Entraining Stepping Movements of Parkinson's Patients to Alternating Subthalamic Nucleus Deep Brain Stimulation

Abstract

Patients with advanced Parkinson's can be treated by deep brain stimulation of the subthalamic nucleus (STN). This affords a unique opportunity to record from this nucleus and stimulate it in a controlled manner. Previous work has shown that activity in the STN is modulated in a rhythmic pattern when Parkinson's patients perform stepping movements, raising the question whether the STN is involved in the dynamic control of stepping. To answer this question, we tested whether an alternating stimulation pattern resembling the stepping-related modulation of activity in the STN could entrain patients' stepping movements as evidence of the STN's involvement in stepping control. Group analyses of ten Parkinson's patients (one female) showed that alternating stimulation significantly entrained stepping rhythms. We found a remarkably consistent alignment between the stepping and stimulation cycle when the stimulation speed was close to the stepping speed in the five patients that demonstrated significant individual entrainment to the stimulation cycle. Our study suggests that the STN is causally involved in dynamic control of step timing, and motivates further exploration of this biomimetic stimulation pattern as a potential basis for the development of deep brain stimulation strategies to ameliorate gait impairments.

Safety and Tolerability of Burst-Cycling Deep Brain Stimulation for Freezing of Gait in Parkinson’s Disease

“…However, several small studies have found that low-frequency stimulation (<100 Hz) can improve gait in PD (Moreau et al, 2008 ; Xie et al, 2016 ). Additionally, physiology studies have shown a dynamic temporal relationship between intrinsic basal ganglia oscillations and the various components of gait (Fischer et al, 2018 , 2020 ). Novel stimulation paradigms have been proposed as a possible alternatives to conventional DBS that may improve the suboptimal responses to classic DBS approaches (Akbar et al, 2016 ).…”

Gait-phase modulates alpha and beta oscillations in the pedunculopontine nucleus

“…Recently, an alternating DBS pattern, consisting of rhythmic intermittent reductions in stimulation intensity with a fixed offset between the right and left STN, was shown to significantly manipulate step timing. 16 These results have raised the possibility that alternating stimulation in the STN may be a promising DBS pattern for gait control in PD. In this study, we showed that alpha and beta oscillations in the PPN were modulated relative to the gait phase of the contralateral foot in both patients with MSA and PD.…”

“…Considering the rhythmic structure of movements during gait, conventional continuous DBS may be suboptimal for improving gait control. 16 Understanding how neural activity in the PPN is modulated during gait could be a crucial step in improving the therapeutic effects of PPN DBS. Increased alpha power in the PPN has been observed in human patients during locomotion including free walking or imaginary gait, 3,17,18 and increased alpha power in the PPN during walking correlated with gait performance.…”

“…It is impossible to distinguish whether the modulation we observed reflects motor output or sensory feedback about the movements. To test the causal role of rhythmic modulation of PPN activity and its potential clinical benefits, we need to test alternating PPN DBS patterns and evaluate their impact on gait control, similarly as previously done with alternating STN DBS 16.…”

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“…However, several small studies have found that low-frequency stimulation (<100 Hz) can improve gait in PD (Moreau et al, 2008;Xie et al, 2016). Additionally, physiology studies have shown a dynamic temporal relationship between intrinsic basal ganglia oscillations and the various components of gait (Fischer et al, 2018(Fischer et al, , 2020. Novel stimulation paradigms have been proposed as a possible alternatives to conventional DBS that may improve the suboptimal responses to classic DBS approaches (Akbar et al, 2016).…”