Cognition, Emotion and Autonomic Responses: The Integrative Role of the Prefrontal Cortex and Limbic Structures

481 Pages·2000·39.619 MB·English

by  H.B.M. Uylings, C.G. Van Eden, J.P.C. De Bruin, M.G.P. Feenstra, C.M.A. Pennartz

PROGRESS IN BRAIN RESEARCH
VOLUME 126
COGNITION, EMOTION AND AUTONOMIC
RESPONSES: THE INTEGRATIVE ROLE OF
THE PREFRONTAL CORTEX AND LIMB IC
STRUCTURES
PROCEEDINGS OF THE 21ST INTERNATIONAL SUMMER SCHOOL OF BRAIN RESEARCH,
HELD AT THE ROYAL NETHERLANDS ACADEMY OF SCIENCES,
AMSTERDAM, THE NETHERLANDS
FROM 23-27 AUGUST 1999
EDITED BY
H.B.M. UYLINGS, C.G. VAN EDEN, J.P.C. DE BRUIN,
M.G.P. FEENSTRA AND C.M.A. PENNARTZ
Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands
ELSEVIER
AMSTERDAM - LAUSANNE - NEW YORK - OXFORD - SHANNON - SINGAPORE - TOKYO
2000
List of Contributors
K. Amunts, Institute of Medicine, Research Center Jiilich, JiJlich, Germany
K. Anstrom, Department of Physiology and Pharmacology, Medical Center Blvd., Wake
Forest University School of Medicine, Winston Salem, NC 27157, USA
M.C.M. Appels, University Hospital Medical Center Utrecht, Department of Psychiatry,
EO. Box 85500, 3508 GA Utrecht, The Netherlands
C. Arens, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
A.ET. Arnsten, Section of Neurobiology, Yale University School of Medicine, 333 Cedar
Street, New Haven, CT 06520-8001, USA
G.S. Aston-Jones, Department of Psychiatry, University of Pennsylvania, VAMC
Medical Research, Building 21, Mall Code 151, University and Woodland Avenues,
Philadelphia, PA 19104, USA
A. Azarov, Department of Physiology and Pharmacology, Medical Center Blvd., Wake
Forest University School of Medicine, Winston Salem, NC 27157, USA
K. Blum, Department of Biological Sciences, University of North Texas, Denton, TX
76203, and Department of Clinical Sciences, PATH Medical Foundation, New York,
NY, USA
L.M. Broersen, Numico Research B.V., P.O. Box 7005, 6700 CA Wageningen, The
Netherlands
R.M. Buijs, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
UE Cahill, Department of Neurobiology and Behavior, Center for the Neurobiology of
Learning and Memory, Qureshy Research Lab., University of California, Lrvine, CA
92697-3800, USA
R.N. Cardinal, Department of Experimental Psychology, University of Cambridge,
Downing Street, Cambridge CB2 3EB, UK
J.-Y. Chang, Department of Physiology and Pharmacology, Medical Center Blvd., Wake
Forest University School of Medicine, Winston Salem, NC 27157, USA
J.-P. Changeux, Neurobiologie Mo16culaire, Institut Pasteur, 25 rue du Dr. Roux, 75015,
France
J. Cohen, Department of Psychology, Princeton University, Princeton, NJ 19104, USA
D.E. Comings, Department of Medical Genetics, City of Hope National Medical Center,
1500 East Duarte Road, Duarte, CA 91010, USA
A.R. Damasio, Department of Neurology, University of Iowa College of Medicine, 200
Hawkins Dr. #2007 RCP, Iowa City, IA 91010, USA
J.P.C. De Bruin, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
vi
S. Dehaene, INSERM, Unit6 334, Service Hospitalier Fr6d6ric Joliot, CEA/DRM/DSV,
4 Place du G6n6ral Leclerc, Orsay, F-91401, France
K. De Vos, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
S. De Vries, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
W.C. Drevets, Departments of Psychiatry and Radiology, Presbyterian University
Hospital, UPMC Health Systems, PET Facility Room B-938 PUH, 200 Lothrop
Street, Pittsburgh, PA 15213, USA
B.J. Everitt, Department of Experimental Psychology, University of Cambridge,
Downing Street, Cambridge CB2 3EB, UK
M.G.E Feenstra, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
E. Fliers, Department of Endocrinology and Metabolism, Academic Medical Center,
University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
H.J. Groenewegen, Research Institute Vrije Universiteit (RIN-VU), Department of
Anatomy, Faculty of Medicine, Van Der Boechorststraat 7, 1081 BT Amsterdam, The
Netherlands
J.R. Hollerman, Department of Psychology, Box 39, Allegheny College, Meadville, PA
16335, USA
W.J.G. Hoogendijk, Valerius Clinic, Department of Psychiatry, Free University,
Amsterdam, The Netherlands
H.E. Hulshoff Pol, Department of Psychiatry, University Hospital Utrecht, EO. Box
85500, 3508 GA Utrecht, The Netherlands
E Janak, Department of Physiology and Pharmacology, Medical Center Blvd., Wake
Forest University School of Medicine, Winston Salem, NC 27157, USA
J.D. Jentsch, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA
15260, USA
R.N.J.M.A. Joosten, Netherlands Institute for Brain Research, Meibergdreef 33, 1105
AZ Amsterdam, The Netherlands
R.S. Kahn, Department of Psychiatry, University Hospital Utrecht, EO. Box 85500,
3508 GA Utrecht, The Netherlands
T. Klingberg, Laboratory of Brain Research, Brain Research, Dept. Neuroscience,
Karolinska Institute, Berzeliusv~igen 3, 171 77 Stockholm Sweden and Astrid
Lindgrens Childrens Hospital, Stockholm, Sweden
B.L. McNaughton, Neural Systems, Memory and Aging, University of Arizona, Tucson,
AZ 85721, USA
A.B. Mulder, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
R. Nordquist, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands.
O. Orgtit, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands.
J.A. Parkinson, Department of Anatomy, University of Cambridge, Downing Street,
Cambridge CB2 3DY, UK
Pans, T., Montreal Neurological Institute, McGill University, 3801 University, Montreal,
PQ H3A 2B4, Canada
vii
C.M.A. Pennartz, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
C.W. Pool, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
G. Rajkowska, University of Missisippi Medical Center, Department of Psychiatry and
Human Behavior, Arthur C. Guyton Laboratory Research Building, 2500 North State
Street, Jackson, MS 39216, USA
J. Rajkowski, Department of Psychiatry, University of Pennsylvania, VAMC Medical
Research, Building 21, Mail Code 151, University and Woodland Aves., Philadelphia,
PA 19104, USA
T.W. Robbins, Department of Experimental Psychology, University of Cambridge,
Downing Street, Cambridge CB2 3EB, UK
R.H. Roth, Departments of Psychiatry and Pharmacology, Yale University School of
Medicine, New Haven, CT 06520, USA
E. Sanz Arigita, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
C.B. Saper, Department of Neurology, Beth Israel Deaconess Medical Center, 330
Brookline Avenue, Boston, MA 02215, USA
W. Schultz, Institute of Physiology, Program in Neuroscience, University of Fribourg,
Rue du Mus6e 5, CH-1700 Fribourg, Switzerland
M.M. Sitskoorn, Department of Psychiatry, University Hospital Utrecht, RO. Box
85500, 3508 GA Utrecht, The Netherlands
W.J.A.J. Smeets, Department of Anatomy, Medical Faculty, Vrije Universiteit, Van Der
Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
D.E Swaab, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
J.E. Taylor, Department of Psychiatry, Yale University School of Medicine, New Haven,
CT 06520, USA
L. Tremblay, INSERM Unit 289, H6pital de la Salp6tri~re, 47 Boulevard de l'H6pital, F-
75651 Paris, France
Uylings, H.B.M., Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
C.G. Van Eden, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
M. Van Leeuwen, .Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ
Amsterdam, The Netherlands
D.J. Veltman, Research Institute Neurosciences, PET Center, Free University, Amster-
dam, The Netherlands
R.A. Wise, National Institute on Drug Abuse, Intramural Research Program, RO. Box
5180 Baltimore, MD 21224, USA
D.J. Woodward, Department of Physiology and Pharmacology, Medical Center Blvd.,
Wake Forest University, School of Medicine, Winston Salem, NC 27157, USA
J.N. Zhou, Anhui Medical University, Hefei, People's Republic of China
K. Zilles, C. and O. Vogt Institute for Brain Research, University of DUsseldorf,
Dfisseldorf, Germany
ix
IN MEMORY OF WALLEJ .H. NAUTA, A SCIENTIFIC PIONEER IN THIS FIELD
Preface
Cognition, Emotion and Autonomic Responses
Ten years ago we edited the book 'The prefrontal cortex: its structures, function and
pathology'. This successful book, also published in the Progress in Brain Research
series, has been completely sold out.
Since its publication many new data have emerged on the prefrontal cortex and its
connections and interactions with structures involved in emotional, motivational and
autonomic responses. Cognition, memory and decision making appear to be influenced
by emot.ional and autonomic responses from viscera and the internal state of the
organism (e.g. 'gut feelings') induced by the outside world. This resulted in a renewed
interest in the interactions of circuits involved in cognition, memory and decision making
with those involved in emotional and motivational responses. Therefore, the 21st
International Summer School of Brain Research, held in Amsterdam, 23-27 August
1999, was entirely devoted to the question to which extent the prefrontal cortex and
related limbic structures function as an integrative center for these interactions. This
book is one of the products of this stimulating Summer School. It contains five
sections.
The first section, Circuitry for Cognition and Emotion (I), reviews the present
knowledge of the circuits important for integration of sensory and limbic information;
for integration of emotion and memory, for integration of visceral control and behavior
and for interactions with autonomic responses.
After this basic section the second one, Attention and Decision Making (II), deals with
reviews on functional analyses of brain structures involved in decision making, attention,
arousal, learning and working memory. Since stress and reward modulate cognition, the
third section, Stress and Reward Systems in Cognition (III), reviews the modulatory role
of transmitters like dopamine, noradrenaline and acetylcholine and glutamate. The
modulatory role of transmitters is revealed in in vivo microdialysis and electrophysio-
logical studies. New data are presented which show the differential actions of neurons in,
e.g. the prefrontal cortex for different aspects of conditioning such as reward, association
of stimulus with reward, etc.
In mental disorders circuits dealt with in the first three sections are affected. In section
IV, Mental Disorders, reviews are given on the genetical aspects of behavioral disorders
like reward deficiency syndrome and functional and structural analyses of schizophrenia
and depression. We aimed at achieving a coherent state of the art picture of the role of
the prefrontal cortex, hypothalamus and neurotransmitters in depression.
In the final section (V), A.R. Damasio and T.W. Robbins considered, each from his
own perspective, the present state of the art of the integrative role of the prefrontal cortex
in cognition, emotion and autonomic responses. Since the topic of Dr. Damasio's lecture
was largely similar to the one of the Huygens lecture he presented a few months later in
The Hague, we acknowledge the Netherlands Organization for Scientific Research
(NWO) for reproducing the Huygens lecture in this volume. We also acknowledge all
contributors to this book for their efforts to write their interesting chapters in spite of
their very busy agendas.
Last, but certainly not least, we would like to express our gratitude to Ms T. Eikelboom
and Ms O. Pach for taking care of most of the organizational and all the secretarial work
required to compile this book.
Harry B.M. Uylings
Amsterdam, February 2000 Corbert G. Van Eden
Jan P.C. De Bruin
Matthijs G.P. Feenstra
Cyriel M.A. Pennartz
xi
Acknowledgements
The 21st International Summer School of Brain Research has been made possible by
financial support from:
Main sponsors:
Pfizer bv
Van den Houten Foundation
Royal Netherlands Academy of Arts and Sciences (KNAW)
N.V. Organon
Other sponsors:
Antec Leyden
Graduate School Neurosciences Amsterdam
Institut de Recherche Pierre Fabre
Janssen Research Foundation
Merck Research Laboratories USA
Noldus Information Technology bv
Novartis Pharma AG, Switzerland
Philips Medical Systems
Sanofi Recherche
Solvay Pharmaceuticals
Stichting het Remmert Adriaan Laan Fonds
Synth61abo Recherche
Yamanouchi Europe B.V.
H.B.M. ~ylings, C.G. Van Eden, J.P.C. De Bruin, M.G.E Feenstra and C.M.A. Pennartz
Progress in Brain Research, Vol 126
© 2000 Elsevier Science BV. All rights reserved.
CHAPTER 1
The prefrontal cortex and the integration of sensory, limbic
and autonomic information
Henk J. Groenewegen 1'* and Harry B.M. Uylings l'a
1 Research Institute Neurosciences, Vrije Universiteit (R1N-VU), Department of Anatomy, Faculty of Medicine, Vrije Universiteit,
Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
z Netherlands Institute for Brain Research (NIBR), Royal Netherlands Academy of Sciences (KNAW), Amsterdam, The Netherlands
Introduction a review of the symptoms of patients with frontal
lobe disorder, Nauta (1971) concluded that "...the
The prefrontal cortex (PFC) constitutes the cerebral frontal-lobe disorder is characterized foremost by a
cortical area in the frontal lobe rostral to the motor derangement of behavioral programming", and that
and premotor cortices. In the human brain, the PFC "...one of the essential functional deficits of the
appears to be the most extensive cortical area of the frontal-lobe patient appears to lie in an inability to
cerebral hemisphere (about 30% of the cerebral maintain in his behavior a normal stability-in-
cortex [Uylings and Van Eden, 1990]) and has time...". Whereas the assignment of a single
reached a high degree of morphological and function for the PFC across various species is very
functional differentiation. In most mammalian difficult, Fuster (1997) has argued that the different
species studied a prefrontal cortical area has been PFC functions identified can be viewed as "variants
identified (e.g. Rose and Woolsey, 1948; Leonard, of a superordinant PFC function of temporal
1969; Reep, 1984; Goldman-Rakic and Porrino, organization of goal-directed actions"
1985; Uylings and Van Eden, 1990). An unequiv- At least one of the clues in understanding the
ocal definition of the PFC, based upon a single functional role of the PFC lies in the answer to the
morphological or functional criterion, has proved to question: What information reaches the PFC and
be very difficult (e.g. Uylings and Van Eden, 1990; which brain areas are influenced by this frontal
Preuss, 1995; Groenewegen et al., 1997). Regions cortical region? In other words the nature of its
of the cerebral hemisphere in different species that afferent and efferent connectivity (see Fig. 1). In
are generally considered to belong to the PFC may reviewing the then existing knowledge about the
differ, for example, considerably in their cytoarchi- neural associations of the PFC, Nauta (1971)
tecture. It has also been difficult to functionally concluded that the PFC has "... a reciprocal
characterize the PFC since this part of the cerebral relationship with two great functional realms,
cortex is not connected in a direct way to any of the namely: (1) parietal and temporal regions of the
primary channels of sensory information nor is it cerebral cortex involved in the processing of visual,
directly linked to (skeleto)motor neurons. Based on auditory and somatic sensory information, and (2)
the telencephalic limbic system and its subcortical
*Corresponding author. Tel: [phone] or correspondents, in particular the hypothalarnus and
4448033; Fax: [phone]; meso- and diencephalic structures associated with
e-mail: HJ.Groenewegen.Anat @m ed.vu.nl the hypothalamus." In the last 30 years a wealth of
I PREFRONTAL CORTEX iI ~ [SOMATOSENSORY [
.. ^ I • TM ~ IVISUAL NEOCORTEX
\ MD thalamus~
\ ~K~ ~ ]LIMBICS YSTEM
4 ~ ~ ] Hippocampus
STRIATUM ~ o Olfactory Cortex
o~..~ = Nucleuso f Sol tap/Tract
HYPOTHALAMUSo~~ MOTORO UTPUT
'It
AUTONOMICO UTPUT
MESO- DIENCEPHALIC ARF-A8
ventral t~mental area
pedaqueductal grey
superior¢ olliculus (Nauta, 1971)
Fig. l. Schematic representation of the organization of the afferent and efferent connections of the prefrontal cortex as they were reviewed
by Nauta (1971) some 30 years ago on the basis his own experimental results, primarily obtained in primates, and data from the literature.
It should be realized that these conclusions were drawn on the basis of experiments performed before the era of the modem tract-tracing
techniques.
details on the connectivity of the PFC in rats and hippocampal projections are in a highly specific
primates has been published, not only largely and complex way involved in these circuits (Groe-
confirming these early observations and inter- newegen et al., 1990, 1996). Further, the PFC
pretations, but also extending the insights in the subserves visceral functions by direct reciprocal
heterogeneous structural organization of the PFC. connections with the hypothalamus (see Saper,
Following the introduction of highly sensitive tract- Chapter 3, this volume) and brainstem structures
tracing and immunohistochemical techniques in the such as the periaqueductal grey and the nucleus of
seventies and eighties of the last century, it could be the solitary tract (Van Eden and Buijs, Chapter 4,
shown that the PFC directly projects to the this volume). Due to its special position in the
cholinergic forebrain system, and the monoaminer- circuitry of the forebrain, the PFC has been implied
gic cell groups in the hypothalamus and brainstem. in psychiatric diseases as depression (see for
In this way, the PFC is in a unique position to example Chapter 24 by Rajkowska and Chapter 25
influence the transmitter systems that modulate by Drevets in this volume) and schizophrenia (see
large parts of the forebrain. Further, it has become also Chapter 21 by Sitskoorn et al. in this volume).
clear that the PFC has a special relationship with As suggested by Nauta (1971), the processing of
the basal ganglia: the PFC not only projects via the not only exteroceptive, but also of interoceptive
cortico-striatal system to the basal ganglia but also (visceral) information by the PFC is crucial for its
receives, via the thalamus, projections from these role in complex cognitive and behavioral functions.
structures, an arrangement which is special for the Nauta (1971) postulated that the interoceptive
frontal lobe (see however, Middleton and Strick, component of the afferents of the PFC may serve as
1996). In this way, the PFC is involved in a number a form of 'navigational marker' in the (temporal)
of largely parallel, functionally segregated cortical- organization of complex goal-directed behavior.
subcortical circuits that subserve sensorimotor, The more recently formulated 'somatic marker'
cognitive, emotional/motivational behavioral and hypothesis of the role of the PFC in such complex
visceral functions (Alexander et al., 1986, 1990; brain functions as processes of reasoning and
Strick et al., 1995). Thalamic, amygdaloid and decision making, that has been put forward by
Damasio and co-workers (1991, 1994), in a sense species, like the rat, the mediodorsal thalamic-
'builds upon' and extends the early observations projection cortex does not contain a granular layer
and interpretations by Nauta (1971). IV and must be characterized as 'agranular'.
Finally, based on the differences in afferent and However, cytoarchitectonic characteristics cannot
efferent connections of various ~eas in the PFC be used to identify a comparable cortical area in
and the differential functional deficits following distant species like rat and rhesus monkey (Uylings
focal lesions of the PFC, Nauta (1971) indicated and Van Eden, 1990). For example, the primary
that the PFC should not be considered as a motor cortex in rats is a granular cortex; con-
functional and anatomical entity. Subsequent ana- nectivity and functionality are, therefore, the main
tomical, physiological and behavioral studies have criteria.
confirmed these early assumptions.
The aim of the present chapter is to provide an Primate
overview of the afferent and efferent connections of
the PFC in primates and rats and to discuss, in the Brodmann (1909) recognized several distinct sub-
light of this circuitry, the presumptive functional areas in his granular 'regio frontalis' and, on the
role of the PFC in integrating sensory, motor, basis of cytoarchitectonic criteria, he excluded the
cognitive, emotional and autonomic functions. anterior cingulate and the limbic cortical areas from
the granular frontal cortex. Likewise, he concluded
Delineation and subdivisions of the prefrontal that a granular frontal cortex is unique for primates
cortex and humans, since in most other species there is no
granular cortical layer present in the frontal lobe. In
The frontal lobe consists of the motor and premotor later cytoarchitectonic studies in primates, it has
cortices and, rostral to these areas, the PFC. been demonstrated that several areas in the 'gran-
Whereas the motor and premotor cortices are ular frontal' cortex of Brodmann (1909), which
concerned with the selection and generation of have been included in the PFC on the basis of their
movements, the PFC is thought to be primarily predominant input from the mediodorsal thalamic
involved in cognitive and motivational/emotional nucleus (Rose and Woolsey, 1948; Goldman-Rakic
processes underlying and guiding complex behav- and Porrino, 1985; Barbas, 1988; see also Uylings
ior (e.g. Passingham, 1993). The distinction and Van Eden, 1990), do not contain a granular
between (pre)motor and prefrontal cortices, and the layer IV or must be characterized as dysgranular.
delineation of the PFC from caudally adjacent Thus, in primates several prefrontal cortical areas
insular and (posterior) cingulate cortical areas in appear to be either agranular (e.g. the anterior
primates has for some time in the past been based cingulate areas in the medial prefrontal cortex, i.e.
upon 'simple' cytoarchitectonic criteria (e.g. Brod- areas 25, 32 and 24; Barbas and Pandya, 1989;
mann, 1909): whereas the primary motor and Carmichael and Price, 1994) or dysgranular (e.g.
premotor cortical areas can be characterized as the more caudal parts of Brodmann areas 12, 11
'agranular' in that they lack a clear granular layer and 74; Barbas and Pandya, 1989; Carmichael and
IV, most of the prefrontal cortex was thought to Price, 1994; for cortical area nomenclature, see also
contain such a granular layer and has been Chapter 22 by Uylings et al., this volume).
indicated as the 'granular' frontal cortex. Since the Generally, the PFC of primates is being sub-
classical studies by Rose and Woolsey (1948), the divided into at least two major subareas, i.e. the
PFC is generally defined as that part of the frontal dorsolateral PFC and the orbital and medial, or
lobe that receives most of its thalamic inputs from orbitomedial PFC (Passingham, 1993; Price et al.,
the mediodorsal nucleus. Taking the connectivity 1996; Fuster, 1997; Roberts, 1998). This topo-
with the mediodorsal thalamic nucleus as the graphical bi-partition of the PFC concurs with a
defining characteristic of the PFC, it follows that crude functional distinction between these larger
most vertebrate species contain a 'prefrontal' area areas: whereas the dorsal and lateral parts of the
in the rostral part of the hemisphere, but in most PFC are considered to play a role in cognitive