Chronic Adaptive versus Conventional Deep Brain Stimulation in Patients with Parkinson's Disease: A Randomized Crossover Trial with Exploratory Analysis of Baseline-Dependent Response Patterns

BackgroundAdaptive deep brain stimulation (aDBS) modulates stimulation based on real-time biomarkers, potentially offering advantages over conventional DBS (cDBS). Clinical evidence under chronic stimulation remains limited. ObjectivesTo compare aDBS versus cDBS efficacy in patients with Parkinsons disease (PD) under chronic stimulation and examine baseline-dependent patterns of treatment response. MethodsThis was a pilot, double-blind, randomized crossover trial in nine PD patients with bilateral subthalamic nucleus DBS. Patients underwent consecutive one-month periods of cDBS and aDBS after a four-month postoperative interval. aDBS used a dual-threshold algorithm adjusting amplitude based on subthalamic beta-band LFP power. Primary outcomes were daily ON/OFF durations and dyskinesia duration under optimized medication. Mixed-effects ANCOVA estimated treatment effects. Bayesian analyses integrated prior evidence to assess probabilities of clinically meaningful differences. Exploratory analyses examined treatment-by-modifier interactions. ResultsNo statistically significant differences emerged between treatments. Directional effects varied: ON duration favored cDBS, while troublesome dyskinesia and UPDRS scores favored aDBS. Bayesian analyses indicated low probabilities that these differences reached clinical importance (29.4% probability for cDBS advantage on ON time, 7.5% for aDBS advantage on UPDRS Part III). Substantial between-patient heterogeneity was observed. Exploratory analyses suggested higher baseline disease burden enhanced cDBS advantages for motor fluctuations and aDBS advantages for motor severity, though modification effects varied across outcome-baseline combinations. ConclusionsaDBS and cDBS showed comparable population-level efficacy. Patient-specific baseline characteristics may influence treatment advantages for specific outcomes. These findings warrant larger trials to identify patient subgroups who may benefit from each stimulation approach under the current form of adaptive stimulation.