Decreased interhemispheric functional connectivity rather than corpus callosum volume as a potential biomarker for autism spectrum disorder.

Previous studies have implicated both structural and interhemispheric functional connectivity alterations in autism spectrum disorder (ASD) although findings are inconsistent. There is evidence that connectivity between corresponding regions in each hemisphere (homotopic) may be of particular importance and therefore the present study used the Autism Brain Imaging Data Exchange data to investigate ASD-related resting-state and structural alterations as well as associations with symptom severity (Autism Diagnostic Observation Schedule - ADOS). We employed a voxel-mirrored homotopic connectivity analysis to compare interhemispheric functional connectivity in 409 ASD and 455 typically developing subjects. Additionally, voxel-based morphology was used to investigate volumetric differences in the corpus callosum, the major commissure for interhemispheric communication. ASD subjects demonstrated significant reductions in interhemispheric functional connections between regions in the default mode network (medial prefrontal, posterior cingulate and precuneus), salience network (anterior cingulate and insula), mirror neuron/motor systems (inferior frontal gyrus, inferior parietal lobule, precentral gyrus, supplementary motor area), thalamus and auditory (superior temporal gyrus) and visual systems (lingual, fusiform and inferior occipital gyri). A support vector machine analysis based on interhemispheric connectivity (but not all homotopic) revealed an average classification accuracy of 88.70% for distinguishing ASD from controls across different sites. In ASD subjects symptom severity as measured by ADOS was negatively associated with posterior cingulate, insula and superior temporal gyrus homotopic functional connectivity. While ASD subjects displayed reduced anterior and posterior callosal volumes they were not associated with either ADOS scores or functional connectivity changes. Our findings suggest that reduced interhemispheric connectivity involving homotopic regions may be a potential biomarker for ASD with bilateral posterior cingulate, insula and superior temporal gyrus connections being associated with symptom severity.