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

ABSTRACT: 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.

SUBMITTER: Yuan J

PROVIDER: S-EPMC7519397 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Adopting a network perspective, the structural connectome reveals the large-scale white matter connectivity of the human brain, yielding insights into cerebral organization otherwise inaccessible to researchers and clinicians. Connectomics has great potential for elucidating abnormal connectivity in congenital brain malformations, especially axonal pathfinding disorders. Agenesis of the corpus callosum (AgCC) is one of the most common brain malformations and can also be considered a prototypical genetic disorder of axonal guidance in humans. In this exploratory study, the structural connectome of AgCC is mapped and compared to that of the normal human brain. Multiple levels of granularity of the AgCC connectome are investigated, including summary network metrics, modularity analysis, and network consistency measures, with comparison to the normal structural connectome after simulated removal of all callosal connections ("virtual callostomy"). These investigations reveal four major findings. First, global connectivity is abnormally reduced in AgCC, but local connectivity is increased. Second, the network topology of AgCC is more variable than that of the normal human connectome, contradicting the predictions of the virtual callostomy model. Third, modularity analysis reveals that many of the tracts that comprise the structural core of the cerebral cortex have relatively weak connectivity in AgCC, especially the cingulate bundles bilaterally. Finally, virtual lesions of the Probst bundles in the AgCC connectome demonstrate that there is consistency across subjects in many of the connections generated by these ectopic white matter tracts, and that they are a mixture of cortical and subcortical fibers. These results go beyond prior diffusion tractography studies to provide a systems-level perspective on anomalous connectivity in AgCC. Furthermore, this work offers a proof of principle for the utility of the connectome framework in neurodevelopmental disorders.

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

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