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Nat Med. 2016 Feb;22(2):138-45. doi: 10.1038/nm.4025. Epub 2016 Jan 18.

Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury.

Author information

1
International Paraplegic Foundation Chair in Spinal Cord Repair, Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
2
Department of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
3
Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
4
Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.
5
Motor Physiology Laboratory, Pavlov Institute of Physiology, St. Petersburg, Russia.
6
Laboratory of Neuroprosthetics, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.
7
Lab of Neurophysiology and Experimental Neurorehabilitation, Children's Surgery and Orthopedic Clinic, Department of Nonpulmonary Tuberculosis, Institute of Physiopulmonology, St. Petersburg, Russia.
8
The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
9
MOVE Research Institute Amsterdam, Faculty of Behavioural and Movement Sciences, VU University Amsterdam, Amsterdam, the Netherlands.
10
Bertarelli Foundation Chair in Neuroprosthetic Technology, Center for Neuroprosthetics and Institute of Bioengineering, EPFL, Lausanne, Switzerland.
11
Micromotive GmbH, Mainz, Germany.
12
Fraunhofer Institute for Chemical Technology-Mainz Institute for Microtechnology (ICT-IMM), Mainz, Germany.
13
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
14
Motac Neuroscience Inc., Beijing, China.
15
University of Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.
16
CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.

Abstract

Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.

PMID:
26779815
PMCID:
PMC5061079
DOI:
10.1038/nm.4025
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

G.C., N.W., P.M., M.C., A.L., J.V., M.C., I.M., E.M.M., S.M. and S.L. hold various patents on electrode implant designs (WO2011/157714), chemical neuromodulation therapies (WO2015/000800), spatiotemporal neuromodulation algorithms (WO2015/063127), and robot–assisted rehabilitation enabled by neuromodulation therapies (WO2013/179230). G.C., S.L., S.M. and J.B. are founders and shareholders of G–Therapeutics SA; a company developing neuroprosthetic systems in direct relationships with the present work.

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