Chronic adaptive versus conventional DBS response patterns in Parkinson’s disease: A pilot randomized crossover trial

Background Adaptive 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.

To compare aDBS versus cDBS efficacy in patients with Parkinson’s disease (PD) under chronic stimulation and examine baseline-dependent patterns of treatment response.

This 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.

No 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.

aDBS 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. Competing Interest Statement Jun Tanimura has received honoraria from Eisai and FP Corporation outside of this work. Takehiro Yako and Takao Hashimoto declare no competing interests. Clinical Trial UMIN000058937 Funding Statement This research received no external funding. All clinical procedures and routine follow-up were conducted as part of standard care at Aizawa Hospital and supported by institutional resources; no company provided financial or in-kind support. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethics Committee of Aizawa Hospital (2020-064: R2-37), and conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes We made following revision: (1) Stimulation settings methods restructured to clarify contacts selection approach; (2) Bayesian results now include probabilities of comparable treatment effectiveness; (3) New Table 2 summarizes outcome-specific effect modification patterns; (4) Limitations reorganized with new acknowledgments; (5) Three references added. Conclusions unchanged. Data Availability All data produced in the present study are available upon reasonable request to the authors.