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Common Electrophysiology Biomarkers Collected at Home Robustly Track Depression Recovery With Deep Brain Stimulation

Fitoz, E. C.; Alagapan, S.; Cha, J.; Choi, K. S.; Figee, M.; Kopell, B.; Obatusin, M.; Heisig, S.; Nauvel, T.; Razavilar, A.; Sarikhani, P.; Trivedi, I.; Gowatsky, J.; Alexander, J.; Guignon, R.; Khalid, M.; Forestal, G. B.; Song, H. N.; Dennison, T.; O'Neill, S.; Karjagi, S.; Waters, A. C.; Riva-Posse, P.; Mayberg, H. S.; Rozell, C. J.

2026-04-20 psychiatry and clinical psychology
10.64898/2026.04.13.26350107 medRxiv
Show abstract

Subcallosal cingulate cortex (SCC) deep brain stimulation (DBS) can provide relief for individuals with Treatment Resistant Depression (TRD), but ongoing clinical management remains challenging due to nonspecific symptom fluctuations that can obscure core depression recovery on standard rating scales. Objective, stable biomarkers that selectively track the therapeutic effects of SCC DBS are therefore essential for developing principled decision support systems to guide stimulation adjustments. Recent bidirectional DBS systems enable chronic recording of local field potentials (LFPs) and prior work using the Activa PC+S device identified an electrophysiological signature of stable clinical recovery. However, translation to practical clinical deployment requires demonstrating that this biomarker is robustly generalizable, specific to the impact of the DBS therapy, and deployable in real-world recording contexts. To address this need, we developed an at-home SCC LFP data collection platform (built on the Medtronic Summit RC+S system) enabling at home data collection for a new cohort of ten SCC DBS participants with TRD (ClinicalTrials.gov identifier NCT04106466). Using longitudinal LFP recordings collected from this system, we report findings demonstrating that the previously reported biomarker of stable recovery generalizes across subject cohorts and devices, is robust to common potential confounds (including time of day and stimulation status), and shows symptom specificity, sensitivity and stability necessary to support clinical decision making. Across both cohorts, biomarker changes show relationships to pre-DBS white matter structure and network function measured using diffusion MRI and resting-state functional MRI (rsFMRI). These findings replicating and extending previous findings support the biomarkers utility as a foundation for scalable, electrophysiology-informed decision support in SCC DBS.

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