Research Article
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Published Online: 11 December 2015

Noninvasive Reactivation of Motor Descending Control after Paralysis

Publication: Journal of Neurotrauma
Volume 32, Issue Number 24

Abstract

The present prognosis for the recovery of voluntary control of movement in patients diagnosed as motor complete is generally poor. Herein we introduce a novel and noninvasive stimulation strategy of painless transcutaneous electrical enabling motor control and a pharmacological enabling motor control strategy to neuromodulate the physiological state of the spinal cord. This neuromodulation enabled the spinal locomotor networks of individuals with motor complete paralysis for 2–6 years American Spinal Cord Injury Association Impairment Scale (AIS) to be re-engaged and trained. We showed that locomotor-like stepping could be induced without voluntary effort within a single test session using electrical stimulation and training. We also observed significant facilitation of voluntary influence on the stepping movements in the presence of stimulation over a 4-week period in each subject. Using these strategies we transformed brain–spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in five out of five subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects. We also observed on-command selective activation of the gastrocnemius and soleus muscles when attempting to plantarflex. At the end of 18 weeks of weekly interventions the mean changes in the amplitude of voluntarily controlled movement without stimulation was as high as occurred when combined with electrical stimulation. Additionally, spinally evoked motor potentials were readily modulated in the presence of voluntary effort, providing electrophysiological evidence of the re-establishment of functional connectivity among neural networks between the brain and the spinal cord.

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Information

Published In

cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 32Issue Number 24December 15, 2015
Pages: 1968 - 1980
PubMed: 26077679

History

Published in print: December 15, 2015
Published online: 11 December 2015
Published ahead of print: 20 August 2015
Published ahead of production: 15 June 2015

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Authors

Affiliations

Yury P. Gerasimenko
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California.
Pavlov Institute of Physiology, St. Petersburg, Russia.
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Daniel C. Lu
Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California.
Neuromotor Recovery and Rehabilitation Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Morteza Modaber
Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California.
Neuromotor Recovery and Rehabilitation Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Sharon Zdunowski
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California.
Parag Gad
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California.
Dimitry G. Sayenko
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California.
Erika Morikawa
Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California.
Neuromotor Recovery and Rehabilitation Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Piia Haakana
Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California.
Neuromotor Recovery and Rehabilitation Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
Adam R. Ferguson
Brain and Spinal Injury Center, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.
Roland R. Roy
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California.
Brain Research Institute, University of California, Los Angeles, Los Angeles, California.
V. Reggie Edgerton
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California.
Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California.
Brain Research Institute, University of California, Los Angeles, Los Angeles, California.

Notes

Address correspondence to:Yury P. Gerasimenko, PhDDepartment of Integrative Biology and PhysiologyUniversity of California, Los AngelesTerasaki Life Sciences Building610 Charles E. Young Drive EastLos Angeles, CA 90095-1527E-mail: [email protected]

Author Disclosure Statement

VRE, YPG, DCL, PG, and RRR researchers on the study team hold shareholder interest in NeuroRecovery Technologies. VRE is president and chair of company's board of directors. VRE, YPG, DCL, and RRR hold certain inventorship rights on intellectual property licensed by the regents of the University of California to NeuroRecovery Technologies and its subsidiaries.

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