Impaired effective functional connectivity in the social preference of children with autism spectrum disorder

The medial prefrontal cortex (mPFC), amygdala (Amyg), and nucleus accumbens (NAc) have been identified as critical players in the social preference of individuals with ASD. However, the specific pathophysiological mechanisms underlying this role requires further clarification. In the current study, we applied Granger Causality Analysis (GCA) to investigate the neural connectivity of these three brain regions of interest (ROIs) in patients with ASD, aiming to elucidate their associations with clinical features of the disorder. Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from the ABIDE II database, which included 37 patients with ASD and 50 typically developing (TD) controls. The mPFC, Amyg, and NAc were defined as ROIs, and the differences in fractional amplitude of low-frequency fluctuations (fALFF) within the ROIs between the ASD and TD groups were computed. Subsequently, we employed GCA to investigate the bidirectional effective connectivity between the ROIs and the rest of the brain. Finally, we explored whether this effective connectivity was associated with the social responsiveness scale (SRS) scores of children with ASD. The fALFF values in the ROIs were reduced in children with ASD when compared to the TD group. In terms of the efferent connectivity from the ROIs to the whole brain, the ASD group exhibited increased connectivity in the right cingulate gyrus and decreased connectivity in the right superior temporal gyrus. Regarding the afferent connectivity from the whole brain to the ROIs, the ASD group displayed increased connectivity in the right globus pallidus and decreased connectivity in the right cerebellar Crus 1 area and left cingulate gyrus. Additionally, we demonstrated a positive correlation between effective connectivity derived from GCA and SRS scores. Impairments in social preference ASD children is linked to impaired effective connectivity in brain regions associated with social cognition, emotional responses, social rewards, and social decision-making. This finding further reveals the potential neuropathological mechanisms underlying ASD.