Functional organization of the human corpus callosum unveiled with BOLD-fMRI gradients

Gradients capture the underlying functional organization of the brain. Cortical gradients have been well characterized, however very little is known about the underlying gradient of the white matter. Here, we proposed a functionally gradient mapping of the corpus callosum by using blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI), which for the first time uncovered three distinct but stable spatial axes: posterior-anterior, dorsal-ventral, and left-right. The three spatial patterns were replicated in another independent cohort and robust across scanning conditions. We further associated the three gradient maps with brain anatomy, connectome, and task-related brain functions, by using structural magnetic resonance imaging, both resting-state and task fMRI, and diffusion tensor imaging data. The posterior-anterior gradient distribution of the corpus callosum showed a similar pattern with the cerebral cortex, gradually extending from the primary cortex to the transmodal cortex. The dorsal-ventral gradient distribution revealed an N-shaped pattern from the primary cortex to the higher-order cognitive cortex. The posterior-anterior and dorsal-ventral gradient maps were also associated with white-matter microstructures, such as fractional anisotropy and myelin water fraction. The left-right gradient showed an inverted V-shaped pattern, which delineated the inter-hemisphere separation. These findings provide fundamental insight into the functional organization of the human corpus callosum, unveiling potential patterns of functional interaction with the cerebral cortex and their associations with cognitive behaviors.