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.

Dynamic functional connectivity analysis reveals decreased variability of the default-mode network in developing autistic brain.

Accumulating neuroimaging evidence suggests that abnormal functional connectivity of the default mode network (DMN) contributes to the social-cognitive deficits of autism spectrum disorder (ASD). Although most previous studies relied on conventional functional connectivity methods, which assume that connectivity patterns remain constant over time, understanding the temporal dynamics of functional connectivity during rest may provide new insights into the dysfunction of the DMN in ASD. In this work, dynamic functional connectivity analysis based on sliding time window correlation was applied to the resting-state functional magnetic resonance imaging data of 28 young children with ASD (age range: 3-7 years) and 29 matched typically developing controls (TD group). In addition, k-means cluster analysis was performed to identify distinct temporal states based on the spatial similarity of each functional connectivity pattern. Compared with the TD group, young children with ASD showed decreased dynamic functional connectivity variance between the posterior cingulate cortex (PCC) and the right precentral gyrus, which is negatively correlated with social motivation and social relating. Cluster analysis revealed significant differences in functional connectivity patterns between the ASD and TD groups in discrete temporal states. Our findings reveal that atypical dynamic interactions between the PCC and sensorimotor cortex are associated with social deficits in ASD. Results also highlight the critical role of PCC in the social-cognitive deficits of ASD and support the concept that understanding the dynamic neural interactions among brain regions can provide insights into functional abnormalities in ASD. Autism Research 2018, 11: 1479-1493. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Social cognitive dysfunction in autism spectrum disorder (ASD) is associated with dysfunction of the default mode network (DMN), a set of brain areas involved in various domains of social processing. We found that decreases in the dynamic functional connectivity variance between the posterior cingulate cortex and the sensorimotor cortex are associated with deficits in social motivation and social relating in young children with ASD. This result suggests that aberrations in the DMN and its dynamic interactions with other networks contribute to atypical integration of information with respect to self and others.