu, M., 194, 435 Kawai, Y., 100
23, 25 Giorgi, E. E., 102 Hansen, Rick, 365 Huber, J. D., 466 Kayser, S., 219
Forgays, D. G., 270 Girardet, C., 443 Hanus, R., 153 Hublet, C., 347 Keating, J. G., 377
Forloni, G., 472 Giussani, Carlo, 268 Hardee, J. E., 192 Hughes, M. E., 444 Keck, T., 75
Foroozani, H., 565 Gleason, M. M., 272 Harker, A., 266 Hughes, S., 451 Kelley, D. D., 459
Foster, F., 387 Glendinning, D. S., 392 Harkness, D. L., 392 Hull, J. T., 296, 451 Kelly, C., 535
Foster, R. G., 451 Glenmullen, J., 161 Harlow, Harry, 271, 400 Huttenlocher, Peter, 257 Kelly, Mark, 2
Foulkes, D., 462 Glickman, Steve, 399 Harmon, F. G., 444 Huxley, Andrew, 112, 113, 114 Kelso, J., 22
Fox, Michael J., 140, 587 Godet, B., 108 Harouthunian, V., 594 Hyde, E. R., 275 Kemegether, E., 594
Fox, N. A., 272 Goebel, J. A., 389 Harris, J., 172 Hyde, K. L., 347 Kempermann, Gerd, 504
Fraga, Mario, 237 Goel, N., 452 Harris, K. M., 163, 166 Hyman, B. T., 488 Kennedy, A. J., 509
Fraioli, Sabina, 180 Gogtay, N., 260, 570 Harvey, T., 553 Hyson, R. L., 76 Kennedy, D. N., 273, 546, 547
Franc, J. L., 443 Goldberg, I. E., 230 Hashimoto, Y., 378 Kennedy, Edward, 83
François, C., 576 Goldin, Y., 580 Hassam, R., 251 Ii, R. A., 579 Kenny, P., 562
François-Bellan, A. M., 443 Goldman-Rakic, P. S., 333 Hasson, U. Y., 300 Iliadis, C., 26 Kern, U., 386
Frankfurt, M., 434, 509 Goldsmith, Charlie, 551 Hastings, N. B., 503 Ilnytskyy, S., 251, 275, 511 Kerr, D. C., 185
Name Index N-3
Keshavan, M., 275 Lahens, N. F., 444 Lubrano, V., 268 Merla, A., 434 Nevler, N., 573
Kessler, R. C., 172 Lajud, N., 206 Lucca, U., 472 Merzenich, Michael, 480, 513 Newman, B., 562
Keyser, D., 562 Laland, K. N., 29 Luciana, M., 257 Mesoudi, Alex, 29 Newsome, William, 522
Khachaturian, A., 584 Lalonde, F. M., 486 Lugert, S., 596 Metz, J., 403 Nguyen, B. M, 198
Khachaturian, Z. S., 584 Lamb, Mary, 455 Lukas, Scott E., 439 Meyer, E., 345, 347 Nichols, T. E., 192
Kidd, J. R., 404 Lamberg, L., 458 Lumer, E., 557 Middelkoop, G., 198 Nickerson, Lisa D., 438, 439
Kidd, K. K., 404 Lan, K. C., 457 Lundstrom, Johan, 404 Mihic, A., 183 Nicolette, F., 594
Kigar, D., 553 Lanctôt, K. L., 160 Lungato, L., 467 Milberg, William, 591 Nir, I., 300
Kim, D., 198 Landgraf, D., 450 Lv, J., 102 Milham, M. P., 535 Nir, Y., 461
Kim, K. H. S., 341 Landré, L., 206 Lyn, H., 9 Miller, B. H., 593 Noble, Kimberly, 246
Kim, N., 517 Lang, A., 276 Miller, B. L., 598 Nobunaga, M., 475
Kim, S. J., 452 Lang, C. E., 361 Ma, W., 456 Miller, Courtney, 509 Nonneman, Arthur, 406
Kimbel, W. H., 21 Lange, S., 183 Maass, W., 131 Miller, D. B., 466 Nordahl, C. W., 255
Kimura, Doreen, 203, 509, 541, Langer, N., 555 MacAndrew, Craig, 192 Miller, J. P., 583 Nordborg, C., 503
546, 547, 548, 549 Langhorne, P., 45 MacDonald, G., 191 Miller, S. L., 480 Nottebohm, Fernando, 350
Kinney, Hannah, 277 Langston, J. William, 161 MacDonald, T. K., 191 Milliken, G. W., 369, 505 Nudo, Randy, 369, 370, 505
Kinnunen, L. H., 403 LaPorte, J. L., 362 MacDougall, M., 502 Milner, B., 392 Nugent, B. M., 203
Kipke, R., 598 LaSasso, C., 555 Mackler, Scott, 356, 363 Milner, Brenda, 218, 268, 488, Nyagu, A. I., 271
Kircanski, I., 160 Lashkari, D., 534 Mädler, B., 219 489, 550
Kirszenblat, L., 469 Lashley, Karl, 218, 359, 488, 489 Magee, J. C., 146 Milner, David, 297, 313, 316, 317 O’Hare, E. D., 258
Kishore, M. G., 596 Latreille, V., 467, 567 Magnusson, M., 389 Milner, Peter, 437 O’Keefe, John, 222, 223,
Klein, Denise, 268 Laureys, S., 468 Magoun, Horace, 470 Milton, Katharine, 25 492, 494
Kleitman, Nathaniel, 458, 461 465 Laver, K. E., 581 Maguire, Eleanor, 503, 504 Mimori, T., 100 Oberman, L. M., 531
Klinger, Eric, 464 Lazar, M. A., 447 Mahncke, H. W., 513 Min, H. K., 572 Obeso, J. A., 382
Klunder, A. D., 570 Leakey, Mary and Louis, 21 Mahowald, M. W., 475 Min, M. O., 276 O’Brien, T., 582
Klüver, Heinrich, 422, 423 Leaman, S., 562 Mahurkar, A., 203 Minichino, A., 594 Obukuru, K., 475
Knight, E. J., 572 Leatherdale, S. T., 193 Makris, N., 273, 546, 547 Minnes, S., 276 O’Callaghan, J. P., 466
Knight, Heather, 80 LeCours, A. R., 261 Malach, R., 300 Mischel, W., 394 Oettingen, G., 193
Knoch, D., 555 LeDoux, Joseph, 422, 498 Malanga, Carl, 276 Mishkin, F., 598 Oiestad, E. L., 198
Ko, A. L., 572 Lee, A. D., 570 Malberg, J. E., 596 Mishkin, Mortimer, 333, 393, Oiu, J., 456
Ko, K. N., 183 Lee, B. Y., 183 Malcolm-Smith, S., 464 495, 498 Olanow, C. W., 591
Koban, L., 394 Lee, C. Y., 100 Mallick, S., 22 Mistlberger, R. E., 450, 451 Olds, James, 437
Koch, C. E., 450 Legenstein, R., 131 Malone, P., 374 Mittleman, G., 179 Olivetti Belardino, M., 434
Koch, Christof, 556 Lehman, M. N, 452 Mamelak, A., 83 Mizuno, Y., 589 Olsson, S. B., 404
Kochunov, P., 570 Lehmann, H., 497 Mandalà, M., 389 Moffitt, T. E., 236 Olulade, O. A., 555
Koelling, R. A., 409 Leljavski, A., 450 Manger, P. R., 24, 25, 76, 82 Mohajerani, M. H, 130 Ommaya, A. K., 393
Kogan, M. D., 255 Lenggenhager, B., 392 Mangun, G. R., 520 Molaison (H. M.), Henry, 488, Osorio, L., 467
Kohl, M., 386 Lenneberg, E., 254, 261 Mann, S., 275 491, 495, 513 Ostergard, T., 583
Kojima, K., 100 Lenroot, R. K., 259, 260 Manoukian, J., 498 Molitoris, D., 275 Ostrom, H. G., 83
Kolb, Bryan, 216, 220, 251, 258, Lent, K. L., 349 Maquet, Pierre, 468 Monecke, S., 452 Oudiette, D., 469
266, 270, 275, 276, 345, 406, Lenz, B., 196 Marin-Padilla, M., 253 Money, John, 432 Overman, William, 264, 274
505, 509, 511, 517, 546 Lenz, K. M., 203 Markowitsch, Hans J., 487, 499 Moniz, Egas, 423 Owen, Adrian, 13, 29
Kolinsky, R., 347 Leonard, Christiana M., 261, 392 Markowski, G., 75 Monrobot, Marilyn, 80 Ozpinar, A., 572
Kolodny, J., 553 Leow, A. D., 570 Marler, P., 349 Montagna, P., 386
Kong, L., 593 Lepage, M., 487 Marsden, C. D., 382 Moore, T. J., 161 Pääbo, S., 22
Koo, D. S., 555 LePort, A. K., 487 Marshall, C. M., 444 Moran, James, 529 Palaniswami, M., 582
Koopowitz, S., 464 Lerch, J. P., 259, 347 Marshall, P. J., 272 Morris, Mark, 160 Palasz, A., 75
Kornek, B., 584 Leritz, E. C., 591 Mårtensson, B., 448 Morris, R. G., 497 Paller, K. A., 469
Korsakoff, Sergei, 496 Leston, J., 454 Martin, Alex, 486 Morris, R. G. M., 215, 216 Pannese, R., 594
Kosofsky, Barry, 276 Lethman, H., 213 Martin, Jean Prudin, 586 Morshead, C., 517 Pantelis, E., 464
Kovalchuk, O., 251, 275, 511 Lettieri, C. F., 464 Mascetti, G. G., 469 Moruzzi, Giuseppe, 470 Papez, James, 57, 417
Kovelman, J. A., 278, 593 Levitin, D. J., 266 Maslin, M. A., 25 Moser, Edvard, 223, 494 Paredes-Gamero, E. J., 467
Kovelman, Joyce, 278 Levy, G., 300 Mateer, C. A., 575 Moser, May-Britt, 222, 494 Park, C. I., 452
Kozyak, B. W., 26 Levy, W. B., 125 Matsumura, K., 378 Mountcastle, Vernon, 391 Park, S., 576
Kraspulski, M., 271 Lewin, R., 24 Matsuzaki, Y., 102 Movshon, J. A., 522 Park, S. Y., 183
Kraus, T., 196 Lewis, D. A., 593 Mattfield, A. T., 487 Mozaffarian, D., 428 Parker, D., 548, 549
Kravitz, A. V., 375 Li, H. C., 535 Mattison, D. R., 161 Muhammad, A., 251, 258, 275 Parkin, B. L., 29
Krebs, M. O., 424 Li, Y., 258, 456 May, L., 210 Mulder, C. K., 456 Parkinson, James, 140
Kreutzmann, J., 467 Li, Y. H., 457 McBride, S. W., 275 Müller, D. J., 184 Parrish, R. R., 509
Krishman, K. R. R., 596 Liao, P., 83 McCabe, B. J., 270 Murphy, D. L., 362 Parrish-Novak, J., 83
Kroger, J. K., 495 Lieberman, Matthew, 536, 537 McCarthy, M. M, 432, 435 Murphy, G. F., 152 Parsons, T., 562
Kross, Ethan, 394 Liewald, J. F., 131 McClay, J., 236 Murray, D., 444 Paterson, David, 277
Kroutil, L. A., 186 Lin, H., 126 McClintock, Martha, 403 Murray, E., 495 Pathihis, Lawrence, 487
Krug, S., 452 Lindquist, M. A., 394 McDonald, R. J., 451 Murray, R., 236 Paulignan, Y., 557
Kruggle, F., 487 Lindvall, O., 161, 588 McEwen, B., 434, 509, 510 Muzio, J., 459 Paus, T., 275
Kuffler, Stephen, 302 Linge, Fred, 2, 13, 14, 34 McGaugh, James, 499 Mychasiuk, Richelle, 237, 251, Pavelko, M., 271
Kuhl, P. K., 266 Liszt, Franz, 552 McGowan, Patrick, 206, 237, 595 258, 275, 276, 510, 511 Pavlov, Ivan, 481
Kuhn, H. G., 504 Little, William, 363 McHugh, Tommy, 597, 598 Myers, K. M., 422 Payne, B. R., 219
Kühn, S., 476 Liu, C., 275 McIntosh, A. R., 487 Myung, J., 447 Paz, M. F., 237
Kuna, S. T., 452 Liu, P., 198 McKenzie, S., 497 Pedroni, A., 555
Kunwar, P. S., 221 Loeb, G. E., 337 McLure, Samuel, 537 Nabokov, Vladimir, 551 Peigneux, P., 468
Kunz, A. R., 26 Loewi, Otto, 138, 139, 140, McNaughton, B. L., 468 Nadel, Lynn, 493 Peirson, S. N., 296, 451
Kuo, C. E., 457 147, 168 McVeigh, E. R., 232 Nakajima, K., 221 Pellegrino, R., 452
Kuo, H. K., 591 Loftus, E. F., 485 Mead, E. A., 183 Nakao, M., 378 Pembrey, M., 105
Kuperman, J. M., 246 Loganovskaja, T. K., 271 Meaney, Michael, 237 Nam, J., 86 Penfield, Wilder, 219, 223, 343,
Kurauchi, Y., 475 Loganovsky, K. N., 271 Mechoulam, Raphael, 153, 190 Namkoong, K., 452 344, 345, 346, 366, 367, 390
Kusakari, S., 102 Lomber, S. G., 219 Meerlo, P., 467 Nariai, N., 100 Penumalli, V., 126
Kusmakar, S., 582 Lømø, Terje, 500 Meitzen, J., 349 Nasri, S., 365 Pepperberg, Irene, 523
Kut, C., 232 Lopez-Escamez, J. A., 389 Melendez-Vasquez, C. V., 86 Nathan, D. E., 562 Peretz, Isabelle, 347
Kwakkel, G., 45 Lorenz, Konrad, 270 Meloni, E. G., 498 Neely, T. R., 202 Perfetti, C. A., 555
Kwong, K. K., 230 Loui, Psyche, 535 Meltzoff, A., 266 Nelini, C., 469 Perfilieva, E., 503
Low, D. W., 26 Melville, John, 363 Nelson, A., 26 Peri, F., 85
Labonté, B., 206 Lu, A., 570 Melzack, Ronald, 386, 387 Nelson, C. A., 257, 272 Perry, R., 557
Labrecque, N., 448 Lu, H., 198 Mendel, Gregor, 10, 11, 74, 96, Nestler, E. J., 596 Persson, M. E., 101
Labrecque, R., 347 Lu, L. H., 261 98, 104 Nevell, L., 21 Pertwee, L. O., 153
Lacroix, M. M., 468 Lubman, D. I., 199 Menon, B. K., 45 Neville, A., 198 Petanjek, Zdravko, 258
N-4 Name Index
Petiau, C., 468 Relkin, N. R., 341 Schallert, T., 219 Smyke, A. T., 272 Tinaz, S., 374
Pettersson, A., 448 Replogle, K., 349 Scheibel, Arnold, 278, 508, 593 Snow, B., 161 Tiwari, A. K., 184
Peuster, A., 264 Respino, M., 573 Scheinost, D., 425 Sodhi, M. S., 271 Toga, Arthur W., 261, 570
Pham, D. L., 562 Rether, K., 266 Schel, A. M., 9 Soga, K., 378 Toga, W., 258
Piaget, Jean, 262, 263, 264 Revonsuo, A., 463 Schellenberg, E. G., 347 Sohlberg, M. M., 575 Tomita, M., 444
Pickering, R., 21 Rezania, K., 126 Schenck, C. H., 475 Soliven, B., 126 Tomlinson, A, 591
Pignatelli, M., 594 Ribeiro-da-Silva, A., 515 Schieber, M. H., 361, 369 Solms, M., 464 Torben-Neilsen, B., 80
Pincus, J. H., 582 Rich, C. L., 186 Schieve, L. A., 255 Song, Y., 275 Torner, L., 206
Piper, W. T., 185 Richards, T. L., 266, 598 Schiff, Bernard, 399 Soules, M. E., 192 Townsend, S. W., 9
Pistorius, Martin, 5, 13 Richter, Curt, 445, 450, 455 Schiff, N. D., 13 Sourkes, T. L., 152 Trachtenberg, F. L., 277
Pitchers, K. K., 196 Rickards, H. E., 100 Schlaepfer, T. E., 219 Sowell, Elizabeth, 258, 261 Tramo, M., 347
Plautz, E. J., 505 Rieder, R. O., 278 Schlaug, G., 535 Spanswick, S. C., 213 Tranel, D., 530
Poldrack, R. A., 480 Riesen, Austin, 271 Schmahmann, Jeremy D., 34 Sparks, F. T., 497 Trauth, M. H., 25
Politis, M., 588 Rimm, E. B., 428 Schmal, C., 447 Spearman, Charles, 28, 29, 553 Tréatikoff, Constantin, 140
Pomplii, M., 573 Rivera, E. J., 202 Schmidt, A., 507 Sperry, Roger, 268, 520, 539 Treffert, D. A., 598
Poncelet, B. P., 230 Rizzo, A., 562 Schmierer, K., 126 Spirito, A., 186 Trehub, Sandra, 347
Ponnusamy, R., 221 Rizzolatti, Giacomo, 531, 532 Schmold, N., 251, 275, 276 Squire, L. R., 497 Triantafyllou, N., 584
Pons, T. P., 393 Roberts, D. M., 198 Schnack, H. G., 246 Stampfer, M., 428 Trotta, A., 199
Popova, S., 183 Robinson, T. E., 178, 179, 180, Schnyer, D. M., 591 Staniloiu, Angelica, 487 Trussel, L. O., 128
Porta, G., 186 194, 196, 437, 511 Scholz, R., 255 Stark, C. E., 487 Tsang, A. H., 450
Posner, M. I., 232 Rockland, M., 386 Schreiber, S. J., 126 Stedman, H. H., 26 Tsien, Roger, 75
Postuma, R. B., 467, 567 Rockstroh, B., 507 Schroeder, C. E., 527 Steen, Eric, 202 Tsivgoulis, G., 584
Potkin, S. G., 278 Rodriguez-Fornells, A., 576 Schroeder, M., 424 Stein, B. E., 527 Tsutsui, M., 475
Potts, R., 25 Roffward, H. P., 459 Schuhmann, E., 274 Stephens, G. J., 131 Tucker, G. J., 582
Pouget, J. G., 184 Rogers, S., 255 Schultheis, C., 131 Stepniewska, I., 390, 506 Tudeau, L., 387
Presley, Elvis, 327 Rogers, S. E., 266 Schwarzfuchs, D., 428 Stern, Karen, 403 Tufik, S., 467
Preux, P. M., 108 Roitman, P., 190 Schyns, P., 530 Stewart, J., 509, 546 Tuineaig, M., 467
Prinz, J., 4 Rojczyk-Gołębiewska, E., 75 Scotto, Pietro, 49 Stieltjes, B., 593 Tulving, Endel, 487
Proal, E., 363 Roland, P. E., 361 Scoville, William, 218, 488, 489 Stier, G., 579 Tuohimaa, P., 362
Prüfer, K., 22 Romanski, L. M, 333 Seeley, Randy, 430 Stodola, D. E., 28 Turing, Alan, 8
Prusiner, Stanley B., 590 Romenets, S. R., 567 Seidl, U., 593 Su, L. T., 26 Turk, Ivan, 322
Purpura, Dominique, 278, 279 Rondi-Reig, L., 468 Seidman, L. J., 273, 546, 547 Sugiura, M., 555 Turner, A., 505
Purves, D., 502, 503 Ropero, S., 237 Seitz, R. J., 553 Sundström, P., 584 Turner, M., 264
Putnam, B., 198 Rosen, C. L., 466 Seki, T., 475 Sunitha Suresh, B, S., 347 Turri, L., 404
Rosenegger, D. G., 84 Sekiguchi, A., 555 Suomi, Stephen, 271 Twitchell, Tom, 260
Qiao, L., 456 Roth, L. S., 101 Sen, S., 236 Suresh, S., 347
Quaglio, E., 472 Rothwell, John, 382 Seneca, 248 Surget, A., 596 Umstattd, M. R., 192
Quinlan, J., 470 Rouse, C., 83 Sepulcre, J., 534 Sutherland, Robert, 213, 497 Ungerleider, L. G., 486
Quinlan, Karen Ann, 470 Roux, F. E., 268 Serafini, G., 573 Suzuki, M., 495, 498 Usdan, S. L., 192
Quinn, T., 83 Rowland, B. A., 527 Sertürner, Friedrich, 187 Suzuki, Y., 469
Rudolph, J. L., 591 Setien, F., 237 Swaab, D. F., 435 Vaisanen, M. L., 275
Rafferty, Mary, 109, 111 Ruiz, S., 576 Sevincer, A. T., 193 Sweatt, J., 408, 509 Valdueza, J. M., 126
Ragert, Patrick, 507 Ruparel, K., 549 Seyoum, C., 21 Szybowska, M., 451 Valli, K., 463
Raichle, M. E., 232 Rushinsky, D. D., 593 Shadlen, M. N., 522 Szyf, Moshe, 206, 237, 595 van Besien, K., 126
Raine, C. S., 86 Rusielewicz, T., 86 Shahar, D. R., 428 Van Brunt, D. E., 186
Raizada, R. D. S, 266 Rutter, Michael, 272 Shai, Iris, 428 Taglialatela, Jared, 9 van Dam, R. M., 428
Rajan, R., 393 Ruttle, P. L., 28 Shakespeare, William, 466 Takeuchi, Hikaru, 555 Van der Zee, E. A., 456
Rakic, Pasko, 253, 257 Ryan, P., 274 Shalev, A., 190 Talbot, L., 591 van Haren, N. E., 246
Ralph, Martin, 451, 452 Ryu, H. M., 183 Shams, T. A., 184 Tallal, P., 480 van Oosten, B. W., 126
Ralvenius, W. T., 387 Sharifi, Z., 565 Tamminga, C. A., 198 van Schaik, A., 80
Ramachandran, Vilayanur, 386, Sabuncu, M. R., 534 Sharon, G., 275 Tanaka, Keiji, 309, 310 Vanderwolf, Case, 471
506, 507, 508, 531 Sacher, J., 200 Shaw, F. Z., 457 Tanapat, P., 503, 510 Vargha-Khadem, D. G.,
Rameson, L. T., 536 Sacks, Oliver, 42, 152, 382, 521, Shaw, Philip, 259 Tang, D., 456 495, 498
Ramirez, V. D., 219 585, 587 Shenton, J. T., 287 Tang, Y. L., 593 Veldhuizen, Maria, 405
Ramón y Cajal, Santiago, 75, 76, Sahakian, B., 172 Shepherd, G. M., 405 Tanner, J., 386 Verwey, M., 451
256, 376, 500 Sahay, A., 185 Sherman, Janet, 34 Tao Hao, M. P. H., 428 Vetrugno, R., 386
Rao, A., 582 Sainsbury, R. S., 499 Sherry, David, 493, 494 Taub, Edward, 581 Vevelstad, M., 198
Rao, J., 570 Saitow, F., 102 Shetty, A. C., 203 Taube, M. M., 382 Vierck, C. J., 392
Rapoport, Judith, 570 Sala-Llonch, Roser, 534 Shi, Q., 591 Tees, Richard, 257, 269 Villmoare, B., 21
Rapoport, S. I., 570 Salat, D. H., 591 Shibasaki, K., 102 Teie, P. U., 326 Villringer, A., 200
Rasch, B., 467 Salehpour, S., 565 Shimomura, Osamu, 75 Teitelbaum, P., 219 von Békésy, George, 331
Raslan, A. M., 572 Sallis, H., 199 Shin, C. Y., 183 Teixeira-Gomes, A., 197 von Helmholtz, Hermann, 111,
Rasmussen, Ted, 392, 550 Salm, A. K., 271 Shin, J. H., 576 Temple, E., 480 330, 331
Rauschecker, J. P., 333, 340 Salzer, J., 584 Shingo, T., 251, 517 Teng, S., 336 Voumvourakis, K., 584
Ravel, Maurice, 346 Sander, J. W., 108 Shors, T. J., 503 Tennstedt, S., 591 Voyvodic, J. T.,
Raven, P. H., 444 Sanders-Bush, E., 271 Shorter, K. R., 593 Terkel, J., 6
Ray, W., 507 Sangrey, T., 125 Shultz, S., 25 Terry, B. M., 202 Wada, Jun, 550
Raza, S., 266 Sankararaman, S., 22 Shweikeh, F., 83 Teskey, Cam, 219 Wade, J., 275
Raza, S. M., 232 Santarelli, Luca, 596 Siegel, Jerome, 475 Testini, P., 572 Walker, D. L., 422
Read, S. L., 598 Santos, V. J., 386 SiFuentes, F., 369 Tetrud, J. W., 161 Walker, J. D., 258
Reazei Zarchi, S., 365 Sapolsky, Robert, 204, 206, 510 Simon, T., 255 Tettamanti, M., 472 Walker, L. C., 492
Reber, P. J., 469 Sarkar, D. K., 183 Singer, L. T., 276 Teuher, H., 489 Walker, M. C., 108
Reckman, G. A., 456 Sarnyai, Z., 131 Sira, C. S., Thach, Tom, 377 Walkey, J., 216
Reeve, Christopher, 364, 365, 421 Sasaki, A., 206 Sirevaag, Anita, 504, 505 Thaler, L., 336 Wall, N. R., 221
Reeve, Dana, 364 Sassa, Y., 555 Sisodiya, S. M., 108 Therrien, A. S., 378 Wall, Patrick, 386
Reeve, R., 80 Sato, Y., 100 Sitaram, R., 576 Thesier, D. M., 26 Wallace, Alfred Russel, 8, 9, 10
Regenold, W. T., 570 Sato-Hashimoto, M., 102 Sjöström, M., 105 Thomas, P. K., 382 Wallace, E. K., 9
Rego, A. C., 102 Satterthwaite, P. D., 548, 549 Skinner, B. F., 408, 483, 484 Thomas, S., 581 Wallace, G. L., 260
Rehm, J., 183 Saturn, S. R., 185 Smarr, B. L., 452 Thompson, C. K., 349 Wallace, P. S., 260
Rehngrona, S., 161 Savage-Rumbaugh, Sue, 9 Smidak, M., 591 Thompson, E. G., 277 Wang, J., 595
Reid, J. L., 193 Savitz, S. I., 572 Smith, A., 548, 549 Thompson, P. M., 258, 261, Wang, X., 83
Reinstatler, L., 186 Saxe, M., 596 Smith, A. D., 185 553, 570 Wang, Y., 102, 579
Reis, C., 579 Schacter, Daniel, 498 Smith, D. V., 405 Thorndike, Edward, 481, 486 Wassermann, E. M., 573
Reiter, Russel, 454 Schall, M., 508 Smith, E. E., 394 Tian, B., 333 Water, T. D., 394
Name Index N-5
Waterman, Ian, 382 West, S., 580 Wilson, S., 467 Wu, M., 276 Young-Min Lee, K., 341
Watkins, Kate, 268 Westwood, D. A., 358 Windt, J., 392 Wu, W., 76 Youssef, N. A, 186
Watson, James, 96 Whishaw, I. Q., 179, 180, 216, Wingenfeld, K., 562 Wulff, K., 296, 451 Yovel, Y., 351
Watson, Michael, 551, 552 219, 260 Wingfield, J., 275 Yücel, M., 199
Watson, Stewart, 9 Whitbread, P., 185 Winkler, A., 178 Xhen, M., 131
Webb, Barbara, 80 White, J. A., 509 Wise, B. M., 369 Xi, J., 232 Zaidi, Farhan, 296, 451
Webb, I. C., 450 Whiten, A., 29 Wise, R. A., 437 Xie, L., 266 Zajonc, Robert, 424
Weber, S. C., 578 Whitfield, C., 258 Wisniewski, T., 492 Xu, N. L., 75 Zanna, M. P., 191
Webster, W., 271 Whitney, D., 336 Witelson, S., 551, 553 Zatorre, Robert, 268, 345, 347, 404
Weesner, K. E., 462 Wiaderkiewicz, R., 75 Witkow, S., 428 Yadav, S. N., 108 Zava, D. T., 185
Wei, M. Z., 457 Widner, H., 161 Wixted, J. T., 497 Yager, L. M, 196 Zeanah, C. H., 272
Weiland, B. J., 192 Wienbruch, C., 507 Wolf, O. T., 562 Yakovlev, P. E., 261 Zeffiro, T. A., 425
Weiner, J., 6 Wiesing, U., 598 Wolpert, D. M., 392 Yamguchi-Kabata, Y., 100 Zelano, C., 405
Weingarten, J. A., 448 Wiggs, C. L., 486 Wonder, Stevie, 552 Yan, B., 582 Zgari, Z., 365
Weinland, C., 196 Wijemanne, S., 460 Wong-Riley, Margaret, 299 Yancey, C. R., 509 Zhang, B. Y., 591
Weiss, S., 517 Wikler, R. E., 177 Woo, C. W., 394 Yang, M., 102 Zhang, F., 444
Weiss, Sam, 250 Wildner, H., 387 Wood, B., 21 Yang, X., 255 Zhang, Y., 102
Weisskoff, R. M., 230 Wilfong, T., 392 Woods, Stephen, 430 Yau, M., 358 Zhao, X., 595
Weizkrantz, Lawrence, 284 Wilke, C., 9 Woodson, R., 406, 407 Ye, X., 232 Zhou, W., 591
Welcome, Suzanne E, 261 Wilkinson, S. T., 199 Woollett, Katherine, 503, 504 Yeo, B. T. T., 534 Ziao, K., 591
Wells, E. M., 260 Willett, W. C., 428 Woolley, C. S., 434, 509 Yeo, Thomas, 534 Zihl, Josef, 316
Welsh, R. C., 192 Williams, V. J., 591 Workman, A. D., 26 Yi, M., 223 Zimmerman, T., 573
Wenger, John, 178 Williamson, K., 266 Worthington, J. J., 75 Yizhar, O., 131 Ziv, Y., 75
Werker, Janet, 210, 257 Wills, T. J., 223 Wright, C. L., 203 Yomogida, Y., 555 Zlomuzica, A., 142
Wernicke, Karl, 342, 343, 347 Wilson, M. A., 468 Wright, D., 101 Yoon, S., 276 Zohary, E., 522
Wess, J., 221 Wilson, M., 407 Wu, H., 102 Young, J. Z., 112 Zollikofer, C. P., 26
this page left intentionally blank
Subjec t Inde x
Note: Page numbers followed by f indicate figures; those followed by t indicate tables.
Abducens nerve, 59, 60f Alpha rhythms, 224, 458 cloned, 101–102, 102f
Ablation studies, 218–219, 218f Alprazolam, 182 diurnal, 442
Abnormal behavior. See Brain/behavioral disorders Alzheimer disease, 70, 160, 492, 498, 588–591 emotional behavior in, 410–411
Absolute pitch, 324, 535, 535f, 554 brain abnormalities in, 85, 167, 588–589, 588f, 589f evolution of, 15–19
Absolutely refractory membrane, 122 in Down syndrome, 100 experimental, 101–102, 239–242. See also
Acetate, 149 Parkinson disease and, 589–590 Animal research
N-Acetylaspartate, in traumatic brain injury, 579 Amacrine cells, retinal, 294, 295f hearing in, 324, 325f
Acetylcholine (ACh), 138, 138f, 148, 155, 157–158, 160f Amblyopia, 269 language in, 8, 9, 522, 523
in autonomic function, 157–158 Amine neurotransmitters, 149t, 150, 150f learning in, 408–409
in brain activation, 471, 471f Amines, synthesis of, 150 prey-killing behavior in, 399, 401, 406–407
identification of, 148 Amino acid(s), 92, 93, 93f. See also Protein(s) scratch reflex in, 364
in muscle contraction, 133–134, 133f, 157, 372, 372f synthesis of, 150 singing in, 322
neurotoxin effects on, 176–177, 176f Amino acid neurotransmitters, 149t, 150, 150f skilled movement in, 368
receptors for, 155, 155t Amino groups, 93 sleep in, 460–461, 461f, 465, 465f, 469
in Renshaw loop, 148, 149f Amnesia, 483–484. See also Memory deficits species-typical movement in, 361–363, 362f
synthesis and breakdown of, 149–150, 150f anterograde, 496 thinking in, 522–524, 545
Acetylcholine psychedelics, 189 Boswell’s, [Patient], 490 tool use by, 29
Acetylcholine receptor, curare and, 176–177 definition of, 483 transgenic, 102
Acetylcholine synapse, drug action at, 176–177, 176f episodic, 486–487 Animal research, 101–102, 239–242
Acetylcholinesterase, 160 postencephalitic, 490 in behavioral disorders, 567
Achromatopsia, 316 psychogenic, 487, 487f benefits of, 240
Acquired savant syndrome, 598 retrograde, 496 conditioning in, 481–482
ACTH, 414t, 595 surgically induced, 488–490, 488f limitations of, 567
Action potential, 120–123. See also Nerve impulse AMPA receptors, in long-term potentiation, regulation of, 240–242
all-or-nothing response of, 124 501–502, 501f Animal Welfare Act, 241
blocking of, 120, 121, 121f Amphetamine, 188–189 Anions, 146. See also Ion(s)
definition of, 120 for attention-deficit/hyperactivity disorder, 172 Anomalous speech representation, 551
measurement of, 120, 120f brain injury from, 198 Anorexia nervosa, 275, 427
nerve impulse and, 123–124 as cognitive enhancer, 172 Anoxia, cerebral, 363
phases of, 122f dosage of, 173–174 Antagonists, 176–177, 176f
postsynaptic potentials and, 127–130 hallucinogenic, 198 Anterior cerebral artery, 43, 43f
production of, 127–130 neuronal effects of, 510–511 Anterior cingulate cortex, 418f, 419, 526, 537
propagation of, 123–124, 123f, 125f, 130f sensitization to, 178–180 Anterior corticospinal tract, 370f, 371, 371f
back, 130–131 Amplification cascade, 155 Anterior, definition of, 38, 39
refractory periods and, 122–123, 124 Amplitude, of sound waves, 324–326, 324f Anterior horn, motor neurons in, 371
single-cell recordings of, 222–223 Amputation, cortical reorganization after, 506–507 Anterior roots, 358
Action test, 8 Amusia, 348 Anterior spinothalamic tract, 383
Activating systems, 158–162 Amygdala, 54f, 57–58, 57f, 417f, 418. See also Anterograde amnesia, 496
Activation-synthesis hypothesis, for dreams, 462–463 Limbic system Antianxiety agents, 181–182, 181t, 425, 597
Adderall, 172 in attention, 530 Anticonvulsants, 582
Addiction. See Substance abuse, addiction in in autism spectrum disorder, 255 Antidepressants, 181t, 185–186
Additive color mixing, 310, 310f in eating, 418, 430 atypical, 185
Adenine, 91f, 92 in emotional behavior, 418, 422–423 hippocampal neurogenesis and, 596
Adolescence, psychiatric disorders presenting in, 275 in emotional memory, 482, 498–499, 499f mechanism of action of, 594, 596
Adrenaline (epinephrine), 138–139, 150, 150f. See also in fear conditioning, 482, 498–499 monoamine oxidase inhibitors, 185
Neurotransmitters neural connections of, 498–499, 499f second-generation, 185
in stress response, 204, 205f in sexual behavior, 434 side effects of, 574
Adrenocorticotropic hormone (ACTH), 414t, 595 Amygdalectomy, Klüver-Bucy syndrome and, 422–423 sleep and, 467
Affective disorders, 424–426 Amyloid plaque, in Alzheimer disease, 492, 492f, 588 tricyclic, 185
Affective states. See under Emotion; Emotional Amyotrophic lateral sclerosis (ALS), 134, 356, 363 Antipsychotics, 181t, 184, 184f
Afferent nerves, 37, 37f Anabolic steroids, 204 side effects of, 574
Afferent sensory signals, 358 Analgesics, 387 Anvil, 329, 330f
Africa, primate evolution in, 21, 24–25 abuse of, 188 Anxiety, 574
Age-related cognitive loss, 591. See also Dementia opioid, 151, 181t, 187–188, 387. See also Opioids Anxiety disorders, 424–426, 592f, 597
Aggression, sex differences in, 548 Anandamide, 151–153 adolescent-onset, 275
Agnosia Anandamide psychedelics, 189–190 treatment of, 181–182, 181t, 425, 597
color, 316 Anatomical organization, of brain, 36 Anxiety dreams, 463–464
facial, 301 Anatomical orientation, of brain, 39 Anxiolytics, 181–182, 181t, 425, 597
visual-form, 315–316, 526 Anatomical terms, 38–39 Apes, 20. See also Primates, nonhuman
Agonists, 176–177, 176f Androgen(s), 200, 273. See also Sex hormones Aphagia, 429
Agoraphobia, 425 behavior and, 401 Aphasia, 545–546, 548
Akathesia, 586 in brain development, 203, 273–275, 432, 546–549 Broca’s, 227, 343
Akinesia, 219 functions of, 200, 202 definition of, 343
Alcohol. See also Substance abuse lifelong effects of, 274–275 Wernicke’s, 343
brain damage from, 198, 495–497 neuroplasticity and, 509 Aplysia californica
disinhibition and, 191–192 sexual behavior and, 433 habituation in, 163, 164f
fetal alcohol spectrum disorder and, 28, 183, in sexual differentiation, 203, 272, 432 sensitization in, 164, 165f
267, 271 Androgen-insensitivity syndrome, 433 Apnea, sleep, 473–474
Korsakoff syndrome and, 495–497 Androgenital syndrome, 433 Apoptosis, 198, 257
as sedative-hypnotic, 182 Anencephaly, 277 Apraxia, 394, 545–546, 548
tolerance to, 177–178, 178f Anesthesia, epidural, 387 2-Arachidonoylglycerol (2-AG), 151–152
Alleles, 97 Aneurysms, cerebral, 347 Arachnoid layer, 37
dominant, 97, 99f Angel dust, 182, 190 Arachnoid membrane, 37f
recessive, 97, 99f Animal(s) Arborization, dendritic, 254–255, 254f, 502–503, 503f
wild-type, 97 auditory communication in, 349–351 Arcuate fasciculus, 342f, 343
Allocortex, 54 auditory processing in, 322, 339–340, 339f Arcuate nucleus, in eating, 429–430
Alpha fetoprotein, 432 chimeric, 102 Area postrema, 174, 175f
S-1
S-2 Subject Index
Arousal, in basic rest-activity cycle, 465, 466f Axoaxonic synapse, 145, 145f Behavioral disorders. See also Brain/behavioral
Artificial intelligence, 80, 81 Axodendritic synapse, 145, 145f disorders; Psychiatric disorders
Asperger syndrome, 255 Axomuscular synapse, 145, 145f research methods for, 565–567
Association cells, 79, 79f Axon(s), 47, 47f, 76, 76f, 77, 78f, 87f vs. neurological disorders, 563–564
Association cortex, 525–533 dendrites and, 76, 76f, 77, 78f, 79–80 Behavioral myopia, 192–193
in attention, 528–530 giant squid, electrical activity in, 112, 112f Behavioral neuroscience
components of, 525–526, 526f growth cones of, 256, 256f definition of, 214
in imitation and understanding, 531–532 myelination of, 124–125 methodology of, 211–244
lesions in, assessment for, 533 nerve impulse along, 123–124, 123f, 125f comparisons for, 238–239, 238t
mirror neurons in, 532 in neural circuits, 80. See also Neural circuits Behavioral sensitization, 510–511
multimodal regions of, 527, 527f sprouting of, 85–86 Behavioral stimulants, 188–189, 189f
multisensory integration in, 527, 527f neuroplasticity and, 502–503, 503f Behavioral tests, 533
neural connections to, 525–526, 526f Axon collaterals, 77, 78f Behavioral therapy, 574–576
in object recognition, 525–526, 527f Axon hillocks, 77, 78f Beliefs, 537
in planning, 530–531 Axosecretory synapse, 145, 145f Bell palsy, 62
in spatial cognition, 527–528, 527f, 528f Axosomatic synapse, 145, 145f Bell-Magendie law, 61, 62
Associative learning, 409 Axosynaptic synapse, 145, 145f Benzedrine, 172, 189
long-term potentiation and, 500–502 Benzodiazepines, 182, 425
Astrocytes (astroglia), 82t, 83–84, 146 Baby connectome, 363 Beta rhythms, 457–458
in blood–brain barrier, 174, 174f Back propagation, 130–131 Bias, 537
Asymmetry, cerebral. See Cerebral asymmetry Balance, vestibular system in, 388–389, 389f Biceps muscle, 372, 372f
Ataxia, 34 Barbiturates, 182 Bilateral, definition of, 39
optic, 317–318 Basal forebrain, in brain activation, 471, 471f Bilateral symmetry, 17, 17f, 18, 46
Athletes, traumatic brain injury in, 577, 578 Basal ganglia, 54, 54f, 57, 57f Bilingualism
Atoms, 88, 89, 89f anatomy of, 373, 373f cognitive advantages of, 555
Atonia, in REM sleep, 458, 460–461, 474–475 functions of, 373–375 cortical areas for, 268
Attention, 528–530 in memory, 489–490, 499 Binding problem, 527
contralateral neglect and, 529, 530f in movement, 357, 373–375, 375f Binocular vision, corpus callosum in, 304
deficits of, 529–530, 530f in Parkinson disease, 57, 374–375 Biological clocks, 442, 443–444. See also Biorhythms
definition of, 528 in Tourette syndrome, 57, 374 eating/feeding behavior and, 450, 455–456
extinction and, 529–530, 530f Bases, nucleotide, 91f, 92 entrained, 446–448
selective, 528–529 Basic fibroblast growth factor, 252 free-running rhythms and, 445–446, 447f
vision and, 528–529 Basic rest-activity cycle (BRAC), 465, 466f neural basis of, 250–456
Attention-deficit/hyperactivity disorder, 162, 172, 240 Basilar membrane, in hearing, 330–331, resetting of, 446–448, 448
Attitudes, 537 330f, 332f suprachiasmatic nucleus as, 450–456, 450f
Atypical antidepressants, 185. See also Antidepressants Bats, echolocation in, 351–352 Biorhythms, 442–456
Auditory communication, in nonhuman species, Behavior, 5–6 basic rest-activity cycle and, 465, 466f
349–351 abnormal. See Behavioral disorders biological clocks and, 443–444. See also Biological
Auditory cortex, 334–335, 525f brain development and, 247–248 clocks
association cortex and, 527f for brain maintenance, 400–401 circadian, 442, 443–449, 445t, 446f. See also
Broca’s area in, 254f, 262, 342–343, 342f, 344f causes of, 399–401 Circadian rhythms
mapping of, 343–346 cerebral control of. See Brain/behavioral disorders circannual, 444, 445t
primary, 334, 334f chemical senses in, 401–406 pacemaking, 454–455
secondary, 334 cognitive stimulation and, 400–401 definition of, 442
structure of, 334–335, 334f comprehension of, 531–532 disturbances of, psychiatric symptoms in, 455, 455f
supplementary speech area in, 344–345, 344f definition of, 5 entrained, 446–448, 449f
tonotopic representation in, 336–338, 337f drinking, 418, 430–431 free-running, 445–446
Wernicke’s area in, 334, 334f, 342–346, 342f, 344 embodied, 4–5 genetic factors in, 452
Auditory flow, 286 emotional, 399, 416–418, 421–426. See also infradian, 444, 445t
Auditory nerve, 333 Emotional behavior innate, 451–452
Auditory pathways, 333, 334f environmental influences on, 408–409 jet lag and, 448, 449f
Auditory processing, 330–331 evolution of, 406–408 measurement of, 444–445
Auditory receptors, 330f, 332 feeding. See Eating/feeding behavior neural basis of, 450–456
Auditory system. See also Hearing; Sound free will and, 399 neural transplantation and, 452, 452f
in animals, 322, 339–340, 339f homeostatic mechanisms and, 411 origins of, 442–443
auditory cortex in. See Auditory cortex inherited, 6, 6f, 406–408 periods of, 444
auditory pathways in, 333, 334f innate releasing mechanisms for, 406–407 pineal gland in, 454
auditory receptors in, 330f, 332 learned, 6, 6f, 408–409. See also Learning in plants, 443, 444f
ear in, 329–331, 330f, 331f, 332f measurement of, 211–216 recording of, 444–445, 445f, 446f
evolution of, 329 motivated. See also Motivation retinohypothalamic tract in, 451, 453
functions of, 329 neuroanatomy of, 410–426 seasons and, 443
insula in, 334f, 335 neural circuits and, 401 suprachiasmatic, 450–456
in language processing, 340–346 neuroanatomy and, 211–214 ultradian, 445, 445t
lateralization in, 334–335, 541–542 nonregulatory, 412 Zeitgebers and, 446–448
in movement, 333 control of, 432–435 Bipolar cells, retinal, 294
music perception in, 327–328, 339–340 olfaction in, 401–404, 403f Bipolar disorder, 186, 594. See also Depression
sensitivity of, 326–327 overview of, 5–6 adolescent-onset, 275
sound perception in, 326–327 prey-killing, 399, 401, 406–407 drug therapy for, 181t
speech perception in, 327–328, 339–340 purposeful, 409–410 mood stabilizers for, 186
structure of, 329–336 purposes of, 399–401 Bipolar neurons, 79, 79f
Auditory vestibular nerve, 59, 60f regulation of auditory, 333
Australopithecus, 20–22, 20f, 21f, 23f amygdala in, 418 retinal, 294, 295f
Autism spectrum disorder, 255 frontal lobe in, 418f, 419–420 Birdsong, 349–351
brain size in, 28 hypothalamus in, 411–416, 429–430, 430f sex differences in, 275, 350
cerebellar dysfunction in, 34 limbic system in, 416–418 vs. language, 349–350
mirror neurons in, 532 prefrontal cortex in, 418f, 419–420 Bitter taste, 404–405
Autobiographical memory, 486–487, 487f regulatory, 411–412 Black widow spider venom, 176
Autoimmune disease, 126, 134, 584 control of, 426–431 Blind spot
Autonomic nervous system, 36f, 37, 63–64 rewarding, 399, 401, 416, 436–439 retinal, 284, 291, 292, 292f
enteric nervous system and, 64–65, 65f selection of, 418f, 419–420 in visual fields, 314–315, 314f
neurochemistry of, 157–158, 157f sex differences in, 548–549 Blindness. See Vision impairment
Autoreceptors, 144 sexual, 412, 433–434 Blindsight, 284
Autosomes, 96, 97 species-typical, 28, 361–363 Blobs, 299, 299f, 312
Aversive childhood experiences, frontal lobe Behavior modification, 575 Block span, 215
development and, 259 Behavioral assessment, 533 Block-tapping test, 214f, 215
Subject Index S-3
Blood vessels, cerebral, 42–43, 43f behavioral development and, 247–248, 260–265 sex differences in, 547–548, 549f
Blood–brain barrier, 83–84 brain injury and, 276 in substance abuse, 197–198
drug therapy and, 174–175 cell death in, 257 temporal lobe, 55
Bodily-kinesthetic intelligence, 553–559 cellular commitment in, 254f teratogens in, 252, 276–277
Body segmentation, 17, 17f, 18, 59–60, 61f cognitive development and, 262–265, 262f, three-legged cat solution and, 514
Body size, brain size and, 22–23, 23f 263t, 264f timing of, 252
Body symmetry, 17, 17f, 18 cortical layering in, 253–254 traumatic. See Traumatic brain injury
Body temperature, regulation of, 411–412 cortical thinning in, 258, 258f treatment of, 13–14
Body weight, regulation of, 426–430. See also critical periods in, 269–270 Brain lesion studies, 218–219
Eating/feeding behavior drug effects on, 276–277 Brain maps, 55, 56f. See also Homunculus
Bonds, 89 enteric nervous system in, 275 cortical function, 343–346, 344f, 366–369, 367f
peptide, 93 environmental influences in, 266–279 cytoarchitectonic, 56, 56f
Bone flute, 322 cortical organization and, 266–268, 267f electrical stimulation and, 219–220
Bonobos. See Primates, nonhuman cultural, 29, 36 event-related potentials in, 224–225, 224f, 225f
Botulinum toxin, 176 environmental stimulation, 266–268, 267f, Flechsig’s, 259–260
Bradycardia, diving, 138 270–271, 555 for infants, 363
Braille, 543 negative experiences, 259, 270–271 movement categories in, 367–368
Brain. See also under Cerebral; Cortical neural connectivity and, 268–269 place cells and, 222–223, 222f
behavioral control by. See Brain/behavior disorders prenatal, 267, 268 of speech/language areas, 343–346
capillary network of, 174, 174f gene expression in, 251 tonotopic, 336–338, 337f
chemical composition of, 88f glial development in, 259–260 topographic, 288, 288f. See also Topographic
cortical organization in. See also Cortical columns growth spurts in, 263–264 organization
environmental influences in, 266–268, 267f gut bacteria in, 275 of motor cortex, 366, 369–370, 369f
sex differences in, 546–549 hormonal influences in, 273–275 of visual cortex, 302–303, 303f
crossed connections in, 43, 67 imprinting in, 270, 270f Brain size
Einstein’s, 552, 553f language development and, 261–262 in animals, 18–19, 18f, 19f, 22, 23, 23f, 24
electrical activity in, 109–127. See also under masculinization in, 203, 273–274, 432 behavior and, 22–23, 23f, 24, 27–29
Electrical motor development and, 260–261, 261f body size and, 22–23, 23f
measurement of, 222–226 music and, 267 in chordates, 18–19, 18f, 19f
evolution of, 15–29, 47–50, 48f. See also Brain myelination in, 259–260, 259f climate and, 25
development neoteny and, 26–27, 26f diet and, 25–26
in animals, 15–19 neural column formation in, 269, 270f encephalization quotient and, 22–23, 23f
culture and, 29 neural connectivity in, 268–269 estimating, 22–23
in humans, 19–29 neural Darwinism in, 257 evolution of, 24–26
functional maintenance of, behavior and, neural placement in, 268–269, 270f heterochrony and, 26
400–401 neurobiology of, 248–260 intelligence and, 23, 24, 28–29
functions of, 35 neurogenesis in, 252, 253f neoteny and, 26–26, 26–27, 26f
behavior as, 35 neuronal development in, 252–258 in neurological disorders, 28
localized vs. distributed, 70 neuronal differentiation in, 253–254, 253f neuroplasticity and, 28–29
movement as, 35 neuronal maturation in, 254–256, 256f in nonhuman primates, 22, 23f
principles of, 72 neuronal migration in, 253–254, 253f packing density and, 23, 24
sensory processing as, 35 neuroplasticity and, 279–280 radiator hypothesis and, 26
growth of, 250f. See also Brain development prenatal, stages of, 248–250, 249f, 250f skull structure and, 26
hemispheres of, 55, 55f in Romanian orphans, 272 variability in, 27–29
hierarchical organization of, 50–58, 68–69, 68f, in schizophrenia, 278 Brain stimulation techniques, 13, 13f, 109–111, 219–220,
357–365, 390–391 sensory input in, 266–268, 267f, 270–271 514–516, 572, 587
information flow in. See Information flow sex differences in, 260f Brain surgery. See Neurosurgery
integration operation of, 127–130 sex hormones in, 202–204, 273–275, 432–433, Brain tumors, 83
lateralization in, 334–335, 346–347. See also Later- 546–549 neurogenesis and, 252
alization sexual differentiation and, 203, 272 Brain–behavior link, 3
levels of function and, 50–58, 67–68 socioeconomic status and, 246, 266–267 brain development and, 260–265. See also Brain
mapping of. See Brain maps stages of, 253t development
masculinization of, 203, 273–274, 432 stress and, 271 brain size and, 22–23, 23f, 27–29
orientation of, 38–39 synaptic development in, 256 in brain/behavioral disorders, 564–567
parallel processing in, 68–69 synaptic pruning in, 257–258 causation vs. correlation and, 265
perceptual world created by, 66 tactile stimulation and, 267 culture and, 36
plasticity of. See Neuroplasticity time line for, 253f dualism and, 7–8, 8f
protective structures for, 37–40 Brain imaging. See Imaging studies evolutionary aspects of, 19–27. See also Evolution
sectioning of, 39, 39f, 43–46, 43f, 46f Brain injury materialism and, 8–12
sex differences in, 202–203, 273–275, 273f, 546–549, astrocytes in, 84 mentalism and, 7
547f, 549f behavioral testing in, 533 research methods for, 565–567
size of behavioral therapy in, 515 unified theory for, 562–564
environmental stimulation and, 504 compensation in, 219 Brain/behavioral disorders. See also specific disorders
intelligence and, 553, 553f compensatory mechanisms in, 567, 597–598 animal models of, 567. See also Animal research
sex differences in, 203, 273f, 546, 547f critical periods for, 276 biorhythms and, 448, 455, 455f
spinal cord integration with, 61–62 depression in, 225 brain abnormalities in, 570, 570f
split, studies of, 520, 542–543, 545 developmental effects of, 276 causes of, 564–565, 565t
staining of, 46–47, 47f, 75, 75f, 211, 212f excitation vs. inhibition in, 70–71 classification of, 568t–569t, 569–571
stimulation of, 35 frontal lobe, 55 compensatory mechanisms in, 567, 597–598
structure of, 3–4, 4f functional asymmetry and, 539–541 degenerative, 584–591, 585t
internal features of, 43–47, 46f, 47f ischemic, 580 diagnosis of, 565–566
layers in, 47, 47f, 56, 56f. See also Cortical layers location of, functional loss and, 70 epidemiology of, 568
microscopic features of, 46–47, 46f, 47f lost neuron replacement solution in, 516–517 epigenetics and, 564
surface features of, 37–43, 37f microglia in, 84–85, 84f neurobiology of, 565–567
symmetry in, 18, 46, 46f minimally conscious state and, 13 neuroimaging studies in, 570–571, 570f
terminology for, 38–39 neurogenesis in, 516–517 neurological, 577–592
vascular, 42–43, 43f neuroplasticity in, 276, 369–370, vs. psychiatric, 563–564
subjective reality and, 35 369f, 513–517 psychiatric, 592–597
summation in, 128–130, 129f, 130f neuropsychological assessment in, 533 vs. neurological, 563–564
Brain cells, 46–47, 46f, 73–106. See also Glial cells; new circuit solution in, 514–516 research challenges for, 566–567
Neuron(s) occipital lobe, 55 research methods for, 565–567
Brain chemistry, measurement of, 234–235 outcome in, 2, 13 sleep problems in, 472–473
Brain connectome, 363, 534 parietal lobe, 55 treatment of, 571–576
Brain development, 247–280 persistent vegetative state and, 13 behavioral, 574–576
in autism spectrum disorder, 255 recovery from, 2, 13–14, 513–517 electrophysiological, 572–573
S-4 Subject Index
neurosurgical, 572 Central nervous system, 3–4. See also Brain; Spinal cord Chemoaffinity hypothesis, 268–269, 270f
pharmacological, 573–574. See also Drug(s) development of, 247–280. See also Brain Chemogenetics, 221
Brain–body orientation, 38 development Children
Brainbow, 75 evolution of brain maps for, 363
Brain-computer interface, 356 in animals, 15–19 dendritic spine density in, 258
Brain-computer-brain interface, 356 in humans, 19–29 Chimeric animals, 102
Brain-derived neurotrophic factor, 236 functional organization of, 36–37, 36f, 50–58, 67–68 Chimpanzees, 15, 20, 20f. See also Primates, nonhuman
in depression, 595 hierarchical organization of, 50–58, 68–69, 68f, Chlamydomonas reinhardtii, light-sensitive ion channels
electroconvulsive therapy and, 572 357–365, 390–391 in, 131
neuroplasticity and, 510 neurotransmission in, 158–162 Chloride ions. See also under Ion(s)
Brain-in-a-bottle experiment, 4–5 sensory and motor divisions in, 69 movement of, 114f, 115–116
Brainstem, 4, 4f, 41–42, 41f, 51–54 structure of, 3–4 resting potential and, 116–119, 117f
in autism spectrum disorder, 255 Central pain, 385 Chlorpromazine, for schizophrenia, 184f
in drinking behavior, 362 Central sulcus, 41f, 42, 55, 55f Choline, 149
in feeding behavior, 362 Cerebellar agenesis, 34 Cholinergic neurons, 156–158
function of, 51–52 Cerebellar dysfunction, in autism spectrum disorder, 34 Cholinergic system, 157–158, 160, 160f
in grooming behavior, 362 Cerebellar homunculus, 375–376, 376f Chordates, 16f, 18–19, 18f, 19f. See also Spinal cord
injury of Cerebellum, 4, 18–19 Chromosomes, 91–92, 91f, 96, 103–105
in locked-in syndrome, 356, 363 anatomy of, 375–376, 376f abnormalities of, 100, 101f
REM sleep deprivation and, 467, 476–477 in cognition, 535–536 histones and, 103–104
in sexual behavior, 362 evolution of, 18–19, 19f number of, 97f
in species-typical movement, 361–363 functions of, 34, 52–54 abnormal, 100, 101f
structure of, 51–54, 51f–53f in movement, 52–54, 375–378, 376f–378f sex, 96–97, 97f
Brain-stimulation reward, 437 structure of, 41f, 42, 51f, 52f sex differences and, 548
Breast cancer, 97 topographic organization of, 375–376, 376f Chronic cerebrospinal venous insufficiency, multiple
Bregma, 218 Cerebral aneurysms, 347 sclerosis and, 584
Broca’s aphasia, 227, 343 Cerebral anoxia, 363 Chronic traumatic encephalopathy, 578
Broca’s area, 254f, 262, 342–346, 342f, 346f Cerebral aqueduct, 44 Chronotypes, 452, 453
mapping of, 343–346, 344f Cerebral arteries, 43, 43f Cigarette smoking, nicotine addiction in, 193, 438–439
Caenorhabditis elegans Cerebral asymmetry, 68, 334–335. See also Cilia, of hair cells, 330, 332f, 336–337
light-sensitive ion channels in, 131 Lateralization Cingulate cortex, 57, 57f
number of brain cells in, 23 anatomical, 539, 540 Circadian genes, mutations in, 453
auditory processing and, 541–542 Circadian rhythms, 442, 443–449, 445t. See also
Caffeine, 190 cognition and, 540–545 Biorhythms
Calcitonin gene–related peptide, 157 dichotic listening and, 541 cognitive, 455–456
Calcium ions. See also under Ion functional, 334–335 emotional, 456
endocannabinoids and, 151–153 handedness and, 334–335, 549–551 entrained, 446–448
in habituation, 164 hypotheses for, 543–545 free-running, 445–446, 446f
in learning, 164, 164f inferential thinking and, 545 pacemaking, 452–454
in neurotransmitter release, 143–144 language and, 334–335, 543–545 Circannual rhythms, 444, 445t
cAMP (cyclic adenosine monophosphate) movement and, 543–545 pacemaking, 454–455
caffeine and, 190 music and, 346–347, 541 Circulation, cerebral, 42–43, 43f
in learning, 165, 166–167 in neurological patients, 540–541 Cladogram, 17f, 18, 18f
Cancer, mutations in, 97 in normal brain, 541–542 Classes, taxonomic, 16, 16f
Cannabidiol, 152–153 overlapping functions and, 543 Classical conditioning, 481–482, 482f. See also
Cannabindoid (CB1) receptor, 152–153 in split-brain patients, 520, 542–543, 545 Conditioning
Cannabis, 152–153, 153, 189–190, 198, 199, 236 visual processing and, 541–542, 542f. See also in substance abuse, 177–178, 195
Capillaries, in blood–brain barrier, 174, 174f Visual fields Clinical trials, 14
Carbamazepine, for bipolar disorder, 186 Cerebral circulation, 42–43, 43f Clorazepam, 182
Carbon monoxide, as neurotransmitter, 153 Cerebral cortex, 40–42, 40f, 54–56. See also specific Cloning, 101–102, 102f
Carbon monoxide poisoning, 315–316 subunits (e.g., Motor cortex) and under Cortical Closed head injury. See Traumatic brain injury
Carboxyl groups, 93 connections of, 56 Cocaine, 172, 189, 189f, 198
Card sorting tasks, 531, 531f, 533 development of, 253f. See also Brain development Coccygeal spine, 60, 61f
Cataplexy, 475 developmental thinning of, 258, 258f Cochlea, 329–330, 330f–332f
Cations, 114. See also Ion(s) layers of. See Cortical layers hair cells of, 330, 330f, 332, 332f, 336–337
Caudal, definition of, 38, 39 neocortex, 54 Cochlear implants, 337–338, 337f
Caudate nucleus, 57, 57f, 373, 373f sensory and motor divisions in, 69 Cochlear nucleus, 333, 334f
Causation, vs. correlation, 265 structure and function of, 54–56, 55f Codominance, 97
CB1 receptor, 152–153 top-down processing in, 56 Codons, 93
Cell. See also specific types Cerebral hemispheres, 4, 4f, 40, 40f, 55, 55f Cognition, 521–560
components of, 86–97, 87f evolution of, 18–19, 19f age-related changes in, 591
electrical properties of, 109–127 surgical removal of, 42 in animals, 522–524, 545
function of, protein structure and, 86 symmetry/asymmetry of, 18, 46, 46f, 68, 334–335, association cortex in, 525–533
internal structure of, 86–96 539–546. See also Cerebral asymmetry attention in, 528–530
nerve. See Glial cells; Neuron(s) Cerebral ischemia, 580, 581f cell assemblies in, 523–525
nucleus of, 87f, 90, 91–92 Cerebral microbleeds, dementia and, 591 cerebellum in, 535–536
as protein factory, 87–90 Cerebral palsy, 363 cerebral asymmetry in, 539–546
Cell assemblies, in cognition, 523–525 Cerebral ventricles, 8, 44, 44f characteristics of, 521–522
Cell body, 76, 76f Cerebral voltammetry, 235 convergent vs. divergent thinking and, 554
Cell cultures, 75 Cerebrospinal fluid, 44 definition of, 521
Cell death, programmed, 198, 257 flow of, 82 emotion and, 526
Cell membrane, 87, 90, 90f. See also Membrane functions of, 82 evolution of, 522
absolutely refractory, 122 in hydrocephalus, 82 imitation and, 531–532
depolarization of, 119–122, 122f in meningitis, 42 inferential thinking in, cerebral asymmetry and, 545
electrical activity in, 111–127 production of, 82 intelligence and, 553
hyperpolarization of, 119–122, 119f, 122f shunts for, 82 language and, 521–522
ion movement across, 114–115, 114f Cerebrum, 4, 4f, 18–19, 19f, 41, 41f, 42. See also under multisensory integration in, 527, 527f
permeability of, 87, 114–116, 114f Cerebral neural circuits in, 522–525
phospholipid bilayer of, 90f, 92 Cervical spine, 60, 61f neural unit of thought in, 522–525
relatively refractory, 122 Channelrhodopsins, 131 object knowledge in, 526–528
repolarization of, 122f Channels. See Ion channels planning and, 530–531
structure of, 90–91, 90f Chemical bonds, 89 psychological constructs in, 520
Cell migration, 253–254 Chemical messengers. See Neurotransmitters sequential thinking and, 521–522
Cell-adhesion molecules, 256 Chemical synapses, 141–142, 142f. See also Synapses sex differences in, 203, 546–549, 547f–549f
Cellular commitment, in brain development, 254f Chemistry basics, 88–89 sleep deprivation and, 466–467
Subject Index S-5
social, 536–538 Convergent thinking, 554 Delta rhythms, 458
spatial, 527–528, 527f, 528f Copulatory behavior. See Sexual behavior Dementia
sex differences in, 546–549 Copycat (cloned cat), 102, 102f Alzheimer, 70, 160, 492, 498, 588–591
in split-brain patients, 520, 542–543, 545 Cornea, 291, 291f brain abnormalities in, 85, 167, 588–589,
studies of, 533–536. See also Cognitive neuroscience Coronal, definition of, 39 588f, 589f
Cognitive development, 262–265, 262f, 263t, 264f Coronal section, 39f, 43–44, 43f, 44f in Down syndrome, 100
cultural aspects of, 29 Corpus callosum, 43f, 45, 46f Parkinson disease and, 589–590
Cognitive enhancement, 172, 598 absence of, 103, 103f concussion and, 578
Cognitive neuroscience, 533–538 handedness and, 551 definition of, 585
applications of, 536–538 severing of, cognitive effects of, 542–543 degenerative vs. nondegenerative, 585, 585t
methods of, 533–536 visual, 304, 304f marginal high blood pressure and, 591
Cognitive organization. See Brain; Cerebral asymmetry; Correlation, vs. causation, 265 types of, 585t
Topographic organization Corsi block-tapping test, 214f, 215 Dementia pugilistica, 578
Cognitive rhythms, 455–456 Cortex. See under Cerebral cortex; Cortical Dendrites, 76, 76f, 77, 78f, 79–80, 87f, 131
Cognitive stimulation Cortical columns, 269, 270f, 298 arborization (branching) of, 254, 254f,
behavior and, 400–401 definition of, 298 502–503, 503f
brain development and, 272 ocular dominance, 269, 270f, 308–309, 309f, changes in, 502–503, 503f. See also Neuroplasticity
brain size and, 504 312, 312f development of, 254–255, 254f
in learning, 504–505, 505f orientation, 308–309, 312, 312f Dendritic spines, 77, 78f, 87f, 167
Cognitive therapy, 575 in temporal lobe, 309–310, 309f age-related density of, 258
Cognitive-behavioral therapy in visual cortex, 269, 270f, 308–309, 309f growth of, 254–255, 254f, 502–503, 503f
for anxiety disorders, 597 Cortical function mapping, 343–346, 344f, 367–368 in learning, 167
for depression, 186, 596 Cortical layers, 47, 47f, 56, 56f, 69, 359 Dendrodendritic synapse, 145, 145f
Cogwheel rigidity, 586 development of, 253–254 Deoxyribonucleic acid (DNA), 91–92, 91f
Colliculus, 53, 53f, 69 in motor cortex, 56, 359 methylation of, 104, 104f, 251, 432
inferior, 333, 334f in neocortex, 359 modification of, 104, 104f
Color agnosia, 316 in occipital cortex, 299–300, 299f Dependence. See Substance abuse
Color blindness, 311 Cortical lobes, 55, 55f. See also Frontal lobe; Occipital Depolarization, 119–122, 119f
Color constancy, 313 lobe; Parietal lobe; Temporal lobe Depolarizing potentials, 130
Color mixing Cortical mapping, 343–346, 344f, 366. See also Depression, 162, 184–185, 186, 424, 594–596
additive, 310, 310f Brain maps adolescent-onset, 275
subtractive, 310, 310f homunculus and, 366, 366f. See also Homunculus in bipolar disorder, 594
Color vision, 310–313 Cortical organization in brain injury, 225
afterimages in, 312 environmental influences in, 266–268, 267f major, 162, 184–185, 186
blobs in, 299, 299f, 312 sex differences in, 546–549 neurobiology of, 594–595
impaired, 311, 316 Cortical thickness seasonal, 448
opponent-process theory of, 311–313, 311f, 312f developmental changes in, 258, 258f sleep problems in, 473
rods and cones in, 293, 293f, 294f intelligence and, 259–260, 259f stress and, 595–596
subtractive color mixing and, 310 language and, 258, 258f, 261f treatment of, 596
trichromatic theory of, 310–311 musical ability and, 348 antidepressants in, 181t, 185, 186, 467, 574, 594,
Columns. See Cortical columns sex differences in, 546, 547f 596. See also Antidepressants
Coma, 470 Corticospinal tracts, 370–371, 370f deep brain stimulation in, 572
reticular activating system in, 470 Cortisol, in stress response, 205–207, 206f, 595 electroconvulsive therapy in, 186, 572
Common ancestor, 15, 20, 22, 22f Coup injury, 578–579, 579f transcranial magnetic stimulation in, 220, 220f,
Compensation, in lesion studies, 219 Crack cocaine, 189f, 198 573, 573f
Competitive inhibitors, 187–188 Cranial nerves, 41f, 59, 60f Dermatomes, 60, 61f, 359
Complex cells, of visual cortex, 307, 307f Creativity, hyperconnectivity and, 535 Designer drugs, 221
Complex tones, 326 Creolization, 341–342 Deuteranopia, 311
Computed tomography (CT), 226–227, 227f Critical periods Development
Computer–brain interface, 356 for brain development, 269–270 brain. See Brain development
COMT gene, 236 for brain injury, 276 cognitive, 262–265, 262f, 263t, 264f
Concentration gradient, 114, 114f for gene expression, 105 gene expression in, 251
Concordance rate, 235 for language acquisition, 341 growth spurts in, 263–264
Concrete operational stage, of cognitive development, Crossed neural connections, 43, 67 language, 254f, 258, 261–262, 341
263, 263t Cross-tolerance, 182 motor, 260–261, 261f
Concurrent discrimination, 264f, 265, 274 cryptochrome gene, 453 prenatal
Concussion, 578, 581, 582. See also Traumatic brain CT scans, 226–227, 227f cross-species similarities in, 248–250, 248f
injury Cultural bias, 537 sexual differentiation in, 203, 272
Conditioned stimulus, 482 Cultural influences, on brain development, 29, 36 Developmental disability
Conditioning Cultures, cell, 75 brain abnormalities in, 278–279
classical (Pavlovian), 481–482, 482f Curare, 176–177 causes of, 278–279, 279t
eye-blink, 481–482, 482f Current, electrical, 110 in fetal alcohol spectrum disorder, 183
fear, 481–482, 498–499 Cyclic adenosine monophosphate (cAMP) in phenylketonuria, 565
in learning, 408–409 caffeine and, 190 Dextroamphetamine, 172
operant (instrumental), 482–483 in learning, 165, 166–167 Diabetes mellitus, 202
respondent, 481–482 Cytoarchitectonic maps, 56, 56f. See also Brain maps Diagnostic and Statistical Manual of Mental Disorders
in substance abuse, 178, 195 Cytochrome P450 enzymes, 175 (DSM-5), 181, 568t–569t, 569–570
Cones (photoreceptors), 293–294, 293f, 294f Cytosine, 91f, 92 Diaschisis, 580
Congenital adrenal hyperplasia, 433 Diazepam, 182
Connectome Daily rhythms. See Circadian rhythms Dichotic listening, 541
baby, 363 Date rape drugs, 182 Diencephalon, 48, 48f, 51, 51f, 53–54, 53f
brain, 534 Daydreams, 464 Diet. See also Nutrition
definition of, 363 Deafferentiation, 382 brain size and, 25–26, 25f
Conscious memory. See Memory, explicit Deafness, cochlear implants for, 337–338, 337f depression and, 184–185
Consciousness, 556–558 Decibel (dB), 325 epigenetic effects of, 105
definition of, 556 Decision making, 538 multiple sclerosis and, 126
nonunitary nature of, 476–477 Declarative memory, 484, 485t weight-loss, 428
sleep and, 476–477 Deep brain stimulation, 13, 13f, 219–220, 516, 572, 587 Diffusion, 114–116
Conservation, in cognitive development, for epilepsy, 582–583 in neurotransmitter deactivation, 144
262f, 263, 263t for Parkinson disease, 375 Diffusion tensor imaging, 229, 229f
Consolidation, of memory, 467–468, 497–498 Deinstitutionalization, antipsychotics and, 184, 184f in tractography, 534, 535, 535f
Constraint-induced therapy, 370 Delayed matching-to-sample test, 495, 495f Digestive system, eating control and, 427, 429f
Contralateral, definition of, 39 Delayed-alternation task, 495, 495f Dimers, 453
Contralateral neglect, 529–530, 530f Delayed-response test, 495, 495f Disinhibition theory, 191–192
Contrecoup injury, 578–579, 579f Delta receptors, 187 Displacement task, 264, 264f
S-6 Subject Index
Distal, definition of, 39 psychoactive, 173 graded, 119–120, 119f
Distributed hierarchical model, 68, 68f antianxiety agents, 181–182, 181t, 425, 597 EEG recording of, 223–224, 223f
Distributed reinstatement theory, 497 antidepressants, 181t, 185, 186. See also summation of, 128–130, 129f, 130f
Diurnal animals, 442 Antidepressants inhibitory postsynaptic, 127–130, 129f, 130f
Divergent thinking, 554 antipsychotics, 181t, 184, 574 miniature postsynaptic, 144
Diving bradycardia, 138 grouping of, 181–191 resting, 116–119, 117f
DNA, 91–92, 91f mood stabilizers, 181t, 186 threshold, 120
methylation of, 104, 104f, 251, 432 names of, 181 Electrical recording studies, 110, 111
modification of, 104, 104f opioid analgesics, 181t, 187–188 Electrical self-stimulation, 219
Dr. Death, 198 psychedelic/hallucinogenic stimulants, 181t, Electrical stimulation studies, 109–111
Dominant alleles, 97, 99f 189–190 Electrical synapses, 142, 145–146
Domino effect, in action potential psychotropics, 181t, 188–190 Electricity, 110
propagation, 123f, 124 sedative-hypnotics, 181–182, 181t, 473 early studies of, 109–113
Domoic acid poisoning, 197, 197f routes of administration for, 173–174, 173f Electroconvulsive therapy, 186, 572
l-Dopa, 150, 150f, 152, 573, 587 sensitization to, 178–180, 510–511 Electrocorticography (ECoG), 223
Dopamine, 150, 150f, 159f, 160–161. See also Drug Addiction Treatment Act of 2000, 196 Electrodes, 110
Neurotransmitters Drug dependence, 193 Electroencephalography (EEG), 108, 111, 210–211,
in attention-deficit/hyperactivity Drug manipulation studies, 220 223–224
disorder, 240, 241 Drug tolerance, 177–178 alpha rhythms in, 458
in enteric nervous system, 158 Drug-dependency insomnia, 473 applications of, 223–224
in memory, 498 Drug-induced behavioral sensitization, 510–511 beta rhythms in, 458
in movement, 375 Drug-induced psychosis, 184, 198, 199, 236 in brain mapping, 223f, 224–225
in Parkinson disease, 140 DSM-5 (Diagnostic and Statistical Manual of Mental definition of, 111
receptors for, 155, 155t Disorders), 5th ed., 181, 568t–569t, 569–570 delta rhythms in, 458
reward and, 437–438, 437f Dualism, 7–8, 8f desynchronized tracings in, 470
in schizophrenia, 161, 184 Dunce, 166 event-related potentials and, 224–225, 224f
stimulants and, 188 Dura mater, 37, 37f in graded potential recording, 223–224, 223f
in substance abuse, 192, 193, 195 Dynorphins, 187 in sleep studies, 223f, 224, 457–459, 457f, 459f,
Dopamine hypothesis, 184 Dyskinesias, 373–374 470–472
Dopamine neuron transplant, 161 Dyslexia, 480 vs. magnetoencephalography, 226
for Parkinson disease, 516, 587–588 Dystonia(s) in waking state, 457–458, 457f, 459f, 471
Dopaminergic system, 159f, 160–161, 567f focal hand, 507 Electrographic seizures, 108
Dopa-responsive dystonia, 74 selective, 375 Electrolytic lesions, 218–219
Dorsal, definition of, 38, 39 Electromyography, in sleep studies, 457, 457f
Dorsal roots, 61, 62f E cells, 452 Electron, 88, 89, 110
Dorsal visual stream, 69–70, 69f, 297, 300f, 313, 527f Ear. See also under Auditory Electron microscope, 140–141, 141f
as how pathway, 297, 317–318 structure of, 329–331, 330f, 331f, 332f Electrooculography, in sleep studies, 457, 457f
injury of, 317–318 in vestibular system, 388–389, 389f Elements, chemical, 88, 88f
location of, 527f Eardrum, 329, 330f Elephants, brain size in, 22, 23f, 24
secondary somatosensory cortex in, 393–394 Eating disorders, 275, 427 Eliminative materialism, 12
in vision for action, 527f Eating/feeding behavior Embodied behavior, 4–5
Dorsolateral prefrontal cortex, 258, 526f amygdala in, 418, 430, 430f Embryonic disc, 249, 249f
theory of mind and, 536 aversive behavior in, 409, 438, 438f Embryos
Dorsomedial nucleus, 54 biological clocks and, 450, 455–456 cross-species similarities in, 248–250, 248f
Dorsomedial prefrontal cortex, 418f, 419 cognitive factors in, 430 development of, 248–252, 249f, 250f
Dorsomedial thalamic nucleus, 53f, 54 dieting and, 428 preformation and, 248
Dosage, 173–174 digestive system and, 427–428, 429f Emotion
Down syndrome, 100, 101f eating disorders and, 427 anterior cingulate cortex and, 526
DREADD, 221 environmental factors in, 427 definition of, 398
Dreams, 461–464 of fly, 409–410 expression of, 410–411, 421–422, 537
activation-synthesis hypothesis for, 462–463 hedonic reactions in, 438, 438f regulation of, 537
anxiety, 463–464 hypothalamus in, 399 Emotional behavior, 399, 416–418, 421–426
avoidance vs. approach behavior in, 463–464 prefrontal cortex in, 430 abnormal, 424–426
content of, 461–464 regulation of, 426–430 amygdala in, 57–58, 57f, 418, 422–423
evolutionary hypothesis for, 463–464 reward and, 437–438 in animals, 410–411
function of, 463–464 Echolocation control of, 537
hallucinations and, 476–477 in bats, 351–352 expressive, 410–411, 421–422
lucid, 464, 476 in blind people, 335 facial expressions and, 423–424
in memory storage, 468 Economic decision making, 538 generation of, 421–422
in REM sleep, 458, 461–464 Ecstasy (MDMA), 190, 198 James-Lange theory of, 421
Drinking behavior, 430–431 EEG. See Electroencephalography (EEG) limbic system in, 57–58, 57f, 416–418, 417f
amygdala in, 418 Efferent nerves, 37, 37f overview of, 421–422
water intoxication and, 431 Efferent sensory signals, 358 prefrontal cortex in, 423–424
Drosophila melanogaster, learning in, 166–167, 167f Ego, 563 somatic marker hypothesis for, 421–422
Drowsy state, 458 Elderly, cognitive loss in, 591. See also Dementia tone of voice and, 424
Drug(s) Electrical activity Emotional disorders, 424–426
of abuse. See Substance abuse in brain, measurement of, 222–226 Emotional memory, 499, 499f
adverse effects of, 574 in cell membrane, 111–127 Emotional pain, 398
agonist/antagonist, 176–177, 176f early studies of, 109–113 Emotional rhythms, 456
for behavioral disorders, 573–574 in giant axon of squid, 112 Emotional therapy, 575
blood–brain barrier and, 174–175 recording of Empathy, 536
classification of, 181t electroencephalographic, 108, 111. See also Encephalitis, 42
cross-tolerance to, 182 Electroencephalography (EEG) L-dopa for, 150, 150f, 152
designer, 221 microelectrodes in, 113–114 memory loss in, 490
dosage of, 173–174 oscilloscope in, 113 Encephalization, 18
effects of, variability in, 176–180 single-cell, 133f Encephalization quotient (EQ), 22, 23f
as environmental contaminants, 175 voltmeter in, 110, 111 End foot, 77, 78f
excretion of, 175 during sleep, 457f, 458–459, 458–459 End plates, 133, 133f, 134
groupings of, 181–191, 181t stimulation of, 109–111 Endocannabinoids, 151–153
individual responses to, 191–194 voltage gradient and, 114–115 Endocrine glands, 202–206. See also Hormones and
mechanism of action of, 175f, 176–177, 176f Electrical charges, 114–116 specific glands
metabolism of, 175 Electrical potentials, 110 regulation of, 200–201, 201f, 412–415. See also
movement disorders due to, 574 action, 120–123. See also Action potential Hypothalamus
neuroplasticity and, 510–511, 511f definition of, 110 Endolymph, 388
prenatal exposure to, brain injury from, 276–277 excitatory postsynaptic, 127–130, 129f, 130f, 164 Endomorphins, 187
Subject Index S-7
Endoplasmic reticulum, 87f, 90, 93 radiator hypothesis and, 26 emotion and, 421–422
Endorphins, 151, 187 of sex differences, 548–549 loss of libido and, 436
Endothelial cells, in blood–brain barrier, 174, 174f Evolutionary psychology, 407–408 in memory, 495
Enkephalins, 151, 187 Excitation, vs. inhibition, 70–71, 80 in planning, 531
Enteric nervous system, 37, 64–65 Excitatory postsynaptic potentials, 127–130, in schizophrenia, 278
autonomy of, 158 129f, 130f in sequential movement, 522
in brain development, 275 in habituation, 164 in sexual behavior, 436
neurotransmitters of, 158 Excitatory synapses, 146, 146f structure and function of, 55, 55f, 418f, 419–420
Entorhinal cortex Executive functions, of frontal lobe, 419–420 Frontal lobotomy, 423–424, 423f
in Alzheimer disease, 589 Exelon (rivastigmine), 492 emotional behavior after, 43–424
in memory, 491–492, 491f Exercise, therapeutic benefits of, 576 Fruit foraging, brain size and, 25, 25f
Entrainment, 446–448, 449f Expectations, 537 Functional brain imaging, 229–234
Environment, epigenetics and, 11. See also Experimental animals, 101–102, 239–242. See also Functional connective magnetic resonance imaging
Epigenetics Animal research (fcMRI), 534–535, 534f
Environmental enrichment Explicit memory. See Memory, explicit Functional levels, 50–58, 67–68
behavior and, 400–401 Extensors, 372 Functional magnetic resonance imaging (fMRI),
brain development and, 270–271 External ear canal, 329, 330f 230–231, 230f
brain size and, 504 Extinction, 529–530, 530f in brain mapping, 534–535, 534f
intelligence and, 555 Extracellular fluid, 87f, 90 real-time, 576
in learning, 504–505, 505f Extracellular recordings, 222 resting-state, 231
Enzymes, 93–94 Extrastriate cortex, 299, 300f Functional near-infrared spectroscopy (fNIRS), 210,
Ependymal cells, 82, 82t Eye. See also under Vision; Visual 231–232, 231f
Epidemiology, 568 structure of, 289–291, 291f Fundamental frequency, 326, 326f, 328
Epidermal growth factor, 252 Eyeblink conditioning, 481–482, 482f Fusiform face area, 301
in brain injury, 516
Epidural anesthesia, 387 Facial agnosia, 301 g factor, 28, 553
Epigenetic code, 103–105 Facial expressions G proteins, 154, 154f
Epigenetic drift, 237 innate releasing mechanisms for, 407, 407f GABA (gamma-aminobutyric acid), 150, 151f, 566
Epigenetics, 11 interpretation of, 424, 530 receptors for, 155, 155t
applications of, 237 loss of, 423–424 GABAA receptor, drug effects at, 182
autism spectrum disorders and, 255 production of, 423–424 Gamma-hydroxybutyric acid (GHB), 182
brain/behavioral disorders and, 564 Facial nerve, 59, 60f Ganglia, 18
changes across populations and, 237 Facial paralysis, 62 basal. See Basal ganglia
critical periods and, 105 False memories, 485, 487 parasympathetic, 63–64
DNA modification and, 104, 104f Families, taxonomic, 16, 16f posterior-root, 381–382, 381f
frontal lobe development and, 258–259, 271 Farsightedness, 290–291 sympathetic, 63–64
histone modification and, 103–104, 104f Fatal familial insomnia, 472 Ganglion cells
intelligence and, 555 Fear conditioning, 481–482, 498–499 melanopsin, 453
life experiences and, 235, 237 Fear, emotional memory and, 498–499 on-center/off-center, 305–306, 306f, 307f
neuroplasticity and, 511 Feedback loops, hormonal, 414–415, 415f retinal. See Retinal ganglion cells
neurotoxins and, 196 Feeding behavior. See Eating/feeding behavior Gap junctions, 142, 142f, 145–146
phenotypic plasticity and, 36, 103–105 Festination, 586 Gaseous neurotransmitters, 153
reflective vs. reflexive systems and, 538 Fetal alcohol spectrum disorder, 28, 183, 267, 271 Gastrointestinal function, enteric nervous system
RNA modification and, 103–104, 104f Fight-or-flight response, 63, 157–158, 204, 205f and, 64–65, 65f
schizophrenia and, 593 Filopodia, 167, 256, 256f Gastrointestinal system, eating control and, 427–428, 429f
sex hormones and, 274–275, 432 Fissures, 41f, 42 Gate theory of pain, 386–387, 387f
sexual orientation and, 435 Flehmen, 403f Gated ion channels, 95, 95f, 117–119, 121f, 122f.
stress effects and, 237, 271 Flexors, 372 See also Ion channels
substance abuse and, 196 Flies, feeding behavior of, 409–410 Gender differences. See Sex differences
synaptic organization and, 555 Flocculus, 375–376, 376f Gender identity, 435
twin studies and, 237 Fluid homeostasis, 430–431 Gene(s), 10–11, 91–92, 96–105
Epilepsy, 108, 581–583. See also Seizures Fluoxetine, 185, 186, 596 alleles and, 97, 99f
brain surgery for, 343, 345 Flupentixol, sensitization to, 180 identification of, 236
Epinephrine (adrenaline), 138–139, 138f, 150, 150f. Flynn effect, 29 transcription of, 93f
See also Neurotransmitters FMRI, real-time, 576 Gene expression, 10–11, 97, 103, 103f
in stress response, 204 Focal hand dystonia, 507 critical period for, 105
Episodic memory, 467, 486–487, 487f Focal seizures, 582 definition of, 236, 251
Equilibrium, vestibular system in, 388–389, 389f Follicle-stimulating hormone (FSH), 414t in development, 251
Estradiol, in brain masculinization, 432 Foraging, brain size and, 25–26, 25f epigenetics and, 11, 103–105, 236–237. See also
Estrogen. See also Sex hormones Forebrain, 4, 4f, 48, 48f, 54, 54f Epigenetics
activating effects of, 433 in movement initiation, 358–361, 360f, 361f measurement of, 236–237
in brain development, 203, 273–275, 546–549 structure of, 54, 54f methylation and, 251, 251f, 432
in brain masculinization, 432 Foreign languages Gene knockout, 102
cognitive function and, 203 cortical localization for, 268 Gene methylation, 104, 104f, 251, 432
functions of, 203 learning of, 340–341 General intelligence, 28–29, 553
lifelong effects of, 274–275 Formal operational stage, of cognitive development, General stimulants, 190
neuroplasticity and, 509, 509f 263, 263t Generalized anxiety disorder, 425, 574, 597. See also
sexual behavior and, 433 Fovea, retinal, 289–292, 291f, 302, 303f Anxiety disorders
Event-related potentials, 224–225, 224f, 225f Free-running rhythms, 445–446 Generalized seizures, 582
vs. magnetoencephalography, 226 Frequency, of sound waves, 323–324, 324f, 326 Genetic code, 93, 93f
Evolution in music, 328, 328f Genetic diseases
of behavior, 406–408 Frontal, definition of, 39 diagnosis of, 74
of brain, 15–29, 47–50, 48f Frontal leukotomy, 423–424, 423f inheritance of, 98–100
brain–behavior link and, 19–27 emotional behavior after, 423–424 Genetic engineering, 101–102, 102f
of cognition, 522 Frontal lobe, 41f, 55, 55f Genetic mutations, 97–100
common ancestor in, 15, 20, 22, 22f agenesis of, 420 beneficial, 98
culture and, 29 in association cortex, 525–526, 526f, 527f disease-causing, 98–100
Darwin’s theory of, 8–12 in attention, 529 learning and, 166–167, 167f
dreams and, 463–464 in cognition, 522, 529 in selective breeding, 101
hierarchical organization of nervous system development of, 258–259, 259f Genetic studies, 235–237
and, 36–37 epigenetic effects on, 258–259, 271 Genetic testing, 74
of language, 8, 322, 340–342 executive functions of, 419–420 Geniculate nuclei. See Lateral geniculate nucleus;
of music, 322 injuries of, 55 Medial geniculate nucleus
natural selection and, 8–12 amnesia and, 487, 495 Geniculostriate pathway/system, 296, 296f,
neoteny and, 26–27 divergent thinking and, 554 297–298, 297f, 298f
S-8 Subject Index
Genome sequencing, 74 Hairy skin, sensory receptors in, 379 Homo neanderthalensis, 21–22, 21f
Genotype, 10, 96 Hallucinations music-making by, 322
Genus, 16, 16f dreams and, 476–477 Homo sapiens, 16. See also Humans
Ghrelin, 202 hypnogogic, 475 evolution of, 19–29
Giant axon of squid, electrical activity in schizophrenia, 278 Homonymous hemianopia, 314
in, 112, 112f in substance abuse, 198 Homosexuality, 434–435
Giant depolarizing potentials, 133 Hallucinogenic amphetamine, 198 Homozygous alleles, 97
Glabrous skin, sensory receptors in, 379 Halorhodopsin, 131 Homunculus
Glasgow Coma Scale, 13 Hammer, 329, 330f cerebellar, 375–376, 376f
Glial cells, 46, 47f, 80–85, 146 Handedness, cortical organization and, 334–335, motor, 366, 366f, 371
in blood–brain barrier, 173 549–551 somatosensory, 390–391, 391f
definition of, 80 Hapsis, 380, 380f Horizontal cells, retinal, 294, 295f
development of, 259–260 Haptic-proprioceptive pathway, 382–383, 383f Horizontal, definition of, 39
formation of, 252 Harrison Narcotics Act of 1914, 196 Horizontal section, 39f
functions of, 82t Head direction cells, 494 Hormones, 139, 202–206
in nerve repair, 85–86, 85f Head trauma. See Traumatic brain injury in brain development, 273–275
properties of, 82t Headaches, migraine, scotoma in, 284 classification of, 201–202
radial, 253, 253f Hearing. See also Auditory system; Sound cognitive function and, 203
types of, 80–85, 82t in animals, 324, 325f early studies of, 200
Glial uptake, in neurotransmitter deactivation, 144 evolution of, 329 eating behavior and, 427–430
Glioblasts, 250 mechanics of, 329–331, 330f–332f feedback loops for, 414–415, 415f
Gliogenesis, 252 movement and, 333 functions of, 200, 201–202
Gliomas, 83 neural activity in, 336–340 glucocorticoid, 202
Globus pallidus, 57, 57f, 373, 373f in owls, 339, 339f neurotoxicity of, 510
electrode placement in, 572, 587 Hebb synapse, 163 homeostatic, 201, 202
in movement, 375, 376f Hebb-Williams mazes, 266–267, 266f neuropeptide, 150–151
in Parkinson disease, 375, 587 Helix neuroplasticity and, 509–510, 509f
Glomeruli, olfactory, 402f, 403 DNA, 91f, 92 organizational hypothesis and, 203
Glossopharyngeal nerve, 59, 60f protein, 93, 93f peptide, 201
Glucocorticoids, 202. See also Hormones Hemianopia, homonymous, 314 pituitary, 200, 210f, 414, 414t
neurotoxicity of, 510 Hemispherectomy, 42 receptors for, 201–202, 201f
Glucose, in eating behavior, 427 Hemispheres. See Cerebral hemispheres regulation of, 200–201, 201f, 412–415, 413f–415f.
Glutamate, 150, 151f Hemispheric connectivity, 534 See also Hypothalamus
in domoic acid poisoning, 197 environmental influences in brain development releasing, 414, 414t
in long-term potentiation, 501–502, 501f and, 268–269 sex (gonadal). See Sex hormones
neurotoxicity of, 197 gender differences in, 548 stress, 204–206, 205f, 206f, 595–596, 595f
receptors for, 155, 155t Hemorrhagic stroke, 45 target glands of, 200, 201f
Glutamate psychedelics, 190 Hemp plant, 152–153 thyroid, 414–415, 414t
Glutamate receptor, 197 Heritability. See Inheritance Horror autotoxicus, 584
Glycine, 150 Heroin, 187, 187f, 188 HPA axis, stress effects on, 595–596
receptors for, 155, 155t synthetic, parkinsonian symptoms from, 161 Humans
Goal trackers, 195–196 Herpes simplex encephalitis, amnesia in, 490 apes and, 20, 20f
Golgi body, 87f, 90, 94–95, 94f Hertz (Hz), 323–324 as chordates, 18–19, 19f
Gollin figure test, 484, 484f Heschl’s gyrus, 334, 334f early ancestors of, 20–21, 21f
Gonadal hormones. See Sex hormones in music processing, 347, 347f evolution of. See also Evolution
Graded potentials, 119–120, 119f Heterochrony, 26 as hominids, 20–21
EEG recording of, 223–224, 223f Heterosexuality, 434–435 as primates, 20, 20f
summation of, 128–130, 129f Heterozygous alleles, 97 taxonomy of, 16–17, 16f
Grammar, universal, 341–342, 521 Hibernation, circannual rhythms and, 454–455 Huntington disease, 99f, 100, 102, 373–374
Grasping Hierarchical organization, of nervous system, 50–58, Hydrocephalus, 82
development of, 260–261, 261f 68–69, 68f, 357–365, 390–391 Hydrogen bonds, 89
hapsis and, 380, 380f High blood pressure, dementia and, 591 Hydrogen sulfide, as neurotransmitter, 153
movements in, 360–361, 361f Higher vocal control center, in birds, 350–351, 351f Hyperactivity, 162
vision in, 300, 313, 316, 316f, 317f Highly superior autobiographical memory, 487 in attention-deficit/hyperactivity disorder, 162, 240
Gray matter, 43, 43f, 46–47, 47f Hindbrain, 48, 48f, 51, 51f, 52–53, 52f in brain stimulation studies, 220
layers of, 56, 56f Hippocampus, 54f, 57–58, 57f, 417, 417f Hypercomplex cells, of visual cortex, 307, 308f
periaqueductal, 53, 53f antidepressants and, 185 Hyperconnectivity, 535
in pain, 388 in domoic acid poisoning, 197f Hyperglycemia, 202
in reticular formation, 52 epigenetic differences in, 237 Hyperkinetic rats, 220
sex differences in, 546, 547f in learning, 212, 213 Hyperkinetic symptoms, 374
spinal, 62f in memory, 212, 213 Hyperopia, 290–291
thickness of, language development and, 258, 258f, in consolidation, 497–498 Hyperphagia, 429
261, 261f, 262 explicit, 497–498 Hyperpolarization, 119–122, 119f
Great apes, 20. See also Primates, nonhuman spatial, 492–494, 493f, 494f Hypertension, dementia and, 591
Grooming behavior, 362 mood and, 595–596 Hypnogogic hallucinations, 475
Growth cones, 256, 256f neurogenesis in, 503–504, 504f Hypoactivity, in brain stimulation studies, 220
Growth factors, 84 antidepressants and, 596 Hypocretin, 475
in brain development, 252 place cells in, 222–223, 222f, 468, 494, 494f Hypoglossal nerve, 59, 60f
neuroplasticity and, 84, 510 in schizophrenia, 278 Hypoglycemia, 202
Growth hormone (GH), 414t in sleep, 468 Hypokinesia, 586
Growth spurts, 263–264 spatial cells in, 494 Hypokinetic rats, 220
Guanine, 91f, 92 stress and, 185, 205–206, 205f, 595–596 Hypokinetic symptoms, 374
Gustation, 404–406 Histamine, 149 Hypothalamic-pituitary-adrenal (HPA) axis, stress effects
Gut bacteria, 65 receptors for, 155, 155t on, 595–596
in brain development, 275 Histones, 103–104 Hypothalamus, 53–54, 53f
Gynandromorphs, 275 Home environment. See also Environmental amygdala and, 418–419
Gyrus, 42, 55, 55f enrichment in behavior generation, 416, 417f
Heschl’s, 334, 334f, 347, 347f experimental effects of, 179 in biorhythms, 450–452
Gyrus fornicatus, 38 Homeostatic hormones, 201, 202 electrical stimulation of, 219
Homeostatic mechanisms, 411, 411f in feeding behavior, 399, 429–430, 430f
Habituation, 163–164, 164f, 500 Homicide, 407 in homeostasis, 411–415, 411f
dendritic spines in, 167 Hominids, 20–21 in hormone regulation, 412–415, 413f–415f
Hair cells Homo erectus, 21, 21f, 22, 24f, 26 limbic system and, 416–418
in auditory system, 330, 330f, 332, 332f, 336–337 Homo floresienses, 21 neurohormone secretion by, 200, 201f
in vestibular system, 388, 389f Homo habilis, 21, 21f, 25 in nonregulatory behaviors, 412
Subject Index S-9
pituitary gland and, 412–415, 414f, 595–596 Intergeniculate leaflet, 450, 451 sex differences in, 546–549
in regulatory behaviors, 411–412 International Classification of Diseases (WHO), 569 as sound, 327–328
in sexual behavior, 434, 435f Interneurons, 78, 79, 79f structural uniformity of, 340–342
in sexual orientation, 434–435 motor, 371–372 syntax of, 341–342, 521–522
in stress response, 204, 205f, 206f Interpersonal intelligence, 553–554 vs. birdsong, 349–350
in temperature regulation, 411–412 Intoxication, toxin action at synapses in, 176–177 Wernicke’s area for, 334, 334f, 342f, 343–346
Hypovolemic thirst, 431 Intracellular fluid, 87f, 90 mapping of, 343–346, 344f
Intracellular recordings, 222 Language acquisition, critical period for, 341
Id, 563 Intracranial self-stimulation, 437 Language deficits
Illusions, perceptual, 288, 288f Intrapersonal intelligence, 553–554 in autism spectrum disorder, 255
Imagination, 554 Invertebrates, learning in, 49 in carbon monoxide poisoning, 315
Imaging studies, 226–234, 238–239, 238t Ion(s), 88, 89, 89f Language test, 8
anatomical, 226–229 electrical charge of, 114–116, 114f Lark chronotype, 451–452, 453
in brain mapping, 533–536, 534f movement of, 114–116 Latent content, of dreams, 462
in brain/behavioral disorders, 570–571, 570f, 579 Ion channels, 95, 95f, 117–118, 117f Lateral corticospinal tract, 370f, 371, 371f
functional, 229–234 gated (voltage-sensitive), 95, 95f, 117–119, 121–122, Lateral, definition of, 38, 39
in traumatic brain injury, 578, 579 121f, 122f Lateral fissure, 41f, 42, 55, 55f
Imitation, 531–532 in learning, 164, 164f, 165f Lateral geniculate nucleus, 53f, 54, 297–298, 298f,
Immune system, 84 light-sensitive, 131 302–303, 302f, 303f
Implicit memory. See Memory, implicit in muscle contraction, 133–134, 133f receptive field of, 302–303
Imprinting, 270, 270f in nerve impulse production, 125, 133f Lateral hypothalamus, in eating, 429
Incentive sensitization theory, 194–196 in sensitization, 164–166, 165f Lateral sulcus, 43f
Induced neurogenesis, 572, 587–588 in sensory processing, 133, 133f Lateral ventricles, 43f
Infants, brain maps for, 363 stretch-sensitive, 133 Lateralization, 334–335. See also Cerebral asymmetry
Inferential thinking, cerebral asymmetry and, 545 transmitter-sensitive, 133 for auditory processing, 541
Inferior colliculus, 53, 53f, 69, 333, 334f Ion pumps, 95, 95f, 117–119, 117f for cognition, 539–546
Inferior, definition of, 38, 39 Ionic bonds, 89 handedness and, 334–335, 549–551
Information flow Ionotropic receptors, 153, 153f for language, 334–335, 543–545
in brain, 296, 296f Ipsilateral, definition of, 39 for music, 346–347, 541
Descarte’s theory of, 108–109 Iris, 219f, 291 overlapping functions and, 305, 306f, 543
electrical activity and, 111, 112f Ischemia, cerebral, 580 in split-brain patients, 520, 542–543, 545
in somatosensory system, 358–359 Ischemic stroke, 45, 580 for visual processing, 540, 542f. See also Visual fields
in visual system, 296, 296f Itch, 364, 385 Law of Bell and Magendie, 61, 62
Infradian rhythms, 444, 445t L-dopa, 150, 150f, 152, 573, 587
Inheritance James-Lange theory, 421 Learned behavior, 6, 6f, 408–409
of dominant traits, 97, 99f Jerison’s principle of proper mass, 303 Learned taste aversion, 409
of genetic diseases, 98–100 Jet lag, 448, 449 Learned tolerance, 178
of intelligence, 555 Learning, 6, 481–483. See also Memory
Mendelian, 98–100, 99f Kainic acid poisoning, 197 associative, 409, 500
of recessive traits, 97, 99f Kappa receptors, 187 behavior and, 408–409
Inherited behavior, vs. learned behavior, 6, 6f Ketamine, 182, 190, 197 cognitive enhancers and, 172
Inherited traits, 10–11, 98–100, 99f as antidepressant, 186 conditioning in, 408–409, 481–483, 482f. See also
Inhibition, vs. excitation, 70–71, 80 Kingdoms, taxonomic, 16, 16f Conditioning
Inhibitory postsynaptic potential, 127–130, Klonopin, 182 definition of, 163, 481
129f, 130f Klüver-Bucy syndrome, 422–423 dendritic spines in, 167
Inhibitory synapses, 146, 146f Knee jerk reflex, 50–51, 384–385, 384f enriched experience in, 504–505, 505f
Innate releasing mechanisms, 406–407 Knock-in/knockout technology, 102 habituation in, 163–164, 164f, 500
Insomnia, 473 Korsakoff syndrome, 495–497 hippocampus in, 212, 213
brainstem injury and, 476–477 in invertebrates, 49
drug-dependency, 473 Landmark-learning task, 215, 216f long-term potentiation and, 500–502
fatal familial, 472 Landmarks, visual processing of, 301, 527–528 mutations affecting, 166–167, 167f
Instrumental (operant) conditioning, 482–483 Language. See also Speech neurogenesis in, 504–505
Insula, 334f, 335 in animals, 8, 9, 522, 523 neuronal changes in, 166–167
in gustation, 405 bilingualism and neuroplasticity and, 35–36, 270–271, 500–502, 508.
Insulin, 202 cognitive advances of, 555 See also Neuroplasticity
Integration, in neurons, 127–131 cortical areas for, 268 object-reversal, 274
Intellectual disability, 571 birdsong and, 349–351 preparedness and, 409
Intellectual potential, 555 Braille and, 543 second messengers in, 165f, 166–167
Intelligence, 552–556. See also Cognition Broca’s area for, 254f, 262, 342–346, 342f, 346f sensitization in, 164–166, 165f
animal, 522–524 mapping of, 343–346, 344f sites of, 485
artificial, 80, 81 cognitive functions of, 521–522 during sleep, 466–467, 468–469
bodily-kinesthetic, 553 consciousness and, 558 studies of, 481–483
brain size and, 23, 24, 28–29, 553, 553f cortical development and, 258 in substance abuse, 178, 192, 195
convergent, 554 cortical localization of, 70, 334–335, 342–346, synapses in, 163–168
cortical thickness and, 259–260, 259f 543–545 loss or formation of, 166–167
divergent, 554 mapping of, 343–346 structural changes in, 166–167
epigenetics and, 555 for second languages, 268 visuospatial, 493
frontal lobe development and, 259, 259f sodium amobarbital test for, 550 Learning disabilities, 480
general, 28–29, 553 creolization of, 341–342 Left-handedness. See also Cerebral asymmetry
heritability of, 555 development of, 254f, 261–262, 341 cortical organization and, 334–335, 549–551
intellectual potential and, 555 evolution of, 8, 322, 340–342 lateralization and, 334–335
interpersonal, 553–554 genetic aspects of, 341 Lens, 291, 291f
linguistic, 553 handedness and, 334–335, 549–551 in refractive errors, 290–291
logical-mathematical, 553 lateralization for, 334–335, 543–545 Leptin, 202
multiple, 29, 553–554 movement and, 543–545 Lesion studies, 218–219
musical, 553, 554 music and, 322, 327, 345 Lesions, brain. See Brain injury
network efficiency and, 555 in newborns, functional near-infrared spectroscopy Leukotomy, frontal, emotional behavior after, 423–424
observed, 555 and, 210 Levels of function, 50–58, 67–68
spatial, 553 pidgin, 342 Lewy body, 590, 590f
synaptic organization and, 555 processing of, 340–346 Liberation therapy, 584
Intelligence A, 555 properties of, 328 Libido, loss of, 436
Intelligence B, 555 second Life forms, classification of, 16–17, 16f
Intelligence tests, 554 cortical localization for, 268 Light
Interaural time difference, 338–339 learning of, 340–341 circadian rhythms and, 446–448
Interblobs, 299 self-regulation and, 537 perception of, 290
S-10 Subject Index
properties of, 290, 290f Membrane neuroplasticity and, 509, 509f
receptors for, 286, 289–294, 291f, 293f, 294f basilar, in hearing, 330–331, 330f, 331f, 332f synchronized cycles in, 403
retinal ganglion cells as, 296, 302, 451 cell. See Cell membrane Mental illness. See Psychiatric disorders
in seasonal affective disorder, 448 postsynaptic, 142, 142f, 144–145 Mental impairment. See Developmental disability
wave form of, 290, 290f presynaptic, 142, 142f, 143 Mentalism, 7, 12
Light pollution, 447 refractory, 122–123, 124 Mescaline, 190
Light-sensitive ion channels, 131 tectorial, of inner ear, 330, 330f Mesencephalon (midbrain), 48, 48f, 51, 51f, 53, 53f
Limbic system, 54, 54f, 57–58, 57f, 416–418 Membrane potential. See Electrical potentials Mesolimbic dopaminergic system, 160–161, 375, 375f
in eating, 418, 430 Membrane proteins, 94f, 95, 95f reward and, 437, 437f
in sexual behavior, 434 Memes, 29 structure and function of, 437, 437f
structure and function of, 416–418, 417f Memory. See also Learning in substance abuse, 195
Linguistic intelligence, 553 accuracy of, 485 Messenger RNA, 93, 93f
Lipid transmitters, 151–153 autobiographical, 486–487 Met allele, 236
Lithium, for bipolar disorder, 186 basal ganglia in, 489–490, 499 Metabolic syndrome, 442, 447, 448
Little disease, 363 brain areas for, 70 Metabolism, drug, 175
Lobectomy, temporal, Klüver-Bucy syndrome and, 422 classification of, 483–485, 485t Metabotropic receptors, 153–155, 154f
Lobotomy, frontal, 423–424, 423f consolidation of, 467–468, 497–498 Metaplasticity, 512
emotional behavior after, 423–424 reconsolidation in, 497 Metastatic brain tumors, 83
Locked-in syndrome, 5, 13, 356, 363 declarative, 484, 485t Metencephalon, 48, 48f
Logical-mathematical intelligence, 553 definition of, 481 Methamphetamine, 189
Loglio vulgaris distribution of, 486, 486f Methylation, 104, 104f, 251, 432
electrical activity in, 112 emotional, 499, 499f Methylphenidate, 172
giant axon of, electrical activity in, 112f encoding in, 485 Microbiome, 65
Longitudinal fissure, 41f, 42, 55, 55f episodic, 467, 486–487, 487f in brain development, 275
Long-term depression, 501 erasing, 498 Microdialysis, 235, 235f
Long-term memory, 486 explicit, 484–485, 485t Microelectrodes, 113–114
Long-term potentiation, 500–502, 501f consolidation of, 497–498 Microfilaments, 87f, 90
Lordosis, in copulation, 434 deficits in, 487 Microglia, 82t, 84–85
Lou Gehrig disease, 134, 356, 363 long-term potentiation and, 500–502 in neuron repair, 85–86
Loudness, 324–325, 324f, 325f Mishkin model of, 495–497, 497f, 498 Microscope, electron, 140–141
detection of, 338–339 neural circuits for, 491–497, 491f, 499f Microsleep, 466
of music, 328 NREM sleep and, 468 Microtubules, 94–95, 94f
LSD (lysergic acid diethylamide), 190 false, 485, 487 Microvilli, of taste buds, 405, 405f
Lucid dreaming, 464, 476 hippocampus in, 212, 213 Midbrain, 48, 48f, 51, 51f, 53, 53f
Lumbar spine, 60, 61f implicit, 467, 483–484, 485t Middle cerebral artery, 43, 43f
Luminance contrast, 284f, 306–307, 306f deficits in, 489–490 Migraine, scotoma in, 286–287
Luteinizing hormone (LH), 414t Mishkin model of, 498, 498f Migration, neuronal, 253–254
Lysosomes, 87f, 90 neural circuits for, 498, 498f Mild cognitive impairment, 492, 591
NREM sleep and, 468–469 Milner-Goodale experiment, 316–317, 317f
M cells, 295–298, 295f, 451 labile stage of, 467 Mind, 7. See also Consciousness
Magnetic resonance imaging (MRI), 227–229, 228f, limbic system in, 57 Freud’s theory of, 563
534–535 long-term, 486 Mind-body problem, 8
in diffusion tensor imaging, 229, 229f medial temporal region in, 491–497, 498f Miniature postsynaptic potentials, 144
functional, 230–231, 230f medial thalamus in, 495–497, 498f Minimally conscious state, 13
in brain mapping, 534–535, 534f multiple process theories of, 468 Minor tranquilizers, 182
real-time, 576 parahippocampal cortex in, 491–492, 491f Mirror neurons, 532
resting-state, 231 personal, 486–487, 487f Mirror-drawing task, 214f, 215
Magnetic resonance spectroscopy (MRS), 229, 579 priming of, 485 Mishkin model
Magnetoencephalography (MEG), 226, 507 procedural, 484, 485t of explicit memory, 495–497, 497f, 498, 498f
Magnocellular (M) cells, 295–298, 295f, 451 processing of, 486 of implicit memory, 498, 498f
Magnocellular nucleus of medulla, in sleep, 472 recall of, 467 Mitochondria, 87f, 90, 143
Major depression. See Depression sequential process theories of, 468 Molecules, 89
Malnutrition, epigenetic effects of, 105 short-term, 486 Monkeys. See Primates, nonhuman
Mania, 162, 186, 594. See also Bipolar disorder tests of, 495, 495f Monoamine oxidase (MAO) inhibitors, 185
Manifest content, of dreams, 462 sites of, 486, 486f Monocular blindness, 314
MAO inhibitors, 185 spatial, hippocampus in, 492–494, 493f, 494f Monosodium glutamate (MSG), neurotoxicity of, 197, 198
Maps. See Brain maps storage of, 486 Monosynaptic reflex, 384
Marijuana, 153, 189–190, 198, 199, 236 neuroplasticity and, 500–509 Mood disorders, 592f, 594–596. See also Bipolar disor-
Masculinization, of brain, 203, 273–274, 432 during sleep, 468–469 der; Depression
Matching-to-place learning task, 215, 216f structural basis of, 500–513. See also Mood stabilizers, 181t, 186
Mate selection, 407–408 Neuroplasticity Morphine, 151, 187–188, 187f
Materialism, 8–12 studies of, 483–485 abuse of, 188
eliminative, 12 terminology of, 485t for pain, 387
religion and, 14 visuospatial, 492 Morris task, variations on, 215–216, 216f
Mathematical intelligence, 553 Memory deficits Motivation
Mating behavior. See Sexual behavior in Alzheimer disease, 492, 498. See also Alzheimer allocortex in, 54
MDMA (ecstasy), 190, 198 disease amygdala in, 434
Medial, definition of, 38, 39 in amnesia, 483–484, 486–487, 487f. See also definition of, 398
Medial forebrain bundle, 412, 413f Amnesia neuroanatomy of, 410–426
reward and, 437 brain lesions and, 488–490 in nonregulatory behavior, 412
Medial geniculate nucleus, 333, 334f explicit-memory, 488–489 in regulatory behavior, 411–412
Medial lemniscus, 383, 383f implicit-memory, 489–490 sexual, 434, 435f
Medial pontine reticular formation (MPRF), in REM in Korsakoff syndrome, 495–497 Motor cortex, 366–372, 366f
sleep, 471–472, 471f, 472f, 473f normal age-related, 591 association cortex and, 527f
Medial preoptic area, in sexual behavior, 434 in Parkinson disease, 489–490 corticospinal tracts and, 370–371
Medial temporal region, in explicit memory, 491–497 in substance abuse, 198 injuries of, 369–370
Medial thalamus, in memory, 495–497, 499f Memory trace, 481, 488 layers of, 56, 56f, 359. See also Cortical layers
Median raphe, in brain activation, 471, 471f Menarche. See Menstruation mapping of, 366, 369–370
Mediterranean diet, 428 Ménière disease, 389 movement categories in, 367–368
Medulla, 53, 53f Meninges, 37, 37f neuroplasticity in, 505–507, 506f
Melanopsin, 451, 453 Meningiomas, 83 posttraumatic reorganization of, 369–370, 369f
Melanopsin ganglion cells, 453 Meningitis, 40, 42 primary, 360–361
Melatonin Menstruation in skilled movement, 368–369
biorhythms and, 454–455 cognitive function and, 203 supplementary, 366
in sleep, 470 as infradian biorhythm, 444 topographic organization of, 56, 366, 366f, 369–370
Subject Index S-11
in animals, 505–506, 506f Multimodal neurons, 418 cells of, 46–47, 46f, 47f. See Glial cells; Neuron(s)
changes in, 369–370, 369f, 505–507, 506f Multiple intelligences, 29, 553–554 central. See Central nervous system
Motor development, 260–261, 261f Multiple sclerosis, 125, 126, 583–584 in chordates, 18–19, 19f
Motor end plate, 133, 133f as autoimmune disease, 126 development of, 247–280. See also Brain
Motor function. See also Movement Murder, 407 development
separation from sensory function, 5, 51, 69 Muscle contraction, nerve impulses in, 133–134, 133f enteric, 37, 64–65, 65f
Motor homunculus, 366, 366f, 371 Muscle control, 372 autonomy of, 158
Motor neurons, 78, 79, 79f, 371–372 Muscle end plates, 133, 133f, 134 in brain development, 275
in muscle contraction, 133–134, 133f, 372 Muscular rigidity, in Parkinson disease, 586 neurotransmitters of, 158
Motor pathways, efferent nerves in, 37, 37f Music evolution of, 47–49, 48f. See also Evolution
Motor sequences, 360–361, 360f, 361f brain development and, 267 in animals, 15–19, 16f–19f
Motor skills. See also Movement, skilled cerebral asymmetry for, 346–347, 541 in humans, 19–29
learning of, explicit vs. implicit memory in, 484 cortical thickness and, 348 functional organization of, 36–37, 36f, 37f
Motor system. See also Movement evolution of, 322, 340–342 functions of, principles of, 66–71, 72
basal ganglia in, 373–375, 373f genetic aspects of, 347–348 hierarchical organization of, 50–58, 68–69, 68f,
cerebellum in, 375–378, 376f–378f language and, 322, 327, 345 357–365, 390–391
corticospinal tracts in, 370–371, 370f, 371f patterns of, detection of, 348 layers of. See Cortical layers
as efferent system, 358 perfect pitch and, 324, 535, 535f parasympathetic, 63–64, 157–158, 204, 205f
motor cortex in, 366, 366f processing of, 346–348, 541 neurotransmission in, 157–158
motor neurons in, 371–372 properties of, 328 in rest and digest response, 157–158, 204–205
in muscle control, 133–134, 133f, 372, 372f as sound, 327–328 peripheral, 3, 3f, 4, 36–37, 36f, 60
organization of, 366–372 sound waves in, 328, 328f somatic, 36f, 37, 59–63, 156–157
in pianists, 507 vs. speech, 327 connections of, 61, 62f
in skilled movements, 368–369 Music processing, 346–348 cranial nerves in, 59, 60f
somatosensory system and, 358–359, 390–394. See Music therapy, 348 neurotransmission in, 156–157
also Somatosensory system Musical intelligence, 553, 554 sensory and motor divisions of, 69
Motor training, neuroplasticity and, 507 Musicians spinal nerves in, 60–61, 61f
Movement, 355–396 focal hand dystonia in, 507 structure of, 3–4, 3f
accuracy of, 376–378, 377f, 378f learning in, 507 sympathetic, 63–64
brainstem in, 361–363 motor skills in, 507 neurotransmission in, 157–158
cerebellar control of, 52–54, 52f, 376–378, 377f, 378f Mutations. See Genetic mutations in stress response, 157–158, 204–206, 205f
cerebral asymmetry and, 543–545 Myasthenia gravis, 134, 177 Netrins, 256
force of, basal ganglia and, 373–375, 375f Myelencephalon, 48, 48f Neural circuits, 47, 47f, 76–80, 76f, 78f, 522–525
forebrain in, 358–361, 360f, 361f Myelination behavior and, 401
globus pallidus in, 375, 375f axonal, 124–125, 124f as cell assemblies, 523–525
hierarchical control of, 357–365 development of, 259f, 260f in cognition, 522–525
experimental evidence for, 361 loss of, in multiple sclerosis, 126, 583, 583f crossed, 43, 67
hindbrain in, 52f, 53 progression of, 259–260, 260f efficiency of, intelligence and, 555
imitation of, 532 Myopia, 290, 291 environmental influences on, 268–269
inhibition of, 70–71 excitation and inhibition in, 70–71, 80
initiation of, 360–361, 360f, 361f Nalorphine, 187 in habituation, 163–164, 164f
integrated control of, 61–62 Naloxone, 187 hyperconnectivity of, 535
involuntary Nanotechnology, for spinal cord injuries, 365 modification of, 502–503, 503f. See also
drug-induced, 574 Narcolepsy, 473–474 Neuroplasticity
in Parkinson disease, 586 sleep paralysis in, 474–475 in movement, 364
language and, 543–545 Narcotics. See Opioids novel, creation of, 503–504, 505f. See also
learning and, 507 Nasal retina, 295, 296f Neurogenesis; Neuroplasticity
modeling of, 367–368 Natural selection, 8–12. See also Evolution in ocular dominance columns, 309, 309f
motor sequences in, 360–361, 360f, 361f behavior and, 406–408 in sensitization, 164–166, 165f
neurotransmitters in, 156–157 Navigational skills, 301, 527–528 spinal, 364
orienting, 53, 69 Neanderthals, 21–22, 21f in visual system, 268–269, 309, 309f
within perceptual world, 66 music-making by, 322 Neural columns. See Cortical columns
posterior roots in, 358 Near-infrared spectroscopy (NIRS), functional, 123f, Neural connectivity, 534
prefrontal cortex in, 360, 360f, 361, 361f 231–232, 231f environmental influences in brain development
premotor cortex in, 360, 360f, 361 Nearsightedness, 290, 291 and, 268–269
primary cortex in, 360–361, 360f, 361 Negative pole, 110 gender differences in, 548
production of, nerve impulses in, 133–134, 133f Neglect, contralateral, 529–530 Neural Darwinism, 257
sensory input in, 69–70, 376–378, 381–382, 390–394. Neocortex, 54. See also Cerebral cortex Neural development. See Brain development
See also Somatosensory system in cognition, 535–536 Neural groove, 249, 249f
sequential, 522 layers in, 359 Neural organization
skilled, 368–369 Neoteny, 26–27, 26f afferent vs. efferent pathways in, 37, 37f
brain injury and, 369–370 Nerve(s), 47, 47f functional, 36–37, 36f, 37f
sleep and, 476–477 afferent, 37, 37f hierarchical, 50–58, 68–69, 68f, 357–365, 390–391
sound in, 333 cranial, 59, 60f plastic patterns of, 35–36. See also Neuroplasticity
species-typical, 361–363, 362f efferent, 37, 37f Neural plate, 249, 249f
spinal circuits in, 364 peripheral, 60 Neural processing, hierarchical vs. parallel circuits in,
spinal cord in, 364–365 regeneration of, in spinal cord injury, 365 68–69
timing of, cerebellum in, 376–378 spinal, 60–61, 61f, 358 Neural relays, in sensory systems, 287
understanding meaning of, 532 Nerve cells. See Neuron(s) Neural shock, 580
urge-to-action system and, 374 Nerve growth factor, neuroplasticity and, 510, 515 Neural stem cells, 250–252
ventral roots in, 61 Nerve impulse, 123–124. See also Action potential transplantation of, 161, 452, 452f, 516, 572, 587–588
vision in, 313, 316, 316f, 317f, 382 definition of, 123–124 Neural streams, 69–70, 69f
visual perception of, 313 input from Neural tube, 249, 249f, 250f
Movement categories, 367–368 integration of, 127–131 Neural tube defects, 277
Movement disorders summation of, 128–130, 129f, 130f Neuritic plaque, in Alzheimer disease, 492, 492f, 588
basal ganglia in, 373–374 in muscle contraction, 133–134, 133f Neuroblasts, 250
drug-induced, 574 production of, sensory input in, 132–133, 133f Neurodegenerative disorders, 583–591. See also
hyperkinetic symptoms in, 374 saltatory conduction of, 125–128, 125f Alzheimer disease; Dementia; Parkinson disease
hypokinetic symptoms in, 374 Nerve injuries, repair of, 85–86, 85f, 365 Neuroeconomics, 538
MPTP, parkinsonian symptoms from, 161 Nerve net, 17, 17f, 76 Neurogenesis, 252, 253f, 503–504, 505f. See also
MRI. See Magnetic resonance imaging (MRI) Nerve roots, 61, 62f Neuroplasticity
mRNA, 93, 93f Nervous system antidepressants and, 596
MSG, neurotoxicity of, 197, 198 autonomic, 36f, 37, 63–64, 157–158, 157f in brain injury, 516–517
Mu receptors, 187 enteric nervous system and, 64–65, 65f induced, 572, 587–588
Müller-Lyer illusion, 288, 288f neurochemistry of, 157–158, 157f Neurohormones, 200, 201f
S-12 Subject Index
Neuroimaging studies, 226–234, 238–239, 238t in brain injury, 276, 369f, 513–517 synthesis and storage of, 143, 143f, 149–150, 150f
anatomical, 226–229 brain size and, 28–29 types of, 147–156
in brain mapping, 533–536, 534f cerebellar agenesis and, 34 Neurotrophic factors, 236, 251
in brain/behavioral disorders, 570–571, 570f, 579 compensatory, 566–567, 597–598 for brain injury, 516–517
functional, 229–234 constraint-induced therapy and, 370 in depression, 595
in traumatic brain injury, 578, 579 definition of, 28, 36 electroconvulsive therapy and, 572
Neurological disorders, 577–592. See also dendritic changes and, 502–503, 503f in induced neurogenesis, 572
Brain/behavioral disorders drug-induced, 510–511, 511f neuroplasticity and, 510, 510t
brain size and, 28 environmental stimulation and, 270–271, Neutrons, 89
organic, 564 504–505, 505f Nicotine, 176, 176f
vs. psychiatric disorders, 563–564 epigenetics and, 36, 103–105 addiction to, 193, 438–439. See also
Neuron(s), 3, 46–47, 46f, 47f. See also Cell experience-dependent, 508 Substance abuse
axons and, 47, 47f, 76, 76f, 77, 78f. See also Axon(s) frontal lobe and, 258–259 in learning, 220
bipolar, 79, 79f growth factors and, 84, 510, 510t Nicotinic acetylcholine receptor, 157, 157f, 176, 176f
auditory, 333 hormones and, 509–510, 509f Night terrors, 464
retinal, 294, 295f learning and, 35–36, 270–271, 500–502, 508 Night vision, age-related decline in, 294
in Caenorhabditis elegans, 23 long-term potentiation and, 500–502, 501f Nigrostriatal dopaminergic system, 159f, 160
cell body of, 76, 76f memory storage and, 500–509 Nitric oxide, 153
cholinergic, 156–158 metaplasticity and, 512 NMDA receptors, in long-term potentiation,
components of, 86–96 modification of existing circuits in, 502–503, 503f 501–502, 501f
connections between, 47, 47f, 77–80, 78f, 79f of motor cortex, 369–370, 369f Nociception, 380, 380f, 382–388, 383f
See also Neural circuits motor training and, 505–507, 506f, 507 Nodes of Ranvier, 124f, 125
culture of, 75 neurogenesis in, 503–504, 505f Noise, 326
death of, 257 neurotrophic factors in, 510, 510t Nomenclature, anatomical, 38–39
dendrites of, 76, 76f, 77, 78f, 79–80 phenotypic plasticity and, 36 Nonmatching-to-sample task, 264f, 265
differentiation of, 253–254, 254f principles of, 511–513 Nonregulatory behaviors, 412
abnormal, 277 of somatosensory cortex, 392–393, 393f control of, 432–435
electrical activity in, 109–127. See also under structural basis of, 500–513 Non-REM sleep. See NREM sleep
Electrical synaptic change in, 163, 502–503, 503f Nontasters, 404–405
evolution of, 16–17 Neuroprosthetics, 356 Noradrenergic neurons, 162
excitation of, 70–71, 80 Neuroprotection, 37–40, 37f, 581 Noradrenergic system, 159f, 161–162
excitatory, 80 Neuropsychoanalysis, 564 Norepinephrine (noradrenaline), 138f, 139, 150, 150f,
functions of, 46, 76, 78–79 Neuropsychological testing, 214–215, 533 161–162. See also Neurotransmitters
shape/size and, 79–80, 79f Neuropsychological therapy, 575 in depression, 596
generation of. See Neurogenesis; Neuroplasticity Neuropsychology, 211 receptors for, 155, 155t
glial cell repair of, 85–86 Neuroscience Norepinephrine psychedelics, 190
growth and development of, 252–258 cognitive, 533–538 Norrbotten (Sweden), epigenetic influences in, 105
information flow through, 77–78, 79f applications of, 536–538 Notes, musical, frequencies of, 328, 328f
inhibition of, 70–71, 80 methods of, 533–536 Notochord, 18
inhibitory, 63–64, 70–71, 80 social, 536–538 NREM sleep, 458–461, 459f, 465. See also Sleep
interneurons, 78, 79, 79f Neurosurgery, 572 disorders of, 473–474
labeling of, 75, 211, 212f frontal lobotomy, 423–424, 423f memory storage during, 468–469
longevity of, 77 for Parkinson disease, 587–588 vs. REM sleep, 459–461
maturation of, 254–256, 254f split brain studies and, 520, 542–543, 545 Nuclear membrane, 87f, 90
migration of, 253–254, 253f Neurotoxic lesion studies, 219 Nucleotide bases, 91f, 92
mirror, 532 Neurotoxins Nucleus, 47
motor, 78, 79, 79f, 371–372 drugs as, 197–199 arcuate, in eating, 429–430
in muscle contraction, 133–134, 133f, 372 epigenetics and, 196 caudate, 57, 57f
multimodal, 418 mechanism of action of, 176–177, 176f, 197t cell, 87f, 90, 92
noradrenergic, 162 Neurotransmission cochlear, 333, 334f
number of, 76 in central nervous system, 158–162 dorsomedial thalamic, 53f, 54
origin of, 250–252, 251f drug effects on, 175f, 176–177, 176f lateral geniculate, 53f, 54, 297–298, 298f, 302–303,
packing density of, 23 in somatic nervous system, 156–157 302f, 303f
plasticity of. See Neuroplasticity steps in, 143–144, 143f, 144f, 175–176, 175f medial geniculate, 333, 334f
posterior-root ganglion, 381–382, 381f Neurotransmitters, 138–140. See also specific types paraventricular, in eating, 429
properties of, 76 actions of, 144 raphe, 451
proteins in, 93 activating systems for, 158–162 red, 53, 53f, 84f
rainbow, 75 amine, 149t, 150 sensory, 69
repair of, 85–86, 85f amino acid, 149t, 150, 151f subcoerulear, 472
retinal, 289, 294–298, 295f autoreceptors for, 144 suprachiasmatic, 450–456, 450f
receptive fields for, 302–303 behavior and, 146 thalamic, 69
sensory, 78, 79, 79f classification of, 148–153 Nucleus accumbens, 375
sex differences in, 546–547, 547f deactivation of, 144 behavioral sensitization and, 511
shape of, 79–80 definition of, 139 Nucleus robustus archistriatalis, in birds, 350–351, 351f
neuroplasticity and, 502–503 degradation of, 144 Nutrition. See also Diet
somatosensory, 79, 79f, 381–382, 381f diffusion of, 144 brain size and, 25–26, 25f
staining of, 75, 75f, 78f evolution of, 146 depression and, 184–185
structure of, 76f, 77–78 gaseous, 153 epigenetic effects of, 105
summation in, 128–130, 129f, 130f glial uptake of, 144 multiple sclerosis and, 126
transplantation of, 161, 452, 452f, 516, identification of, 147–148, 147f Nystagmus, 314
572, 587–588 interaction of, 156
types of, 78–79, 79f in learning, 162–167, 164f, 165f Obesity, 426–427
as unit of cognition, 522–525, 529 lipid, 151–153 biologic clocks and, 447, 448
ventrolateral thalamic, 383 peptide, 150–151, 151t dieting and, 428
Neuron theory, 76 properties of, 147–148 metabolic syndrome and, 442, 447, 448
Neuronal migration, 253–254, 253f putative, 148 Object knowledge, 526–527
Neuronal networks, 77, 79–80, 79f. See also Axon(s); quanta of, 144 Object location, in visual system, 302–304, 302f, 303f
Neural circuits receptors for, 153–156, 153f, 154f. See also Object manipulation, mental, 527f, 528, 528f
Neuropeptides, 150–151, 151t Receptor(s) Object permanence, 262, 262f, 263t
Neuroplasticity, 35–36, 67, 76, 162–163 activation of, 143–144, 143f Object position test, 493, 493f
adolescent-onset psychiatric disorders and, 275 release of, 143, 144f Object recognition, 69–70, 526–527
in adults, 267 regulation of, 145–146 Object-reversal learning, 274
axonal sprouting in, 502–503, 503f reuptake of, 144 Obsessive-compulsive disorder, 597. See also Anxiety
in brain development, 279–280 second messengers and, 154–155, 154f disorders
in brain disorders, 566–567 small-molecule, 149–150, 158–162 serotonin in, 162
Subject Index S-13
Occipital lobe, 41f, 55, 55f perception of, 385, 387f Photoreceptors, 286–287, 289–294, 291f, 293f, 294f
in association cortex, 525–526, 527f phantom-limb, 385, 386 retinal ganglion cells as, 296, 302, 451
injury of, 55 referred, 388, 388f Photosensitive retinal ganglion cells, 451, 453
structure and function of, 55, 55f response to, 385–387 Phototherapy, for seasonal affective disorder, 448
visual regions of, 299–300, 299f treatment of, 387–388 Phyla, 16, 16f
Ocular dominance columns, 269, 270f, 308–309, 309f, Pain gate, 386–387, 387f Physical activity, therapeutic benefits of, 576
312, 312f Panic disorder, 425, 597. See also Anxiety disorders Physostigmine, 177
Oculogyric crisis, 586 Papaver somniferum, 187, 187f Phytocannabinoids, 152–153
Oculomotor nerve, 59, 60f Papez circuit, 417 Pia mater, 37
Off-center ganglion cells, 305–306, 306f, 307f Papilledema, 292 Piaget’s cognitive theory, 262–264, 262f, 263t
Olfaction, 401–404, 402f, 403f Parahippocampal cortex, 416 Pianists. See also Musicians
in animals, 403 in memory, 491–492, 491f motor skills in, 507
in humans, 404 Parallel processing, 68–69, 68–70 Picrotoxin, 182
Olfactory bulbs, 41f, 58f, 402f, 403 Paralysis, 86, 364, 365. See also Spinal cord injury Pidgin, 342
Olfactory epithelium, 402, 402f facial, 62 Pigments, in rods vs. cones, 293
Olfactory nerve, 59, 60f Paramethoxymethamphetamine (PMMA), 198 Pincer grip, 360–361
Olfactory pathways, 403 Parasympathetic nervous system, 63–64 movements in, 361f
Olfactory receptors, 402–403, 402f neurotransmission in, 157–158 Pineal gland, 7–8, 8f, 46
Olfactory system, 58, 58f, 401–404, 402f in rest and digest response, 157–158, 204–205 in biorhythms, 450, 454–455
accessory, 403 Paraventricular nucleus, in eating, 429 blood–brain barrier and, 174, 175f
Oligodendroglia, 82t, 85, 124 Parietal lobe, 41f, 55, 55f melatonin secretion by, 454–455
On-center ganglion cells, 305–306, 306f, 307f in association cortex, 525–526, 527f in sleep, 470
Operant (instrumental) conditioning, 482–483 in attention, 529, 530 Pinna, 329, 330f
Opioids, 151, 181t, 187–188, 387 in cognition, 525–526, 528, 529, 530 Pitch, 324, 324f, 328
abuse of, 188 injury of, 55 perception of, 336–338
physical effects of, 187 in spatial cognition, 528 perfect (absolute), 324, 535, 535f, 554
synthetic, 187 structure and function of, 55, 55f Pituitary gland, 200, 201f
Opium, 187, 187f Parietal reach region, 301 blood–brain barrier and, 174, 175f
Opponent-process theory, 311–313, 312f Parkinson disease, 42, 57, 71, 140, 374–375, 585–588 definition of, 412
Optic ataxia, 317–318 Alzheimer disease and, 590 hormones of, 200, 201f, 414, 414t
Optic chiasm, 295, 296f basal ganglia in, 374–375 hypothalamus and, 412–415, 414f, 595–596
Optic disc, 291, 291f, 292 causes of, 587 structure and function of, 414, 414f
swelling of, 292 deep brain stimulation for, 375 PKU (phenylketonuria), 565, 566t
Optic flow, 286 globus pallidus in, 375 Place cells, 222–223, 222f, 468, 494, 494f
Optic nerve, 59, 60f, 291, 292, 295, 296f L-dopa for, 150, 150f, 152, 573, 587 Place-learning task, 216f
inflammation of, 292 lesion studies of, 218–219 Planning, 530–531
Optic neuritis, 292 Lewy bodies in, 590, 590f Plants, biorhythms in, 443, 444f
Optical tomography, 210, 231–232, 231f memory deficits in, 489–490, 498 Planum temporale, 334, 334f
Optogenetics, 131, 221 neuron transplant for, 516, 587–588 Plaque
Orbital prefrontal cortex, 526f prevalence of, 585 in Alzheimer disease, 85, 492, 492f, 588
Orbitofrontal cortex, 418f, 419 progression of, 586 in multiple sclerosis, 126
in eating, 430 symptoms of, 219, 585–586 Plasticity
in gustation, 405 toxins and, 161 neural. See Neuroplasticity
in olfaction, 403, 403f treatment of, 150, 150f, 152, 572, 573, 587–588 phenotypic, 36, 103–105
Orders, taxonomic, 16, 16f tremor in, 140, 161, 586 Pleasure, reward and, 436–439
Orexin, 475 Parrots, cognition in, 522, 545 Plexus, 65
Organ of Corti, 330, 330f Parvocellular (P) cells, 295–298, 295f PMMA (paramethoxymethamphetamine), 198
hair cells of, 330, 330f, 332f, 336–337 Patellar reflex, 50–51, 384–385, 384f Poisoning
Organelles, 90 Pavlovian conditioning, 481–482. See also Conditioning carbon monoxide, 315–316
Organic neurological disorders, 564 in substance abuse, 195 domoic acid, 197
Organizational hypothesis, 203 PCP (phencyclidine), 182, 190, 197 kainic acid, 197
Organophosphates, 177 Peptide bonds, 93 MPTP, 161
Orientation, to sound, 338–339, 339f Peptide hormones, 201. See also Hormones toxin action at synapses in, 176–177
Orientation columns, 308–309, 312 Peptide transmitters, 150–151, 151t Polar molecule, 89
Orientation detectors, 307 Perception, 35, 288 Polypeptide chains, 93, 93f. See also Protein(s)
Orienting movements, 53, 69 subjective reality and, 35 Pons, 53, 53f
Oscilloscope, 113, 113f Perceptual illusions, 288, 288f Poppy, opium, 187, 187f
Osmotic thirst, 431 Perceptual world, creation of, 66 Positive pole, 110
Ossicles, 329, 330f Perfect pitch, 324, 535, 535f, 554 Positron emission tomography (PET), 232–234
Otoconia, 388 Periaqueductal gray matter, 53, 53f in auditory cortex mapping, 345–346
Otolith organs, 388, 389f in pain, 388 Posterior cerebral artery, 43, 43f
Oval window, 329, 330f Peribrachial area, in REM sleep, 471–472, Posterior, definition of, 38, 39
Ovarian hormones 471f, 472f, 473f Posterior roots, 358
activating effects of, 433 period gene, 453 Posterior spinothalamic tract, 383, 383f
in brain development, 203, 273–275, 546–549 Periodic limb movement in sleep, 460 Posterior-root ganglion neurons, 381–382, 381f
cognitive function and, 203 Periods, in activity cycle, 444 Postsynaptic membrane, 142, 142f, 143–144
functions of, 203 Peripheral nervous system, 3, 3f, 4, 36–37, 36f, 60 Postsynaptic potentials
neuroplasticity and, 509, 509f Peripheral vision, 292, 292f excitatory/inhibitory, 127–130, 129f, 130f
sexual behavior and, 433 Perirhinal cortex, in memory, 491–492, 491f miniature, 144
Overtones, 326, 326f Perseveration, 531 Posttraumatic stress disorder (PTSD), 164–165, 206,
Overweight, 426–427 Persistent vegetative state, 13 424, 562, 597
Owl, hearing in, 339, 339f Personal memory, 486–487, 487f Potassium ion(s). See also under Ion(s)
Owl chronotype, 451–452, 453 PET scan, 232–234 resting potential and, 116–119, 117f, 119f
Oxytocin, 413, 415f, 416 in auditory cortex mapping, 345–346 Potassium ion channels, in sensitization, 165, 165f
Peyote, 190 Potentials. See Electrical potentials
P cells, 295–298, 295f Phagocytosis, 84 Poverty, brain development and, 246, 266–267
Pacemakers. See also Biological clocks Phantom-limb pain, 385, 386 Power grasp, 361f
circadian rhythms as, 452–454 Phencyclidine (PCP), 182, 190, 197 Power grip, 361
circannual rhythms as, 454–455 Phenotype, 9, 96 Precursor cells, 250
Packing density, 23, 24 Phenotypic plasticity, 36, 103–105 Preformation, 248
Pain, 385–388, 387f, 388f Phenylketonuria (PKU), 565, 566t Prefrontal cortex, 419–420
central, 385 Pheromones, 403, 403f, 412 association, 525–533
emotional, 398 Phobias, 425, 597. See also Anxiety disorders in behavior selection, 419–420
expectation of, 537 Phosphenes, 220 dorsolateral, 258, 526f
gate theory of, 386–387, 387f Phospholipid bilayer, 90f, 91 theory of mind and, 536
S-14 Subject Index
dorsomedial, 418f, 419 Psychoanalysis, 563 patellar tendon (knee jerk), 50–51, 384f
in eating, 430 Psychobiotics, 65 scratch, 364
in emotional behavior, 423–424 Psychogenic amnesia, 487, 487f spinal, 51, 364, 384–385, 384f
executive functions of, 360, 419–420 Psychological constructs, 520 Refractive errors, 290–291
in memory, 498, 498f Psychology, evolutionary, 407–408 Refractory membrane, 122
in movement, 360, 360f, 361, 361f Psychomotor activation, in substance abuse, 193 Refractory periods, 122–123, 124
orbital, 526f Psychopathology. See Psychiatric disorders Regional cooling, 219
in planning, 360, 530–531 Psychopharmacology. See also Drug(s) Regulatory behaviors, 411–412
structure of, 418f, 419–420, 419f, 526, 526f definition of, 172 control of, 426–431
ventromedial, 418f, 419, 526f principles of, 173–181 Reinforcers, 408
Pregnancy, alcohol use in, 28, 183, 267, 271 Psychosis, 184, 592–594, 592f. See also Schizophrenia Relatively refractory membrane, 122
Premotor cortex, 418, 418f adolescent-onset, 275 Releasing hormones, 414, 415f
in memory, 498, 498f amphetamine, 184 Religion, science and, 14
in movement initiation, 360, 360f, 361 drug-induced, 199, 236 REM sleep, 458–461. See also Sleep
Prenatal influences, in brain development, 267, 268 Psychosurgery, 423–424, 423f. See Neurosurgery atonia in, 458, 460–461, 474–475
Preoperational stage, of cognitive emotional behavior after, 423–424 basic rest-activity cycle and, 465
development, 263, 263t Psychotherapy, 575 definition of, 458
Preparedness, 409 Psychotropics, 181t, 188–190 deprivation of, 467
Presbyopia, 290 Puffer fish, 120 disorders of, 474–476
Presynaptic membrane, 142, 142f, 143 Pulvinar, 298 dreaming in, 461–464. See also Dreams
Prey-killing behavior, 399, 401, 406–407 Pumps, ion, 95, 95f, 116–119, 117f implicit memory and, 468–469, 469f
Primary auditory cortex, 334, 334f. See also Pupil, 291, 291f memory storage during, 469
Auditory cortex Pure tones, 326 neural basis of, 471–472, 471f–473f
Primary motor cortex, 360–361, 360f. See also Purkinje cells, 79, 79f vs. NREM sleep, 459–461
Motor cortex Pursuit-rotor task, 484, 484f without atonia, 476–477
Primary protein structure, 94f Putamen, 57, 57f, 373, 373f REM sleep behavioral disorder, 467, 475–476
Primary visual cortex. See Visual cortex, primary Putative neurotransmitter, 148 Renshaw loop, 148, 149f
(striate) Puzzle box, 482–483, 483f Repetitive transcranial magnetic stimulation, (rTMS),
Primates Pyramidal cells, 79, 79f, 80 220, 220f, 573
characteristics of, 20 Pyramidal tracts, 370–371, 370f, 371f Reproduction, sex hormones in, 202. See also
humans as, 20, 20f. See also Humans Pyriform cortex, 58 Sex hormones
nonhuman Research methods, 211–244, 565–567
brain size in, 22, 23f Quadrantanopia, 314, 314f comparison of, 238–239, 238t
classification of, 20, 20f Quadriplegia, 364, 365. See also Spinal Respondent conditioning, 481–482
evolutionary link to humans and, 15, 20, 22 cord injury Rest and digest response, 157–158, 204–205
language in, 8 Quanta, 144 Rest-activity cycle, 465
music and, 322 Quaternary protein structure, 94f Resting potential, 116–119, 117f
relationships among, 20, 20f Resting-state fMRI, 231
Priming, 485 Radial glial cells, 253, 253f Restless legs syndrome, 460
Principle of proper mass, 22, 303 Radiator hypothesis, 26 Reticular activating system, 470, 470f
Procedural memory, 484, 485t Radiosurgery, 571 Reticular formation, 52, 53f
Progenitor cells, 250 Rainbow neurons, 75 Retina, 291, 291f
Programmed cell death, 198, 257 Raphe nucleus, 451 blind spot in, 284, 291, 291f, 292, 292f
Prolactin, 250, 414, 414t Rapid eye-movement sleep. See REM sleep; Sleep nasal, 295, 296f
Proper mass principle, 303 Rapidly adapting receptors, 381 receptive fields in. See Receptive fields
Proprioception, 380, 380f Rasmussen encephalitis, 42 temporal, 295, 296f
loss of, 382 Rate-limiting factor, 150 Retinal ganglion cells, 294–298, 295f
Prosencephalon, 48, 48f Rats, behavioral analysis of, 215–216 lateral geniculate nuclei and, 297–298, 298f,
Prosody, 328, 424 Real-time fMRI, 576 302–303, 302f, 303f
Prosopagnosia, 301 Recency memory task, 214f, 215 on-center/off-center, 305–306, 306f, 307f
Protanopia, 311 Receptive fields, 286, 302–303, 302f as photoreceptors, 296, 302, 451
Protein(s), 94–96 of lateral geniculate nucleus, 302–303 photosensitive, 451, 453
amino acids in, 92, 93, 93f, 94f, 150 overlapping, 305, 306f receptive field of, 302–303, 302f, 305–308, 306f
cell function and, 86 of primary visual cortex, 305–308, 307f, 308f in shape perception, 305–308, 306f
definition of, 93 in shape perception, 305–310, 306f–308f, Retinal neurons, 289, 294–298, 295f
destinations of, 94–956, 94f 307f, 308f receptive fields for, 302–303, 302f, 305–308, 306f
enzyme, 93–94 Receptor(s), 95, 95f Retinohypothalamic tract, 296, 451, 453
export of, 94–95, 94f auditory, 330f, 332 Retrograde amnesia, 496
genes coding for. See Gene(s) autoreceptors, 144 Rett syndrome, 255
membrane, 94f, 95, 95f ionotropic, 153, 153f Reuptake, of neurotransmitters, 144
shape-changing, 95, 95f light, 289–294, 291f, 293f, 294f Reward
structure of, 93–94, 94f metabotropic, 153–155, 154f behavior and, 399, 400, 416, 436–439
synthesis of, 91–92, 93f neurotransmitter, 153–156, 154f in conditioning, 481–482
transport of, 94f, 95 activation of, 143–144, 143f wanting and liking and, 437
transporter, 143 olfactory, 402–403, 402f Rhombencephalon (hindbrain), 48, 48f, 51, 51f,
Protein channels. See Ion channels rapidly adapting, 381 52–53, 52f
Protein receptors, 95, 95f sensory, 132–133, 285–287, 379–381 Rhythms, biological. See Biorhythms
Protons, 89 density of, 286–287 Ribonucleic acid (RNA), 92, 93, 93f
Proximal, definition of, 39 sensitivity of, 286–287 modification of, 104, 104f
Prozac, 186, 187 slowly adapting, 381 Ribosomes, 93
Psilocybin, 190 small-molecule transmitter, 155, 155t Right-handedness. See also Cerebral asymmetry
Psyche, 7 somatosensory, 379–381 cortical organization and, 334–335, 549–551
Psychedelics, 181t, 189–190 subtypes of, 155–156, 155t lateralization and, 334–335
Psychiatric disorders, 592–597. See also taste, 405 Rigidity, in Parkinson disease, 585
Brain/behavioral disorders transmitter-activated, 143–144 Ritalin, 172
adolescent-onset, 275 vestibular, 388–389, 389f Rivastigmine (Exelon), 492
anxiety, 181–182, 181t, 424–426, 592f, 597. See also Recessive alleles, 97, 99f RNA, 92, 93, 93f
Anxiety disorders Reconsolidation, of memory, 497 modification of, 104, 104f
mood, 592f, 594–596. See also Bipolar disorder; Recreational drugs. See Drug(s); Substance abuse Robots, 80, 80f, 81
Depression Red nucleus, 53, 53f, 84f Robustus archistriatalis, in birds, 350–351, 351f
psychotic, 184, 592–594, 592f. See also Referred pain, 388, 388f Rods (photoreceptors), 293–294, 293f
Schizophrenia Reflective vs. reflexive systems, 538 Romanian orphans, brain development in, 272
types of, 592f Reflexes Rostral, definition of, 38, 39
vs. neurological disorders, 564–565 knee jerk, 384–385 Round window, 330, 330f
Psychoactive drugs. See Drug(s); Substance abuse monosynaptic, 384 Routes of administration, 173–174, 173f
Subject Index S-15
Rubin’s vase illusion, 288, 288f integrated control of, 61–62 sex hormones and, 434
rutabaga gene, 166 midbrain in, 51, 53 sexual identity and, 434–435
motor control and, 69–70 sexual orientation and, 434–435
Saccule, 388, 389f neural streams in, 69–70, 69f Sexual dimorphism, 272, 432. See also Sex
Sacral spine, 60, 61f for object recognition, 69–70, 527 determination
Sagittal, definition of, 39 separation from motor function, 5, 51, 69 Sexual identity, 434–435
Sagittal section, 39f, 45–46, 46f Sensory input Sexual orientation, 434–435
Saltatory conduction, 125, 125f in brain development, 266–268, 267f, 270–271 gender identity and, 435
Salts, 89. See also under Ion(s) habituation to, 163, 164f Shape perception, 305–310, 305f–310f
Savant syndrome, 598 integration of, 127–131 Shift work, biorhythms and, 447–448
Schizophrenia, 277, 278, 592–594, 592f in movement, 376–378, 381–382. See also Shock, neural, 580
adolescent-onset, 275 Somatosensory system Short-term memory, 486
adult-onset, 570, 570f in nerve impulse production, 132–133, 133f tests of, 495, 495f
biochemical changes in, 594t summation of, 128–130, 129f, 130f Shunts, cerebrospinal fluid, 82
brain abnormalities in, 570, 570f, 593, 593f Sensory neurons, 78, 79, 79f Side chains, 93
definition of, 161 Sensory nuclei, 69. See also Nucleus SIDS (sudden infant death syndrome), 162, 474
diagnosis of, 592 Sensory pathways, afferent nerves in, 37, 37f Sight. See Vision
dopamine in, 161, 184 Sensory perception, 35 Sign trackers, 195–196
drug therapy for, 181t, 184, 184f subjective reality and, 35 Simple cells, of visual cortex, 307, 307f
early-onset, 570, 570f Sensory processing, 285–288 Singing, 322, 345, 347, 576
epigenetics in, 593 synesthesia in, 551–552 by birds, 275, 349–351
imaging studies in, 570–571, 570f Sensory receptors, 132–133, 379–381. See also carbon monoxide poisoning and, 315
neurochemistry of, 594 specific types Single nucleotide polymorphism (SNP), 97–98
serotonin in, 162 density of, 286–287 Single-cell recordings, 222–223
symptoms of, 592 sensitivity of, 286–287 Skilled-reaching tasks, 216, 217f
transcranial magnetic stimulation for, 573 Sensory systems Skin
Schwann cells, 82t, 85–86, 85f coding and representation in, 287–288 sensory receptors in, 379–381
in neuron repair, 85–86 distinguishing between, 287–288 two-point sensitivity in, 379, 379f
Science, religion and, 14 neural relays in, 287 Skinner box, 408, 408f, 483
Sclera, 291 receptive fields in, 286 Slave oscillators, in suprachiasmatic nucleus, 452–453,
Scotomas, 314, 314f receptors in, 285–287 453f, 455
migraine, 284 Serotonergic system, 159f, 162 Sleep, 456–478
Scratch reflex, 364 Serotonin, 150, 162. See also Neurotransmitters alpha rhythms in, 458
Seasonal affective disorder, 448 in brain activation, 471, 471f in animals, 460–461, 461f, 465, 465f, 469
Second languages in depression, 596. See also Selective serotonin antidepressants and, 467
cortical localization for, 268 reuptake inhibitors (SSRIs) in basic rest-activity cycle, 465, 466f
learning of, 340–341 in enteric nervous system, 158 beta rhythms in, 458
Second messengers, 154–155, 154f receptors for, 155, 155t as biological adaptation, 465
in learning, 165f, 166–167 in sudden infant death syndrome, 277 brainstem injury and, 467, 476–477
Secondary auditory cortex, 334. See also synthesis of, 150 circadian rhythms and, 442, 443–449, 445t, 446f
Auditory cortex Serotonin psychedelics, 190 consciousness and, 476–477
Secondary protein structure, 94f Serotonin synapse, antidepressant action at, 185f, 186 delta rhythms in, 458
Secondary (extrastriate) visual cortex, 299, 299f, 300f. Setpoint, in temperature regulation, 411 in depression, 473
See also Visual cortex Sex chromosomes, 96–97, 97f dreaming in, 461–464. See also Dreams
Second-generation antidepressants, 185 sex differences and, 548 drowsy state in, 458
Sections, of brain, 39f, 43–46, 43f, 46f Sex determination, 203, 432, 433 duration of, 456–457, 465, 465f
Sedative-hypnotics, 181–182, 181t brain development and, 203 electroencephalography in, 457, 470–472
insomnia and, 473 disorders of, 433 energy conservation and, 465
Segmentation, 18 Sex differences function of, 464–469
Seizures, 108, 581–583 in addiction, 193–194 hippocampus in, 468f
brain surgery for, 343, 345 in behavior, 548–549 learning during, 468–469
focal, 582 in birdsong, 275 medial pontine reticular formation in, 471–472,
generalized, 582 in brain development, 273–375, 273f 471f, 472f
Selective attention, 528–529 in brain injury, 547–548, 549f melatonin in, 470
Selective awareness, 284 in brain size, 546, 547f in memory storage, 469
Selective breeding, 101 in cognition, 203, 546–549, 547f–549f microsleep and, 466
Selective dystonias, 375 in cortical thickness, 546, 547f neural basis of, 470–472
Selective serotonin reuptake inhibitors (SSRIs), 185, evolution of, 548–549 normal variations in, 456–457
186. See also Antidepressants in language, 546–549 NREM, 458–461, 459f, 465
side effects of, 574 in neural connectivity, 548 disorders of, 473–474
Self-concept, 537 in neuron structure, 546–547, 547f explicit memory and, 468, 468f
Self-recognition, 536–537 Sex hormones, 202, 203. See also Hormones peribrachial area in, 471–472, 471f–473f
Self-regulation, 537 activating effects of, 433 pineal gland in, 470
Semicircular canals, 388, 389f behavior and, 401 REM, 458–461, 465
Sensation, 286–288. See also Sensory function and in brain development, 203, 273–275, 432, 546–549 atonia in, 460–461, 474–475
specific senses cognitive function and, 203, 546–549 definition of, 458
vs. perception, 288 epigenetic changes and, 274–275, 432 deprivation of, 467
Sensitive periods function of, 202 disorders of, 474–476
for brain development, 269–270 lifelong effects of, 274–275 memory storage during, 468, 468f
for brain injury, 276 neuroplasticity and, 509, 509f neural basis of, 471–472, 471f–473f
for gene expression, 105 organizing effects of, 432 without atonia, 476–477
for language acquisition, 341 sexual behavior and, 433 as restorative process, 466–467
Sensitization, 164–166, 165f, 167 in sexual differentiation, 203, 272, 432 reticular activating system in, 470
behavioral, 510–511 steroid, 201 slow-wave, 458, 459f
dendritic spines in, 167 target glands of, 200–201, 201f stages of, 457–458, 459f
drug, 178–180, 510–511 Sexual behavior, 412, 433 waking and, 470–471
habituation to, 163–164, 164f, 167, 500 amygdala in, 434 Sleep aids, insomnia and, 473
Sensorimotor stage, of cognitive development, 263, 263t cerebral cortex in, 436 Sleep apnea, 473–474
Sensory coding and representation, 287–288 cognitive influences in, 436 Sleep deprivation
Sensory cortex frontal lobe in, 436 brainstem injury and, 476–477
association cortex and, 527, 527f hypothalamus in, 434, 435f REM, 467
layers of, 56, 56f. See also Cortical layers loss of libido and, 436 Sleep disorders, 460, 473–476
Sensory deprivation, 5, 400–401, 400f motivational, 434, 435f genetic factors in, 453
Sensory function neural circuits and, 401 of NREM sleep, 473–474
dorsal roots in, 61 neural control of, 434 of REM sleep, 474–476
S-16 Subject Index
Sleep paralysis, 474–475 localization of Spinothalamic tracts, 382–384, 383f
Sleep studies, 223f, 224, 457–458, 457f, in bats, 351–352 Split-brain studies, 520, 542–543, 545
459f, 470–472 in humans, 338–339, 339f SRY gene, 203
electroencephalography in, 470–472 loudness (intensity) of, 324–325, 324f, 325f, 328 SSRIs (selective serotonin reuptake inhibitors), 185, 186.
electromyography in, 457, 457f detection of, 338–339 See also Antidepressants
electrooculography in, 457, 457f music as, 327–328. See also Music Staining, brain tissue, 46–47, 47f, 75, 75f, 78f, 211, 212f
Sleeping sickness, 42 patterns of, detection of, 339–340 Stellate cells, 79, 79f
Sleep-producing substance, 470 perception of, 326–327 Stem cells, neural, 250–252
Sleepwalking, 459 pitch of, 324, 324f, 328 transplantation of, 161, 452, 452f, 516, 572, 587–588
Slowly adapting receptors, 381 perception of, 336–338 Stereotaxic apparatus, 218, 218f
Slow-wave sleep, 458, 459f. See also NREM sleep properties of, 323–327, 324f Steroid hormones, 201. See also Hormones
Small-molecule neurotransmitters, 149–150, 149t, source of, detection of, 339–340, 339f anabolic, 204
158–162 timbre (quality) of, 324f, 328 neurotoxicity of, 510
receptors for, 155, 155t Sound waves, 323–329 Stimulants, 188–190, 189f
Smell. See under Olfaction; Olfactory amplitude of, 324–325, 324f, 325f. See also brain damage from, 198
Smoking, nicotine addiction in, 193, 438–439 Loudness general, 190
Social cognition, 537–538 complexity of, 324f, 326 psychedelic/hallucinogenic, 189–190, 198
mirror neurons in, 532 curves of, 336–337, 336f Stimulus
Social neuroscience, 536–538 cycles of, 323, 324f conditioned, 482
Social phobia, 597. See also Anxiety disorders definition of, 323 unconditioned, 482
Socioeconomic status, brain development and, 246, frequency of, 323–324, 324f, 326. See also Pitch Stimulus equivalence, 309
266–267 production of, 323, 323f, 324f Stirrup, 329, 330f
Sodium amobarbital test, 550 Spatial cells, in hippocampus, 222–223, 222f, Storage granules, 142, 142f
Sodium ions. See also under Ion(s) 468, 494, 494f Stress
resting potential and, 117–119, 117f, 119f Spatial cognition, 527–528, 527f, 528f anxiety and, 597
Sodium-potassium pump, 117, 118 sex differences in, 549 brain development and, 271
Solitary tract, 405 Spatial intelligence, 553 depression and, 595–596
Soma, 76, 76f Spatial localization, visual, 302–304, 302f, 303f epigenetic changes and, 237, 271
Somasomatic connections, 146 Spatial memory, hippocampus in, 492–494, 493f, 494f frontal lobe development and, 259
Somatic marker hypothesis, 421–422 Spatial orientation, of brain, 38 hippocampus and, 185, 205–206, 205f, 595–596
Somatic nervous system, 36f, 37, 59–63 Spatial summation, 129, 129f hypothalamic-pituitary-adrenal axis (HPA) and,
connections of, 61, 62f Special K (ketamine), 182, 190, 197 595–596
cranial nerves in, 59, 60f Species, 9, 16, 16f neuronal death and, 510
neurotransmission in, 156–157 between-species vs. within-species comparisons posttraumatic stress disorder and, 206
sensory and motor divisions of, 69 and, 28 Stress response, 204–206, 205f, 206f
spinal nerves in, 60–61, 61f Species-typical behavior, 28 activation of, 204–205, 205f
Somatosensory cortex, 390–394 motor, 361–363 hormones in, 204–206, 205f, 206f, 595–596, 595f
anatomy of, 390, 391f Specific phobias, 507. See also Anxiety disorders termination of, 205–206
in gustation, 405 Speech. See also Language Stretch-sensitive channels, 133
hierarchical organization of, 390–391 acquisition of, 254f, 261–262 Striate cortex. See Visual cortex, primary (striate)
homunculus of, 390–391, 391f Broca’s area for, 254f, 262, 342–346, 342f, 346f Striatum, 235, 373, 373f
injury of, 392–393 cortical localization of, 342–346 Stroke, 43, 45, 580–581
plasticity of, 392–393, 393f mapping of, 343–346 mild cognitive impairment and, 591
primary, 390 lateralization for, 334–335, 543–545 sleep disturbances after, 476–477
secondary, 390, 393–394 motor aspects of, 543–545 stem cell transplant for, 572
topographic organization of, 390–391, motor sequences in, 360, 360f Subcoerulear nucleus, in sleep, 472, 473f
391f, 393f musicality of, 328 Subcortical regions, 46, 46f
Somatosensory neurons, 79, 79f perception of, 327–328 Subsong, 350
Somatosensory receptors, 379–381, 389f production of, 342f, 343, 344–345 Substance abuse, 191–200
distribution and density of, 379 rate of, 327 addiction in, 193
haptic, 380, 380f vs. music, 327, 345 definition of, 193
nociceptive, 380, 380f Wernicke’s model of, 342–346, 342f dopamine in, 193, 195
proprioceptive, 380, 380f Speech arrest, 344–345 neural basis of, 194–196
rapidly adapting, 381 Speech discrimination, 339–340 psychomotor activation in, 193
slowly adapting, 381 Speech patterns, detection of, 339–340 sex differences in, 193–194
types of, 389f Speech-sound discrimination task, in brain mapping, treatment of, 196–197
Somatosensory system, 379–394 345–346, 346f types of, 195–196
as afferent system, 358 Speed (methamphetamine), 189 withdrawal in, 193
anterior spinothalamic tract in, 383 Spider venom, 176 adolescent-onset, 275
in balance, 388–389 Spina bifida, 277 behavior and, 191–192
dorsal spinothalamic tract in, 383f Spinal accessory nerve, 59, 60f brain damage from, 197–198
functions of, 379 Spinal anesthesia, 387 conditioning in, 178, 195
in hapsis, 380 Spinal cord, 3, 50–51 criminalization of, 196–197
medial lemniscus in, 383, 383f evolution of, 18, 47–49, 48f definition of, 193
motor system and, 358–359, 390–394 functions of, 364 disinhibition and, 191–192
in nociception, 380, 385–388 integrated, 61–62 dopamine in, 193
overview of, 379 interneurons in, 371–372 epigenetics and, 196
in pain perception, 388 motor neurons in, 371–372 genetic factors in, 196
pathways to brain in, 382–384 orientation of, 38 learning in, 192
in perception and movement, 379–394 posterior-root ganglia in, 381–382, 381f narcotics in, 188
in pianists, 507 segments of, 60–61, 61f, 358–359 psychomotor activation in, 193
posterior spinothalamic tract in, 383 spinal nerves and, 60–61, 61f psychotic symptoms in, 199, 236
posterior-root ganglion neurons in, 381–382, 381f structure of, 60–61, 61f, 358–359 rates of, 196, 197f
in proprioception, 380, 382 Spinal cord injury, 86, 365 reward and, 438–439
receptor distribution in, 379 dorsal vs. ventral root damage in, 61, 62f risk factors for, 196
segregation and synthesis in, 391 emotion in, 421, 421f sensitization in, 178–180, 510–511
somatosensory cortex in, 390–394. See also nerve regeneration in, 365 tolerance in, 177–178, 178f
Somatosensory cortex permanence of, 86 treatment of, 196–197
spinal reflexes and, 384–385, 384f treatment of, 365 twin studies of, 196
ventral spinothalamic tract in, 383f unilateral, somatosensory deficits in, 383f, 384 wanting-and-liking theory of, 194–196
ventrolateral thalamus in, 383, 383f Spinal nerves, 60–61, 61f, 358–359 Substantia nigra, 42, 53, 53f
vestibular system in, 388–389, 389f Spinal reflexes, 51, 364, 384–385, 384f in Alzheimer disease, 590
Sorting tasks, 531, 531f, 533 Spine electrode placement in, 218, 218f
Sound. See also Auditory system; Hearing segments of, 60–61, 61f, 358–359 in Parkinson disease, 140, 587, 590
language as, 327–328. See also Language structure of, 358–359 Subtraction, in positron emission tomography, 233, 233f
Subject Index S-17
Subtractive color mixing, 310, 310f neural columns in, 309–310, 309f Transcription-translation-inhibition feedback loop, 453
Subunits, 154, 155 in shape perception, 309–310 Transfer RNA, 93
Subventricular zone, 250 structure and function of, 55, 55f Transgender, 435, 534
Sudden infant death syndrome (SIDS), 162, 277, 474 in visual system, 300–301, 300f, 309–310 Transgenic animals, 102
Suicide, antidepressant-related, 186 Temporal lobectomy, Klüver-Bucy syndrome and, 422 Translation, 93, 93f, 104
Sulci, 41f, 42, 55, 55f Temporal retina, 295, 296f in transcription-translation-inhibition feedback
Summation, 128–130, 129f, 130f Temporal summation, 129, 129f loop, 453
ions in, 129–130 Teratogens, 252, 276–277 Transmembrane proteins, 95, 95f
spatial, 129, 129f Terminal button, 77, 78f Transmitter-activated receptors, 143–144
temporal, 129, 129f Terminology, anatomical, 38–39 Transmitter-sensitive channels, 133
Superego, 563 Tertiary protein structure, 94f Transplantation, of neurons, 161, 452, 452f, 516, 572,
Superior colliculus, 53, 53f, 69 Testes-determining factor, 548 587–588
Superior, definition of, 38, 39 Testosterone, 200. See also Sex hormones Transporters, 143
Superior olive, 333, 334f behavior and, 401 Transsexuals, 435, 534
Supertasters, 404–405 in brain development, 203, 273–275, 432, 546–549 Trapezoid body, 333, 334f
Supplementary speech area, 344–345, 344f functions of, 200, 202 Traumatic brain injury, 2–3, 13–14, 577–580, 577f.
Suprachiasmatic nucleus lifelong effects of, 274–275 See also Brain injury
in biorhythms, 450–456, 450f neuroplasticity and, 509 in athletes, 577, 578
slave oscillators in, 452–453, 453f, 455 sexual behavior and, 434 chronic traumatic encephalopathy (CTE) and, 578
structure of, 451, 451f in sexual differentiation, 203, 272, 432, 433 concussion and, 577, 578
transplantation of, 452, 452f Tetrahydrocannabinol (THC), 152–153, diagnosis of, 579
Surgery. See Neurosurgery 189–190, 198, 199 incidence of, 577, 577f
Swimming pool tasks, 215–216, 216f Tetrodotoxin, 120 mechanics of, 577–579, 579f
Sympathetic nervous system, 63–64 Thalamic nuclei, 69 neuroplasticity in, 513–517
neurotransmission in, 157–158 Thalamus, 53, 53f, 54 recovery from, 513–517, 580
in stress response, 157–158, 204–206, 205f association cortex and, 525 symptoms of, 577–579
Synapses, 77, 78f electrode placement in, 572 Tremor, in Parkinson disease, 140, 161, 586
axoaxonic, 145, 145f in gustation, 405 Triceps muscle, 372, 372f
axodendritic, 145, 145f medial, in memory, 495–497, 498f Trichromatic theory, 310–311
axomuscular, 145, 145f in olfaction, 402f, 403 Tricyclic antidepressants, 185. See also
axosecretory, 145, 145f ventrolateral, 383, 383f Antidepressants
axosomatic, 145, 145f Theory of mind, 536 Trigeminal nerve, 59, 60f
axosynaptic, 145, 145f Thermoregulation, 411–412 Trisomy 21, 100, 101f
chemical, 141–142, 142f Thiamine deficiency, in Korsakoff syndrome, 495–497 Tritanopia, 311
dendrodendritic, 145, 145f Thinking. See Cognition; Thought tRNA, 93
drug action at, 175f, 176–177, 185, 185f Thirst. See also Drinking behavior Trochlear nerve, 59, 60f
electrical, 142, 145–146 hypovolemic, 431 Trophic factors, 252
excitatory, 146, 146f osmotic, 431 for brain injury, 516–517
formation of, 257, 502–503. See also Neuroplasticity Thoracic spine, 60, 61f neuroplasticity and, 510, 510t
Hebb, 163 Thorndike’s puzzle box, 482–483, 483f Tropic molecules, 256
inhibitory, 146, 146f Thought. See also Cognition Tubules, 90
in learning, 163–167, 507. See also Learning characteristics of, 521–522 Tumors, brain, 83
plasticity of, 162–163, 502–504, 503f. See also neural unit of, 522–525, 524f, 529 Tuning curves, 336–337, 336f
Neuroplasticity as psychological construct, 520 Tuning fork, 323, 323f, 324f
structure of, 140–142, 142f Three-legged cat solution, 514 Twin studies
types of, 145 Threshold potential, 120 epigenetics and, 237
Synaptic cleft, 141, 142f Thymine, 91f, 92 of substance abuse, 196
Synaptic organization, intelligence and, 555 Thymus gland, in myasthenia gravis, 134 Two-point sensitivity, 379, 379f
Synaptic pruning, 257–258, 257f Thyroid gland, 415–416, 415f Tyrosine, 150, 150f
Synaptic transmission. See Neurotransmission Thyroid hormones, 414t, 415–416
Synaptic vesicles, 141, 142f Thyroid-stimulating hormone (TSH), 414t Ultradian rhythms, 445, 445t
Synesthesia, 288, 551–552 Tickling, 392 Umami receptor, 405
Syntax, 521–522 Tight junctions, in blood–brain barrier, 174, 174f Unconditioned response, 482
definition of, 521 Timbre, 324f, 328 Unconditioned stimulus, 482
uniformity of, 341–342 Tissue plasminogen activator (t-PA), 45, 580–581 Unconscious memory. See Memory, implicit
Systematic desensitization, 575 Tolerance, drug/alcohol, 177–178, 178f Uracil, 93
Tone deafness, 348 Urge-to-action system, 374
Tactile stimulation Tone of voice, 328, 424 Utricle, 388, 389f
brain development and, 267 Tongue, taste receptors on, 405, 405f
sensory processing in, 132–133, 133f Tonotopic representation, 336–338, 337f Vagus nerve, 59, 60f, 65
Tardive dyskinesia, 574 Top-down processing, 56 Val allele, 236
Taste, 404–405 Topographic maps, 288, 288f Valium, 182
reactions to, 437–438, 438f Topographic organization. See also Brain maps; Ho- Valproate, for bipolar disorder, 186
Taste aversions munculus Ventral, definition of, 38, 39
behavior in, 437–438, 438f of auditory cortex, 343–346 Ventral roots, 61, 62f
learned, 409 of cerebellum, 375–376 Ventral spinothalamic tract, 383f
Taste buds, 404, 405, 405f definition of, 367 Ventral thalamus, in memory, 498, 498f
Taste preferences, 409 experience-based changes in, 369–370, 506f, 508 Ventral visual stream, 69–70, 69f, 297, 300f, 527f
Taxonomy, 16–17, 16f of motor cortex, 366, 366f, 369–370 injury of, 315–316, 316f
Tay-Sachs disease, 98–99 changes in, 369–370, 369f, 505–507, 506f location of, 526
Tectopulvinar pathway, 296, 296f, 298 of somatosensory cortex, 390–391, 391f, 393f in object recognition, 526, 527f
Tectorial membrane, of inner ear, 330, 330f of visual cortex, 302–303, 303f secondary somatosensory cortex in, 394
Tectum, 53, 53f Touch, sensory processing in, 132–133, 133f as what pathway, 297, 315–316, 316f
Tegmentum, 53, 53f Tourette syndrome, 57, 71, 374 Ventricles, 8, 44, 44f
Telencephalon, 48, 48f Tower of Hanoi test, 247, 247f Ventrolateral thalamic neurons, 383
Telodendria, 77, 78f t-PA (tissue plasminogen activator), 45, 580–581 Ventrolateral thalamus, 383, 383f
Temperature perception, 380, 382–388 Tractography, 534, 535, 535f Ventromedial hypothalamus
Temperature regulation, 411–412 Tracts, 47, 47f, 61, 62f, 358. See also specific types in eating, 429, 430f
Temporal auditory cortex, 334 Tranquilizers in sexual behavior, 434
tractography of, 534, 535, 535f insomnia and, 473 Ventromedial prefrontal cortex, 418f, 419, 526f
Temporal lobe, 41f, 55, 55f minor, 182 Verbal fluency, sex differences in, 546–549
in association cortex, 525–526, 527f Transcranial magnetic stimulation (TMS), 220, 220f, Vertebrae, 59–60, 61f, 359. See also under Spinal
in cognition, 525–526, 527 573, 573f Vertigo, 389
injury of, 55 repetitive, 220, 573 Vesicles, synaptic, 141, 142f
in memory, 494–495, 498f Transcription, 92, 93f, 104 Vestibular system, 388–389, 389f
S-18 Subject Index
Virtual Afghanistan, 576 Visual streams. See Dorsal visual stream; Ventral visual Vitamin D deficiency
Virtual Iraq, 562, 576 stream depression and, 185
Virtual reality exposure therapy, 562, 576 Visual system, 283–319 multiple sclerosis and, 126, 584
Vision anatomy of, 289–301 Vocal tone, 328, 424
attention and, 528–529 chemoaffinity in, 268–269, 270f Volt, 110
binocular, corpus callosum in, 304 coding of location in, 302, 302f, 303f Voltage gradient, 114–115
color, 310–313. See also Color vision corpus callosum in, 304 Voltage-sensitive ion channels, 117–119, 121–122, 121f,
light in, 290 dorsal, 313 122f. See also Ion channels
in movement, 382 how function of, 297, 300, 313 Voltmeter, 111
neuropsychology of, 314–317 impairment of, 317–318 Vomeronasal organ, 403
night, age-related decline in, 294 lateralization in, 541–542, 542f. See also Vomiting, 174
peripheral, 292, 292f Visual fields
refractive errors and, 290–291 in movement, 313, 316, 316f, 382 Waking state, 457–458, 476–477. See also Sleep
shape perception in, 305–310, 305f–310f movement perception and, 313 electroencephalogram in, 457f, 459f, 470–471
spatial localization in, 302–304 neural connectivity in, 268–269 Wanting-and-liking theory, 194–196, 437
Vision impairment, 314–317 neural streams in, 69–70, 69f Water, chemistry of, 89
agnosia and, 301, 315–316 neuronal activity in, 304–313 Water intoxication, 431
in carbon monoxide poisoning, 315–316 ocular dominance columns in, 269, 270f, 308–309, Wave effect, 111, 111f
echolocation in, 335 309f, 312, 312f Waves
monocular blindness and, 314 ocular structures in, 289–291, 291f light, 290, 290f
refractive errors and, 290–291 parallel processing in, 68–70, 69f sound, 323–329
Visual agnosia, 315–316 photoreceptors in, 219f, 289–294, 294f, 296f Weight, regulation of, 426–430. See also Eating/feeding
in Klüver-Bucy syndrome, 422–423 primary (striate) cortex in, 296, 296f, 297f, 299, 299f, behavior
Visual cortex 302–303, 303f, 307–309. See also Visual cortex, Weight-loss strategies, 428
association cortex and, 527, 527f primary (striate) Wernicke’s aphasia, 343
complex cells of, 307, 307f receptive fields in, 302–303, 302f, 305–308 Wernicke’s area, 334, 334f, 342–346, 342f
hypercomplex cells of, 307, 308f retinal neurons in, 294–298, 294f, 295f mapping of, 343–346, 344f
ocular dominance columns in, 269, 270f, 308–309, secondary (extrastriate) cortex in, 299, 300f White matter, 43f, 44, 47f
309f, 312, 312f secondary visual cortex in, 299f in reticular formation, 52
primary (striate), 296, 296f, 297f, 299, 299f segregated visual input in, 297–298, 298f spinal, 62f
processing in, 307–309 temporal lobe in, 300–301, 300f, 309–310 Wild-type alleles, 97
in shape perception, 307–309 topographic maps in, 302–303, 303f Wisconsin Card Sorting Task, 531, 531f, 533
topographic organization of, 302–303, 303f visual pathways in, 295–296, 296f, 297–298, 298f Withdrawal symptoms, 193
secondary (extrastriate), 299, 299f visual streams in, 297–298, 300f, 314–317, 394, 526, Women. See Sex differences
simple cells of, 307, 307f 527f. See also Dorsal visual stream; Ventral World Health Organization, 569
Visual fields, 295–296, 301–304, 301f visual stream
blindness of, 284, 314–315, 314f what function of, 297, 300 Xanax, 182
cerebral asymmetry and, 542, 542f impairment of, 315–316 Xenon, in memory erasing, 498
Visual illuminance, 294 where function of, 298
Visual pathways, 295–296, 296f Visual-form agnosia, 315–316, 526 Y chromosome, SRY gene of, 203
geniculostriate, 296, 296f, 297–298, 297f, 298f Visuospatial learning, 493 Yips, 375
tectopulvinar, 296, 296f, 298 Visuospatial memory, 492
Visual recognition task, 493, 493f Vitamin B1 deficiency, in Korsakoff syndrome, 495–497 Zeitgebers, 446–448
this page left intentionally blank
Study Smarter with LearningCurve! A link to the e-Book
makes it easy to review.
What is ?
LearningCurve is a cutting-edge study tool Stuck on a question?
Ask for a hint!
designed to increase your understanding and
memory of the core concepts in every chapter. Instant feedback allows
The activity is over
Based on insights from the latest learning and you to learn as you go.
when the progress bar
memory research, the LearningCurve system is complete.
pairs multiple-choice and fill-in-the-blank questions
with instantaneous feedback and a rich array of
study tools including videos, animations, and lab
simulations.
The LearningCurve system is adaptive, so the quiz
you take is customized to your level of understand-
The Personalized Study Plan
ing. The more questions you answer correctly, the keeps track of your progress
more challenging the questions become. Best of on individual topics and links
you to videos, tutorials, and
all, the e-Book of An Introduction to Brain and other study tools.
Behavior, Fifth Edition, is fully integrated, so you
can easily review the text as you study and answer
questions.
LearningCurve is a smart and fun way to master
each chapter and prepare for your exam.
is available as part of the LaunchPad for An IntroductIon to BrAIn
And BehAvIor, Fifth Edition. To find out more or purchase access, go
to http://www.macmillanhighered.com/launchpad/kolbintro5e
An IntroductIon to BrAIn And
BEhAvIor, Fifth Edition
LaunchPad for An Introduction to Brain and Behavior, Fifth Edition
Available July 2016 at http://www.macmillanhighered.com/launchpad/kolbintro5e
Each chapter in LaunchPad for An Introduction to Brain and Behavior, Fifth Edition features a collection of
activities carefully chosen to help master the major concepts. The site serves students as a comprehensive
online study guide, available any time, with opportunities for self-quizzing that include instant feedback, exam
preparation, and further exploration of topics from the textbook. For instructors, all units and activities can be
instantly assigned, and students’ results and analytics are collected in the Gradebook.
For StudentS For InStructorS
n Full e-Book of An Introduction to Brain n Lecture Slides
and Behavior, Fifth Edition n Chapter Figures, Photos, and Tables
n LearningCurve n Downloadable Diploma Computerized Test
n Video Activities Bank
n Summative Quizzes n Instructor’s Resources
n Neuroscience Tool Kit Activities
n Interactive Flashcards
You might also like
- The Subtle Art of Not Giving a F*ck: A Counterintuitive Approach to Living a Good LifeFrom EverandThe Subtle Art of Not Giving a F*ck: A Counterintuitive Approach to Living a Good Life4/5 (6453)
- Daniel J. Fox - The Borderline Personality Disorder Workbook An Integrative Program To Understand A100% (63)Daniel J. Fox - The Borderline Personality Disorder Workbook An Integrative Program To Understand A274 pages
- Treating Adult Survivors of Childhood Emotional Abuse and Neglect PDF97% (30)Treating Adult Survivors of Childhood Emotional Abuse and Neglect PDF328 pages
- List_ICD_10_2010_Indonesian_ModificationNo ratings yetList_ICD_10_2010_Indonesian_Modification90 pages
- Hidden Figures: The American Dream and the Untold Story of the Black Women Mathematicians Who Helped Win the Space RaceFrom EverandHidden Figures: The American Dream and the Untold Story of the Black Women Mathematicians Who Helped Win the Space Race4/5 (1022)
- The World Is Flat 3.0: A Brief History of the Twenty-first CenturyFrom EverandThe World Is Flat 3.0: A Brief History of the Twenty-first Century3.5/5 (2289)
- The 4 Hour Workweek, Expanded and Updated by Timothy Ferriss - Excerpt23% (954)The 4 Hour Workweek, Expanded and Updated by Timothy Ferriss - Excerpt38 pages
- The 36 Questions That Lead To Love - The New York Times92% (36)The 36 Questions That Lead To Love - The New York Times3 pages
- Converted - vdoc.pub_vagus-nerve-2-books-in-1-vagus-nerve-daily-vagus-nerve-exercises-a-complete-self-help-guide-to-stimulate-vagal-tone-practical-exercises-for-chronic-illness-depression-anxiety-and-trauma copyNo ratings yetConverted - vdoc.pub_vagus-nerve-2-books-in-1-vagus-nerve-daily-vagus-nerve-exercises-a-complete-self-help-guide-to-stimulate-vagal-tone-practical-exercises-for-chronic-illness-depression-anxiety-and-trauma copy121 pages
- Head and Neck - Schwartz's Principles of Surgery 11th EdNo ratings yetHead and Neck - Schwartz's Principles of Surgery 11th Ed42 pages
- Neural Control and Coordination Class 11 Notes CBSE Biology Chapter 21 (PDF)No ratings yetNeural Control and Coordination Class 11 Notes CBSE Biology Chapter 21 (PDF)10 pages
- Week 3 or 4 Eye Assessment Health AssessmentNo ratings yetWeek 3 or 4 Eye Assessment Health Assessment34 pages
- TITLE: Pediatric Rhinosinusitis SOURCE: Grand Rounds Presentation, UTMB, Dept. of OtolaryngologyNo ratings yetTITLE: Pediatric Rhinosinusitis SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology10 pages
- Electrophysical Therapy II Written Exam NotesNo ratings yetElectrophysical Therapy II Written Exam Notes63 pages
- Idh1, Idh2 Idh2 1p19q Co-Deletion, IDH1, IDH2, BRAF, EGFR Amplification100% (1)Idh1, Idh2 Idh2 1p19q Co-Deletion, IDH1, IDH2, BRAF, EGFR Amplification12 pages
- Answer Key-Ch-10 Our Nervous System- WorksheetNo ratings yetAnswer Key-Ch-10 Our Nervous System- Worksheet4 pages
- Diagnostic Palpation in Osteopathic Medi-7437305No ratings yetDiagnostic Palpation in Osteopathic Medi-7437305324 pages
- PDF CPC Practice Test 1 - MedicalCodingAce100% (2)PDF CPC Practice Test 1 - MedicalCodingAce87 pages
- The Hold Me Tight Workbook - Dr. Sue Johnson100% (17)The Hold Me Tight Workbook - Dr. Sue Johnson187 pages
- Workbook For Adult Children of Emotionally Immature Parents - How To Heal From Distant, Rejecting, or Self-Involved Parents88% (16)Workbook For Adult Children of Emotionally Immature Parents - How To Heal From Distant, Rejecting, or Self-Involved Parents77 pages
- Attachment Theory Workbook - Powerful Tools To Promote Understanding, Increase Stability, and Build Lasting Relationships, The - Annie Chen LMFT97% (108)Attachment Theory Workbook - Powerful Tools To Promote Understanding, Increase Stability, and Build Lasting Relationships, The - Annie Chen LMFT62 pages
- The Body Image Workbook An Eight-Step Program For Learning To Like Your Looks92% (61)The Body Image Workbook An Eight-Step Program For Learning To Like Your Looks200 pages
- The Therapist's Ultimate Solution Book - Essential Strategies, Tips & Tools To Empower Your Clients100% (67)The Therapist's Ultimate Solution Book - Essential Strategies, Tips & Tools To Empower Your Clients324 pages
- Never Split the Difference: Negotiating As If Your Life Depended On ItFrom EverandNever Split the Difference: Negotiating As If Your Life Depended On It4.5/5 (1005)
- The Gifts of Imperfection: Let Go of Who You Think You're Supposed to Be and Embrace Who You AreFrom EverandThe Gifts of Imperfection: Let Go of Who You Think You're Supposed to Be and Embrace Who You Are4/5 (1175)
- The Hard Thing About Hard Things: Building a Business When There Are No Easy AnswersFrom EverandThe Hard Thing About Hard Things: Building a Business When There Are No Easy Answers4.5/5 (361)
- Devil in the Grove: Thurgood Marshall, the Groveland Boys, and the Dawn of a New AmericaFrom EverandDevil in the Grove: Thurgood Marshall, the Groveland Boys, and the Dawn of a New America4.5/5 (280)
- A Heartbreaking Work Of Staggering Genius: A Memoir Based on a True StoryFrom EverandA Heartbreaking Work Of Staggering Genius: A Memoir Based on a True Story3.5/5 (233)
