Optimal stimulation sites of the subthalamic nucleus for the treatment of gait symptoms of Parkinson's disease

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a widely adopted therapy for mitigating motor symptoms in Parkinson's Disease (PD). Although the electrode placement site has been proposed as a significant factor influencing motor outcomes, the specific relationships between electrode location and therapeutic effects on gait performance remain unclear. This study seeks to identify optimal stimulation sites within the STN to effectively address gait symptoms in patients with PD (PwPD). We assessed overground gait performance in 49 PwPD who underwent bilateral STN-DBS surgery, both before treatment initiation and six months post-implantation, comparing the results to 51 asymptomatic individuals. Our evaluation focused on treatment-induced changes in the mean (mean set) and coefficient of variability (variability set) of ten commonly used spatio-temporal gait parameters, such as stride length and walking speed. We also examined their correlation with the location of the active contacts of the DBS electrodes utilized for therapeutic stimulation. Our findings indicate that DBS treatment resulted in a significant reduction in stride time, stance time, swing time, and step time, in addition to an increase in the variability of double limb stance time, stride time, stance time, and step time. Furthermore, we observed that the location of the active contacts resulted in alterations in mean step length, stride length, and walking speed, as well as changes to cadence, stride time, stance time, and step width. We identified the postero-superior region of the STN as the most effective region for improving the mean set, whereas the antero-superior region of the STN emerged as the most effective region for improving the variability set. This study provides empirical evidence on how STN-DBS, in tandem with the location of active lead contacts, impacts both mean and variability of spatio-temporal gait parameters in PwPD. Importantly, our results indicate specific STN spatial targets for DBS implantation to address patient specific gait symptoms. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was financially supported by grants from The LOOP Zurich and the Vontobel Foundation. ### 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 (approval no: 201500141) by the Zurich Cantonal Ethics Commission and carried out in accordance with the Declaration of Helsinki, the guidelines of Good Clinical Practice, and the Swiss regulatory authority's requirements. 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 Due to ethical considerations, open publication of the dataset for further use by researchers outside of the investigating team is not possible. Please contact the corresponding author for collaborations and requests.