The Amygdala, Autism and Anxiety
Preview:
DESCRIPTION
Citation preview
- 1. The Amygdala, Autism and Anxiety
David G. Amaral, Ph.D.1,2 and Blythe A. Corbett, Ph.D.2
1Department of Psychiatry, Center for Neuroscience and California
Regional Primate Research Center
2The M.I.N.D. (Medical Investigation of Neurodevelopmental
Disorders) Institute
University of California, Davis, Center for Neuroscience, 1544
Newton Ct., Davis, CA, 95616
Number of pages: 20
Number of words: 3755
Number of tables: 0
Number of figures: 0
Running Title: Amygdala and Autism
Send correspondence and reprint requests to:
David G. Amaral, Ph.D.
Center for Neuroscience
1544 Newton Court
Davis, CA. 95616 USA
Telephone(530) 757-8813
Fax(530) 754-7016
e-maildgamaral@ucdavis.edu
Abstract
Brothers
MQBGAEEANwA1AEQAMgA0ADAAMAA3AEEAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAwAEIAMAAyADAAMAAwADAAMAAwADEAMAAwADAAMQBEADMAQgAxAEMAMAAyADAAMAAwADAAMAAwADEANgA1AEIANAAyADcAMgA2AEYANwA0ADYAOAA2ADUANwAyADcAMwAyAEMAMgAwADMAMQAzADkAMwA5ADMAMAAyADAAMgAzADMANAAzADEAMwAzADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (1990) has proposed that the amygdala is an important
component of the neural network that underlies social cognition.
And, Bauman and Kemper
OABEAEUAMQA1AEUAQgBFADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAwAEUAMAAyADAAMAAwADAAMAAwADEAOQAzADgAQQBBADcARQBGADAAMAAyADAAMAAwADAAMAAwADEANAA1AEIANAAyADYAMQA3ADUANgBEADYAMQA2AEUAMgBDADIAMAAzADEAMwA5ADMAOAAzADUAMgAwADIAMwAzADQAMwAxADMANAA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (1985) observed signs of neuropathology in the amygdala
of the postmortem autistic brain. These findings, in addition to
recent functional neuroimaging data, have led Baron-Cohen et al.
QQBEADcANABFADAAMwA3ADAAMAA4ADAAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAxADAAMAAyADAAMAAwADAAMAAwADEAQQA3ADMAMgAwAEQAOAA0ADgAMAAyADAAMAAwADAAMAAwADEAOQA1AEIANAAyADYAMQA3ADIANgBGADYARQAyAEQANAAzADYARgA2ADgANgA1ADYARQAyAEMAMgAwADMAMgAzADAAMwAwADMAMAAyADAAMgAzADMANAAzADAAMwA4ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (2000) to propose that dysfunction of the amygdala may
be responsible, in part, for the impairment of social functioning
that is a hallmark feature of autism. Recent data from studies in
our laboratory on the effects of amygdala lesions in the macaque
monkey are at variance with a fundamental role for the amygdala in
social behavior. If the amygdala is not essential for normal social
behavior, as seems to be the case in both nonhuman primates and
selected patients with bilateral amygdala damage, then it is
unlikely to be the substrate for the abnormal social behavior of
autism. However, damage to the amygdala does have an effect on a
monkeys response to normally fear-inducing stimuli, such as snakes,
and removes a natural reluctance to engage novel conspecifics in
social interactions. These findings lead to the conclusion that an
important role for the amygdala is in the detection of threats and
mobilizing an appropriate behavioral response, part of which is
fear. If the amygdala is pathological in subjects with autism, it
may contribute to their abnormal fears and increased anxiety rather
than their abnormal social behavior.
Introduction
In the best of biomedical research endeavors, there is a natural
symbiosis between basic, and often basic animal research, and
careful assessment of clinical populations. The issues raised in
this paper draw from efforts to establish the neurobiological basis
of primate social behavior, on the one hand, and attempts to
determine brain systems that are impacted in autism and lead to
impairments of social behavior, on the other hand. One effort has
enormous potential to inform the other. If for example, a neural
system, lets call it the Social System, is established that
underlies the various components of social interaction, and given
that impairments of social interaction are a major deficit in
autism spectrum disorders, then a reasonable hypothesis might be
that a region of primary brain pathology might be in the Social
System. Conversely, if specific and reproducible areas of brain
pathology were identified in autism spectrum disorder, this
information might provide a useful heuristic as to which brain
regions might be components of the Social System.
Life, of course, is rarely so simple and autism is certainly one of
the most complex of neurological disorders. It is complex because
it has many diverse symptoms including social impairment, language
problems and motor stereotypies. These symptoms are observed
heterogeneously throughout the population that makes up the autism
spectrum. There are also a number of co-morbid conditions, such as
sleep disturbances, gastrointestinal distress and psychiatric
symptoms including anxiety and obsessive-compulsive behavior. The
following is a short summary of the thought and experimental
process that we have followed - starting with the notion that the
amygdala is a fundamental component of the Social System and likely
to be heavily involved in the pathophysiology of autism - to our
current view that the amygdala is involved in detecting and
reacting to environmental threats. And, if the amygdala is impaired
in autism, it may be more responsible for alterations in fear and
anxiety rather than social behavior.
The Amygdala
The primate amygdala is a relatively small brain region located in
the temporal lobe, just anterior to the hippocampus. In the macaque
monkey it is approximately 0.6 cm3 in volume and in the human it is
about 3.0 cc3. The amygdala is comprised of at least 13 nuclei and
cortical regions, many of which are partitioned into two or more
subdivisions. The amygdala has widespread extrinsic connections
including those with the neocortex, hippocampal formation,
cholinergic basal forebrain, striatum, hypothalamus and brainstem.
While neocortical inputs to the amygdala arise mainly from higher
order unimodal and polymodal association cortices, projections back
to the neocortex extend monosynaptically even to primary sensory
areas such as visual area V1. There is an extensive network of
intrinsic connections within the amygdala that generally brings
information from more laterally situated nuclei, such as the
lateral nucleus, to more medially situated nuclei, such as the
central nucleus. The amygdala contains a plethora of neuroactive
substances and has some of the highest brain levels of
benzodiazepine receptors and opiates. Detailed descriptions of the
neuroanatomy of the amygdala can be found in Amaral et al.
MgAyADEAOQBEADUAQgBDADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAxADIAMAAyADAAMAAwADAAMAAwADEANQAwADMAQgBDADAANwAxADYAMAAyADAAMAAwADAAMAAwADEANAA1AEIANAAxADYARAA2ADEANwAyADYAMQA2AEMAMgBDADIAMAAzADEAMwA5ADMAOQAzADIAMgAwADIAMwAzADQAMwAxADMAOQA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (1992). One can conclude from the neuroanatomy of the
amygdala that it is privy to much of the sensory processing that
occurs in the neocortex and, that through its widespread efferent
connections, it has the ability to influence the activity of
numerous functional systems that range from elemental physiological
processes such as heart rate and respiration to the highest
processes of perception, attention and memory.
The Amygdala and Social Behavior
Several lines of evidence have indicated that the amygdala plays an
important role in socioemotional behavior. Macaque monkeys with
bilateral lesions that include the amygdala are typically more tame
than normal animals, demonstrate abnormal food preferences and have
alterations of sexual behavior
QQAyAEUAOQA2ADMAMgA1ADAAMAA3ADQAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAxADQAMAAyADAAMAAwADAAMAAwADEAOQAzADkAOAAzAEYARQAyAEMAMAAyADAAMAAwADAAMAAwADEAMwA1AEIANAAyADcAMgA2AEYANwA3ADYARQAyAEMAMgAwADMAMQAzADgAMwA4ADMANwAyADAAMgAzADMANAAzADIAMwAwADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (Brown and Schafer 1887)
(MgAzADAARAA5ADMARgBFADAAMAA5AEMAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAxADYAMAAyADAAMAAwADAAMAAwADEARABDADkANwBFAEUAOABFADUAMAAyADAAMAAwADAAMAAwADIANwA1AEIANABCADYAQwA3ADUANwA2ADYANQA3ADIAMgBDADIAMAAzADEAMwA5ADMAMwAzADgAMgAwADIAMwAzADQAMwAyADMAMQAzAEIAMgAwADQAQgA2AEMANwA1ADcANgA2ADUANwAyADIAQwAyADAAMwAxADMAOQAzADMAMwA5ADIAMAAyADMAMwA0ADMAMgAzADIANQBEADAAMAAwAEUAMAAwADAAMAAwADAA
ADDIN ENRfu Kluver and Bucy 1938, 1939). Rosvold et al.
NwA0ADUAMAA2ADIARgBFADAAMAA3ADgAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAxADgAMAAyADAAMAAwADAAMAAwADEANgAwADcANwA4ADAAQgAyADgAMAAyADAAMAAwADAAMAAwADEANQA1AEIANQAyADYARgA3ADMANwA2ADYARgA2AEMANgA0ADIAQwAyADAAMwAxADMAOQAzADUAMwA0ADIAMAAyADMAMwA0ADMAMgAzADMANQBEADAAMAAwAEUAMAAwADAAMAAwADAA
ADDIN ENRfu (1954) designed studies to explicitly evaluate changes
in social behavior in macaque monkeys following amygdala damage.
They established artificial social groups of male rhesus monkeys
and studied the dominance hierarchy that emerged. They then carried
out two stage bilateral destructive lesions of the amygdala of the
most dominant animal and studied the dominance hierarchy as the
group reorganized. They found that the lesions led to a decrease in
social dominance with the lesioned animal typically falling to the
most subordinate position of the group.
A more extensive program of studies was carried out by Kling and
colleagues using both captive and free ranging nonhuman primates
MwA2ADYANAAxADQANQBGADAAMAA5ADgAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAxAEEAMAAyADAAMAAwADAAMAAwADIARABFAEQAQgA5ADkANwBCAEQAMAAyADAAMAAwADAAMAAwADIANQA1AEIANABCADYAQwA2ADkANgBFADYANwAyAEMAMgAwADMAMQAzADkAMwA3ADMAMAAyADAAMgAzADMANAAzADIAMwA0ADMAQgAyADAANABCADYAQwA2ADkANgBFADYANwAyAEMAMgAwADMAMQAzADkAMwA3ADMAMQAyADAAMgAzADMANAAzADIAMwA1ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (Kling et al. 1970, Kling and Cornell 1971)
QgBBADcAOAA0ADIAMgA3ADAAMAA3ADQAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARAAwADAANQBCAEQAMQAxAEMAMAAyADAAMAAwADAAMAAwADEAOQAzAEEARQBBAEEARQBDADYAMAAyADAAMAAwADAAMAAwADEAMwA1AEIANABCADYAQwA2ADkANgBFADYANwAyAEMAMgAwADMAMQAzADkAMwA3ADMANgAyADAAMgAzADMANAAzADIAMwA2ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (Kling and Steklis 1976). Dicks et al.
QQBGAEEAOABCADIAQQA2ADAAMAA3ADQAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAxAEUAMAAyADAAMAAwADAAMAAwADEANAAwADEARQA4ADAAMAA0AEMAMAAyADAAMAAwADAAMAAwADEAMwA1AEIANAA0ADYAOQA2ADMANgBCADcAMwAyAEMAMgAwADMAMQAzADkAMwA2ADMAOAAyADAAMgAzADMANAAzADIAMwA3ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (1968), for example, retrieved rhesus monkeys from
social troops on the island of Cayo Santiago. These animals were
subjected to bilateral amygdalectomy and then returned to their
social groups. While it was difficult to follow the
minute-to-minute interactions of the lesioned animals, the typical
finding was that they were invariably ostracized and would often
perish without the support of the social group.
From the results of these and similar studies carried out by
several laboratories, Brothers
MQBGAEEANwBCAEIAMgA2ADAAMAA3AEEAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAyADAAMAAyADAAMAAwADAAMAAwADEAMAAwADAAMQBEADMAQgAxAEMAMAAyADAAMAAwADAAMAAwADEANgA1AEIANAAyADcAMgA2AEYANwA0ADYAOAA2ADUANwAyADcAMwAyAEMAMgAwADMAMQAzADkAMwA5ADMAMAAyADAAMgAzADMANAAzADEAMwAzADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (1990) formalized the view that the amygdala is one of
a small group of brain regions that form the neural substrate for
social cognition. This view predicts that the amygdala is essential
for certain aspects of the interpretation and production of normal
social gestures such as facial expressions and body postures. It
also predicts, consistent with the literature that damage to the
amygdala would invariably lead to a decrease in the amount or
quality of conspecific social interactions.
The Amygdala and Autism
In their seminal studies on the neuropathology of the autistic
brain, Bauman and Kemper
OABEAEUAMQBCADAAQgBDADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAyADMAMAAyADAAMAAwADAAMAAwADEAOQAzADgAQQBBADcARQBGADAAMAAyADAAMAAwADAAMAAwADEANAA1AEIANAAyADYAMQA3ADUANgBEADYAMQA2AEUAMgBDADIAMAAzADEAMwA5ADMAOAAzADUAMgAwADIAMwAzADQAMwAxADMANAA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (1985) noted that the medially situated nuclei of the
amygdaloid complex had clusters of small, tightly packed neurons
that were not observed in control brains. The amygdala
neuropathology was only one area among many that included
alterations in the hippocampus, septum, cerebellum and other
structures. Unfortunately, these observations have not yet been
independently replicated. Neuroimaging studies have thus far
produced conflicting results on whether there is a gross change in
the volume of the amygdala. Abell et al.
MwA4ADgAOQA0ADMARQA3ADAAMAA3ADQAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAyADUAMAAyADAAMAAwADAAMAAwADEANAAwADEARgAyADAAMwBDAEEAMAAyADAAMAAwADAAMAAwADEAMwA1AEIANAAxADYAMgA2ADUANgBDADYAQwAyAEMAMgAwADMAMQAzADkAMwA5ADMAOQAyADAAMgAzADMANAAzADQAMwA2ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (1999) reported an increased left amygdala volume in
cases of autism and Asperger syndrome. Howard et al.
MQA2ADYANwBEADAAOQBDADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAyADcAMAAyADAAMAAwADAAMAAwADEANQAwADMAOQA5ADAANgBFAEMAMAAyADAAMAAwADAAMAAwADEANAA1AEIANAA4ADYARgA3ADcANgAxADcAMgA2ADQAMgBDADIAMAAzADIAMwAwADMAMAAzADAAMgAwADIAMwAzADEAMwA4ADMANAA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (2000) also reported an increased amygdala volumes in
both hemispheres of the brain in subjects with autism. In contrast
to these studies, Aylward et al.
NQBFADMARgA1ADIARQAyADAAMAA3ADgAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAyADkAMAAyADAAMAAwADAAMAAwADEANgAwADcAQwA4ADAARABGAEUAMAAyADAAMAAwADAAMAAwADEANQA1AEIANAAxADcAOQA2AEMANwA3ADYAMQA3ADIANgA0ADIAQwAyADAAMwAxADMAOQAzADkAMwA5ADIAMAAyADMAMwA0ADMAMwAzADgANQBEADAAMAAwAEUAMAAwADAAMAAwADAA
ADDIN ENRfu (1999), reported the amygdala to be decreased in volume
compared to age matched control cases. Pierce et al.
RgA4ADYARQA1AEMAQgBFADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAyAEIAMAAyADAAMAAwADAAMAAwADEANQAwADMAOQAxADAANQAwADQAMAAyADAAMAAwADAAMAAwADEANAA1AEIANQAwADYAOQA2ADUANwAyADYAMwA2ADUAMgBDADIAMAAzADIAMwAwADMAMAAzADEAMgAwADIAMwAzADQAMwAzADMAOQA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (2001) also reported amygdala volumes to be
significantly smaller. Thus, these studies appear inconclusive as
to whether there is a size difference in the autistic amygdala.
Even if the size was significantly different, it is unclear whether
this would imply better or worse function.
More suggestive evidence for a role of the amygdala in autism comes
from a variety of functional imaging studies. Individuals with high
functioning autism or Asperger syndrome showed significantly less
amygdala activation than control subjects during a task that
required them to judge what a person might be feeling or thinking
from images of their eyes (Baron-Cohen et al. 1999). A more recent
fMRI study, comparing adult males with autism to control subjects,
measured the neural activation in areas of the brain that are
associated with a social perception task
MwA1AEYAOQAzAEMAMwBGADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAyAEQAMAAyADAAMAAwADAAMAAwADEANQAwADMAOQAxADAANgBGADYAMAAyADAAMAAwADAAMAAwADEANAA1AEIANAAxADcAMwA2ADgANwA3ADYAOQA2AEUAMgBDADIAMAAzADIAMwAwADMAMAAzADEAMgAwADIAMwAzADQAMwA0ADMANQA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (Ashwin et al. 2001). Subjects were shown images of
real faces that varied in intensity of facial affect from neutral
expressions to extreme fear expressions, as well as scrambled
faces. The subject was simply required to press a button every time
they saw a picture on the screen. During this social perception
task, the subjects with autism showed less activation of the
amygdala and orbitofrontal cortex. Moreover, the subjects with
autism showed increased activity (implying greater reliance) on the
superior temporal gyrus and anterior cingulate cortex. These data
would appear to suggest that when normal subjects are carrying out
tasks that require social evaluation, the amygdala is activated.
And this activation is decreased in individuals with autism.
The Amygdala Theory of Autism
Based on these converging lines of evidence, Baron-Cohen et al
QQBEADcANABFADIAMwA1ADAAMAA4ADAAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAzADAAMAAyADAAMAAwADAAMAAwADEAQQA3ADMAMgAwAEQAOAA0ADgAMAAyADAAMAAwADAAMAAwADEAOQA1AEIANAAyADYAMQA3ADIANgBGADYARQAyAEQANAAzADYARgA2ADgANgA1ADYARQAyAEMAMgAwADMAMgAzADAAMwAwADMAMAAyADAAMgAzADMANAAzADAAMwA4ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (2000) wrote a very compelling review that concluded,
The amygdala is therefore proposed to be one of several neural
regions that are abnormal in autism. An implication of the paper is
that pathology of the amygdala leads to an impairment in social
intelligence, which is a hallmark feature of autism. That the
amygdala might be at the heart of the pathophysiology of autism was
also suggested somewhat earlier by Bachevalier
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
ADDIN ENRfu (1994, 1996) based on observations of neonatal macaque
monkeys who had been subjected to bilateral medial temporal lobe
lesions. Bachevalier described these monkeys (at 6 months of age)
as dramatically decreasing their social behavior as compared to
controls in dyadic social encounters with conspecifics. The
lesioned animals actively avoided social contacts and had blank,
inexpressive faces and poor body expression (i.e. lack of normal
playful posturing) and they displayed little eye contact.
Furthermore, animals with early medial temporal lobe lesions
developed locomotor stereotypies and self-directed activities
OQA1ADcAOQBEADUAOAAzADAAMAA4ADAAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAzADUAMAAyADAAMAAwADAAMAAwADEAMwAwADAARQAxADkARgAxADAAMAAyADAAMAAwADAAMAAwADEAOQA1AEIANAAyADYAMQA2ADMANgA4ADYANQA3ADYANgAxADYAQwA2ADkANgA1ADcAMgAyAEMAMgAwADMAMQAzADkAMwA5ADMANAAyADAAMgAzADMANAAzADMAMwA2ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (Bachevalier 1994). Since selective lesions of the
hippocampus did not produce this pattern of behavioral alterations,
Bachevalier attributed them to damage of the amygdala.
The literature that figured prominently in the generation of the
amygdala theory of autism and the notion that the amygdala is
essential for normal social behavior was very influential on our
own program of studies aimed at unraveling the neurobiology of
primate social behavior. While we would have been delighted to have
generated data consistent with the hypothesis that the amygdala is
central to social behavior, the data we did generate has led us to
a distinctly different conclusion.
The Amygdala is not Essential for Social Behavior in the Adult
Monkey
We have carried out a series of experimental studies to re-examine
the role of the amygdala in conspecific social behavior using the
rhesus monkey as a model system
NABEADgANwAyADcAMgA2ADAAMAA3ADQAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAzADgAMAAyADAAMAAwADAAMAAwADEANAAwADEAQwA4ADgAMABCAEUAMAAyADAAMAAwADAAMAAwADEAMwA1AEIANAA1ADYARAA2ADUANwAyADcAOQAyAEMAMgAwADMAMgAzADAAMwAwADMAMQAyADAAMgAzADMANAAzADIAMwA4ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (Emery et al. 2001). Adult, male rhesus monkeys with
bilateral ibotenic acid lesions of the amygdala, and age, sex and
dominance matched control monkeys were observed during dyadic
interactions with stimulus monkeys (two males and two females).
This stereotaxic, neurotoxic lesion technique has the merit of
removing the neurons of the amygdala while sparing fibers that pass
through it. A variety of both affiliative (groom, present sex etc.)
and agonistic, (aggression, displace etc.) behaviors were
quantitatively recorded while animals interacted in a large (18ft X
7ft X 6.5ft) chain link enclosure. Each experimental animal
interacted with each stimulus animal for four, twenty-minute
periods in what we called the unconstrained dyad format. In what
was initially a very surprising observation, the amygdala-lesioned
monkeys generated significantly greater amounts of affiliative
social behavior towards the stimulus monkeys than the control
monkeys. Control monkeys, when they first met the stimulus monkeys,
demonstrated a typical and appropriate reluctance to engage in
social interactions. They appeared to go though a period of
evaluation to determine the intentions of the other animal. The
lesioned monkeys, in contrast, appeared to be socially uninhibited
since they did not go through the normal period of evaluation of
the social partner before engaging in social interactions.
The inevitable conclusion from this study is that in dyadic social
interactions, monkeys with extensive bilateral lesions of the
amygdala can interpret and generate social gestures and initiate
and receive more affiliative social interactions than normal
controls. In short, they are clearly not critically impaired in
carrying out social behavior. We would suggest that the lesions
have produced a socially uninhibited monkey since their normal
reluctance to engage a novel animal appears to have been
eliminated. This, as well as evidence that the amygdala-lesioned
animals are not fearful of normally fear-inducing stimuli such as
snakes, has led us to the hypothesis that a primary role of the
amygdala is to evaluate the environment for potential threats or
dangers. Without a functioning amygdala, macaque monkeys do not
evaluate other novel conspecifics as potential adversaries and
whatever system(s) are involved in mediating social interactions
run in default mode of approach.
Early Amygdala Lesions do not Eliminate Social Behavior
One caveat of this conclusion that the amygdala is not essential
for social behavior is that these experiments were carried out in
mature monkeys. One might argue that while the amygdala is not
necessary for generating social behavior, perhaps it is essential
for gaining social knowledge. We have carried out a series of
studies in which the amygdala is lesioned bilaterally in primates
at two weeks of age
MwAzADgARQA2AEEARgA1ADAAMAA3ADgAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAzAEIAMAAyADAAMAAwADAAMAAwADEANgAwADcAMgAyADAAMgA0ADgAMAAyADAAMAAwADAAMAAwADEANQA1AEIANQAwADcAMgA2ADEANwA0ADYAOAA2ADUANwAyADIAQwAyADAAMwAyADMAMAAzADAAMwAxADIAMAAyADMAMwA0ADMAMQAzADIANQBEADAAMAAwAEUAMAAwADAAMAAwADAA
ADDIN ENRfu (Prather et al. 2001). This is at a point in time when
infant macaque monkeys are mainly found in ventral contact with
their mothers and there is virtually no play or other types of
social interactions with other animals. We found that the
interactions of the lesioned animals with their mothers was similar
to that of control animals. Moreover, we found that, like adult
animals with bilateral amygdala lesions, they showed little fear of
normally fear-provoking objects such as rubber snakes. However,
they showed increased fear, as indicated by more fear grimaces and
more screams during novel dyadic social interactions. Most germane
to the discussion, however, is the finding that the lesioned
animals generated substantial social behavior that was similar to
that generated by age-matched controls. In a larger replication
study that is currently under way (Prather et al., unpublished
observations 2002) the quality and quantity of social interactions
in a number of social formats is being investigated and there may
be subtle differences in these parameters. However, the inescapable
conclusion from observation of these animals is that there are none
that are markedly impaired in generating species typical social
behaviors such as grooming, play and facial expressions. All of the
animals appear to be visually attentive of the other animals when
they are involved in large play groups comprised of 2 control
animals, 2 animals with amygdala lesions and 2 animals with
hippocampal lesions as well as male and female adult animals. And
none appear to have developed motor stereotypies despite the fact
that they have now reached one year of age.
The results from studies carried out both in adult and mature
rhesus monkeys with complete bilateral lesions of the amygdala have
forced us to consider the conclusion that the amygdala is not
essential either for interpretation or expression of species
typical social behaviors or for gaining social knowledge. If the
amygdala is not a central component of the Social System, it is
unlikely that pathology of it would lead directly to the
impairments of social behavior that are observed in autism.
Subject S.M.
There are relatively few human subjects who have bilateral and
discrete lesions of the amygdala. One outstanding exception is
patient S.M. who has been extensively studied by Adolphs and
colleagues
MgBGAEQAOQBDADgAMwA3ADAAMABBADAAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQAzAEUAMAAyADAAMAAwADAAMAAwADIAQwBDADcARAA5AEMAMQAwADIAMAAyADAAMAAwADAAMAAwADIAOQA1AEIANAAxADYANAA2AEYANgBDADcAMAA2ADgANwAzADIAQwAyADAAMwAxADMAOQAzADkAMwA1ADIAMAAyADMAMwA0ADMAMwAzADEAMwBCADIAMAA0ADEANgA0ADYARgA2AEMANwAwADYAOAA3ADMAMgBDADIAMAAzADEAMwA5ADMAOQAzADQAMgAwADIAMwAzADQAMwAzADMAMAA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (Adolphs et al. 1994, Adolphs et al. 1995). Patient
S.M. suffers from Urbach-Wiethe syndrome that has produced
bilateral space occupying lesions of the amygdala. Interestingly,
she is impaired in her ability to identify fearful faces despite
the fact that she can reliably detect happiness and other emotions
in faces. S.M. is also unable to determine which individuals would
typically be considered untrustworthy based on their facial
appearance
RAAxADYAMgA5ADgARQAyADAAMAA3ADgAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA0ADEAMAAyADAAMAAwADAAMAAwADEANgAwADcARAA4ADAAMwAwADIAMAAyADAAMAAwADAAMAAwADEANQA1AEIANAAxADYANAA2AEYANgBDADcAMAA2ADgANwAzADIAQwAyADAAMwAxADMAOQAzADkAMwA4ADIAMAAyADMAMwA0ADMAMwAzADIANQBEADAAMAAwAEUAMAAwADAAMAAwADAA
ADDIN ENRfu (Adolphs et al. 1998).
Despite these difficulties, patient S.M. leads a reasonably normal
life. She is capable of holding a job, has been married and is
raising children. One is impressed not so much with the deficits in
this subject who has no amygdala but rather by how intact is much
of her everyday behavior, including social behavior. A similar
conclusion can be drawn from patient H.M. who had bilateral
temporal lobectomies for intractable seizures. His surgery has
completely removed the amygdala and rostral half of the hippocampal
formation
OAA3ADQAMQBFAEQAQgBDADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA0ADQAMAAyADAAMAAwADAAMAAwADEANQAwADMAOQA0ADAANwA5ADIAMAAyADAAMAAwADAAMAAwADEANAA1AEIANAAzADYARgA3ADIANgBCADYAOQA2AEUAMgBDADIAMAAzADEAMwA5ADMAOQAzADcAMgAwADIAMwAzADQAMwAzADMAMwA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (Corkin et al. 1997). While H.M. is densely amnesic, he
is nonetheless capable of normal social interactions. And neither
he nor patient S.M. demonstrate typical autistic symptomatology.
These patients would seem to support the contention that the
amygdala is not essential for normal social behavior and that
damage to the amygdala does not necessarily lead to autistic
behavior.
Anxiety in Autism
How does the concept of threat detection figure into the picture of
autism? In Kanners
QgBGAEMARgBDADYAMwBDADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA0ADcAMAAyADAAMAAwADAAMAAwADAARQAwADAAMAA3ADEANAA4AEEAMAAyADAAMAAwADAAMAAwADEANAA1AEIANABCADYAMQA2AEUANgBFADYANQA3ADIAMgBDADIAMAAzADEAMwA5ADMANAAzADMAMgAwADIAMwAzADQAMwA0ADMAMQA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (1943) original report on autism, not only did he
describe social and language impairments, but he also highlighted
the anxious behavior exhibited in his initial sample of children.
Fear of threatening events is considered a common experience among
primates and an adaptive response in humans
RAAyADIAQwA4AEEAMAA0ADAAMAA3AEEAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA0ADkAMAAyADAAMAAwADAAMAAwADEARAA4ADQAMwBGAEEANwBEADMAMAAyADAAMAAwADAAMAAwADEANgA1AEIANQAyADYANQA3ADkANgBFADYARgA2AEMANgA0ADcAMwAyAEMAMgAwADMAMQAzADkAMwA5ADMANAAyADAAMgAzADMANAAzADQAMwAzADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (Reynolds and Richmond 1994). Anxiety, on the other
hand, is an emotional response evoked when an individual perceives
a situation as threatening even in the absence of direct danger. We
would suggest that dysregulation of the amygdala might manifest
itself in the individual with autism as alterations either of fear
or anxiety. Although the presence of anxiety has been alluded to in
descriptions (American Psychological Association 1994) and
classifications of autism
QgBFADEAQQBGADQANgA2ADAAMAA3AEEAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA0AEMAMAAyADAAMAAwADAAMAAwADEAMAAwADAAMQBGADAAMgBEADAAMAAyADAAMAAwADAAMAAwADEANgA1AEIANQAyADYANQA3ADMANgAzADYARgA3ADIANgBDADYAMQAyAEMAMgAwADMAMQAzADkAMwA4ADMAOAAyADAAMgAzADMAMQAzADAAMwA0ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (Rescorla 1988,
NAAyAEMAQwAyAEQAQwBBADAAMAA3ADIAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA0AEUAMAAyADAAMAAwADAAMAAwADEANgAwADcAQQA5AEIARgA2ADIAMAAyADAAMAAwADAAMAAwADEAMgA1AEIANQA3ADYAOQA2AEUANgA3ADIAQwAyADAAMwAxADMAOQAzADcAMwA5ADIAMAAyADMAMwA0ADMANAAzADAANQBEADAAMAAwAEUAMAAwADAAMAAwADAA
ADDIN ENRfu Wing and Gould 1979), the characteristics and
pervasiveness of this has not been well studied. However, recent
studies suggest that anxiety is an extremely common feature of the
autism spectrum disorders.
Muris et al.
NAA5ADEAOABCADUAOABEADAAMAA3ADIAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA1ADAAMAAyADAAMAAwADAAMAAwADEANAAwADEARgA2ADAAMAA4ADYAMAAyADAAMAAwADAAMAAwADEAMgA1AEIANABEADcANQA3ADIANgA5ADcAMwAyAEMAMgAwADMAMQAzADkAMwA5ADMAOAAyADAAMgAzADMANQAzADIANQBEADAAMAAwAEUAMAAwADAAMAAwADAA
ADDIN ENRfu (1998) examined the presence of co-occurring anxiety
symptoms in 44 children with autism spectrum disorder. The sample
included 15 children with autism, and 29 with pervasive
developmental disorder-not otherwise specified (PDD-NOS). They
found that 84.1% of the children met criteria for at least one
anxiety disorder. In descending order, the percentage of children
meeting diagnostic criteria for an anxiety disorder were as
follows: simple phobia (63.6%), agoraphobia (45.5%), separation
anxiety (27.3%), overanxious (22.7%), social phobia (20.5%),
avoidant disorder (18.2%), obsessive-compulsive disorder (11.4%),
and panic disorder (9.1%). While the authors raised the caveat that
anxiety symptoms were assessed via parental interview, they noted
that parents often underreport internalizing symptoms, such an
anxiety.
More recently, Gillott et al.
NwBCADUANgBBADcANQA1ADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA1ADMAMAAyADAAMAAwADAAMAAwADEANgAwADcAMgAyADAANAA0ADIAMAAyADAAMAAwADAAMAAwADEANAA1AEIANAA3ADYAOQA2AEMANgBDADYARgA3ADQANwA0ADIAQwAyADAAMwAyADMAMAAzADAAMwAxADIAMAAyADMAMwAxADMAMQA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (2001) compared high-functioning children with autism
to two control groups including children with specific language
impairment and normally developing children on measures of anxiety
and social worry. Children with autism were found to be more
anxious on both indices. In fact, four of the six factors on the
anxiety scale were elevated with obsessive-compulsive disorder and
separation anxiety showing the highest elevations.
These studies do not provide much insight into the pervasiveness of
anxiety in autism. Both clinical and parental reports indicate that
not all children with autism demonstrate symptoms of anxiety. The
DSM-IV summarizes that children with autism may exhibit a lack of
fear in response to real dangers, and an excessive fearfulness in
response to harmless objects (APA 1994, p. 68). Wing and Gould
NAAyAEMAQwBDAEEAQwBBADAAMAA3ADIAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA1ADYAMAAyADAAMAAwADAAMAAwADEANgAwADcAQQA5AEIARgA2ADIAMAAyADAAMAAwADAAMAAwADEAMgA1AEIANQA3ADYAOQA2AEUANgA3ADIAQwAyADAAMwAxADMAOQAzADcAMwA5ADIAMAAyADMAMwA0ADMANAAzADAANQBEADAAMAAwAEUAMAAwADAAMAAwADAA
ADDIN ENRfu (1979) highlighted the heterogeneity in the occurrence
of anxiety in their classification system. Specifically, the
active-but-odd subtype tend to exhibit extreme reactions to social
situations, whereas the aloof subtype may be completely oblivious
to environmental changes. Rescorla
QgBFADEAQQAxADEANgA2ADAAMAA3AEEAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARQAwADAANQBCAEQAMQA1ADgAMAAyADAAMAAwADAAMAAwADEAMAAwADAAMQBGADAAMgBEADAAMAAyADAAMAAwADAAMAAwADEANgA1AEIANQAyADYANQA3ADMANgAzADYARgA3ADIANgBDADYAMQAyAEMAMgAwADMAMQAzADkAMwA4ADMAOAAyADAAMgAzADMANAAzADMAMwA0ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (1988), conducted a factor and cluster analysis using
the Child Behavior Checklist (CBCL,
RQA5ADgARQAxADQARgBDADAAMAA3AEMAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARgAwADAANQBCAEQAMQA1AEIAMAAyADAAMAAwADAAMAAwADEAMQAwADAAMwBBAEQAMgBGADYAMAAyADAAMAAwADAAMAAwADEANwA1AEIANAAxADYAMwA2ADgANgA1ADYARQA2ADIANgAxADYAMwA2ADgAMgBDADIAMAAzADEAMwA5ADMAOQAzADEAMgAwADIAMwAzADQAMwA0ADMANAA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu Achenbach 1991), a general instrument of childhood
behavior, to distinguish boys with autism from other disorders.
Among many differences, the analysis demonstrated that the more
severe cases of autism were distinguished from the milder ones
based on the presence or absence of anxiety.
The Amygdala and Anxiety
A number of recent studies have provided evidence that the amygdala
may be dysregulated in emotional disorders such as anxiety and
depression
OQA4AEEAQgA0ADYANgBBADAAMAA3AEEAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARgAwADAANQBCAEQAMQA1AEUAMAAyADAAMAAwADAAMAAwADEANwAwAEYAOQAwADEAOQBDADQAMAAyADAAMAAwADAAMAAwADEANgA1AEIANAA0ADYAMQA3ADYANgA5ADYANAA3ADMANgBGADYARQAyAEMAMgAwADMAMQAzADkAMwA5ADMAOQAyADAAMgAzADMANAAzADMAMwA1ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (Davidson et al. 1999). Tillfors et al.
NQA4AEMAMAAwAEMAMwBEADAAMAA3AEEAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARgAwADAANQBCAEQAMQA2ADEAMAAyADAAMAAwADAAMAAwADEANwAwAEUANAA0ADAARAA4ADQAMAAyADAAMAAwADAAMAAwADEANgA1AEIANQA0ADYAOQA2AEMANgBDADYANgA2AEYANwAyADcAMwAyAEMAMgAwADMAMgAzADAAMwAwADMAMQAyADAAMgAzADMANAAzADEAMwA3ADUARAAwADAAMABFADAAMAAwADAAMAAwAA==
ADDIN ENRfu (2001), for example, demonstrated increased blood flow
in the amygdala in social phobics anticipating a public
presentation. Recently, Thomas et al.
OAA4ADYAQgA4ADUAQgA4ADAAMAA3ADYAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARgAwADAANQBCAEQAMQA2ADMAMAAyADAAMAAwADAAMAAwADEANQAwADMAOQAxADAAMQA2ADgAMAAyADAAMAAwADAAMAAwADEANAA1AEIANQA0ADYAOAA2AEYANgBEADYAMQA3ADMAMgBDADIAMAAzADIAMwAwADMAMAAzADEAMgAwADIAMwAzADQAMwAxADMANgA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (2001) used fearful faces as probes and demonstrated
that the amygdala of anxious children showed heightened activity in
the amygdala. De Bellis
MgBDADEAQQAyADcAOAA3ADAAMAA3AEMAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADcAMgA2ADYAMAAwAEIAOQAyADYARAAzADQARgAwADAANQBCAEQAMQA2ADcAMAAyADAAMAAwADAAMAAwADEAOAAxAEMAQwA4ADAAMgBCADQAMAAyADAAMAAwADAAMAAwADEANwA1AEIANAA0ADYANQAyADAANAAyADYANQA2AEMANgBDADYAOQA3ADMAMgBDADIAMAAzADIAMwAwADMAMAAzADAAMgAwADIAMwAzADQAMwAxADMAOAA1AEQAMAAwADAARQAwADAAMAAwADAAMAA=
ADDIN ENRfu (2000) also showed that the right amygdala of children
with generalized anxiety disorder was larger than age matched
controls. These findings are consistent with the results of our
studies in nonhuman primates in that removal of the amygdala
produced animals that were less fearful of inanimate objects as
well as other monkeys.
Conclusions
The amygdala has been proposed to play an essential role in the
elucidation of normal social behavior. And, its dysfunction has
been proposed to play a role in the social pathology of autism.
Studies both in the rhesus monkey and data from human subjects with
bilateral lesions of the amygdala indicate that the amygdala is not
essential for many facets of normal social interaction. Rather, it
appears that the amygdala may have a more selective role in
detecting threats in the environment. If this proves to be correct,
it would be unlikely that dysfunction of the amygdala alone could
provide the substrate for the impairments of social interaction
that are a hallmark feature of autism. If, however, the amygdala is
indeed dysfunctional in autism, this could contribute to the
abnormalities of fear and anxiety that appear to be a common
feature of autism. If this were the case, one might expect the
amygdala to be hyperfunctional in autism rather than hypofunctional
as predicted by the current theories of the role of the amygdala in
autism.
Acknowledgements
This original research described in this paper was supported, in
part, by grants from the National Institute of Mental Health and by
the base grant of the California National Primate Research Center.
This work was also supported through the Early Experience and Brain
Development Network of the MacArthur Foundation.
Literature Cited
MQAyADUAMgBGADkAMgA2ADAAMAA0ADIAQQAzADYAOAA1ADYAMQAwADAAMAAwADgAMwAyAEMARgA2ADUANgBFADYAMgA2ADIAMAAwAEIAOQAyADYARAAzADYAMAAwADAANQBCAEQANQA2ADcAMAAyADAAMAAwADAAMQA2ADkAQgAxAEQAQQAyAEUARgBCAEYAMAAwADAAMAAwADAA
ADDIN ENBbu Abell F, Krams M, Ashburner J, et al. 1999 The
neuroanatomy of autism: a voxel-based whole brain analysis of
structural scans. Neuroreport 10:1647-1651
Achenbach TM 1991 Manual for the child behavior checklist/4-18 and
1991 profile. University of Vermont, Burlington
Adolphs R, Tranel D, Damasio AR 1998 The human amygdala in social
judgment. Nature 393:470-474
Adolphs R, Tranel D, Damasio H, Damasio A 1994 Impaired recognition
of emotion in facial expressions following bilateral damage to the
human amygdala. Nature 372:669-672
Adolphs R, Tranel D, Damasio H, Damasio AR 1995 Fear and the human
amygdala. J Neurosci 15:5879-5891
Amaral DG, Price JL, Pitkanen A, Carmichael T 1992 Anatomical
organization of the primate amygdaloid complex. In: Aggleton J (ed)
The amygdala: Neurobiological aspects of emotion, memory, and
mental dysfunction. Wiley-Liss, New York p 1-66
Ashwin C, Baron-Cohen S, Fletcher P, Bullmore E, Wheelwright S 2001
fMRI study of social cognition in people with and without
autism.
(International Meeting for Autism Research abstr B-32)
Aylward EH, Minshew NJ, Goldstein G, et al. 1999 MRI volumes of
amygdala and hippocampus in non-mentally retarded autistic
adolescents and adults. Neurology 53:2145-2150
Bachevalier J 1994 Medial temporal lobe structures and autism: A
review of clinical and experimental findings. Neuropsychologia
32:627-648
Bachevalier J 1996 Brief report: Medial temporal lobe and autism: A
putative animal model in primates. J Autism and Dev Disord
26:217-220
Baron-Cohen S, Ring HA, Bullmore ET, Wheelwright S, Ashwin C,
Williams SC 2000 The amygdala theory of autism. Neurosci Biobehav
Rev 24:355-364
Bauman M, Kemper TL 1985 Histoanatomic observations of the brain in
early infantile autism. Neurology 35:866-874
Brothers L 1990 The social brain: A project for integrating primate
behaviour and neurophysiology in a new domain. Concepts in
Neuroscience 1:27-51
Brown S, Schafer EA 1888 An investigation into the functions of the
occipital and temporal lobes of the monkey's brain. Phil Trans
Royal Soc London: Biological Sciences 179:303-327
Corkin S, Amaral DG, Gonzalez RG, Johnson KA, Hyman BT 1997 H.M.'s
medial temporal lobe lesion: Findings from magnetic resonance
imaging. J Neurosci 17:3964-3979
Davidson RJ, Abercrombie H, Nitschke JB, Putnam K 1999 Regional
brain function, emotion and disorders of emotion. Curr Opin
Neurobiol 9:228-234
De Bellis MD, Casey BJ, Dahl RE et al. 2000 A pilot study of
amygdala volumes in pediatric generalized anxiety disorder. Biol
Psychiatry 48:51-57
Dicks D, Myers RE, Kling A 1968 Uncus and amygdala lesions: Effects
on social behavior in the free-ranging rhesus monkey. Science
165:69-71
Emery NJ, Capitanio JP, Mason WA, Machado CJ, Mendoza SP, Amaral DG
2001 The effects of bilateral lesions of the amygdala on dyadic
social interactions in rhesus monkeys (Macaca mulatta). Behav
Neurosci 115:515-544
Gillott A, Furniss F, Walter A 2001 Anxiety in high-functioning
children with autism. Autism 5:277-286
Howard MA, Cowell PE, Boucher J, et al. 2000 Convergent
neuroanatomical and behavioural evidence of an amygdala hypothesis
of autism. Neuroreport 11:2931-2935
Kanner L 1943 Autistic disturbances of affective contact. Nervous
Child 2:217-250
Kling A, Cornell R 1971 Amygdalectomy and social behavior in the
caged stumped-tailed macaque (Macaca speciosa). Folia Primat
14:190-208
Kling A, Steklis HD 1976 A neural substrate for affiliative
behavior in nonhuman primates. Brain, Behavior and Evolution
13:216-238
Kling A, Lancaster J, Benitone J 1970 Amygdalectomy in the
free-ranging vervet (Cercopithecus aethiops). J Psychiatr Res
7:191-199
Kluver H, Bucy PC 1938 An analysis of certain effects of bilateral
temporal lobectomy in the rhesus monkey, with special reference to
"psychic blindness". J Psychology 5:33-54
Kluver H, Bucy PC 1939 Preliminary analysis of functions of the
temporal lobes in monkeys. Arch of Neurol and Psychiatry
42:979-997
Muris P, Steerneman P, Merckelbach H, Holdrinet I, Meesters C 1998
Comorbid anxiety symptoms in children with pervasive developmental
disorders. J Anxiety Disord 12:387-393
Pierce K, Muller RA, Ambrose J, Allen G, Courchesne E 2001 Face
processing occurs outside the fusiform 'face area' in autism:
evidence from functional MRI. Brain 124:2059-2073
Prather MD, Lavenex P, Mauldin-Jourdain ML, et al. 2001 Increased
social fear and decreased fear of objects in monkeys with neonatal
amygdala lesions. Neuroscience 106:653-658
Rescorla L 1988 Cluster analytic identification of autistic
preschoolers. J Autism Dev Disord 18:475-492
Reynolds CR, Richmond BO 1994 Revised childrens manifest anxiety
scale. Western Psychological Services, Los Angeles p 1-45
Rosvold H, Mirsky A, Pribram K 1954 Influence of amygdalectomy on
social behavior in monkeys. J Comp and Phys Psychol
47:173-178
Thomas KM, Drevets WC, Dahl RE, et al. 2001 Amygdala response to
fearful faces in anxious and depressed children. Arch Gen
Psychiatry 58:1057-1063
Tillfors M, Furmark T, Marteinsdottir I, et al. 2001 Cerebral blood
flow in subjects with social phobia during stressful speaking
tasks: a PET study. Am J Psychiatry 158:1220-1226
Wing L, Gould J 1979 Severe impairments of social interaction and
associated abnormalities in children: epidemiology and
classification. J Autism Dev Disord 9:11-29.