Social brain dysfunctionality in individuals with autism spectrum disorder and their first-degree relatives: An activation likelihood estimation meta-analysis

The social brain hypothesis is regarded as a powerful theory to understand social cognition. Individuals with autism spectrum disorder (ASD) have specific deficits in social and communicative behavior, but the exact relationship between these deficits and abnormalities in the social brain remains unclear. The high heritability of this disorder makes it important to focus on the first-degree relatives of those affected. Research focusing on genetically at-risk (yet healthy) relatives of patients with ASD is critical to the study of neuroimaging endophenotypes. We conducted a voxel-wise activation likelihood estimation (ALE) meta-analysis of 9 functional neuroimaging studies published during the period from 2006 to 2018. These studies included 200 individuals with ASD, 216 unaffected family members (UF), and 235 typical development controls (TD). The voxel-wise significance threshold was p < 0.01 (uncorrected p = 0.001).The ALE meta-analyses showed hyperactivation in the inferior frontal gyrus (IFG) and superior temporal gyrus (STG) among individuals with ASD and UF, compared with TD individuals. Group comparisons showed greater likelihood of hyperactivation in the amygdala for ASD, compared with UF and TD.