Chapter I: Introduction
1.2 Background and Context
1.2.5 Abnormal brain structure and connectivity in autism
Altered brain connectivity and neuroanatomical differences are thought to contribute to many of the symptoms observed in individuals with ASD, particularly in the area of social behavior.
Current theories regarding brain abnormalities in people with autism emphasize differences in
connectivity between regions, or anomalies in several functionally related structures that can affect a number of cognitive processes and result in the behaviors commonly observed in people with ASD. Early abnormal overgrowth is found in regions underlying functions that are known to be impaired in autism, such as language, social skills, and cognitive skills.
Courchesne (2004) reported abnormal overgrowth in both white and grey cerebral matter—
particularly dorsolateral and medialfrontal regions—and white cerebellar matter. In addition, atypical growth of the cerebellum is believed to play a role in cognitive and motor dysfunctions that lead to the stereotyped behaviors and reduced exploration commonly reported in children with autism (Courchesne, 2004; Pierce & Courchesne, 2001). Bilateral amygdala enlargement and cerebellar and hippocampal enlargement have also been reported in young children (Courchesne, 2004) and older children (Schumann, 2004) with autism. In particular, the degree of enlargement in the amygdala is closely associated with the severity of impairment in social and communication skills (Munson, Dawson, Abbott, & Faja, 2006), including difficulty recognizing facial expressions (Bachevalier, 2006) and detecting eye gaze (Howard et al., 2000).
Regions that show overgrowth and enlargement in early childhood also show atypically slow growth as well as degeneration and volumetric loss later in life, in some cases. In adolescents and adults with autism, the structures comprising the limbic system—particularly the amygdala, hippocampus, basal ganglia, and prefrontal cortices—are most often implicated in symptoms related to social dysfunction (Uddin, Menon, Young, Ryali, & Chen, 2011).
Amygdala dysfunction is known to contribute to disruptions in face perception, which includes decreased eye movements to key features of the face and a lack of orienting toward social and emotional information. However, the exact nature of this abnormality is unclear. For example, Howard et al. (2000) reported impairment in facial expression recognition associated with an increase in amygdala volume (Howard et al., 2000), whereas Nacewicz et al. (2006) found smaller than normal amygdalae in people with autism (Nacewicz et al., 2006).
Studies have also revealed structural abnormalities in the Superior Temporal Sulcus (STS) in the form of decreased gray matter (Boddaert et al., 2004), and functional abnormalities in the STS in the form of decreased activity during social judgments (Pelphrey, Shultz, Hudac, &
Vander Wyk, 2011). Disruptions in STS function may drive some of the impairments related to social perception in autism, such as communication deficits involving speech perception and difficulty in understanding the intentions of others from movements of the eyes, mouth, and body.
There is increasing evidence that abnormal functioning of the cerebellum also contributes to motor and cognitive impairments in ASD. The cerebellum is a key brain structure for coordination of cognitive functions involving attention and perception. In children with autism, disruptions in cognitive functions are expressed behaviorally in a restricted range of interests, reduced exploration, and stereotyped behaviors—all three of which have been linked to cerebellar dysfunction (Pierce & Courchesne, 2001). Cerebellar function may similarly be compromised in adults with ASD, as there is evidence of increased cerebellar volumes (Sparks et al., 2002), as well as abnormal neuronal densities in this region in the form of decreased numbers of Purkinje cells (Belmonte et al., 2004).
In addition to the structural differences reported in key brain regions, there is substantial evidence of abnormal functional and structural connectivity linking the various brain regions in adults and adolescents with ASD. The hypothesis of underconnectivity proposes that underfunctioning long-range circuitry in people with autism might cause functional deficits in integrating and synchronizing information between related brain regions (Just, Cherkassky, Keller, & Minshew, 2004), and such deficits would cause a wide range of impairments in language processing, motor coordination and social processing. Structural abnormalities appear as atypically high neuronal connectivity between local regions and low neuronal connectivity between brain regions that lie further apart (Courchesne & Pierce, 2005;
Kleinhans et al., 2008), and might also contribute to social impairments observed in autism.
Indeed, one study by Barnea-Goraly and colleagues (2004) reported disruptions in white matter tracts between brain regions in subjects with autism (Barnea-Goraly et al., 2004). These regions—including the ventromedial prefrontal cortex, anterior cingulate gyrus, superior temporal sulcus, and amygdala—are strongly implicated in social functioning. Taken together, these studies demonstrate that the brain regions and functional connectivity involved in social
processing are abnormal in individuals with ASD, and that these abnormalities likely contribute to impairments in face processing.
The role of the amygdala in ASD has also been given greater attention in recent years, as the amygdala’s function or connections may be compromised in autism (Adolphs, 2002; Baron- Cohen et al., 2000). In neurotypicals, the amygdala is an integral part of the cognitive network for processing social information, and modulates social processing by directing visual attention to salient features of the face (Adolphs, 1999; Brothers, 1990). It is therefore important to have a broader understanding of the role the amygdala plays in social processing, which will be discussed next.