The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-Hippocampal System

443 Pages·2003·2.61 MB·English

by  Jeffrey A. Gray

The Neuropsychology of
Anxiety: An Enquiry
into the Functions of the
Septo-Hippocampal System,
Second Edition
Jeffrey A. Gray
Neil McNaughton
OXFORD UNIVERSITY PRESS
The Neuropsychology of Anxiety
ii Overview
1111 OXFORD PSYCHOLOGY SERIES
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311 Editors
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Nicholas J. Mackintosh James L. McGaugh
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Timothy Shallice Daniel Schacter
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711 Anne Treisman Lawrence Weiskrantz
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1 1. The neuropsychology of anxiety: an enquiry into the functions of the
2 septo-hippocampal system (first edition)
3111 Jeffrey A. Gray
4 2. Elements of episodic memory
5 Endel Tulving
6 3. Conditioning and associative learning
7 Nicholas J. Mackintosh
8 4. Visual masking: an integrative approach
9 Bruno G. Breitmeyer
20111 5. The musical mind: the cognitive psychology of music
1 John Sloboda
2 6. Elements of psychophysical theory
3 Jean-Claude Falmagne
4 7. Animal intelligence
5 Edited by Lawrence Weiskrantz
6 8. Response times: their role in inferring elementary mental organization
7 R. Duncan Luce
8 9. Mental representations: a dual coding approach
9 Allan Paivio
30111 10. Memory, imprinting, and the brain
1 Gabriel Horn
2 11. Working memory
3 Alan Baddeley
4 12. Blindsight: a case study and implications
5 Lawrence Weiskrantz
6 13. Profile analysis
7 D. M. Green
8 14. Spatial vision
9 R. L. DeValois and K. K. DeValois
40111 15. The neural and behavioural organization of goal-directed movements
1 Marc Jeannerod
2 16. Visual pattern analysers
3 Norma V. Graham
4 17. Cognitive foundations of musical pitch analysis
45111 C. L. Krumhansl
Contents iii
1111 18. Perceptual and associative learning
2 G. Hall
3 19. Implicit learning and tacit knowledge
4 A. S. Reber
5 20. Neuropsychology of communicative behaviour
6 D. Kimura
7 21. The frontal lobes and voluntary action
8 R. E. Passingham
9 22. Classification and cognition
1011 W. Festes
1 23. Vowel perception and production
2 B. D. Rosner and J. B. Pickering
3111 24. Visual stress
4 A. Wilkins
5 25. Electrophysiology of mind
6 Edited by M. D. Rugg and M. G. H. Coles
7 26. Attention and memory: an integrated framework
8 N. Cowan
9 27. The visual brain in action
20111 A. D. Milner and M. A. Goodale
1 28. Perceptual consequences of cochlear damage
2 B. J. C. Moore
3 29. Binocular vision and stereopsis
4 Ian P. Howard and Brian J. Rogers
5 30. The measurement of sensation
6 Donald Laming
7 31. Conditioned taste aversion
8 Jan Bures, F. Bermudez-Rattoni, and T. Yamamoto
9 32. The developing visual brain
30111 Janette Atkinson
1 33. The neuropsychology of anxiety: an enquiry into the functions of the
2 septo-hippocampal system (second edition)
3 Jeffrey A. Gray and Neil McNaughton
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iv Contents
1111 UN COUP DE DÉS
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311 JAMAIS
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5 N’ABOLIRA LE HASARD
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711 Toute Pensée émet un Coup de Dés
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9 Stéphane Mallarmé
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1 ———
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3111 ‘The hippocampus—an organ of hesitation and doubt’
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5 P.V. Simonov, 1974
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Contents v
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2 The Neuropsychology
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of Anxiety
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An Enquiry into the Functions of the
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Septo-Hippocampal System
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2 SECOND EDITION
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JEFFREY A. GRAY
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7 Department of Psychology, Institute of Psychiatry,
8 De Crespigny Park, London
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20111 and
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NEIL McNAUGHTON
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3 Department of Psychology,
4 University of Otago, Dunedin, New Zealand
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vi Contents
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311 Great Clarendon Street, Oxford OX2 6DP
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Oxford University Press is a department of the University of Oxford.
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It furthers the University’s objective of excellence in research, scholarship,
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Oxford is a registered trade mark of Oxford University Press
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Published in the United States
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by Oxford University Press Inc., New York
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6 © Jeffrey A. Gray and Neil McNaughton 2000, 2003
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The moral rights of the author have been asserted
8 Database right Oxford University Press (maker)
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First edition 1982
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Second edition 2000 (Published in paperback 2003)
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2 All rights reserved. No part of this publication may be reproduced,
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without the prior permission in writing of Oxford University Press,
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30111 A catalogue record for this book is available from the British Library
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4 ISBN 0 19 852271 1
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Typeset by
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Printed in Great Britain
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Preface to the paperback edition
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6 In the comparatively short time since the hardback edition of this book went to press
7 in 2001, there have been three developments which readers of this paperback edition
8 might wish to note.
9 The first lies in the rapidly moving field of research on the different molecular subunits
1011 of the GABA receptor, of which there are at least 18 different varieties in the central
A
1 nervous system (Möhler et al. 2002). It has long been known that the diverse behav-
2 ioural and physiological effects of the benzodiazepine class of anxiolytic drugs are mediated
3111 in general by action at receptors allosterically coupled to the GABA receptor. It is now
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4 clear that different classes of these effects are mediated by benzodiazepine binding sites
5 that are coupled to GABA receptors of different subunit compositions. In particular,
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6 studies of mice with point mutations in specific subunits of the GABA receptor appear
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7 to rule out as receptors for the specifically anxiolytic effects of the benzodiazepines all
8 subtypes other than those coupled to GABA receptors that contain the (cid:2) and/or the
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9 (cid:2)3 subunit (Möhler et al. 2002; Reynolds et al. 2001; G. Dawson, pers. comm. 2003).
20111 Consistent with the views expressed in this book, the (cid:2)2 subtype is strongly enriched
1 in the hippocampus, though also in the cerebral cortex; and the (cid:2) subtype, in the
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ascending noradrenergic and serotonergic pathways (Möhler et al. 2002). The earliest
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statements of our hypothesis that anxiolytic drug action is mediated by the hippocampal
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system and its ascending monoaminergic afferents go back several decades (Gray 1970a,
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1982), and they were based largely on behavioural data. It is encouraging to see the
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hypothesis now supported by the latest neurochemical data.
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Second, the analysis of quantitative trait loci (QTL; see Chapter 12, section 12.3)
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related to emotional behaviour has recently been extended from the mouse to the rat,
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with results that are again encouraging for our model of anxiety. In a study of an F
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intercross from the selectively inbred Roman High and Roman Low Avoidance rat strains,
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Ferandez-Teruel et al. (2002) gathered a wide variety of behavioural measures from a
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range of different tests, including the open field, the elevated plus maze, the startle
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response, fear conditioning and two-way (shuttlebox) active avoidance. One locus, on
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chromosome 5, was found to influence behaviour across many measures; and to do so
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in a manner consistent with the effects on the same measures of anxiolytic drugs. Thus,
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one of the alleles at this QTL was associated with increased shuttlebox avoidance, decreased
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fear conditioning to both cue and context, increased time spent in the open arms of the
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elevated plus maze, increased locomotor activity in the open field, and increased rearing
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behaviour. These effects are all in the direction observed after administration of an
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anxiolytic drug. Conversely, there was no association between the chromosome 5 QTL
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and spontaneous activity, the unconditioned startle response or defecation in the open
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3 field – all measures that are unaffected by anxiolytic drugs. Correspondence in this way
4 between psychopharmacological profile and genetic architecture provides good support
45111 for our overall integrative model of the neuropsychology of anxiety.
viii Preface to the paperback edition
1111 Third, despite the difficulties of conducting experimental research on anxiety in human
2 subjects, the recent, almost explosive, expansion of neuroimaging studies is beginning to
311 pay dividends. In one cleverly designed study using functional magnetic resonance imaging
4 (fMRI), Ploghaus et al. (2001) measured patterns of brain activity when the subject was
5 presented with a painful heat stimulus under conditions of either high or low anxiety,
6 the higher level being induced by an associated visual stimulus which indicated the possi-
711 bility that a more painful stimulus might occasionally be delivered. In the high-anxiety
8 condition fMRI activity was augmented in the hippocampal formation, along with corre-
9 lated activity in a region of the insular cortex specialised for pain perception. This pattern
1011 of results is consistent with our hypothesis (see Figure 1.7) that the hippocampal system
1 helps resolve conflict by augmenting negatively affective bias.
2 The Ploghaus et al. study employed normal subjects. A second study, by Furmark et al.
3111 (2002), investigated patients with social phobia, applying positron emission tomography
4 to study brain activity during a public speaking task. Activity was measured in a no-
5 treatment control group and before and after treatment of two kinds: pharmacotherapy
6 and cognitive behavioural therapy. Both types of treatment were successful with some but
7 not all patients. In treatment-responders, irrespective of type of treatment, improvement
8 was accompanied by a decrease in regional cerebral blood flow in the hippocampus, amyg-
9 dala and the periamygdaloid, rhinal and parahippocampal cortices. These findings are
20111 consistent with the analysis of social phobia offered in this book as reflecting dysfunction
1 in both the amygdala and the hippocampal formation (section 11.16), in contrast to the
2 pervasive amygdalocentricity of many contemporary approaches to the neuropsychology
3 of anxiety.
4 In these diverse ways, then, our model of the neuropsychology of anxiety continues
5 to provide a useful framework for understanding accumulating new data.
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7 March 2003 J.A.G.
8 A.M.
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Contents ix
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Preface
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6 This second edition of The neuropsychology of anxiety provides an updated theory of
7 septo-hippocampal function and an updated theory of anxiety, both of which we believe
8 are superior to competing theories in either domain. The overall theory is summarized
9 in the first chapter. We believe it provides a single account for normal anxiety and gener-
1011 alized anxiety disorder, and for normal memory and clinical amnesia.
1 The specific details of the theory are important for its correct working, as are precise
2 definitions of the terms involved. Our interpretation of experimental results
3111 often runs somewhat counter to conventional views of the data (for example, we do not
4 accept the view that the firing of a hippocampal cell at a particular point in space repre-
5 sents a ‘place field’ in any normal sense). To appreciate it fully, then, one must read
6 the whole book, including the appendices available on the internet (http://www.oup.
7 co.uk/neuropsychol_anxiety). This is particularly important since we believe that our
8 theory, like its competitors, must be judged in terms of how far it accounts for all of
9 the details of the data reviewed, particularly in the appendices. We believe our theory
20111 is unique in the degree (admittedly still incomplete) to which it successfully integrates
1 all of the data.
2 The book is also nearly unique in its attempt to integrate data across so many different
3 domains of the literature. This led to a logistical problem with this second edition: it
4 has become very large. For this reason, the basic argument is laid out with only a modest
5 amount of supporting detail in the main text; for those who require the full version of
6 any specific argument, we have relegated what would otherwise be additional chapters
7 of the main text to the appendices. For those reading this book from a purely hippocampal
8 or memorial perspective these probably represent the most critical portions of the book,
9 and they may find it advantageous to start with the hippocampally oriented appendices
30111 (4–9) and then read Chapters 7–10. Chapter 8 of the main text deals with the nature
1 of temporal lobe amnesia and attempts to resolve the conflict between the different
2 current views of ‘types of memory’ that are sensitive or insensitive to hippocampal forma-
3 tion damage. Hopefully our hippocampal analysis will then persuade them to read the
4 rest of the book. For those interested in anxiety, we recommend that they start at the
5 beginning and we hope that they will then find themselves sufficiently impressed by our
6 arguments for the importance of the septo-hippocampal system to read the remainder
7 of the book. The key arguments with respect to the clinical aspects of anxiety are presented
8 in Chapters 11–13.
9 Despite the advances of the last 20 years, our theory does not yet claim to be complete.
40111 So, within certain artificially limited data domains (e.g. the effects of hippocampal lesions
1 on tests, which are supposedly specific to certain types of memory function), aficionados
2 may feel that certain other theories are superior or at least more parsimonious.
3 However, as will be seen in the various sections of the book, we believe our theory
4 to be at least the equal of the opposition even within each of these specialized domains.
45111 Furthermore, we feel that comparative judgements between the theories should be made