Subcallosal cingulate DBS (Area 25)

Deep-brain stimulation of the subcallosal cingulate white matter (Brodmann area 25), the first and most-studied target for treatment-resistant depression. Early open-label work reported striking and sustained remissions in a subset of patients, generating great optimism.

A multicenter randomized sham-controlled trial (BROADEN) was, however, halted for futility at its six-month primary endpoint. Longer-term open-label follow-up then showed response and remission rates rising over years, and connectivity-guided targeting — aiming at a shared bundle of fibers rather than a fixed coordinate — improved the consistency of contact placement. The trajectory illustrates a recurring pattern in psychiatric DBS: promising open-label results, a negative short-horizon controlled trial, and slowly emerging chronic benefit that is difficult to prove under blinding.