Intracranial electrophysiological biomarkers of compulsivity in obsessive-compulsive disorder

There is an emerging need for objective neural biomarkers of obsessive-compulsive disorder (OCD) to improve the efficacy of neuromodulatory interventions, most notably deep-brain stimulation (DBS), and develop closed-loop stimulation paradigms. Preliminary data suggest that such biomarkers may be derived from local field potentials (LFPs) recorded in individual patients implanted with sensing DBS devices. However, reliable LFP signatures that are generalizable across OCD patients have yet to be identified. Here, we relate LFPs recorded from sensing DBS electrodes in different basal-ganglia structures to core symptoms of OCD in 11 patients during personalized provocation of obsessions and compulsions. We identify two general markers of compulsion: delta and alpha LFP power was significantly increased during all compulsions in the external globus pallidus (GPe), nucleus accumbens, anterior limb of the internal capsule (ALIC) and anterior lateral anterior commissure. In mental compulsion subtypes, similar low-frequency increases were observed only in GPe (delta/alpha) and ALIC (alpha), suggesting that these signals possibly reflect more universal biomarkers of compulsivity unconfounded by motor function. GPe delta power correlated with OCD symptom severity, establishing a meaningful connection between subcortical sensing DBS readout and patient experience. ALIC alpha power was modulated by the phase of theta oscillations during compulsions, possibly reflecting pathological coupling of cortical networks in OCD. Our results demonstrate unique, group-level LFP correlates of core OCD symptoms across disease-relevant basal-ganglia structures. These electrophysiological signatures help pave the way toward the development of biomarker-targeted neuro-modulatory intervention for OCD. Netherlands Trial Register ID: NL7486.