Longitudinal tracking of ventral anteromedial subthalamic nucleus theta bursts in Obsessive Compulsive Disorder: bridging the gap towards a neurophysiological marker

Background: Deep Brain Stimulation (DBS) to treat treatment-resistant obsessive-compulsive disorder (OCD) is still considered off-label in most countries worldwide, despite numerous publications showing significant relief of symptoms and guidelines provided. To enhance therapeutic efficacy, there is an urgent need for further studies to refine stimulation target and promote patient-tailored adaptive DBS by identifying potential neurophysiological markers for OCD. However, limited research has investigated such markers so far. Methods: In this prospective interventional study, we implanted three refractory OCD patients (2 men and 1 woman) with ventral anteromedial subthalamic nucleus (vamSTN) DBS at the border with the OCD response tract (ORT). We recorded intra- and post-operatively spiking and local field potential (LFP) activity at the target for over two years to evaluate neural markers that correlate with OCD severity and clinical response. Outcomes: All patients responded to vamSTN DBS with a 54 ± 5·5% (18·6 ± 1·7 scores) mean reduction in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) at last follow-up. VamSTN LFP activity showed a prominent theta frequency peak. Theta burst duration, power, and entropy significantly correlated with OCD severity and stimulation-induced clinical response. Theta power was more robust and correlated more strongly with clinical scores in the left vamSTN. DBS response also resulted in a wake-sleep diurnal variation in theta power, which was larger in the left vamSTN. Interpretation: Due to the ease of vamSTN targeting, clinical efficacy, and the strong and stable neural biomarker, we suggest vamSTN theta burst power as a potential neural marker and possible target for adaptive DBS in OCD. Funding: The research was supported by the Israeli Science Foundation (ISF), Clalit healthcare services, the UTSW-Rabin medical center joint research grant and the Kahn Foundation. This study is registered in “ClinicalTrials.gov” (ID NCT05995951) under the name: “Deep Brain Stimulation Surgery for the Treatment of Refractory Obsessive-Compulsive Disorder”.