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

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 physiologi...

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Published inFrontiers in human neuroscience Vol. 14; p. 194
Main Authors Molina, Rene, Hass, Chris J., Sowalsky, Kristen, Schmitt, Abigail C., Opri, Enrico, Roper, Jaime A., Martinez-Ramirez, Daniel, Hess, Christopher W., Foote, Kelly D., Okun, Michael S., Gunduz, Aysegul
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 04.06.2020
Frontiers Media S.A
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ISSN1662-5161
1662-5161
DOI10.3389/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. Clinicaltrials.gov identifier; NCT02318927.
AbstractList 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.
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.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.
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. Clinicaltrials.gov identifier; NCT02318927.
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.
This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus (GPi) in a Parkinson’s disease (PD) cohort. Though much is known about the PPN region through animal studies, there is 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 five months post-operatively 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 was 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.
Author Sowalsky, Kristen
Okun, Michael S.
Molina, Rene
Hass, Chris J.
Martinez-Ramirez, Daniel
Foote, Kelly D.
Schmitt, Abigail C.
Roper, Jaime A.
Hess, Christopher W.
Opri, Enrico
Gunduz, Aysegul
AuthorAffiliation 2 Norman Fixel Institute for Neurological Diseases and the Program for Movement Disorders and Neurorestoration, University of Florida , Gainesville, FL , United States
8 Department of Neurosurgery , University of Florida, Gainesville, FL , United States
3 Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, FL , United States
1 Department of Electrical and Computer Engineering, University of Florida , Gainesville, FL , United States
6 Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud , Monterrey , Mexico
7 Department of Neurology , University of Florida, Gainesville, FL , United States
5 School of Kinesiology, Auburn University , Auburn, AL , United States
4 J. Crayton Pruitt Department of Biomedical Engineering, University of Florida , Gainesville, FL , United States
AuthorAffiliation_xml – name: 1 Department of Electrical and Computer Engineering, University of Florida , Gainesville, FL , United States
– name: 4 J. Crayton Pruitt Department of Biomedical Engineering, University of Florida , Gainesville, FL , United States
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– name: 3 Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, FL , United States
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– name: 2 Norman Fixel Institute for Neurological Diseases and the Program for Movement Disorders and Neurorestoration, University of Florida , Gainesville, FL , United States
– name: 6 Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud , Monterrey , Mexico
– name: 7 Department of Neurology , University of Florida, Gainesville, FL , United States
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Keywords Parkinson’s disease (PD)
brainstem
deep brain stimulation (DBS)
DBS
gait
deep brain stimulation
Language English
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These authors share senior authorship
Reviewed by: Chiung-Chu Chen, Linkou Chang Gung Memorial Hospital, Taiwan; Petra Fischer, University of Oxford, United Kingdom
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Snippet This study aimed to characterize the neurophysiological correlates of gait in the human pedunculopontine nucleus (PPN) region and the globus pallidus internus...
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StartPage 194
SubjectTerms Basal ganglia
brainstem
Data collection
DBS
Deep brain stimulation
deep brain stimulation (DBS)
Dopamine
Dopamine receptors
Gait
Globus pallidus
Human Neuroscience
Movement disorders
Neurodegenerative diseases
Parkinson's disease
Parkinson’s disease (PD)
Pedunculopontine tegmental nucleus
Physiology
Signal processing
Surgery
Synchronization
Transplants & implants
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Title Neurophysiological Correlates of Gait in the Human Basal Ganglia and the PPN Region in Parkinson’s Disease
URI https://www.ncbi.nlm.nih.gov/pubmed/32581744
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