Asymmetric Cingulum Bundle Connectivity Is Modulated by Paracingulate Sulcus Morphology

The cingulum bundle (CB) is a group of axons supporting connectivity among several functional brain networks relevant in healthy and diseased states. The paracingulate sulcus (PCS) is present in at least one cerebral hemisphere across 70% of the population. PCS presence versus absence is linked to differences in structure and function of the anterior cingulate cortex, though the influence of PCS on the white matter of the CB remains unknown. The objective of this work was to define the CB electrographic connectivity profile and determine the impact of PCS morphology on CB engagement. Single-pulse electrical stimulation in combination with stereo-electroencephalography recordings was used to measure neural responses to left and right CB stimulation in 19 patients undergoing intracranial monitoring for treatment of refractory epilepsy. Evoked potential responses were extracted from brain areas, and a connectivity robustness ratio was computed. Network-level responses were compared across left and right CB, and with consideration of PCS morphology. CB electrographic connectivity demonstrated leftward dominance, but this was strongly impacted by PCS morphology in both cerebral hemispheres. Maximal left CB connectivity was observed in the presence of left PCS morphology, while right CB connectivity was strongest in its absence. These data strongly suggest that bilateral CB engagement is modulated by PCS morphology in the left hemisphere. These findings are particularly relevant when considering the CB as a target for treating neuropsychiatric disorders.