Longitudinal Changes in Cortical Response Dynamics with Deep Brain Stimulation to the Subcallosal Cingulate for Treatment-Resistant Depression

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Abstract
Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is a promising intervention for treatment-resistant depression, yet objective biomarkers that track recovery remain limited. This study examined longitudinal changes in stimulation-evoked potentials (SEPs) to characterize how SCC-driven cortical communication evolves during treatment. Ten patients across three SCC-DBS trials underwent high-density EEG recordings at 4 and 24 weeks. SEP features were extracted from source-localized SCC signals and related to clinical outcomes and fractional anisotropy (FA) of midcingulate cingulum. Cortical responses showed a consistent reduction in latency and an increase in magnitude over time, indicating faster and stronger electrocortical signaling with chronic stimulation. Higher baseline midcingulate FA predicted greater latency acceleration, linking SEP timing to white-matter integrity. These findings identify temporal SEP dynamics as candidate mechanistic biomarkers that reflect circuit engagement during SCC-DBS and offer a pathway toward physiology-guided optimization of neuromodulation for depression. Highlights: Reduced latency of stimulation evoked potential after 6 months of DBS Larger cortical evoked response to single pulse perturbation after 6 months of DBS Baseline myelin integrity in MCC predicts magnitude of change in EP latency
Funding Information
  • Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative (UH3NS103550)
  • Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative (UH3NS141080)
  • National Institute of Mental Health (R01MH102238)
  • Hope for Depression Research Foundation

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