Disruption of Circadian Rhythmicity in Globus Pallidus Internus and Ventral Striatum as a Neural Signature of Clinical Improvement Following Deep Brain Stimulation for Obsessive Compulsive Disorder

Introduction: Disruption of pathological local field potential (LFP) predictability within the ventral striatum (VS) reliably indicates clinical response in individuals receiving DBS for OCD (Provenza et al. Nature Medicine 2024). Here, we investigated whether this neural effect is specific to the VS or also present in other regions of the network, specifically the globus pallidus interna (GPi).

Methods: Four patients with OCD and Tourette Syndrome (TS) were implanted with recording-capable DBS systems in the VS and GPi bilaterally. We recorded chronic 9 Hz power at 10-minute intervals, and we performed simultaneous synchronized broadband streaming. To determine disruption in neural periodicity, we quantified daily goodness-of-fit using a linear autoregressive model. To assess signal similarity across DBS targets, we performed Pearson’s correlation on time-power data.

Results: Two of four patients achieved OCD responder status. In the pre-DBS symptomatic state, GPi 9 Hz activity demonstrated similar circadian rhythmicity as that seen in the VS. Responders demonstrated disruption of neural predictability of the 9 Hz power in both VS and GPi (VS p = 1.65E-40, 1.68E-15; GPi p = 3.65E-15, 2.42E-19). Non-responders did not show this effect (VS p = 0.452, 0.406; GPi p = 0.098, 0.270). Despite concordance in disrupted neural periodicity across the VS and GPi, the time-power signals were not significantly correlated across sites (R2 range = 0.001 - 0.130, p range = 8.1E-255 - 4.8E-5). The circadian patterns in respective locations had different phase shifts across patients and across weeks within patients.

Conclusion : Our cohort of dually-implanted subjects provides a window into neural activity changes across the network affected by VC/VS DBS. Its detectability in the ventral pallidum, another region of the cortico-basal-thalamo-cortical network implicated in OCD, suggests the network-wide extent of this neural signature.