Neurophysiological Correlates of Gait in the Human Basal Ganglia and the PPN Region in Parkinson's Disease.

Rene Molina,Kristen Sowalsky,Christopher W Hess,Daniel Martinez-Ramirez,Aysegul Gunduz,Jaime A Roper,Enrico Opri,Abigail C Schmitt,Michael S Okun,Kelly D Foote,Chris J Hass

doi:10.3389/fnhum.2020.00194

Rene Molina, Kristen Sowalsky + Show 9 more

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https://doi.org/10.3389/fnhum.2020.00194

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Abstract

This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in Parkinson’s disease (PD) cohort. Though much is known about the PPN region through animal studies, there are limited physiological recordings from ambulatory humans. The PPN has recently garnered interest as a potential deep brain stimulation (DBS) target for improving gait and freezing of gait (FoG) in PD. We used bidirectional neurostimulators to record from the human PPN region and GPi in a small cohort of severely affected PD subjects with FoG despite optimized dopaminergic medications. Five subjects, with confirmed on-dopaminergic medication FoG, were implanted with bilateral GPi and bilateral PPN region DBS electrodes. Electrophysiological recordings were obtained during various gait tasks for 5 months postoperatively in both the off- and on-medication conditions (obtained during the no stimulation condition). The results revealed suppression of low beta power in the GPi and a 1–8 Hz modulation in the PPN region which correlated with human gait. The PPN feature correlated with walking speed. GPi beta desynchronization and PPN low-frequency synchronization were observed as subjects progressed from rest to ambulatory tasks. Our findings add to our understanding of the neurophysiology underpinning gait and will likely contribute to the development of novel therapies for abnormal gait in PD.Clinical Trial Registration: Clinicaltrials.gov identifier; NCT02318927.

Highlights

The pedunculopontine nucleus (PPN) region has recently generated much interest as a deep brain stimulation (DBS) target for the treatment of freezing of gait (FoG) in Parkinson’s disease (PD; Stefani et al, 2007, 2013; Moreau et al, 2009; Moro et al, 2010; Khan et al, 2012; Welter et al, 2015; Hamani et al, 2016)
The rostral face of the PPN region resides in an area laterally and ventrally bound by the spinothalamic tract, the lateral lemniscus, and medial lemniscus, as well as dorsal-medially by the spinal cerebellar peduncle (SCP) decussation (Hamani et al, 2016)
Our findings showed suppression of low beta power in the globus pallidus internus (GPi) in response to medication, and a 1–8 Hz modulation in four subjects in the PPN region correlating with human gait in the on medication state

Summary

Introduction

The pedunculopontine nucleus (PPN) region has recently generated much interest as a deep brain stimulation (DBS) target for the treatment of freezing of gait (FoG) in Parkinson’s disease (PD; Stefani et al, 2007, 2013; Moreau et al, 2009; Moro et al, 2010; Khan et al, 2012; Welter et al, 2015; Hamani et al, 2016). Several clues point to the PPN region as an important node in human gait-related activities. It has been shown that gait-related symptoms have been closely associated with diseases associated with prominent PPN degeneration (e.g., PD and progressive supranuclear palsy). The PPN has been shown in animals to be a critical node in the gait cycle. Altered gait has been reported in lesional studies of the PPN region, and gait deficits are improved by electrical stimulation in both rat and non-human primate PD models (Aziz et al, 1998; Breit et al, 2001, 2005; Jenkinson et al, 2006; Nandi et al, 2008; Karachi et al, 2010; Grabli et al, 2013)

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