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(42) Pathway-Specific Stimulation of Subcallosal White Matter Differentially Modulates Prefrontal and Parietal Connectivity

Thursday, June 12, 2025
4:30 PM - 5:10 PM ET
Location: Sky View
Introduction: Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) region is an emerging therapy for the treatment of patients with treatment-resistant major depressive disorder (trMDD). Previous work has shown that there are unique electroencephalography (EEG) responses to selective stimulation of the forceps minor (FM) or unilateral cingulum bundle (CB). Our objective is to further explore these unique responses using source localization methodologies.

Methods: A total of 17 trMDD patients underwent implantation of bilateral deep brain stimulation (DBS) electrodes targeting the SCC. Individualized models of the FM and CB pathways were created for each patient using their preoperative high-resolution magnetic resonance imaging (MRI) data. Patient-specific volume conduction models were also created to estimate the DBS electric field distributions across these tracts. Field-cable models were employed to simulate white matter dynamics in the FM and CB from DBS. These models were used to identify two sets of stimulation parameters: one maximizing recruitment of FM and the other maximizing recruitment of ipsilateral CB. A third parameter set was also identified based on the monopolar contact used for each patient’s DBS therapy. The cortical EEG response to each DBS setting was captured by collection of high-density 256-lead recordings. For each patient and parameter set, cortical source activity was reconstructed using standardized low-resolution brain electromagnetic tomography (sLORETA), implemented within the MNE-Python software package. Vector AutoRegression (VAR) was utilized to identify consistent relationships in the activity between several cortical regions on an individual and a cohort level.

Results: Connectivity varied as a function of the volume of bundle activation identified from field-cable models. Recruitment of the FM was associated with strong positive connectivity between ipsilateral dorsolateral prefrontal cortex and both ipsilateral and contralateral orbital and polar frontal cortex. This held true with coactivation of the ipsilateral CB, unless a higher ratio of CB was recruited compared to FM. In contrast, isolated CB activation was associated with increased positive connectivity between the orbital and polar frontal cortex and the contralateral inferior parietal cortex.

Conclusion: Pathway-specific SCC DBS modulates distinct cortical connectivity patterns based on the relative recruitment of the CB and FM. These findings emphasize the importance of targeted pathway modulation in refining DBS strategies for trMDD