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

Nikolaus Wenger, Eduardo Martin Moraud, Jerome Gandar, Pavel Musienko, Marco Capogrosso, Laetitia Baud, Camille G Le Goff, Quentin Barraud, Natalia Pavlova, Nadia Dominici, Ivan R Minev, Leonie Asboth, Arthur Hirsch, Simone Duis, Julie Kreider, Andrea Mortera, Oliver Haverbeck, Silvio Kraus, Felix Schmitz, Jack DiGiovanna, Rubia van den Brand, Jocelyne Bloch, Peter Detemple, Stéphanie P Lacour, Erwan Bézard, Silvestro Micera, Grégoire Courtine
Nat Med. 2016-01-18; 22(2): 138-145
DOI: 10.1038/nm.4025

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1. 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.

Wenger N(1)(2)(3), Moraud EM(4), Gandar J(1), Musienko P(1)(5)(6)(7), Capogrosso
M(4)(8), Baud L(1), Le Goff CG(1), Barraud Q(1), Pavlova N(1)(5), Dominici
N(1)(9), Minev IR(10), Asboth L(1), Hirsch A(10), Duis S(1), Kreider J(1),
Mortera A(4), Haverbeck O(11), Kraus S(11), Schmitz F(12), DiGiovanna J(4), van
den Brand R(1), Bloch J(13), Detemple P(12), Lacour SP(10), Bézard E(14)(15)(16),
Micera S(4)(8), Courtine G(1)(13).

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,
(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,
(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,
(16)CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.

Comment in
Nat Med. 2016 Feb;22(2):125-6.

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.

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

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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