Stimulation-evoked orbitofrontal activity as a biomarker for DBS personalization in depression.

Area of Science:

• Neuroscience
• Neurology
• Biomedical Engineering

Background:

• Treatment-resistant depression (TRD) poses a significant challenge in neuropsychiatric care.
• Deep brain stimulation (DBS) offers a promising avenue for TRD, but patient-specific efficacy varies.
• Optimizing DBS settings through objective, electrophysiologically driven strategies is crucial for improving clinical outcomes.

Purpose of the Study:

• To investigate the utility of cerebro-cerebral evoked potentials (CEPs) in personalizing DBS for TRD.
• To determine if CEPs can objectively identify effective DBS configurations and engagement of neural circuits.
• To explore CEPs as a tool for real-time verification of circuit engagement and understanding antidepressant mechanisms.

Main Methods:

• Eight patients with TRD received DBS targeting the subcallosal cingulate and ventral capsule/striatum.
• Single-pulse electrical stimulation was delivered via DBS devices, and CEPs were recorded using stereo-electroencephalography probes.
• Retrospective analysis correlated CEP features with clinical improvement across multiple stimulation programming sessions over 9 months.

Main Results:

• Clinically effective DBS configurations were associated with significantly larger CEPs in the orbitofrontal cortex.
• Increased CEPs were observed across dorsal and ventral prefrontal regions for effective configurations.
• Waveform similarity analysis indicated that multiple DBS configurations could yield similar therapeutic effects, suggesting a subspace of effective parameters.

Conclusions:

• CEPs provide an objective, acute method to assess network engagement during DBS for TRD.
• Stimulation-evoked prefrontal responses measured by CEPs correlate with antidepressant effects.
• CEPs show potential for guiding DBS contact selection, minimizing trial-and-error, and advancing mechanistic understanding.