THE PREFRONTAL CORTEX “Joaquín Fuster is one of the leading scientists in the field of cognitive neuroscience He is famous not only for his discovery of “memory cells” in the frontal lobe of the monkey, but also for his excellent books Among them the most famous and influential is The Prefrontal Cortex I remember the first edition of it back in 1980 It was a mere intellectual pleasure reading it The book reviewed an amazing amount of data from anatomy, ontogeny, and physiology to the effect of lesions on innate and conditioned behavior and synthesized them in a coherent theory In this new completely re-written edition of the book, Fuster has been able to repeat the enterprise In spite of the enormous amount of new data, many coming from the rather messy field of brain imaging, he has been able to review them and put them in a clear theoretical frame I am sure the new generation of neuroscientists will be influenced by this book in the same way as I was more than 20 years ago and will receive, by reading it, the same intellectual pleasure.” Giacomo Rizzolatti, Professor of Human Physiology, Department of Neuroscience, Section of Physiology, University of Parma, Italy “Once again, Dr Fuster, the world’s pre-eminent expert on the frontal lobes, has delivered an instant classic that should be read by everyone interested in understanding the link between brain and behavior.” Mark D’Esposito, Professor of Neuroscience and Psychology, Director, Henry H Wheeler Jr Brain Imaging Center, University of California, Berkeley, USA “The frontal lobe serves the highest cognitive functions of the brain, including symbolic representation of the world, decision making, and planning for the future Arguably, the enormous development of these functions distinguishes the human from other species Joaquín Fuster has devoted his life to studying the many complex roles of the frontal cortex in behavior and cognition This book is the product of his efforts to make these issues comprehensible in an exciting and fast-growing field Even it you possess earlier editions of his book you should have this one to stay informed about the brain structure that makes us human For that, this vastly updated edition is a must-have, whether you are a specialist or not.” Pasko Rakic, Chairman, Department of Neurobiology, and Director, Kavli Institute for Neuroscience, Yale Medical School, USA “The Prefrontal Cortex is a classic, and the classic has just been updated, expanded and thought anew, with the depth and wisdom that characterize Fuster’s work As before, this is an indispensable volume for neuroscientists.” Antonio Damasio, Dornsife Professor of Neuroscience and Director, Brain and Creativity Institute, University of Southern California, USA “The frontal lobes are central to cognitive neuroscience The revision of this important volume provides the crucial background needed to grasp their role In a final chapter Fuster brings together all that is known by emphasizing the temporal course of brain networks in a way which serves to illuminate action, consciousness and free will.” Michael I Posner, Professor, Department of Psychology, Institute of Cognitive and Decision Sciences, University of Oregon, USA The Prefrontal Cortex is not only a classic, but also an essential book for anyone interested in higher brain function One might think there’s nothing left to say but Fuster proves that wrong The fourth edition is fresh and vibrant, and itself essential, destined to be a classic in its own right.” Joseph LeDoux, University Professor, New York University, USA, and author of The Emotional Brain and Synaptic Self “A classic that has graced the library of many of us since its first edition appeared 28 years ago now returns, splendidly updated As a result this book will continue to be the go-to reference on the prefrontal cortex as we strive to understand more fully its critical role in brain function.” Marcus E Raichle, Professor of Radiology and Neurology, Washington University School of Medicine, USA THE PREFRONTAL CORTEX Fourth Edition Joaquín M Fuster, md, phd Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine University of California at Los Angeles Los Angeles, California AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD PARIS • SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Acadamic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 32 Jamestown Road, London NW1 7BY, UK 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, CA 92101-4495, USA Fourth edition 2008 Copyright © 2008 Elsevier Ltd All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in 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by Charon Tec Ltd., A Macmillan Company (www.macmillansolutions.com) Printed and bound in China 08 09 10 11 12 10 To the memory of my father – physician, educator, historian, and man of infallible common sense This page intentionally left blank Contents Preface xi Introduction Anatomy of the Prefrontal Cortex I Introduction II Evolution and Comparative Anatomy III Development and Involution 12 IV Microscopic Architecture 20 V Connections 27 A Afferents 28 B Efferents 37 VI Summary 42 References 44 Chemical Neurotransmission 59 I Introduction 59 II Development and Involution 63 III Transmitters in the Prefrontal Cortex 65 A Glutamate 66 B GABA 68 C Norepinephrine 70 D Dopamine 75 E Serotonin 85 F Acetylcholine 87 G Neuropeptides 90 IV Neuropsychiatric Implications 91 A Attention Disorders 92 B Schizophrenia 94 C Drug Abuse 98 vii viii CONTENTS D Depression 101 E Neurodegenerative Disease 102 V Summary 103 References 105 Animal Neuropsychology 125 I Introduction 125 II Historical Background 126 III Motility 127 A Hyperactivity 127 B Disinhibition 127 IV Emotional Behavior 129 A Basic Drives 130 B Social Behavior 131 V Cognitive Functions 133 A Attention: Set 133 B Discrimination Tasks: Inhibitory Control 135 C Delay Tasks: Working Memory 138 Anatomical Factors 140 Sensory Factors 143 Spatial Factors 143 Temporal Factors 144 Memory Factors 146 Motor Factors 147 Inhibitory Factors 147 VI Reversible Lesion 148 A Prefrontal Cooling on Delay Tasks 150 VII Development and Involution 153 VIII Summary 155 References 156 Human Neuropsychology 171 I Introduction 171 II Historical Background 172 III Affect, Emotion, and Social Behavior 174 A Apathy 174 B Depression 174 C Euphoria 175 D Motion and Emotion 175 E Theory of Mind: Empathy 177 F Social Behavior 177 IV Executive Function 178 A Attention 179 Alertness 180 Set 180 Spatial attention 181 Sustained attention 183 Interference Control 183 CONTENTS V VI VII VIII IX B Memory 184 C Working Memory 185 D Planning 187 E Temporal Integration 189 F Decision-making 190 G Monitoring 192 H Inhibitory Control 192 Language 193 Intelligence 195 Prefrontal Syndromes 196 A Lateral 197 B Orbital 198 C Medial/Anterior Cingulate 199 Development and Involution 200 Summary 205 References 208 Neurophysiology 221 I Introduction 221 II Historical Background 222 III Sensory Function 223 IV Motor Function 226 V Visceral and Emotional Function 231 VI Executive Functions 234 A Attention 235 Expectancy 235 Set 237 B Working Memory 239 The Memorandum 240 The Delay: Persistent Neuronal Activity 243 The Choice 247 The Reward 250 C Mechanisms of Working Memory 251 D Anticipatory Activity 259 Motor Preparation 259 Rules 260 Reward Value 261 E Monitoring 266 VII Summary 267 References 270 Neuroimaging 285 I Introduction 285 II Functional Imaging: Value and Limitations 286 A Spatial and Temporal Resolution 287 B Functional Module or Functional Network 287 C Interdependence of Cognitive Functions 288 ix 396 INDEX Frontal cortex, 1, development, 17 executive networks in, 340–2 Frontal cortical tissue, transplants, 155 Frontal dynamic aphasia, 194, 198 Frontal eye field (area 8), 39, 173, 224 in animals, 127, 142 connections, 35, 39, 228 electrical stimuli applied to, 229 eye movements, 173, 181 lesions, 186, 198 in motility, 302 selective sensorial attention, 224 stimulus-movement linkage, 224 transitional zone, 23, 26 Frontal granular cortex, 1, 2, 11, 12, 44 Frontal lobe, 334 clinical literature, 173 connectivity, 40 psychosurgery, 173 tumors, 172 Frontotemporal dementia (FTD) (Pick’s disease), 19, 102, 103 cholinergic system, 103 in the elderly, 208 familial, 105 genetics, 205 Functional activation disorders, in schizophrenia, 313 Functional cell selection, 17 Functional imaging, value and limitations, 286–9 Functional magnetic resonance imaging (fMRI), 286, 287, 317 blood oxygen level-dependent (BOLD) method, 286, 287, 291 Functions overview, 333–85 concepts, 333–6 past/future perspectives, 342 see also Prefrontal function(s)and individual functions Fusiform gyrus, face recognition, 295 G-protein activation, 60–1 GABA, see Gamma-aminobutyric acid GABAergic interneurons, 252 GAD, see Glutamic acid decarboxylase Gage, Phineas, 172, 174, 178, 187 Galvanic skin response, 191 Gambling tasks, 87, 202 Gamma-aminobutyric acid (GABA), 68–70 in ADHD, 94 brain content, 68 computational models, 252 DA systems interaction, 79 development of, 64 in drug abuse, 105 inhibitory role, 69, 87, 104, 105 memory formation, 67 neurons, 69, 86 neurotransmission, 60, 65–6, 104 receptors, 68 in schizophrenia, 97, 98, 105 synaptic processes, 61 Genes involved in ADHD, 93 neurotransmission and, 63 in schizophrenia, 95, 105 Genetic disorders, 63 Gestalt cycle, 358 Gestalt psychology, 363 Gestalts, 381 of action, 345, 381 temporal, 345, 358 verbal, 308 Gilles de la Tourette syndrome, 379 Globus pallidus, 30, 41, 42 Glucose utilization in cortical regions, 293 Glutamate, 66–8 in ADHD, 94 DA systems interaction, 79 in drug abuse, 105 involved in sustained attention, 93 neurotransmission, 60, 65, 68, 104 reward role, 83 in schizophrenia, 97 synaptic processes, 61 Glutamate prefrontal pyramids, 91 Glutamate receptors, categories, 67 Glutamic acid, 66 Glutamic acid decarboxylase (GAD), 68, 97 in schizophrenia, 97 Glutamine, in schizophrenia, 98, 105 Glycine, 70 Go/no go tasks, 136, 142, 190, 193, 238, 244 Goal-directed actions, 239, 268, 335, 357–8, 364 Goal-directed behavior, 368 Goal neglect, 196 Goals cognitive functions determined by, development of ability to form, 202 Golgi type II cells, 24–6 Gonadal hormones, maturation, 154 Grammar, syntax of, 368 Granule cells, 25–6 INDEX Gray matter in aging, 315, 318 in attention-deficit hyperactivity disorder, 311, 318 in dementia, 315 in depression, 314 frontal, regional cerebral blood flow (rCBF) in, 290 in schizophrenia, 313, 318 volume loss of, 17, 44 Group selection, 337 Growth factors, 91 Guanfacine, 73, 94 Gustatory afferents, 35 Gustatory cortex, 34 Gustatory stimuli, 291 neurons reacting to, 224 Gyrification, 9–10 Gyrus proreus, 21–2, 35 Haloperidol, 83 in schizophrenia, 96–7 Heart rate and orbitofrontal stimulation, 231 responses, in animals, 131 Hemidecortication, 200 Hemispheric Encoding/Retrieval Asymmetry (HERA), 308 Heterarchy, 341 Hippocampal cortex, 38 Hippocampus efferent connections, 340 and learning, 82 and memory formation, 338 neocortical development, 8–9 neonatal lesion, 96 projections from, 30–1, 34 role in long-term potentiation, 68 synaptic plasticity in, 82 Hippocampus-prefrontal connections, 244 Hodology, 21 Homeostatic equilibrium, 379 Hormones, gonadal, maturation, 154 Human neuropsychology, 171–219 affect and emotion, 174–7 development, 200–3 executive function, 178–93 historical background, 172–3 involution, 203–5 language, 193–6 orbital cortex, 198–200 prefrontal syndromes, 196–8 lateral, 198 397 orbital, 198–9 social behavior, 177–8 summary, 205–8 tests, 190 6-Hydroxydopamine (6-OHDA), 154 5-Hydroxytryptamine (5-HT), 65–6 see also Serotonin Hyperactivity, 175, 206 effects of ablation in animals, 127, 155 Hyperfrontality, 290 Hyperkinesia, 176 Hypermetamorphosis, 128 Hypermotility, 176 in animals, 146 orbitofrontal, 199 Hyper-reactivity, 175, 176, 206, 353 in animals, 127 Hypersexuality, 178 Hypoactivity, in animals, 127 Hypocretin, 91, 105 Hypofrontality in depression, 314 in schizophrenia, 311–12, 318 Hypokinesia, 176, 199 Hypomania, 101, 175, 176 Hypothalamus afferents to orbitofrontal cortex, 35 afferents to prefrontal cortex, 31 behavior control, 233 drive, 346 efferents from prefrontal cortex, 38 emotional behavior, 345 Hypothermia, to induce reversible cortical lesions, 149 Hypotonia, muscular, 199 ICSS (intracranial self-stimulation), 83–4, 98 IGT (Iowa Gambling Task), 176–7, 191–2, 202 Immediate matching-to-sample (IMS), 293 Impulsivity, 104, 353 angry, 178 decontrol of, 86 development of restraint, 202 orbitofrontal pathology and, 100 Inattention, unilateral, 182 Inclusive (selective) attention, 5, 92, 193, 198, 225 development, 201, 207 Indifference, 174 Indoleamines, 63 Inferior convexity in animals, 137, 141 lesions, 137, 143 398 Inferior frontal fissure, 10 Inferior frontal gyrus, set shift, 239 Inferior lateral cortex, 318 Inferior precentral fissure, 43 Inferior prefrontal cortex (IPC), 310 Inferior temporal cortex, 29 Inferior thalamic peduncle, cryogenic blockade of, 225 Inferotemporal cortex, reversible lesion, 143 Inhalation, radioisotope administration by, 290 Inhibition, in animals, 128–9 conditioned, 136 lateral, 353 targets of, 353 Inhibitory (exclusionary) attention, 69, 92, 193, 198 development, 201, 207 Inhibitory control, 5, 192–3 effects of ablation in animals, 135–8, 148 Inhibitory factors, in delay tasks for animals, 147–8 Inhibitory interference control, 4, Initiative, lack of, 176 Innovation, children’s drive towards, 370 Inputs, orders of, 371 Instability of motor points, 222 Instinctive behavior, 44 Instinctual disinhibition, 176 Insular (parapiriform) area, 10 Integration cross-temporal, 235, 238, 240 sensory-motor, 235, 238, 240 see also Temporal integration Intelligence, 207 age of maturity, 207 in animals, abstract, 126 components of, 196 creative, 196 creative, see Creative intelligence definition, 195–6 development of, 202 fluid, 196 Intelligence tests, 195 Interference, 186–7, 202 in animals, 148 inhibition of, 201 proactive, 352 Interference control, 183–4, 335 components, 352 motor interference, 349 overview, 352–3, 380–1 Intracranial self-stimulation (ICSS), 83–4, 98 Intraproreal (proreal) fissure, 10 INDEX Inverse-inference fallacy, 288 Inverted-U function dopamine agonists, 79, 80–1 norepinephrine, 74, 104 Involution, 19, 44 animal neuropsychology, 155 human neuropsychology, 203–5 neurotransmitters, 64–5 Iontophoresis (cellular infusion), 73 Iowa Gambling Task (IGT), 176–7, 191–2, 202, 304 Ipsilateral cortex, 39 IQ, and cortical thickness, 202, 203 Irascibility, in animals, 130 Irritability, 176 Isocortex, 20, 23, 24, 44 Isomorphism, 377–8 Kainate, 67 Knowledge, children acquiring fund of, 370 Korsakoff patient, 184 L-dopa, in Parkinson’s disease/dementia, 92, 95, 103 Lability, emotional, 176 Language, 185, 193–6, 207, 307–10, 336 age of maturity, 207 development, 370 integrative domain, 310 overview, 368–9, 382 phonological, 310 propositional, 362 semantic, 310 spoken, 198, 344, 362 see also Aphasia Lateral geniculate body, 225 Lateral gyrus, 39 Lateral inhibition, 353 Lateral lesions, 207 Lateral prefrontal cortex, 197–8 actions, 231, 239 in animals, 138 ablation, 141, 153 cooling, 151, 152 lesions, 156 attention and, 92–3 cells, 230 connections, 31, 41, 44 decision-making, 304 increasing blood flow in, 95 lesions, 156, 174, 180, 187 maturity, 207 memory acquisition and retrieval in, 79 phyletic development, 11 INDEX role in attentive gating, 296 in schizophrenia, 312 set, study methodology, willed sequential acts, 302 working memory, 4, 295, 317 Lateral prefrontal syndrome, 197–8, 207 Lateral thalamus, 44 Law, rule of, 378, 379 Law of proximity, 345 Learning, structures involved in, 82 Lebadea principle of prefrontal function, 352 Lesions arcuate cortex, 142 behavioral abnormalities in animals resulting from, 155, 156 Broca’s area, 207 cryogenic, 156 dorsolateral, 141, 155–6 dorsolateral prefrontal cortex, 145, 146, 147 frontal eye field (area 8), 186, 198 inferior convexity, 137, 143 inferotemporal cortex, 143 lateral, 198, 200, 205, 206, 207 lateral prefrontal cortex, 156, 174, 180, 187 medial, 198, 200, 205, 206 medial prefrontal, 138 neonatal, in hippocampus, 96 neostriatum caudolaterale in pigeons, 137 orbital, 133, 135, 137, 144, 155, 156 orbitofrontal, 128, 129, 178 prefrontal, 365 premotor cortex, 147 reversible, 143, 148–53, 156 set shift and, 135 social behavior and, 206 sulcus principalis, 144 Leukotomy, 173, 174 orbitofrontal, 175 Limb movements, 229 supplementary motor area (SMA), 229, 230 Limbic cortex, afferents from, 35 Limbic DA system, 77 Limbic regions, afferents from, 36 Limbic structures, inputs from, 371 Limbic system afferents to prefrontal cortex, 31 in animals, 130 Line set, 135 Lipofuscin, 19 Lithium, 102 Lobectomies, 172 399 Lobotomy, 173, 174 prefrontal, 130 Locus coeruleus, 31, 70, 74 NE system, 89, 91 Logical reasoning, 362 Long-term memory, 3, 34, 82, 184 action rules, 261, 269 constituents of, 251 declarative, 206 task components in, 297 Long-term potentiation (LTP), 67, 82, 244 Magnet reaction, 129 Magnetic resonance imaging (MRI), 286, 287 development of frontal cortex, 17 Magneto-electroencephalography (MEG), 239 Mammals, phylogenic development, Mania, 101, 199, 314 Manipulation, 368 MAO (monoamine oxidase) inhibitors, 101, 105 Mass action, principle of, 141 Matching auditory-visual, 142 tactile-visual, 142 Matching-to-sample in animals, 143 delayed, 150 effect of cooling, 150 Mathematical reasoning, 362 Maturity, ages of, 207 Maze tests, 188 Medial cingulate syndrome, 207 Medial cortex, role in stress and defense, 233 Medial prefrontal cortex, 197, 199 and attention, 92, 93 connections, 34, 44 and drug abuse, 100 and emotions, 304 role in attentive gating, 296 and serotonin, 86 Medial prefrontal lesions, in animals, 138 Mediodorsal thalamic nucleus, 21, 30 connections, 11, 28, 29 efferents to, 38 functions, magnocellular component (pars magnocellularis), 28, 29 parvocellular component (pars parvocellularis), 11, 28, 29 Mediodorsal thalamic projection, 76 Medulla, 260 Melodic memory, 307 400 Memorandum, 240–3, 252, 268–9, 349, 351 Memory, 184–5, 196 acquisition, 79 active, 349 associative, 67, 68, 91 conceptual, 338 context memory, 376 delay tasks for animals, factors in, 146–7 dualistic concept of, episodic, 307, 308–9 formation of, 67, 337–8 of the future, 187 melodic, 307 metamemory, 185 new, 39 perceptual, 185, 337, 338–9 phyletic, 335, 343–4 phyletic sensory, 338 polysensory, 338 prospective, 187, 335 recent, 184 relationship with planning, 185 remote, 184 retrieval, 39, 79 semantic, 307, 308–9, 310, 338, 341 short-term, 146 source memory, 185 unimodal, 338 see also Executive memory; Long-term memory; Motor memory; Short-term memory; Working memory Memory cells, 5, 243–4, 247, 251 cue-coupled, 246, 248 delay-activated, 244, 248, 268 for eye saccades, 247 pyramidal, 69 Memory fields, 247 Memory of the future, 342, 350, 354 Memory load, prefrontal activation and, 295 Memory organization packet, 345 Memory tests, 201 Mental arithmetic, 295 Mental calculation, 290 Mental disorders, prefrontal neuroimaging, 310–16 attention-deficit hyperactivity disorder (ADHD), 311, 318 dementia, 315–16 depression, 314–15 obsessive-compulsive disorder, 313–14, 318 schizophrenia, 311–13 Mesencephalic reticular formation, 104 Mesencephalon, 38, 85 INDEX afferents to prefrontal cortex, 31 drive, 346 efferents from prefrontal cortex, 38 Mesocortical dopaminergic system, 75–6 Mesocorticolimbic dopaminergic system, 76, 82, 83, 104 Mesoprefrontal DA subsystem, 76 Mesostriatal dopaminergic system, 75 Metabolism, 285, 289 local metabolic rate, 290 Metamemory, 185 Methamphetamine, 100 Methylphenidate, 87, 94 MGluR, 67 Microarchitecture, 20–7, 43 Microelectrode studies, 226, 267, 268 Microgenesis, 362 Microiontophoresis, 89 Midline thalamic nuclei, and orbitofrontal cortex, 225 Midline thalamic system, nonspecific, 223 Mirror neurons, 343 Mnemonic scotomas, 247 Models parallel distributed processing models, 375 prefrontal function(s), 371–6, 383 modular models, 372, 373–4 network models, 372, 374–6 Modular models of prefrontal functions, 372–3, 373–4 Monitoring, 192, 266–7, 268, 363 deficit, 192 Monkeys abstract action, 231 afferents from, 28–9, 30, 31, 35, 36, 44 age-related cell loss, 18–19 connections, 27, 29, 32 corticocortical pathways, 34 cytoarchitectonic map, 24 efferents to, 38, 39, 40 eye-saccades, 266–7 frontal eye field, 26 mediodorsal nucleus, 29 monoamine development, 17 myelination, 15 norepinephrine pathways, 70, 72 prefrontal cortex, 12, 21, 23–4 rewards and reinforcement, 234 sensory function, 223–4 single-unit activity, 240 sulci development, 10 supplementary eye field, 228 INDEX Monoamine oxidase (MAO) inhibitors, 101, 105 Monoaminergic systems, 63, 66, 104 maturation, 154 in the rat, 71 Monoamines, 60, 63, 155 development, 17–18 Moral restraints, 178 Moral sense, 378 Moria, 175 Morphemes, 344 Morphine, 98 Motility, 175–6, 206 effects of ablation in animals, 127–9 Motion, 175–6 Motivation, 82–3, 92, 104, 236 in animals, 129–30, 131, 156 role of orbital prefrontal cortex, 101 Motivational context, 262 Motor actions, 380 coordination, 260 Motor attention, 189, 237, 268, 367 inhibition of motor interference, 348–9 Motor behavior, goal-directed, 175–6 Motor control, 42, 301–7 Motor cortex, 10, 336 Motor-coupled cells, 248, 248–9, 260 Motor-coupled discharge, anticipatory, 248 Motor factors, in delay tasks for animals, 147 Motor function, 40, 41–2, 44 neurophysiology, 226–31, 268 Motor habits, learned, 126 Motor inhibition, 226, 228, 303–4, 348–9 Motor memory, 248–9, 339, 340 development of ability to form and retain, 202 phyletic, 147 retrieval (recall), 340 Motor organization packets (MOPs), 373 Motor points, instability of, 222 Motor preparation, anticipatory, 248, 259–60 Motor sequencing, computer simulation, 374 Motor set, 180, 292 Movement, 30, 42, 79 execution and inhibition of, 226 goal-directed, 126 limb movements, 229, 230 prefrontal control of, 267 preparation for and execution of, 236, 237 readiness potential, 236, 237 voluntary, 260, 301–2 Movement-preparation cells, 229–30 MRI (magnetic resonance imaging), 286, 287 development of frontal cortex, 17 401 Muscarine, 88 Muscarinic receptors, 87, 89 deficiency, 103 Muscular hypotonia, 199 Muscular movements, elementary, 343 Mutism, 176 akinetic, 199 Myelin, prefrontal, 43 Myelin sheaths, 15 Myelination of cortical areas, 15, 16, 17 Myelogenesis, 200 Myelogenetic stages, 15–17 Myopia of the future, 191 N-methyl-D-aspartate (NMDA) conductances, 80 receptors, 67–8, 82, 97 and working memory, 104 NE, see Norepinephrine Near-infrared spectroscopy (NIRS), 286, 287 Necturus, philogenetic development, Neocortex cognitive and emotional functions, 2–3 connections, 44 development in mammals, 8–9 dual evolutionary development, 10 neural elements, vertical arrays, 26 “Neocorticalization”, evolutionary, Neostriatum caudolaterale lesions, in pigeons, 137 Nerve-cell degeneration, 19 Network models of prefrontal functions, 372, 374–6 Networks default network, 290 executive memory, 184 in frontal cortex, 340–2 neural, 252 perceptual, 336–9 prefrontal function(s), 334, 372, 374–6 see also Cognitive networks Neural inhibition, 286 Neural network computer model, 252 hidden units, 252 Neural substrate, 236, 257 Neurodegenerative disease, 102–3 Neuroeconomics, 355 Neuroimaging, 146–7, 285–331 functional imaging, value and limitations, 286–9 imaging prefrontal functions, 289–310 attention, 290–2 executive set, 301 language, 307–10 402 INDEX Neuroimaging (Continued) motor control, 301–7 perception, 290–2 working memory, 292–301 prefrontal imaging in neuropsychiatric illness, 310–16 attention-deficit hyperactivity disorder (ADHD), 311, 318 dementia, 315–16 depression, 314–15 obsessive-compulsive disorder, 313–14, 318 schizophrenia, 311–13 resolution, 287 studies, 17 subtraction method, 317 summary, 316–18 variability, 286–7 Neuroleptics, 95, 96 Neurological syndromes, 27 Neuromodulators, 59 vs neurotransmitters, 60 Neuron discharge, 286 Neuronal architecture, development, 12–13 Neuronal reactions to stimuli, 223–4 Neuronography chemical, 222–3 strychnine, 223 Neurons ACh-containing, 88 auditory stimuli, 224 cholinoceptive, 88 communication between, 59 density, 15 development, 43 encoding abstract action sequences, 231 GABA, 69, 86 gustatory stimuli, 224 involution, 19 and movement, 229 olfactory stimuli, 224 in orbital (paralimbic) regions, 17 postsynaptic, 60 prefrontal, 229, 231 prefrontal pyramidal, 86 pyramidal, 15 raphe serotonergic, 86 reward-anticipating, 262 visual stimuli, 223–4 volume loss of, 44 Neuropeptides, 63, 90–1, 104 neuropeptide Y, 90 Neurophysiology, 221–83 emotional function, 231–4 executive functions, 234–9 historical background, 222–3 motor function, 226–31, 268 sensory function, 223–6, 268 summary, 267–9 visceral function, 231–4 working memory, 239–67 Neuropsychiatric illness, see Mental disorders Neuropsychiatric implications, 91–103 Neuropsychological tests, 190 Neuropsychology animals, see Animal neuropsychology humans, see Human neuropsychology Neurotensin, 90, 91, 104 Neurotransmission, chemical, 59–124 summary, 103–5 Neurotransmitter receptors ionotropic, 60, 62 metabotropic, 60, 62 Neurotransmitter systems, 5, 31 Neurotransmitters, 59, 60 age-dependent loss, 65 classes, 63 development, 63–4 involution, 64–5 maturation, 154 methods of study, 63 vs neuromodulators, 60 in prefrontal cortex, 65–91 acetylcholine, 87–90 dopamine, 75–85 GABA, 68–70 glutamate, 66–8 neuropeptides, 90–1 norepinephrine, 70–5 serotonin, 85–7 regional concentration, 62 studies, 62–3 study methods, 63 synaptic processes for, 60, 61 Nicotine, 88, 98 Nicotinic receptors, 87–8 Nigrostriatal DA system, 79, 102 NIRS (near-infrared spectroscopy), 286, 287 Nitric oxide, 67, 90, 91 NMDA (N-methyl-D-aspartate) conductances, 80 receptors, 67–8, 82, 97 and working memory, 104 Non-emotional planning, 303 Nonpyramidal interneurons, 70 INDEX Nonspecific midline thalamic system, 223 Nonverbal fluency, 195 Noradrenergic system, 104 Norepinephrine (NE), 31, 70–5 DA systems interaction, 79 depletion, 154 development, 17–18 in drug abuse, 100, 105 functions, 73 inverted-U function, 74 involved in sustained attention, 93 neurotransmission, 65–6 receptor agonists, 73 receptor antagonists, 73 receptors, 73 in schizophrenia, 98, 105 synaptic processes, 61 Novelty, 365–6 hyper-reaction to, in animals, 136 Nucleus accumbens, 41 in drug abuse, 98, 100, 105 emotional behavior, 345 and feeding behavior, 83 and learning, 82 in schizophrenia, 96 Nucleus basalis of Meynert, 88, 103, 104 electrical stimulation of, 89 Nucleus reticularis, 225 Nucleus ventralis anterior, 30 Object alternation in animals, 148 Obsessive-compulsive disorder (OCD), 379 apathy, 174 leukotomy/lobotomy in, 174 prefrontal imaging, 313–14, 318 Ocular motility, 39, 127, 343 Oculomotor abnormalities, in schizophrenia, 312 6-OHDA (6-hydroxydopamine), 154 Olanzapine, in schizophrenia, 97 Olfactory afferents, 35 Olfactory area, primary, 291 Olfactory cortex, 34 Olfactory stimuli, neurons reacting to, 224 Onomatopoeia, 291 Ontogeny, 17, 43, 338, 368 Operant memory, 147 Opiates, 98 Opioids, 98, 100 Opossum, philogenetic development, Optokinetic centers, 229 Orbital action domain, 345 Orbital cortex, 141, 142 development, 154 lesions, 137, 156 Orbital gyrus, 22, 39 Orbital lesions, in animals, 133, 135, 144, 155 Orbital prefrontal cortex, 197, 228 attention and, 93 cholinergic cells and, 90 connections, 44, 355 and drug abuse, 100, 101 emotional behavior, 304, 356 inhibitory control role, 87 motivation, 131 as pleasure center, 98 reward, 131, 355 Orbital prefrontal syndrome, 207 Orbital system, in animals, 138 Orbitofrontal cortex, 1, 198–200 connections, 38 emotional behavior, 355–6 inhibitory control role, 87 inputs, 34, 35 and midline thalamic nuclei, 225 reward information, 345 Orbitofrontal hypermotility, 199 Orbitofrontal lesions, 178 in animals, 128, 129 Orbitofrontal stimulation, 228, 231–2, 233 Orbitomedial cortex, 304 in animals, 138 Orbitomedial prefrontal cortex connections, 42, 104 destruction of left, 172 dopamine deficit, 105 in drug abuse, 98 emotional behavior, 35, 138 reward, study methodology, Orexin, 91, 105 Organ of creativity, 379 Orienting reactions, 128 Oscillation (electrical), 256–7 absence of, 257 Overlearned sequences, 303 Ownership, 377 Pain, 304 visceral, 233 Paired image subtraction, 288–9 Paired-associate tests, 187 Parahippocampal (cingular) area, 10 Paralimbic cortex, 356 Paralimbic prefrontal cortex, 27 403 404 Parallel distributed processing models, 375 Parapiriform (insular) area, 10 Parietal cortex, posterior, cooling, 151 Parietal regions, afferents from, 36 Parkinson’s dementia, 102–3 Parkinson’s disease, 91–2, 102, 105 advanced, 105 basal ganglia and, 63 nigrostriatal system, 79 schizophrenia coexisting with, 95 striatal interneurons, 88 Pars magnocellularis (magnocellular component), 28, 29 Pars paralamellaris, 28, 29 Pars parvocellularis (parvocellular component), 11, 28, 29 Pars reticularis, 29 Parvalbumin, 26, 69, 70, 97 Parvocellular nuclear component, 11 Pavlovian extinction blockage, 131 PCP, see Phencyclidine Penfield’s speech area, 307 Perception, 340 abstract (symbolic), 341 interaction with behavior, 183 neuroimaging studies, 290–2 relationship with memory, 338 Perception cycle, 358 Perception–action cycle, 44, 179, 183, 336 adaptive behavior, 268 behavior and, 317 connections serving, 223, 371 cortical component networks, 360 discrete components, 179 dynamics, 364 emotional information, 356, 358, 372 feedback, 6, 266, 358, 362 functional anatomy, 358–62 goal-directed actions, 307 internal, 258–9 language, 309, 310, 318, 369 operation of, 258 overview, 358–68, 382 position of prefrontal cortex, 335, 355 sensory-motor integration, 235 temporal integration, 362–8 visceral information, 356 working memory and, 296, 301 Percepts, 126 Perceptual attention, 347, 351 Perceptual cells, 310 Perceptual memory, 185, 337, 338–9 INDEX Perceptual networks in posterior cortex, 336–9 formation of, 337 Perceptual set, 180 Performance, relationship to delay activation, 244–5 Periaqueductal gray, afferents to orbitofrontal cortex, 35 Perseveration, 176, 198–9, 353 in animals, 137, 148 of central sets, 137 maladaptive tendencies, 86 PET, see Positron emission tomography Phencyclidine (PCP), 96, 98 in schizophrenia, 97 Phenylketonuria (PKU), 63 Philogenetic development of the cortex, 9, 10 Phonemes, 344 Phonological language, 310 Phonological loop, 295 Phyletic development, 11 Phyletic memory, 335, 343–4 Phyletic motor memory, 147 Phyletic sensory memory, 338 Phylogeny, 17, 43, 338, 368 Physostigmine, 89–90, 103 Piaget’s developmental concepts, 200–1 Pick’s disease (frontotemporal dementia - FTD), 19, 102, 103 cholinergic system, 103 in the elderly, 208 familial, 105 genetics, 205 Pictures, viewing, 303 Pimozide, 83 Piriform area (lobe), 8–9 Pitch discrimination, 307 PKU (phenylketonuria), 63 Place reversal, 136, 140 Planning, 4, 317, 335 behavioral, 187–9, 196 decline in the elderly, 208 development of ability, 202 emotional, 303 failure of, 206–7 inability to plan, 187 non-emotional, 303 overview, 353–5, 381 plateau of maturity, 207 relationship with memory, 185 Plaques, in animals, 155 Plasma cortisol, 232 Pleasure, 233, 269, 304 Pleasure centers, 98 INDEX Polysensory memory, 338 Pons, 260 efferents from prefrontal cortex, 38 Pontine nuclei, 41, 44 Porteus mazes, 188, 292 Position-response tasks, in animals, 142 Positron emission tomography (PET), 285–6, 287 and aging, 316 cognitive functions, 317 depression, 102 neurotransmission studies, 87, 102 sensory stimulus, 291 Post-traumatic stress disorder (PTSD), 74–5 Posterior association cortex, inputs from, 371 Posterior cortex, 338 perceptual networks in, 336–9 Posterior parietal area (area 7), 34, 39 Posterior parietal cortex, cooling, 151 Posterior putamen, 42 Postsynaptic change, 82 Postsynaptic neurons, 60 Potassium channels, 74 Potentiation, long-term (LTP), 67, 82 Prazosin, 74–5 Prearcuate area, see Presylvian (prearcuate) area Prearcuate prefrontal region, 225–6 Precentral primary motor area, 77 Precruciate area, 36 Prefrontal activation, and memory load, 295 Prefrontal area, 21, 23 Prefrontal cortex anatomy, see Anatomy of prefrontal cortex “Balkanization” of, 5–6 definition, 1–2, 43 development, 12–19 essentially integrative, 230 functions, 1, 2, 2–6 in mammals, 12 relative size, 8, 43 size, specialized areas, terminology, Prefrontal dynamics, 357–8 Prefrontal function(s) alternative models, 371–6, 383 disorders in schizophrenia, 313 imaging, 289–310 Lebadea principle, 352 model of, 379–83 modular models, 372, 373–4 modular view of, 334 network models, 372, 374–6 network view of, 334 principles, 334 see also Functions Prefrontal imaging in neuropsychiatric illness, neuroimaging, 315–16 Prefrontal neopallium, Prefrontal neurons, 229, 231 Prefrontal pyramidal neurons, 86 Prefrontal syndromes, 196–8 in humans, 196–8 lateral, 197–8 Prefrontal-posterior coherence, 256–7 Pregenual area, 141 Premotor areas, 42 Premotor cortex, 42, 229 lesions, 147 Preoptic region, projections to, 38 Preparatory set, 4–5, 5, 335, 347, 348 see also Set Preperiform cortex, 29 Presylvian fissure, 10, 43 Presylvian (prearcuate) area, 10 Presyntheses, 345 Pretectal region, 39 Primary motor cortex, 42, 344 Primary olfactory area, 291 Principalis cortex, 39 Principalis lesions, 144 Principles, system of, 378 Problem-solving, 196 in animals, 126 Procedural memories, 344, 356 Projection nucleus, 11 Prolactin, 86 Propositional language, 362 Proprioceptive cues, 143 Proreal (intraproreal) fissure, 10 Prospective coding, 261 Prospective memory, 335, 343 Protein kinase C, 74, 102 Provisional memory, 147 Proximity, law of, 345 Pseudodepression, 174 Psychological tests, 173 Psychosurgery of frontal lobe, 173, 205 PTSD (post-traumatic stress disorder), 74–5 Pulvinar, 30, 39 Putamen, 40 posterior, 42 Pyramidal cells, 19, 26 Pyramidal memory cells, 69 Pyramidal neurons, 15, 27 405 406 Radial maze, 137 Radiographic scanning procedures, 285 Radioisotope administration by inhalation, 290 Rage, in animals, 130 Raphe nuclei, 31, 69, 85, 103, 104 electrical stimulation of, 86 Raphe serotonergic neurons, 86 Rats afferents, 28, 30 age-related cell loss, 18 corticocortical connections, 36 dendrite development, 14 efferents, 39, 40 mediodorsal nucleus, 25 norepinephrine pathways, 70, 71 prefrontal cortex, 21 rewards and reinforcement, 234 see also Rodents RCBF, see Regional cerebral blood flow Reaction, delayed, in animals, 126 Readiness potential, 236, 237, 348 Reading, 202 Reality testing, 192 Reason, in decision-making, 191 Reasoning, 196 development of, 201, 202 Recall, false, 185 Recency tests, 186 Recognition, false, 185 Recognition tests, 186 Reentrant circuits, 351, 366 Reentry, 366, 367, 375 reverberant, 297, 301, 317 “Regio frontalis”, 7, 21 Regional cerebral blood flow (rCBF), 285, 291 in frontal gray matter, 290 increases in, 302, 307 and local metabolic rate, 290 in schizophrenia, 311–12 working memory study, 292–3 Reinforcement, 234 Remembered present, 351, 377 Reptiles, philogenetic development, Reserpine, 101 Resolution, spatial and temporal, 287 Respiratory system, 232, 268 Response control, 141 Response inhibition, 129 Resting state, 290 Restlessness, 176 Retrieval task, 292 Retrosplenial cortex, 38 INDEX Reverberating reentry in internal perception-action cycle, 258–9 oscillation, 256 working memory, 252, 269, 297, 301, 317, 351, 366, 369 Reversal tasks, 193, 201, 353 Reverse inference error, 288 Reversible lesions, 143, 148–53, 156 Reward ablation studies, 131 activation of pathways, 100 in a delayed response task, 90 discriminanda and, 137 dopamine and, 79, 83, 84–5, 101 gambling task, 87 incentive abolished, 245 mesocorticolimbic system and, 104 neuroimaging studies, 304 neurons anticipating, 262 neurophysiological studies, 234, 250–1, 269 in the rat, 83, 131 Reward cells, 261–2, 269 Reward-anticipating cells/neurons, 262–3 Reward-related cells, 250–1 Reward value, 261–6, 269 Risk, 304 Risk-taking, development of restraint, 202 Risperidone, in schizophrenia, 97 Rodents, 10, 14, 233 see also Rats Rolandic fissure, 336, 380 Rostral intralaminar nuclei, 30 Rule adoption, 304 Rule-guided set, 239 Rule of law, 378, 379 Rule-shifting tasks, 261 Rule shifts, 260–1, 269 Rule switching, 304–5 Rules, 304 Schema of action, 345, 363, 381 anticipatory, 345 source schemas, 373 Schizophrenia, 94–8 animal model, 96 apathy, 174 behavioral pathology model of, 376 cognitive abnormalities, 312 COMT and, 63 dopamine receptors, 96 genetic factors, 95, 105 hallucinations in, 81 INDEX hypo-reactivity of frontal rCBF, 312 hypofrontality in, 311–12, 318 leukotomy/lobotomy in, 174 morphometric studies, 318 oculomotor abnormalities, 312 Parkinson’s disease coexisting with, 95 prefrontal imaging, 311–13 symptoms, 95 negative/positive, 311 Scopolamine, 103 Scripts, 345, 354, 373 Searchlight theory of attention, 225 SEF (supplementary eye field), 228, 267, 268 Selective (inclusive) attention, 5, 92, 134, 193, 198, 225, 347 development, 201, 207 Selective serotonin reuptake inhibitors (SSRIs), 85, 101, 105 Selective stabilization, 18 Self-stimulation, 233 Semantic language, 310 Semantic memory, 338, 341 language, 307, 308–9, 310 Sensation–action cycle, 358 “Sensor cortex”, Sensorial attention, 267 Sensorium, 291 Sensory evoked potentials, 225 Sensory factors, in delay tasks for animals, 143 Sensory function, neurophysiology, 223–6, 268 Sensory inputs, 32–4 Sensory organs, inputs from, 371 Sensory stimulus, 291 behavioral significance, 241–3 Sensory-motor cross-temporal contingency, 365 Sensory-motor integration, 235, 238, 240 Septum, 88 efferents from prefrontal cortex, 38 Sequential tasks, 344 Serotonergic (5-HT) system, 63, 104 Serotonergic cells, 85 Serotonin, 31, 85–7 bipolar illness, 175 in depression, 101, 102 development, 18 in drug addiction, 100, 105 inhibitory control function, 86 interaction with other transmitters, 104 prefrontal, research, 86 prefrontal depletion, 87 in schizophrenia, 97, 98, 105 synaptic processes, 61 407 see also 5-Hydroxytryptamine (5-HT) Serotonin agonists, 86 Serotonin receptors, 85 in schizophrenia, 97 Serotonin transporter (SERT), 85 Set, 4–5, 180–1, 189, 365–6 in animals, 134–5 neurophysiological studies, 237–9 overview, 347–9, 380 and planning, 335 preparatory set, 4–5, 5, 335, 347, 348 vs working memory, 366 Set shift attentional, 261 behavioral tests, 181 lesions and, 135 magnetic stimulation, 239 working memory deficit, 348 Set-shifting task, 81 see also Wisconsin Card Sorting Test Sexual behavior, 234 Sexual drive, 178 Short-term memory, 4, 147, 246 see also Working memory Sigmoid gyrus, 39 Skeletal motility domain, 342–3 Skin temperature, and orbitofrontal stimulation, 231 Sleep inducement, 228, 233 SMA (supplementary motor area), 228, 229, 230 activations, 292, 302, 303 Social behavior, 27, 42, 177–8 effects of ablation in animals, 131–3 effects of orbital lesions in humans, 206 Social functions, 173 Sociopathy, 178 criminal, 199 Somatic markers, 176, 355, 357 Somatic-marker hypothesis, 177 Somatic stimuli, neurons reacting to, 224 Somatosensory stimuli, 291 Somatostatin, 90, 91, 104 Somatotopy, 292, 342 Somesthesis, 32, 34, 35 Somesthetic stimulation tests, 293 Spatial attention, 181–3 Spatial creativity, 370 Spatial factors, in delay tasks for animals, 143–4 Spatial information, coded with language, 185 Spatial neglect, 182 Spatial relationships, 129 Spatial resolution, imaging, 287 Spatial working memory, 293, 298–300 408 Spearman’s test, 196 Speech, 27, 307–10 complex, 318 prefrontal disorders of, 195, 207 Speech domain, 343 Speech sequences, 344 Spinal cord, 260 Spinal reflex arcs, 361 Spiroperidol, 83 Split-brain procedures, in animals, 142–3 Spoken language, 198, 344, 362 SSRIs (selective serotonin reuptake inhibitors), 85, 101, 105 Stanford-Binet Test, 196 Stellate cells, 26 Stimulation auditory, 291 behavioral association trial, 226 neurons reacting to, 224 auditory stimulation tests, 293 basal forebrain, 228 electrical, 186, 221, 222, 223 in animals, 149 of area (frontal eye field), 229 difficulties in use of, 222 eating behavior in cats, 233 evoked-potential method, 223, 226 of nucleus basalis of Meynert, 89 of raphe nuclei, 86 gustatory, neurone reacting to, 224 intracranial self-stimulation (ICSS), 83–4, 98 olfactory, neurone reacting to, 224 orbitofrontal, 228, 231–2, 233 blood pressure and, 231 cardiac dynamics, 231 heart rate and, 231 skin temperature and, 231 prefrontal, and visual cortex, 225 self-stimulation, 233 sensory, 291 behavior and, 242–3 prefrontal cells, 224 somatic, neurons reacting to, 224 somatosensory, 291 somesthetic tests, 293 transcranial magnetic stimulation (TMS), 186, 228, 239 unimodal, 290–1 verbal, 291 visual, 291 behavioral association trial, 226 INDEX neurons reacting to, 223–4 tests, 293 Stimulus discrimination task, 291 Stimulus–response compatibility/conflict task, 292 Stop-signal task, 304 Strattera, 94 Stream of consciousness, 377 Stress 5-HT levels, 86 dopamine and, 79, 82 inhibiting long-term potentiation, 68 medial cortex role, 233 norepinephrine and, 73–4 Stress response, 81 Striate cortex, 15 Striatum cholinergic interneurons, 88 emotional behavior, 345 Stroop task attention, 201, 292, 317 computer simulation, 374 interference, 184, 204 model, 376 suppression of alternatives, 190, 193 Strychnine neuronography, 223 Substance P, 90, 91, 104 Substantia innominata, 88 Substantia nigra, 29, 31, 41, 42 Subthalamus afferents to prefrontal cortex, 31 efferents from prefrontal cortex, 38 Successive discrimination, 136, 353 Suicide victims, 101–2 Sulcal cortex, in rodents, 138 Sulci, 10 Sulcus frontomarginalis, 10 Sulcus principalis, 10, 23, 34, 37 in animals, 141, 143–4 connections, 39–40, 40 lesions, 144 spatial tasks, 143, 144 Superior colliculus, 39 Supervisory attentional system, 347, 373 Supplementary eye field (SEF), 228, 267, 268 Supplementary motor area (SMA), 42 activations, 292, 302, 303 goal-directed behavior, 229 limb movements, 229, 230 Suppressor areas, 199 Supramarginal gyrus, 239 set shift, 239 Suprasylvian cortex, 35 INDEX Suprasylvian gyrus, 39 Surface negativity, 237–8 Sustained attention, 183 Synapses, 43 Synaptic contact, 59 Synaptic density, age-related decrease, 15, 19, 44 Synaptic dynamics, 366 Synaptic processes for neurotransmitters, 60, 61 Synaptogenesis, 15 Synaptogenic lag, 15 Synchronous synaptic convergence, 337, 340 Syntax of action, 6, 362, 363, 368, 376, 382 Syntax of grammar, 368 System of principles, 378 Taste, sensitive area for, 291 TCMA (transcortical motor aphasia), 194, 198 Tectum, 260 Teleokinetic system, 229 Teleology, Temporal concreteness, 190, 191, 207 Temporal discontinuities, 365 Temporal factors, in delay tasks for animals, 144–5 Temporal gestalt, 345, 358 Temporal integration, 189–90, 354, 382 language, 368 overview, 362–8, 382 plateau of maturity, 207 see also Cross-temporal integration Temporal lobe resection, in monkeys, 128, 133 Temporal ordering tests, 186, 202 Temporal organization, 3, 4, 5, of action, overview, 357–71, 382 of behavior in animals, 145 Temporal regions, afferents from, 36 Temporal resolution, in neuroimaging, 287 Temporal synthesis, see Temporal integration Tests neuropsychological, 190 of planning, 184 see also individual tests TH (tyrosine hydroxylase), 63, 105 Thalamic fibers, 21 Thalamic projection system, 30 Thalamocortical projection, 12 Thalamus, 42 retrograde degeneration, 27 Theory of mind (ToM), 177, 206 Thorndike’s puzzle-boxes, 126 Time, see see Temporal entries TMS (transcranial magnetic stimulation), 186, 228, 239 409 Tools, viewing, 303 Tortoise, philogenetic development, Tower of Hanoi test, 202 Tower of London test, 188 attention, 292 planning, 303, 354 schizophrenia and, 312, 318 Trail Making Test, 181 Transcortical motor aphasia (TCMA), 194, 198 Transcranial magnetic stimulation (TMS), 186, 228, 239 Transient global amnesia, 309 Transporters, 62 Tricyclic antidepressants, 101, 105 Tryptophan, 85, 86, 87 Tryptophan hydroxylase, 85 Tyrosine hydroxylase (TH), 63, 105 Uncertainty, 304 Uncinate fasciculus, 38 Unilateral inattention, 182 Unimodal memory, 338 Unity, 377 Universal grammar, 369 Upper dorsolateral convexity, 247 Valence of external stimuli, 304 Vasoactive intestinal polypeptide (VIP), 90 Ventral cortex, 141 Ventral pallidum, 88 Ventral prefrontal cortex, 193 Ventral tegmental area, 31 Ventrolateral (VL) thalamus, 42 Ventromedial frontal cortex, 356 Ventromedial prefrontal cortex, 191, 192 Verb-generation task, 303, 317 anterior cingulate cortex, 292, 303, 309 dorsolateral prefrontal cortex, 292 Verbal expression, 196, 207 Verbal fluency, 207 Verbal gestalts, 308 Verbal stimuli, 291 Verbal working memory, 295, 298–300 Viewing pictures and tools, 303 VIP (vasoactive intestinal polypeptide), 90 Visceral function, neurophysiology, 231–4 Visceral pain, 233 Vision, 32, 34, 35, 39 Benton Visual Retention Test, 187 ocular motility in animals, 127 search tasks, 127 Visual attention, 39, 127 410 Visual cortex, prefrontal stimulation and, 225 Visual discrimination task, cooling and, 254 Visual stimulation tests, 293 Visual stimuli, 291 behavioral association trial, 226 neurons reacting to, 223–4 Visual working memory, 293, 298–300 Visuomotor defects, 143 Visuomotor tasks, 241 Vocal expressions, inability to interpret and to respond to, 177 Volumes of interest (VOIs), 314–15 Voluntary movements, 260, 301–2 Voracity, 178 in animals, 129, 130–1 WAIS (Wechsler Adult Intelligence Scale), 196 War injuries, 172 Wechsler Adult Intelligence Scale (WAIS), 196 Wechsler Memory Scale, 187 Wernicke’s area, language, 362, 382 White matter, 43 age-related volume, 17, 19 in aging, 315, 318 in attention-deficit hyperactivity disorder, 311 in dementia, 315 hyperintensity (WMH) in the elderly, 204–5 Willed sequential acts, 302 Wisconsin Card Sorting Test (WCST), 180–1 attention, 201, 292 computer simulation, 374, 375 depression, 314 interference, 204 internal interference, 184, 202 schizophrenia, 312, 318 set shifting, 239 temporal integration, 190 variants of, 376 visual working memory, 293 working memory, 206 Wisconsin General Test apparatus, 139 Witzelsucht, 175 WMH (white matter hyperintensity), 204–5 Words manipulation of, 307–8 structure of, 307 Working memory, 4, 5, 185–7, 239–51 acetylcholine and, 89 in animals, 146–7, 148 delay tasks, 156 mnemonic aspect, 141 tests, 155 INDEX associative character, 349–50 auditory, 298–300 computational model, 69 and consciousness, 351, 377 content, 4, 295–6 cross-temporal contingencies, 369 decision-making, 268 decline in the elderly, 204, 208 deficit, 206–7 definition, 138, 349 delay tasks, 268–9 discarding obsolete material, 350 dopamine and, 80, 81, 82 dynamics of, 296, 297–301 for faces, 295, 298–300 as form of attention, 69, 92, 93, 349, 351 future perspective, 350 glutamate and, 68 goal-directed action, 268 language, 369 left-frontal vs right-frontal patients, 186 maintenance of, 296 mechanisms of, 251–67 memorandum, 240–3, 252, 268–9, 351 methylphenidate and, 87 neuroimaging studies, 292–301, 317 neurophysiology, 239–67 neurotransmitters/neuromodulators and, 60 NMDA receptors and, 104 norepinephrine and, 73 overview, 349–51, 380 plateau of maturity, 207 relationship with attention, 349 role of prefrontal cortex, 350 schizophrenia, 312 vs set, 366 spatial, 293, 298 and temporal integration, 365–6, 382 topography, 350–1 verbal, 295, 298–300 visual, 293, 298–300, 317 what-where integration, 201–2 see also Short-term memory Working-with-memory, 374 WSCT, see Wisconsin Card Sorting Test Ziprasidone, in schizophrenia, 97 ... hierarchical levels of the nerve axis, from the spinal cord to the cortex The prefrontal cortex sits in the highest cortical level of the cycle, wherefrom it regulates the interactions of the organism... primates the prefrontal cortex is commonly referred to simply as frontal cortex, implicitly excluding the motor and premotor cortex of the frontal lobe In rodents and carnivores the prefrontal cortex. .. of the lateral prefrontal cortex The longer the series, the greater is the need for that cortex Time is only one factor, however, among those determining that need; other factors include the