The amygdala theory of autism

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Abstract

Brothers (Brothers L. Concepts in Neuroscience 1990;1:27–51) proposed a network of neural regions that comprise the “social brain”, which includes the amygdala. Since the childhood psychiatric condition of autism involves deficits in “social intelligence”, it is plausible that autism may be caused by an amygdala abnormality. In this paper we review the evidence for a social function of the amygdala. This includes reference to the Kluver–Bucy syndrome (which Hetzler and Griffin suggested may serve as an animal model of autism). We then review evidence for an amygdala deficit in people with autism, who are well known to have deficits in social behaviour. This includes a detailed summary of our recent functional magnetic resonance imaging (fMRI) study involving judging from the expressions of another person's eyes what that other person might be thinking or feeling. In this study, patients with autism or AS did not activate the amygdala when making mentalistic inferences from the eyes, whilst people without autism did show amygdala activity. The amygdala is therefore proposed to be one of several neural regions that are abnormal in autism. We conclude that the amygdala theory of autism contains promise and suggest some new lines of research.

Section snippets

The amygdala2

The amygdala is a collection of nuclei. It lies beneath the uncus of the temporal lobe at the anterior end of the hippocampal formation and the inferior horn of the lateral ventricle. It develops relatively early in gestation (embryonic day 30–50), but the separate nuclei do not differentiate until postnatal life, suggesting plasticity in the cues to which the amygdala responds [13]. The old view of the amygdala was that it was mainly only interconnected with the hypothalamus, but evidence over

The amygdala nuclei

The amygdala is not a single entity, but comprises a collection of 13 nuclei, located in the medial temporal lobe [16]. For this reason, the amygdala is sometimes called the amygdaloid complex. Traditional classification of the 13 nuclei are into three clusters:

  • The deep nuclei (lateral, basal, accessory, basal, and paralaminar), which have the greatest interaction with the neocortex and hippocampal formation, and the most connectivity with sensory processing.

  • The superficial regions (medial,

Amygdalar function

As the amygdala has extensive connections with the septal area and hypothalamus and with prefrontal cortex, it influences both drive-related behaviour and the related emotions. In the first of these two roles, the amygdala modulates the hypothalamus. Visceral or somatic activity that can be elicited by stimulating the hypothalamus (such as feeding, or cardiovascular and respiratory changes) can also be elicited by stimulating the amygdala. The role of the amygdala in emotions has also been

Evidence for the importance of the amygdala in primate social behaviour

There are several important lines of evidence implicating the amygdala in primate social behaviour. Extensive reviews exist elsewhere [9]. Here we summarise the main lines of evidence.

Evidence for an amygdala abnormality in autism

We turn now to consider six lines of evidence for an amygdala deficit in autism.

fMRI Study of high functioning autism/asperger syndrome

The following is a summary of the above fMRI study [49]. Six subjects with autism (4m, 2f) were matched for mean age, handedness, IQ, socioeconomic status, and educational level, with 12 subjects in the normal group (6m, 6f). IQ was assessed with the full Wechsler Adult Intelligence Scale (WAIS-R). Subjects were only included if their IQ was in the normal range (i.e. above 85 both in terms of full-scale IQ, and in terms of performance and verbal IQ). Individuals in the clinical group all had a

Other brain areas that might be abnormal in autism

Whilst this paper highlights the necessary role on amygdala abnormality might play in autism, we do not suggest that this is the only abnormal neural region. For example, the case has been made for anomalous functioning in the cerebellum [82], hippocampal formation [83], medial frontal cortex [84], and fronto-limbic connections [85] in autism. Reduced neuron size and increased cell-packing density has also been found in the limbic system, specifically the hippocampus, subiculum, entorhinal

Future work

The literature reviewed in this paper hints at the validity of an amygdala theory of autism, but future studies will be needed to test this more extensively. For example, it will be important to test if the amygdala in autism can be activated to normal levels using other cognitive tasks, or if the deficit associated with the Eyes Task extends to other tests of social intelligence.

Secondly, it is known that the amygdala plays a role in the recognition of fear [45], [46], [91]. Related to this,

Acknowledgements

This work was funded by a grant to SBC, HR, and SCW from the Wellcome Trust, and by a grant to the first author from the Gatsby Foundation. EB is also supported by the Wellcome Trust. We are grateful to Barry Everitt for comments on the first draft of this paper. We have also benefited from review papers by Nathan Emery and colleagues (Emery and Perrett, in press; [93].

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