Interhemispheric Resting-State Functional Connectivity and Corpus Callosum Volume Changes in Autism

Background: Autism spectrum disorder (ASD) has been associated with a number of potential structural and functional brain biomarkers using both region of interest and brain-wide approaches. A number of previous studies have suggested that reductions in functional interhemispheric connectivity and corpus callosum volume, may be associated with ASD¹, although this remains to be fully established in large datasets.

Objectives: We investigated whether resting-state interhemispheric functional connectivity and corpus callosum volumes were altered in ASD compared to healthy control subjects and if they were associated with symptom severity.

Methods: The present study used resting state fMRI and T1-weighted MRI data from 402 subjects with autism spectrum disorder (ASD) and 496 controls from the ABIDE database (http://fcon_1000.projects.nitrc.org/indi/abide). Interhemispheric resting state functional connectivity was computed using the ‘voxel-mirrored homotopic connectivity’ function implemented in the DPARSF software. We also conducted a structural region of interest (ROI) analysis on white matter segments using the corpus callosum mask from the Talairach Daemon database atlases. Group differences of the interhemispheric functional connectivity and the corpus callosum size were examined using a two-sample t-test, and a threshold of p < 0.05 false discovery rate (FDR) corrected at peak level was set for multiple comparisons. Associations with symptom severity in the ASD group (using ADOS scores) were also calculated by Pearson correlation.

Results: Two-sample t-tests on interhemispheric functional connectivity revealed decreased interhemispheric connectivity in the default mode network (dorsal medial prefrontal cortex (mPFC), ventral mPFC and posterior cingulate cortex (PCC)) the salience network (posterior insula (PI)), the mirror neuron system including inferior parietal lobule, precentral gyrus and superior temporal gyrus, thalamus and visual processing regions (lingual, fusiform and inferior occipital gyri) in ASD relative to control groups (P_FDR < 0.05). The PCC interhemispheric functional connectivity was negatively correlated the total ADOS scores (all 3 subscales - r = -0.189, p = 0.004) and both the communication (r = -0.220, p = 0.001) and social sub-scales (r = -0.133, p = 0.044). The PI interhemispheric connectivity was also negatively correlated with the ADOS communication sub-scale (r = -0.147, p = 0.026). The white matter ROI analysis of the corpus callosum showed significantly reduced volumes in both the anterior and posterior parts of the corpus callosum in the ASD compared to the control groups (P_FDR < 0.05), but these were not associated with ADOS scores. Results remained significant after including total brain volume and either full or verbal IQ measures as covariates.

Conclusions: Our findings provide evidence for both reduced resting-state interhemispheric functional connectivity and corpus callosum volumes in ASD subjects. Changes in posterior cingulate and insula interhemispheric functional connectivity are also associated with symptom severity and may represent useful potential ASD biomarkers.

References

1. Anderson JS et al (2011) Cerebral Cortex 21:1134-1146