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Neuroimaging has revealed numerous atypical functional connectivity of default mode network (DMN) dedicated to social communications (SC) in autism spectrum disorder (ASD), yet their nature and directionality remain unclear. Here, preschoolers with autism received physical intervention from a 12-week mini-basketball training program (12W-MBTP). Therefore, the directionality and nature of regional interactions within the DMN after the intervention are evaluated while assessing the impact of an intervention on SC. Based on the results of independent component analysis (ICA), we applied spectral dynamic causal modeling (DCM) for participants aged 3–6 years (experimental group,  N  = 17, control group,  N  = 14) to characterize the longitudinal changes following intervention in intrinsic and extrinsic effective connectivity (EC) between core regions of the DMN. Then, we analyzed the correlation between the changes in EC and SRS-2 scores to establish symptom-based validation. We found that after the 12W-MBTP intervention, the SRS-2 score of preschoolers with ASD in the experimental group was decreased. Concurrently, the inhibitory directional connections were observed between the core regions of the DMN, including increased self-inhibition in the medial prefrontal cortex (mPFC), and the changes of EC in mPFC were significantly correlated with change in the social responsiveness scale-2 (SRS-2) score. These new findings shed light on DMN as a potential intervention target, as the inhibitory information transmission between its core regions may play a positive role in improving SC behavior in preschoolers with ASD, which may be a reliable neuroimaging biomarker for future studies.   Clinical Trial Registration:  This study registered with the Chinese Clinical Trial Registry (ChiCTR1900024973) on August 05, 2019.

Alteration of Effective Connectivity in the Default Mode Network of Autism After an Intervention