Neural Correlations Between Executive Function and Social Function in Autism Spectrum Disorder: A Mediation Analysis of fMRI

Background: Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders with high heterogeneity. The co-occurrence of social deficits and executive dysfunction is frequently reported in individuals with ASD. The present study evaluated the association between social deficit and executive dysfunction in ASD subjects and explored the underlying neural mechanisms that may mediate this association.Methods: A total of 186 patients with ASD, 5-18 years old (10.25 ± 2.72 years old), from the Autism Brain Imaging Data Exchange II database were enrolled in the final sample. Social function was evaluated by the parent-reported Social Responsiveness Scale (SRS), and executive function (EF) was measured by the parent-reported Behavior Rating Inventory of Executive Function (BRIEF). We selected bilateral amygdala, caudate and putamen as regions of interests, and used the region of interest-based resting-state functional connectivity (FC) analysis to explore the shared and specific brain mechanisms underlying EF and social function. The association analysis of EF, social deficits and FC was conducted using linear regression by controlling covariates, including age, gender, full IQ, handedness, and current medication. Results: The result showed that social functions in ASD children and adolescents were positively associated with EF (r = 0.612, p <0.01). Additionally, 14 and 21 FC links were associated with social deficits and executive dysfunction separately, in which five FC links (right amygdala and right inferior frontal gyrus opercular part, left caudate and right supramarginal gyrus, left putamen and right superior frontal gyrus medial orbital, right putamen and left gyrus rectus, and right putamen and left paracentral lobule) were simultaneously correlated with social function and EF in ASD subjects. We also found that connectivity between the right amygdala and right inferior frontal gyrus mediated the effects of EF on social deficit. Limitations: All the included participants in the present study were ASD patients and male participants, which might limit the generalization of our findings.Conclusion: We found a significant association between social deficits and executive dysfunction in ASD subjects. This association might be mediated by FC between the right amygdala and the right inferior frontal gyrus, which may further illustrate the underlying mechanism of ASD and co-occurrence of social deficits and executive dysfunction in this population.