Electrophysiological Biomarkers Reflect Target Engagement and Response Using Deep Brain Stimulation for...

Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) is an effective treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). However, optimizing lead placement and stimulation parameters remains a challenge. DBS evoked potentials (EPs) recorded with electroencephalography (EEG) during surgical lead placement could serve as intraoperative biomarkers for target engagement and clinical efficacy.

We obtained intraoperative EEG recordings on the forehead from 10 patients (2 nonresponders) undergoing ALIC DBS surgery for OCD. Monopolar stimulation at 2 Hz was delivered through all electrode contacts, and EEG EPs were analyzed in relation to stimulation contact, white matter connectivity to the prefrontal cortical regions of interest (assessed via probabilistic tractography), and reduction in symptom severity (assessed with the Yale-Brown Obsessive Compulsive Scale).

We observed consistent DBS EPs with 3 oscillatory peaks (∼35, ∼75, and ∼120 ms) across all patients. EP amplitude varied across contacts, with the largest responses occurring when the location of stimulation overlapped with the preoperatively defined tractographic target. Higher EP amplitudes recorded on the forehead correlated with greater white matter connectivity to the ventromedial prefrontal cortex/orbitofrontal cortex and ventrolateral prefrontal cortex. Treatment nonresponders exhibited less consistent EP waveforms across lead contacts.

These findings suggest that intraoperative EPs provide valuable insights into ALIC DBS target engagement. EP characteristics may serve as biomarkers to refine DBS targeting and predict clinical response, offering a potential tool for optimizing DBS therapy for OCD.