title: Mechanisms Underlying the Neuromodulation of Spinal Circuits for Correcting Gait and Balance Deficits after Spinal Cord Injury.
abstract: Epidural electrical stimulation of lumbar segments facilitates standing and walking in animal models and humans with spinal cord injury. However, the mechanisms through which this neuromodulation therapy engages spinal circuits remain enigmatic. Using computer simulations and behavioral experiments, we provide evidence that epidural electrical stimulation interacts with muscle spindle feedback circuits to modulate muscle activity during locomotion. Hypothesis-driven strategies emerging from simulations steered the design of stimulation protocols that adjust bilateral hindlimb kinematics throughout gait execution. These stimulation strategies corrected subject-specific gait and balance deficits in rats with incomplete and complete spinal cord injury. The conservation of muscle spindle feedback circuits across mammals suggests that the same mechanisms may facilitate motor control in humans. These results provide a conceptual framework to improve stimulation protocols for clinical applications.
authors: Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
authors: Eduardo Martin
authors: EM
authors: Moraud
authors: Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland; BioRobotics Institute, Scuola Superiore Sant'Anna, 56127 Pisa, Italy.
authors: Marco
authors: M
authors: Capogrosso
authors: Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
authors: Emanuele
authors: E
authors: Formento
authors: Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland; Department of Neurology and Experimental Neurology, University of Berlin, 10098 Berlin, Germany.
authors: Nikolaus
authors: N
authors: Wenger
authors: Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
authors: Jack
authors: J
authors: DiGiovanna
authors: Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland. Electronic address: gregoire.courtine@epfl.ch.
authors: Grégoire
authors: G
authors: Courtine
authors: Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland; BioRobotics Institute, Scuola Superiore Sant'Anna, 56127 Pisa, Italy. Electronic address: silvestro.micera@epfl.ch.
authors: Silvestro
authors: S
authors: Micera
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D003198:Computer Simulation; D004599:Electric Stimulation Therapy; D004576:Electromyography; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology* / Q000534:rehabilitation*; D006614:Hindlimb / Q000503:physiopathology; D008124:Locomotion / Q000502:physiology; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology; D009415:Nerve Net / Q000502:physiology; D004856:Postural Balance / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D012678:Sensation Disorders / Q000209:etiology / Q000628:therapy*; D013119:Spinal Cord Injuries / Q000150:complications*