Acknowledgements
We thank Chun
Chao, Hans-Peter
Hartung andJean
Merrill for providing
preprints, and the
NIH (SM), National
Multiple Sclerosis
Society (DLF, DJR),
DGICYTand the
FundacioM. F.
Roviralta (LA,A6),
NA TO (fellowship to
EG)and the Health
and Life Insurance
Medical Research
Fund(MLS) for
support.
Abstr. 18, 1004
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Thecontributionof the amygdalato normalandabnormal
emotionalstates
John P. Aggleton
John P. Aggleton is at
the Dept of
Psychology,
Universityof Ourham,
South Road,Durham,
UK DH13LE.
Lesion studies in monkeys have provided some of the
most compelling evidence for the involvement of the
amygdala in emotional and social behaviour. In spite of
this it has proved surprisingly difficult to uncover the
precise nature of the role of the amygdala. A number of
recent studies now indicate that the amygdala is
involved in a specific class of stimulus-reward associations and this discovery, combined with important
anatomical findings, has made it possible to gain a
much more detailed appreciation of the contribution of
the amygdala to emotion in non-human primates. In
parallel with this, it appears increasingly likely that
amygdala dysfunction contributes to the emotional
changes that accompany certain neurological disorders,
including dementia and schizophrenia.
The involvement of the amygdala in emotion was first
highlighted by the extraordinary loss of social and
affective behaviour that follows bilateral removal of
this structure in monkeys 1. While the importance of
the amygdala has been repeatedly confirmed since, its
precise role remains elusive. However, recent anatomical and behavioural findings have significantly
advanced our understanding of the functions of the
primate amygdala. In addition, there is growing
evidence that the amygdala contributes to various
clinical conditions characterized by prominent changes
in emotion. By integrating findings from these areas of
328
© 1993,ElsevierScience Publishers Ltd, (UK)
research, new ideas concerning the contribution of
the amygdala to both normal and abnormal emotional
states are emerging.
Anatomical considerations
The amygdala, named after its fanciful resemblance
to an almond, lies in the anterior medial portion of
each temporal lobe. It is composed of approximately a
dozen nuclei, each with a distinctive set of cytological,
histochemical and connectional features 2. Many of its
cells closely resemble those in adjacent cortical
regions 3. The structure is further characterized by a
complex array of intrinsic connections 2-4 and by the
enormous range of neuroactive substances found
within its boundaries.
It was originally thought that the principal connections of the amygdala were with the hypothalamus,
but it is now clear that the primate amygdala has many
other dense, subcortical and cortical connections (Fig.
1). Studies of the monkey brain have shown that the
amygdala receives direct projections from unimodal
sensory cortex (visual, auditory and somatosensory),
the afferents arising from relatively late stages in the
hierarchy of sensory processing"~'5. In addition, it
receives afferents from polysensory and 'limbic'
association areas including the cingulate gyrus, temporal pole, superior temporal sulcus, insula, perirhinal
cortex and frontal cortex a'5. Thus, the amygdala
TINS, Vol. 16, No. 8, 1993
sponse TM. Thus, the animals are able to acquire and
maintain general strategies for getting food as long as
they do not depend on linking the memory of food
rewards with specific items. More remarkably,
amygdalectomized monkeys show normal learning
rates for some pattern and object discriminations 13'18'19, even though such tasks should tax
specific stimulus-reward associations. To account for
this it is argued that normal monkeys can solve foodrewarded discriminations in several ways 2°. While
they may choose the correct stimulus because it is
associated with the intrinsic value of the reward (how
good it tastes), they may select the correct item
because it is linked with the external aspects of the
reward, i.e. the monkey chooses the stimulus that
leads to the sight of the food reward.
It is supposed that the former mechanism is
impaired by amygdalectomy while the latter is left
intact ~5. Evidence for this distinction comes from the
finding that amygdalectomized monkeys can perform
well on visual discrimination tasks when they are
required to displace the correct item to find a reward,
Behavioural studies of monkeys
i.e. they can use the sight of the food reward to signal
Bilateral removal of the amygdala produces a a correct choice. In contrast, amygdalectomized
permanent disruption of social and emotional be- monkeys show abnormal preferences among novel
haviour (part of the 'Kliiver-Bucy syndrome'). From foods21, and are impaired on discrimination tasks
studying its anatomical connections, the simplest when the reward cannot be seen 15'21 (Fig. 3). In both
explanation is that amygdalectomy disconnects in- situations the animal must link the sensory features of
coming sensory information from subcortical affective a specific stimulus with the palatability of food. Recent
and autonomic centres 7'8. However, this account is findings indicate that this amygdala function depends
insufficient since it overlooks the extensive amygdala- on its direct and indirect connections with the
cortical projections and the particular patterns of ventromedial prefrontal cortex 22.
learning and behavioural deficits associated with
Although there is much evidence that amygdala
amygdala damage. It has, for example, been reported lesions disrupt stimulus-reward associations, it is
that while amygdalectomy can produce socioemotional quite possible that damage to this structure has some
changes in monkeys only two months old9, these additional effects brought about by a corticalchanges become increasingly evident with age 9'1°. subcortical disconnection. A consideration of the
Such findings imply a role in learning about social neuroanatomy of the amygdala (Fig. 1) strengthens
information rather than simply a global loss of af[ective this possibility. Furthermore, the apparent lack of
behaviour brought about by a lack of sensory inputs. responsiveness to stimuli that might be regarded as
A more explicit proposal concerning the contri- innate, such as an air puff or being handled 23, along
bution of this region to learning is that the amygdala with the abnormal galvanic skin responses to novel
enables the formation of stimulus-reward associ- tones 24 or mild shock is consistent with a disconations 8'1~. These associations then help to establish nection rather than an associative deficit. While it is
the emotional significance of external events, includ- undesirable to propose multiple impairments following
ing social actions. Evidence comes from the disruptive amygdalectomy (i. e. a loss of associative abilities and
effects of amygdala lesions on tests that tax stimulus- a sensory-affective disconnection), this may prove a
reward associations. These include learning-set 12, fairer reflection of the complexity of the region.
discrimination reversals 11-13, and win-stay loseRecent research has shown that the rhinal cortex
shift 14'15 tests. The fact that amygdalectomized plays a critical role in anterograde memory25'26. This
monkeys are unresponsive to stimuli that evoked is important as virtually all of the amygdalectomized
emotion prior to surgery suggests that this impair- animals described so far received aspiration lesions
ment includes a failure to use previously learnt via a rostral and medial approach that involves
stimulus-reward associations.
removing rhinal tissue. This additional damage may
In an important refinement Gaffan 15 has proposed alter the interpretation of previous findings. Indeed,
that the amygdala is involved in a specific class of there is good evidence that the apparent contribution
stimulus-reward associations - those between dis- of the amygdala to memory tasks such as delayed
crete stimuli and their intrinsic, reward value. nonmatching-to-sample and delayed response was a
Examples include the precise association between consequence of such damage TM. Only a handful of
how a particular food item appears and how pleasant it studies have used a dorsal, stereotaxic route to lesion
tastes, and the link between a specific animal in a the amygdala, thereby sparing the rhinal cortex.
social troop and its level of agonistic behaviour. The These stereotaxic studies have confirmed that lesions
need for such a refinement stems from the fact that of the amygdala, but not the rhinal cortex, disrupt
extensive
amygdalectomized monkeys still appear sensitive to emotional responses 13'27, although
reward or punishment 16'17, and are able to perform amygdala damage is required to produce the full
normally on a number of food-rewarded tasks such as hypoemotionality~3. Stereotaxic amygdala lesions also
delayed nonmatching-to-sample and delayed re- impair discrimination reversals ~3, so strengthening
receives an enormous array of convergent sensory
information (Fig. 1A). Given its numerous subcortical
projections to regions such as the hypothalamus,
substantia innominata, ventral striatum, and various
autonomic centres in the midbrain 3 (Fig. 1), the
amygdala represents an important route by which
external stimuli could influence and activate emotions.
This view had to be modified with the discovery
that the amygdala has extensive projections back upon
the cortex 3'5. These projections not only reciprocate
the afferent connections but reach many other regions
of association cortex (Fig. 1B). This is most striking in
the visual system where amygdala efferents terminate
in almost every visual region in the temporal and
occipital lobes, including the striate cortex 5 (Fig. 2).
In association with its many subcortical afferents, the
amygdala may therefore be involved in the modulation
of sensory processing by affective states. Finally, the
lack of amygdala-parietal connections highlights the
affinity of the structure with stimulus identification
rather than location 6.
TINS, Vol. 16, No. 8, 1993
329
A
,,
//
.
Posterior thalamus
SPf/VPMpc
SG/PO/MGmc
L~
Midline
thalamus
_LHA
,PB
OLT
VMH
PB
NTS/DNX
RF
AH
OLT
CS
/
IP
~°°°.°o
,,,.°o°
330
~N~ Vo1.16, No. 8,1993
Fig. 1. (opposite). Summary diagram showing (A) the main afferent and (B) efferent connections of the monkey
amygdala. The cortical connections are shown from a medial (left), lateral (middle), and ventral (right) perspective. The
density of the cortical shading corresponds to the relative density of the various amygdala-cortical connections (black
being the densest). The sylvian fissure (SF) has been opened to expose the insula. The amygdala, which lies in the
centre of each illustration, is shown using a standard coronal section. Due to their complexity the termination sites of the
cortical afferents to the amygdala are not depicted. Abbreviations of amygdala nuclei: AB, accessory basal; AHA,
amygdalo-hippocampal area; B, basal; CE, central; L, lateral; M, medial. Other abbreviations: CC, corpus callosum;
CIN, cingulate sulcus; CS, central sulcus; DNX, dorsal motor nucleus of vagus; INS, insula; IP, inferior parietal sulcus; IT,
inferior temporal sulcus; LHA, lateral hypothalamic area; L TN, lateral tuberal nucleus; MGmc, magnocellular part of
medial geniculate nucleus of thalamus;/vlD, nucleus medialis dorsalis; NA, nucleus accumbens; NBM, basal nucleus of
Meynert; NTS, nucleus of the solitary tract; OL T, olfactory tubercle; OS, orbital sulcus; OT, occipito-temporal sulcus;
OS, orbital sulcus; P, putamen; PAG, periaqueductal gray; PB, parabrachial nucleus; PO, posterior nuclear complex of
thalamus; PP, peripenduncular nucleus; RF, reticular formation; RS, rhinal sulcus; SF, sylvian fissure; SG,
suprageniculate nudeus of thalamus; SN, substantia nigra; SP, sulcus principalis; SPf, subparafascicular nucleus; STS,
superior temporal sulcus; TC, tail of caudate; VA4H, ventromedial hypothalamic nucleus; VPMpc, ventroposteromedial
nucleus (parvicellular part); VTA, ventral tegmental area. (Modified, with permission, from Ref. 5.)
the link between stimulus-reward learning and
emotionality. Clearly, further selective lesion studies
are required, and it may prove particularly advantageous to use cytotoxins that spare fibre pathways2a.
It will also be necessary to consider the impact of
rhinal damage when describing the effects of amygdala
pathology in humans.
Clinical reports of amygdala damage in
humans
Selective amygdala damage is very rare in humans.
The large majority of cases concern surgeries for
epilepsy, behavioural disturbances, or both. Many of
these used stereotaxic methods, often producing
unilateral, subtotal lesions of an amygdaloid region
that may well have been abnormal prior to surgery. It
is therefore not surprising that some cases show no
overt change in emotion28 . Other reports stress a
decrease in aggressionzs'z9 or an increase in placidity
and indifference 2s'3°. In one detailed report a woman
described how her emotions felt dissociated following
amygdala surgery31. Clearly amygdala damage can
alter emotionality in humans, but it need not produce
the dramatic changes observed in monkeys.
One explanation for this species difference concerns the possible existence of additional corticallimbic routes in humans, so reducing the impact of
amygdala damage. Indirect support comes from the
finding that bilateral amygdala lesions in humans can
leave galvanic skin responses intact3z'33, unlike the
case in monkeys24. Furthermore, the extreme hypoemotionality of the Kltiver-Bucy syndrome is only
observed in humans when there is a combination of
cortical and subcortical temporal damage28. It is
also the case that the extreme emotional changes
observed in amygdalectomized monkeys can diminish
quite markedly with timez3, so further reducing any
species difference. As a consequence it is quite
possible that the human amygdala, in concert with
the prefrontal cortex, enables associations between
discrete stimuli and their incentive reward in a manner
similar to that presumed in other primates. While this
remains to be tested, there is recent evidence that
the amygdala may not be necessary for covert
affective behaviour 34 (which may rely on striatal
function).
Most neuropsychological studies have concentrated
on memory, revealing that selective amygdala damage
has little or no effect on most tests 28. This fits with
recent discoveries concerning the rhinal region and
memory. However, amygdala damage can disrupt
TINS, Vol. 16, No. 8, 1993
face recognition zs'31. This has been studied in particular detail in a woman with bilateral amygdala
damage following surgery for epilepsy (Broks, pers.
commun.). Although she shows no obvious loss of
emotionality and is able to identify famous faces and
match unfamiliar faces, she is impaired in her ability to
recognize unfamiliar faces, to label the affective
meaning of different facial expressions, and to identify
eye-gaze directions. These findings may be linked
with the discovery of amygdala neurones sensitive to
faces3'~. The same subject also shows marked difficulties in judging those aspects of speech associated
with attitude or emotions (prosody), indicating that
her problems are not restricted to vision. These
deficits, which have obvious links with the changes in
social behaviour observed in amygdalectomized
monkeys1, highlight the involvement of the structure
with affective stimuli.
The involvement of the amygdala in emotion may
have an important bearing on several forms of
dementia. In Alzheimer's disease the amygdala consistently shows neuronal loss, numerous neurofibrillary tangles and senile plaques 36. These changes are
severe and may occur early in the course of the
v
Fig. 2. The anatomical relationship between the amygdala and visually related
cortical areas in the temporal and occipital lobes (letters correspond to cortical
areas described by van Bonin and Bailey52). The amygdala receives a
substantial input from the highest levels of the cortical processing hierarchy
(area TEL while efferents from the basal amygdala nucleus terminate in all
levels of visually related cortex in the temporal and occipital lobes. Intrinsic
connections within the amygdala may permit a processing loop back to the
visual cortices. Abbreviations: AB, accessorybasal nucleus; CE, central nucleus;
L, lateral nucleus;/Pl, medial nucleus. (Taken, with permission, from Ref. 5.)
331
psychotic behaviour, often resembling paranoid
schizophrenia42. Besides the presence of neurofibrillary tangles in the cortex, amygdala and nucleus
basalis, the only commonly reported change was
extensive gliosis in the amygdala (Fig. 4).
100
90
80 70 -
]
I
Acquisition
~
Reversal
60
o
iii
50
\l
40
\
\
\
\
\
30
20
2~
10
i
0
1
2
3
4
5
Normal control
6
2
3
AM
Fig. 3. Acquisition (Acquis.) and reversal deficit shown by
monkeys with amygdalectomy (AM) on the performance
of an object discrimination task for an unseen reward. The
open bar represents errors made in 80 trials of initial
acquisition, and the hatched bar represents errors made in
a subsequent 80 trials with the reward values of the two
objects reversed• (Taken, with permission,from Ref. 21 .)
disease 36. In Pick's disease the amygdala shows
intense gliosis and atrophy36'37, while in Huntingdon's
chorea the amygdala can be considerably shrunken38.
One of the diagnostic features of these dementias is
a change in emotion. The most frequent change in
Alzheimer's disease is an increase in passivity, and
other common changes including an increase in
agitated and self-centred behaviour as well as a loss of
spontaneity and aesthetic appreciationa9-~1. In Pick's
disease, apathy, irritability, or depression are often
first symptoms37, while in Huntingdon's chorea
changes such as euphoria, depression, or paranoia are
prominent. In all three disorders pathology is present
in multiple sites capable of influencing emotion.
Nevertheless, amygdala dysfunction is a common
feature and obvious similarities can be drawn between
the hypoemotionality of monkeys with amygdala
damage and the more negative mood changes associated with these dementias. Furthermore, in Alzheimer's and Pick's disease the emotional changes can
be unrelated to the severity of the accompanying
memory loss 37'4°. This finding echoes the differential
effects of selective amygdala and hippocampal-rhinal
damage in monkeys. Clearly the challenge is now to
determine whether amygdala pathology is directly
linked to these disruptions in emotion.
A relatively high incidence of psychotic symptoms
is associated with dementia. Of particular interest is
the recent report of a familial presenile dementia in
which an early symptom was prominent antisocial and
332
The amygdala and schizophrenia
The possible involvement of amygdala dysfunction
in schizophrenia has often been ignored; yet there is
sufficient evidence to warrant a closer look. It is
known, for example, that the lateral ventricles can be
enlarged in schizophrenia and that this change is often
most pronounced adjacent to the arnygdala43.
Furthermore, post mortem studies have shown that
the amygdala can appear shrunken 44'45, a change unrelated to medication. Further evidence comes from
the connectivity between the amygdala and those
other brain regions that show pathological or activity
changes in schizophrenia, i.e. the hippocampus,
entorhinal cortex, parahippocampal gyrus, cingulate
gyrus and frontal cortex4s.
Neurochemical studies also implicate the amygdala
in the aefiology of schizophrenia. It is accepted that
the therapeutic actions of neurolepfic drugs depend on
their antagonism of dopamine D2 receptors. It is
therefore relevant that the amygdala both receives a
dopaminergic innervation from the mesolimbic pathway40 and has direct projections to other dopaminergic sites, including the ventral striatum and nucleus
accumbens2. Furthermore, an increase in dopamine
and its metabolite homovanillic acid has been found in
the left amygdala of schizophrenics45. While this may
be a consequence of drug treatment it would imply a
somewhat surprising asymmetrical effect. Other
Fig. 4. Coronal section showing striking atrophy of the
amygdala (arrowed) in a woman who suffered from a
familial presenile dementia associated with prominent
psychotic behaviour. (Luxol fast blue-periodic acid-Schiff
reaction-hematoxylin.) (Taken, with permission, from Ref.
42.)
TINS, Vol. 16, No. 8, 1993
reported neurochemical changes in the amygdala
include a decrease in GABA, a decrease in cholecystokinin and an increase in vasoactive intestinal
polypeptide 4~.
While it is unlikely that the malfunctioning of any
one brain site will prove sufficient to produce the
array of cognitive, emotional and attentional disorders
associated with schizophrenia, the link between the
amygdala and emotional changes in schizophrenia
seems worthy of further study. Not only do schizophrenics often display inappropriate mood or a lack
of affect, they also have difficulty identifying the
emotional status of other people 47'48. These problems
are reminiscent of those that follow amygdala damage,
and it is tempting to postulate that they involve a
dysfunction of stimulus-reward associations. This
proposal seems all the more plausible as this associative function depends on amygdala-prefrontal connections 15'22, and it has been argued that abnormalities in frontal lobe function are a central feature of
schizophrenia 49'5°. A further proposal that can be
derived from animal studies is that the changes in
affect and memory 51 observed in schizophrenia reflect
pathologies in different regions (amygdala-frontal
cortex and the rhinal-hippocampal region, respectively). If so they may prove dissociable.
Finally, a number of similarities have been noted
between childhood autism and the negative features of
schizophrenia 5°. Indeed, it has been argued that
common cognitive abnormalities may occur in both
conditions~°. Furthermore, the behavioural effects of
amygdala lesions in the infant monkey bear a similarity
to those socioemotional changes observed in autism9,
leading to the speculation that amygdala dysfunction
contributes to autism9. From this it can be seen that
there are a number of recent proposals concerning the
involvement of the amygdala in a variety of disorders,
all characterized by changes in emotion. The task now
is to test for the involvement of the amygdala in a
more direct manner.
Selected references
1 Kling, A. S. and Brothers, L. A. (1992) in The Amygdala:
Neurobiological Aspects of Emotion, Memory, and Mental
Dysfunction (Aggleton, J. P., ed.), pp. 353-377, Wiley-Liss
2 Price, J. L., Russchen, F. T. and Amaral, D. G. (1987) in
Integrated Systems of the CNS (Handbook of Chemical
Neuroanatomy, Vol. 5) (Bjorklund, A., Hokfelt, T. and
Swanson, L. W., eds), pp. 279-381, Elsevier Scientific
Publishers
3 McDonald, A. J. (1992) in The Amygdala: Neurobiological
Aspects of Emotion, Memory, and Mental Dysfunction
(Aggleton, J. P., ed.), pp. 67-96, Wiley-Liss
4 Aggleton, J. P. (1985) Exp. Brain Res. 57, 390-399
5 Amaral, D. G., Price, D. L., Pitk~nen, A. and Carmichael, S. T.
(1992) in The Amygdala: Neurobiological Aspects of
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ed.), pp. 1-66, Wiley-Liss
6 Ungerleider, L. G. and Mishkin, M. (1982) in Analysis of
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R. W. J., eds), pp. 549-586, MIT Press
7 Downer, J. L. de C. (1961) Nature 191, 50-51
8 Aggleton, J. P. and Mishkin, M. (1986) in Biological Foundations of Emotion (Plutchik, R. and Kellerman, H., eds),
pp. 281-300, Academic Press
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Acknowledgements
I wouldlike to thank
And)/Young, David
6affan, Shirley
Whiteleyand Paul
Broksform their
help. Partsof the
researchcitedin this
paper weresupported
by grants from the
MRC
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