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Updated: Oct 2, 2026
Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method
Published on: August 2, 2021
Connectomic Determinants of Subcallosal Cingulate Deep Brain Stimulation for Depression
Ha Neul Song1, Ki Sueng Choi1, Brian H Kopell2
1Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York.
Objective:
Subcallosal cingulate (SCC) deep brain stimulation (DBS) has shown promise for treatment-resistant depression. This study retrospectively evaluated a large curated SCC-DBS dataset to identify connectomic factors associated with sustained clinical improvement across patients, focusing on the white matter bundles consistently implicated in patient-specific connectome-based targeting.
Methods:
A total of 131 patients (mean age=46.67 years, SD=9.79; 60.31% female) with treatment-resistant depression from three independent cohorts received bilateral SCC-DBS using site-specific targeting methods. Clinical improvements were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D). Based on individual DBS settings, volumes of tissue activated were reconstructed, and voxel-wise stimulation mapping and normative fiber-wise analyses were performed to assess contributions of white matter bundles to therapeutic response.
Results:
Responders (patients with ≥50% reduction in HAM-D score) exhibited a less variable spatial distribution of volumes of tissue activated than nonresponders. Probabilistic stimulation mapping identified a focal cluster associated with clinical improvement. Fiber-wise analyses showed that stimulation of predefined white matter tracts targeted by connectome-based SCC-DBS contributed to clinical efficacy. Notably, failure to activate the left cingulum bundle and medial uncinate fasciculus decreased the therapeutic effects of SCC-DBS.
Conclusions:
This study highlights the significance of stimulating critical white matter bundles for effective SCC-DBS. Available evidence supports the idea that precisely targeting the lateralized cingulum bundle and medial uncinate fasciculus is essential for sustained clinical improvement. These findings suggest potential advantages of connectome-based targeting for SCC-DBS over targeting based solely on anatomical landmarks or normative atlases, using a method that is precise, reliable, and scalable for future use in individual patients.
