Circadian limbic and thalamic beta oscillations drive slow-adapting dual-threshold adaptive deep brain stimulation in...

Objective.Patients with Tourette syndrome (TS) may benefit from lower DBS current during sleep to reduce side effects and habituation, yet manual adjustment can be challenging. We tested the feasibility of an adaptive deep brain stimulation (aDBS) paradigm in which circadian fluctuations in beta activity serve as a biomarker to reduce stimulation during sleep.Approach.We analyzed chronic beta-band local field potentials (LFPs) recorded from sensing-enabled DBS leads in bilateral ventral capsule/ventral striatum (VC/VS) and centromedian-parafascicular nucleus of the thalamus (CM-Pf) in a patient with refractory TS and obsessive-compulsive disorder. We used circadian beta fluctuations in the VC/VS and CM-Pf to drive a dual-threshold algorithm that we configured to function as a slowly adapting single-threshold system. Because the clinically optimal electrode configuration created sensing constraints, we linked VC/VS and CM-Pf within each hemisphere so beta activity from either target could trigger automatic nighttime stimulation reduction.Results.Multi-week recordings showed clear circadian beta rhythmicity in both VC/VS and CM-Pf. The slowly adapting single-threshold aDBS algorithm with cross-target tethering reduced stimulation during sleep while maintaining stable daytime stimulation. A 16-night period in which aDBS was inadvertently disabled created a direct comparison between aDBS and continuous DBS (cDBS). Clinical measures showed modest reductions in tic severity and substantial reductions in depression during aDBS compared with cDBS.Significance.This proof-of-concept study demonstrates: (1) circadian modulation of beta rhythms in limbic and thalamic targets, supporting the feasibility of leveraging these signals for adaptive DBS; (2) that cross-target tethering is feasible (i.e. adapting stimulation in the VC/VS off of sensing in the CM-Pf and vice versa); and (3) that a dual-threshold algorithm can be configured to enable gradual transitions between maximal and minimal stimulation. The patient's observed improvements during circadian-driven aDBS compared with cDBS suggest potential clinical benefit, warranting testing in larger samples.