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

• Published in: Nature Medicine Vol. 22; no. 2; pp. 138 - 145
• Main Authors: Wenger, Nikolaus, Moraud, Eduardo Martin, Gandar, Jerome, Musienko, Pavel, Capogrosso, Marco, Baud, Laetitia, Le Goff, Camille G, Barraud, Quentin, Pavlova, Natalia, Dominici, Nadia, Minev, Ivan R, Asboth, Leonie, Hirsch, Arthur, Duis, Simone, Kreider, Julie, Mortera, Andrea, Haverbeck, Oliver, Kraus, Silvio, Schmitz, Felix, DiGiovanna, Jack, van den Brand, Rubia, Bloch, Jocelyne, Detemple, Peter, Lacour, Stéphanie P, Bézard, Erwan, Micera, Silvestro, Courtine, Grégoire
• Format: Journal Article Magazine Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2016; Nature Publishing Group
• Subjects: 631/378/2632/1823; 692/617; Animal models; Animals; Biomechanical Phenomena; Biomedicine; Cancer Research; Care and treatment; Cellular biology; Computer Simulation; Electrodes; Evoked Potentials, Motor - physiology; Feedback, Sensory - physiology; Female; Hindlimb - innervation; Hindlimb - physiopathology; Infectious Diseases; Kinetics; Life Sciences; Locomotion - physiology; Medical treatment; Metabolic Diseases; Molecular Medicine; Motor ability; Motor Neurons - physiology; Muscle, Skeletal - innervation; Muscle, Skeletal - physiopathology; Neural stimulation; Neurons; Neurosciences; Physiological aspects; Physiology; Rats; Rats, Inbred Lew; Rodents; Spinal Cord - physiology; Spinal cord injuries; Spinal Cord Injuries - pathology; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - rehabilitation; Spinal Cord Stimulation; Spinal Nerve Roots - physiopathology; Time Factors; X-Ray Microtomography
• ISSN: 1078-8956; 1546-170X; 1744-7933
• DOI: 10.1038/nm.4025

Analysis of synergistic muscle activations during locomotion and anatomical tracing of muscle synergy representations in the rodent spinal cord guide the development of a new spinal implant for neuromodulation therapy. In multiple rodent models of spinal cord injury, spatiotemporal stimulation that mimics naturalistic muscle activation patterns promotes improved functional recovery over previously described continuous stimulation protocols. 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.