Structural Anatomy of the Social Brain in Autism: An Activation Likelihood Meta-Analysis

Background: Voxel-based morphometry (VBM) studies of autism, that measure cortical volume and thickness, have provided mixed and occasionally conflicting results. This may in part be due to a large extent of heterogeneity among the study samples. Nevertheless, reports of grey and white matter volumetric differences in regions associated with social cognition and executive function have been relatively consistent. The goal of this study is to characterize the anatomical differences within social brain regions in autism using activation likelihood estimation (ALE) meta-analysis of structural morphometry studies in autism.

Objectives: To consolidate the patterns of anatomical alterations in the brains of individuals with ASD through a comprehensive meta-analysis of structural neuroimaging studies.

Methods: Twenty-three structural neuroimaging studies of autism that met the following inclusion criteria were considered for this meta-analysis: 1) whole-brain VBM method of analyses; 2) participants with IQs > 70; and 3) participants had no comorbid conditions. The foci of results from increased and decreased grey and white matter contrasts between ASD and control participants from these studies were used to conduct ALE using GingerALE 2.3 (Laird et al., 2005; Laird, Lancaster, & Fox., 2008; Turkeltaub et al., 2002). Two analyses of pooled grey and white matter, one of increased and one of decreased, were conducted and reported at a false discovery rate (FDR) of 0.05 with a minimum cluster size of 200mm3 for significant clusters as the threshold (Turkeltaub, 2012). Maxima results were verified using the 2mm MNI 152 brain template in FSL (Smith et al., 2004; Woolrich et al., 2009; Jenkinson et al., 2012).

Results: Clusters of increased cortical matter in ASD, relative to controls, were found in the right medial prefrontal cortex (MPFC), premotor cortex, left frontal pole, superior frontal gyrus (SFG), superior temporal gyrus (STG), and fusiform gyrus. Significant clusters of decreased cortical matter in ASD relative to controls were found in the left anterior cingulate cortex (ACC), inferior occipital gyrus (IOG), angular, and postcentral gyrus. Increases were also found in subcortical structures like the left caudate and putamen and right cerebellar vermis. Other structures that showed group differences included the right amygdala and the white matter underlying the ACC.

Conclusions: Significant alterations in grey and white matter were primarily found in clusters within areas (e.g., ACC, MPFC, Amygdala, STG, Caudate, Fusiform, Putamen, and Cerebellum) associated with social and executive processing, both of which are impaired in ASD. These findings provide further insight into functional deficits within social brain areas in ASD by providing evidence of the underlying anatomical abnormalities. This meta-analysis, which strictly controlled for IQ and comorbid conditions, to our knowledge is the first one to apply such stringent criteria to morphometric meta-analysis in autism.