Background: The corpus callosum, the main interhemispheric connection in the brain, may serve to preserve functional asymmetry between homologous cortical regions.

Methods: To test this hypothesis, 30 healthy adult subjects underwent combined transcranial magnetic stimulation (TMS)-electroencephalography procedures. Nineteen of these subjects also completed diffusion tensor imaging and tractography procedures. We examined the relationship between microstructural integrity of subdivisions of the corpus callosum with TMS-induced interhemispheric signal propagation.

Results: We found a significant inverse relationship between microstructural integrity of callosal motor fibers with TMS-induced interhemispheric signal propagation from left to right motor cortex. We also found a significant inverse relationship between microstructural integrity of genu fibers of the corpus callosum and TMS-induced interhemispheric signal propagation from left to right dorsolateral prefrontal cortex (DLPFC). We then demonstrated neuroanatomic specificity of these relationships.

Conclusions: Taken together, our findings suggest that TMS-induced interhemispheric signal propagation is transcallosally mediated and neuroanatomically specific and support a role for the corpus callosum in preservation of functional asymmetry between homologous cortical regions. Delineation of the relationship between corpus callosum microstructure and interhemispheric signal propagation in neuropsychiatric disorders, such as schizophrenia, may reveal novel mechanisms of pathophysiology.