Abstract
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.
Highlights
Autism spectrum disorder (ASD) is an early onset developmental disorder which persists throughout life and has an increasing prevalence rate over the last decades, with a general average of around 1% of the population being affected [1]
Based on inter-hemispheric, but the homotopic resting state functional connectivity (rsFC) changes, pattern classification analysis achieved an average accuracy of 88.70% for distinguishing ASD subjects from typically developing (TD) controls across sites [23], which is slightly higher than a previous study (82.87%) using the same pattern classification approach based on whole brain-wide rsFC changes [11], there is no direct statistical comparison
Correlations between the inter-hemispheric rsFC changes and symptom severity in social impairments and the superior classification performance in distinguishing ASD subjects from TD controls based on the interhemispheric rsFC changes together suggest that inter-hemispheric rsFC changes, a typical form of long-distance connection, may be a more promising biomarker for ASD diagnosis than whole brain wide rsFC and structural abnormalities
Summary
Autism spectrum disorder (ASD) is an early onset developmental disorder which persists throughout life and has an increasing prevalence rate over the last decades, with a general average of around 1% of the population being affected [1]. The human callosal dysgenesis studies reporting normal interhemispheric rsFC would have been partial Another gene knockdown study in rodents has further emphasized the importance of inter-hemispheric connectivity in ASD symptomatology, such that permanent deficits in callosal projections and associated inter-hemispheric connections caused by downregulation of Wnt signaling induced ASD-like impairments, including social interaction deficits and repetitive motor behavior [79]. Using the ABIDE database, another voxel-based study using a graph theory analysis approach examined inter- and intra-hemispheric rsFC in ASD subjects and reported that they had reduced inter and intra-hemispheric functional connectivity strength in regions of the DMN and the visual system relative to TD subjects [21]. Using only data from children included in the ABIDE database, a more recent study using a sliding-window analysis has shown increased inter- and intra-hemispheric
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