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Autism spectrum disorder (ASD) is an early onset developmental disorder which persists throughout life and is increasing in prevalence over the last few decades. Given its early onset and variable cognitive and emotional functional impairments, it is generally challenging to assess ASD individuals using task-based behavioral and functional MRI paradigms. Consequently, resting state functional MRI (rs-fMRI) has become a key approach for examining ASD-associated neural alterations and revealed functional alterations in large-scale brain networks relative to typically developing (TD) individuals, particularly those involved in social-cognitive and affective processes. Recent progress suggests that alterations in inter-hemispheric resting state functional connectivity (rsFC) between regions in the 2 brain hemispheres, particularly homotopic ones, may be of great importance. Here we have reviewed neuroimaging studies examining inter-hemispheric rsFC abnormities in ASD and its associations with symptom severity. As an index of inter-hemispheric functional connectivity, we have additionally reviewed previous studies on corpus callosum (CC) volumetric and fiber changes in ASD. There are converging findings on reduced inter-hemispheric (including homotopic) rsFC in large-scale brain networks particularly in posterior hubs of the default mode network, reduced volumes in the anterior and posterior CC, and on decreased FA and increased MD or RD across CC subregions. Associations between the strength of inter-hemispheric rsFC and social impairments in ASD together with their classification performance in distinguishing ASD subjects from TD controls across ages suggest that the strength of inter-hemispheric rsFC may be a more promising biomarker for assisting in ASD diagnosis than abnormalities in either brain wide rsFC or brain structure.

Reduced Inter-hemispheric Resting State Functional Connectivity and Its Association With Social Deficits in Autism