Attenuated link between the medial prefrontal cortex and the amygdala in children with autism spectrum disorder: Evidence from effective connectivity within the “social brain”

Although accumulating neuroimaging studies have reported that social behavior deficits in children with autism spectrum disorders (ASD) are commonly attributed to the dysfunction of social brain regions underlying social cognition, the dynamic interaction within the social brain network and its association with social deficits remain unclear. Here, resting-state functional magnetic resonance imaging data obtained from Autism Brain Imaging Data Exchange (I and II) were analyzed in 105 children with ASD and 102 demographically matched typically developing controls (TDCs) (age range: 7-12 years old). Term-based meta-analysis combined the prior reference and anatomical labeling were used to define the regions of interests of the social brain network, and multivariate Granger causality analysis with blind deconvolution was employed to assess the effective connectivity within the social brain network in the ASD and TDC groups. Between-group comparison revealed significantly attenuated effective connectivity from the medial prefrontal cortex (mPFC) to the bilateral amygdala in children with the ASD group compared with TDC group. In addition, raw values of the effective connectivity from the mPFC to the bilateral amygdala were used to predict social deficits in ASD. Our findings indicate the impaired mPFC-amygdala pathway and its association with social deficits in children with ASD and provide a new perspective into the neuropathology of the developing autistic brain.