Background: Treating medication-refractory freezing of gait in Parkinson’s disease remains challenging despite several trials reporting improvements in motor symptoms using subthalamic nucleus or globus pallidus internus deep brain stimulation. Pedunculopontine nucleus region DBS has been used for medication-refractory FoG, with mixed findings. FoG, as a paroxysmal phenomenon, provides an ideal framework for the possibility of closed-loop DBS.Methods: In this clinical trial, five subjects with medication-refractory FoG underwent bilateral GPi DBS implantation to address levodopa-responsive PD symptoms with open-loop stimulation. Additionally, PPN (...) DBS leads were implanted for CL-DBS to treat FoG. The primary outcome of the study was a 40% improvement in medication-refractory FoG in 60% of subjects at 6 months when “on” PPN CL-DBS. Secondary outcomes included device feasibility to gauge the recruitment potential of this four-lead DBS approach for a potentially larger clinical trial. Safety was judged based on adverse events and explantation rate.Findings: The feasibility of this approach was demonstrated as we recruited five subjects with both “on” and “off” medication freezing. The safety for this population of patients receiving four DBS leads was suboptimal and associated with a high explantation rate of 40%. The primary clinical outcome in three of the five subjects was achieved at 6 months. However, the group analysis of the primary clinical outcome did not reveal any benefit.Interpretation: This study of a human PPN CL-DBS trial in medication-refractory FoG showed feasibility in recruitment, suboptimal safety, and a heterogeneous clinical effect in FoG outcomes. (shrink)

Research in basic and clinical neuroscience of music conducted over the past decades has begun to uncover music’s high potential as a tool for rehabilitation. Advances in our understanding of how music engages parallel brain networks underpinning sensory and motor processes, arousal, reward, and affective regulation, have laid a sound neuroscientific foundation for the development of theory-driven music interventions that have been systematically tested in clinical settings. Of particular significance in the context of motor rehabilitation is the notion that musical (...) rhythms can entrain movement patterns in patients with movement-related disorders, serving as a continuous time reference that can help regulate movement timing and pace. To date, a significant number of clinical and experimental studies have tested the application of rhythm- and music-based interventions to improve motor functions following central nervous injury and/or degeneration. The goal of this review is to appraise the current state of knowledge on the effectiveness of music and rhythm to modulate movement spatiotemporal patterns and restore motor function. By organizing and providing a critical appraisal of a large body of research, we hope to provide a revised framework for future research on the effectiveness of rhythm- and music-based interventions to restore and train motor function. (shrink)