Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis

Abstract

Background: Functional neuroimaging studies of autism spectrum disorders (ASD) have examined social and nonsocial paradigms, although rarely in the same study. Here, we provide an objective, unbiased survey of functional brain abnormalities in ASD, related to both social and nonsocial processing.

Methods: We conducted two separate voxel-wise activation likelihood estimation meta-analyses of 39 functional neuroimaging studies consisting of 24 studies examining social processes (e.g., theory of mind, face perception) and 15 studies examining nonsocial processes (e.g., attention control, working memory). Voxel-wise significance threshold was p<.05, corrected by false discovery rate.

Results: Compared with neurotypical control (NC) subjects, ASD showed greater likelihood of hypoactivation in two medial wall regions: perigenual anterior cingulate cortex (ACC) in social tasks only and dorsal ACC in nonsocial studies. Further, right anterior insula, recently linked to social cognition, was more likely to be hypoactivated in ASD in the analyses of social studies. In nonsocial studies, group comparisons showed greater likelihood of activation for the ASD group in the rostral ACC region that is typically suppressed during attentionally demanding tasks.

Conclusions: Despite substantial heterogeneity of tasks, the rapidly increasing functional imaging literature showed ASD-related patterns of hypofunction and aberrant activation that depended on the specific cognitive domain, i.e., social versus nonsocial. These results provide a basis for targeted extensions of these findings with younger subjects and a range of paradigms, including analyses of default mode network regulation in ASD.

Figure 1

Article Selection Flow. Number of studies selected and reasons for exclusion.

Figure 2

Medial-wall task-based group difference emerging from the separately conducted group subtractions including social studies only (orange) and non-social studies only (purple). The top panel shows greater probability of activation in neurotypical controls (NC) compared to autism spectrum disorders (ASD) in a cluster centered at the perigenual anterior cingulate cortex (ACC; x= 0, y= 47, z= 6) and posterior cingulate (x= 0, y= −49 , z= 18) for the analysis limited to social studies (red orange), while greater activation in a cluster centered at the pre-supplementary motor area (x= 0, y=19, z= 46) resulted from the analysis limited to non-social studies (blue-violet). The bottom panel shows ASD > NC activation likelihood estimate maps in a cluster centered in ventral ACC (x= 0, y= 40, z= 8), and in the supplementary motor area (x= 0, y= −10, z= 58) appearing only in the analysis of non-social studies. Images are displayed in neurological convention (right is right).

Figure 3

For social studies, neurotypical controls (NC) showed greater likelihood of activation in the right anterior insula when compared to participants with autism spectrum disorders (orange; x= 47, y= 11, z= −6). For non-social studies, NC exhibited greater activation in the middle frontal gyrus (purple; x = 40; y = 13; z = 27; x= 42; y=27; z= 26). Image displayed in neurological convention.