title: Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury.
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.
authors.affiliation: 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.|Department of Neurology with Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Wenger
authors.affiliation: Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.
authors.forename: Eduardo Martin
authors.initials: EM
authors.lastname: Moraud
authors.affiliation: 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.
authors.forename: Jerome
authors.initials: J
authors.lastname: Gandar
authors.affiliation: 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.|Motor Physiology Laboratory, Pavlov Institute of Physiology, St. Petersburg, Russia.|Laboratory of Neuroprosthetics, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia.|Lab of Neurophysiology and Experimental Neurorehabilitation, Children's Surgery and Orthopedic Clinic, Department of Nonpulmonary Tuberculosis, Institute of Physiopulmonology, St. Petersburg, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Musienko
authors.affiliation: Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.|The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Capogrosso
authors.affiliation: 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.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Baud
authors.affiliation: 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.
authors.forename: Camille G
authors.initials: CG
authors.lastname: Le Goff
authors.affiliation: 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.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Barraud
authors.affiliation: 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.|Motor Physiology Laboratory, Pavlov Institute of Physiology, St. Petersburg, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pavlova
authors.affiliation: 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.|MOVE Research Institute Amsterdam, Faculty of Behavioural and Movement Sciences, VU University Amsterdam, Amsterdam, the Netherlands.
authors.forename: Nadia
authors.initials: N
authors.lastname: Dominici
authors.affiliation: Bertarelli Foundation Chair in Neuroprosthetic Technology, Center for Neuroprosthetics and Institute of Bioengineering, EPFL, Lausanne, Switzerland.
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Minev
authors.affiliation: 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.
authors.forename: Leonie
authors.initials: L
authors.lastname: Asboth
authors.affiliation: Bertarelli Foundation Chair in Neuroprosthetic Technology, Center for Neuroprosthetics and Institute of Bioengineering, EPFL, Lausanne, Switzerland.
authors.forename: Arthur
authors.initials: A
authors.lastname: Hirsch
authors.affiliation: 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.
authors.forename: Simone
authors.initials: S
authors.lastname: Duis
authors.affiliation: 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.
authors.forename: Julie
authors.initials: J
authors.lastname: Kreider
authors.affiliation: Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mortera
authors.affiliation: Micromotive GmbH, Mainz, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Haverbeck
authors.affiliation: Micromotive GmbH, Mainz, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Kraus
authors.affiliation: Fraunhofer Institute for Chemical Technology-Mainz Institute for Microtechnology (ICT-IMM), Mainz, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Schmitz
authors.affiliation: Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.
authors.forename: Jack
authors.initials: J
authors.lastname: DiGiovanna
authors.affiliation: 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.
authors.forename: Rubia
authors.initials: R
authors.lastname: van den Brand
authors.affiliation: Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Bloch
authors.affiliation: Fraunhofer Institute for Chemical Technology-Mainz Institute for Microtechnology (ICT-IMM), Mainz, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Detemple
authors.affiliation: Bertarelli Foundation Chair in Neuroprosthetic Technology, Center for Neuroprosthetics and Institute of Bioengineering, EPFL, Lausanne, Switzerland.
authors.forename: Stéphanie P
authors.initials: SP
authors.lastname: Lacour
authors.affiliation: Motac Neuroscience Inc., Beijing, China.|University of Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bézard
authors.affiliation: Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.|The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Silvestro
authors.initials: S
authors.lastname: Micera
authors.affiliation: 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.|Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Courtine
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D003198:Computer Simulation; D019054:Evoked Potentials, Motor / Q000502:physiology*; D056228:Feedback, Sensory / Q000502:physiology*; D005260:Female; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology*; D007700:Kinetics; D008124:Locomotion / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000502:physiology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology* / Q000534:rehabilitation; D062187:Spinal Cord Stimulation; D013126:Spinal Nerve Roots / Q000503:physiopathology*; D013997:Time Factors; D055114:X-Ray Microtomography