Mount Sinai researchers analyzed the largest multi-cohort dataset to date of patients receiving subcallosal cingulate deep brain stimulation (SCC DBS) for treatment-resistant depression. Using computer models of electrical fields and brain connectivity maps, they estimated which white-matter pathways were stimulated across patients from several clinical studies, including the BROADEN trial and a University of Toronto cohort.
The results, published in the American Journal of Psychiatry, showed that sustained improvement was consistently associated with stimulation reaching three specific pathways: the cingulum bundle, forceps minor, and medial uncinate fasciculus/ventral amygdalofugal pathways. Notably, patients who did not respond after two years shared a pattern of insufficient engagement with the left cingulum bundle. The researchers did not test whether moving electrodes to target this pathway would improve outcomes, but the pattern offers a possible explanation for why similar electrode placements can yield different results.
These findings reinforce the case for connectome-based targeting, where electrode placement is guided by detailed maps of brain connections rather than anatomical landmarks alone. That approach is already shaping the ongoing Abbott TRANSCEND clinical trial. As Helen Mayberg of Mount Sinai noted, precise lead placement and confirmation that the intended brain target has been engaged are essential first steps in any neuromodulation trial.