Nigral stimulation for freezing of gait: kinematic gait parameters inform optimization of stimulation frequency

Innovative technology allows for personalization of stimulation frequency in dual-site deep brain stimulation (DBS), offering promise for challenging symptoms in advanced Parkinson's disease (PD), particularly freezing of gait (FoG). Early results suggest that combining standard subthalamic nucleus (STN) stimulation with substantia nigra pars reticulata (SNr) stimulation may improve FoG outcomes. However, patient response and the optimal SNr stimulation frequency vary. Our randomized controlled trial studied patients with advanced PD and persistent FoG, while recording gait kinematics through wearable inertial sensors, along with clinical assessments and patient-reported outcomes. In a with-subjects design, we compared a no-stimulation control with four stimulation conditions: Mono-site STN stimulation at 119 Hz and three dual-site protocols (STN + SNr) with SNr stimulation at 119 Hz, 71 Hz, or 30 Hz, keeping total electrical energy delivered (TEED) constant between SNr conditions. Significant interindividual variability was observed for the optimal stimulation protocol, with comparable proportions favoring STN, STN + SNr119, and STN + SNr71. Changes in spatial and temporal gait parameters, such as stride length and swing time, correlated significantly with FoG clinical improvements, with high correlation coefficients (> 0.8). Optimized stimulation parameters also led to improvements in patient-reported outcomes, highlighting the potential of digital biomarkers in tailoring DBS protocols for individualized outcomes.