The structural basis for interhemispheric functional connectivity: Evidence from individuals with agenesis of the corpus callosum.

Agenesis of the corpus callosum (AgCC) is a rare congenital malformation characterized by partial or complete absence of the corpus callosum (CC). The effects of AgCC on cerebral structural and functional networks are not clear. We aimed to utilize AgCC as a model to characterize the relationship between brain structure and function. Diffusion tensor imaging and resting-state fMRI data were collected from nine AgCC and ten healthy subjects. The interhemispheric functional connectivity (FC) was quantified using a voxel-mirrored-homotopic-connectivity (VMHC) method, and its correlation with the number (FN) and fractional anisotropy (FA) of the fibers crossing the CC was calculated. Graph-based network analyses of structural and functional topologic properties were performed. AgCC subjects showed markedly reduced VMHC compared to controls. VMHC was significantly correlated with the FN and FA of the fibers crossing the CC. Structural network analyses revealed impaired global properties, but intact local properties in AgCC compared to controls. Functional network analyses showed no significant difference in network properties between the groups. Finally, in both groups, brain areas with more fiber connections were more likely to build a positive FC with each other, while areas with decreased white matter connections were more likely to result in negative FC. Our observations demonstrate that interhemispheric FC is highly dependent on CC structure. Increased alternative intrahemispheric SC might be a compensatory mechanism in AgCC that helps to maintain normal global brain function. Our study provides insights into the underlying neurological pathophysiology of brain malformations, thereby helping to elucidate the structure-function relationship of normal human brain.