title: Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury.
abstract: Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders.
authors.affiliation: International Paraplegic Foundation Chair in Spinal Cord Repair, Center for Neuroprosthetics and Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Wenger
authors.affiliation: Translational Neural Engineering Lab, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland. Automatic Control Laboratory, Swiss Federal Institute of Technology (ETHZ), Zurich CH-8092, Switzerland.
authors.forename: Eduardo Martin
authors.initials: EM
authors.lastname: Moraud
authors.affiliation: Translational Neural Engineering Lab, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland. The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa IT-56025, Italy.
authors.forename: Stanisa
authors.initials: S
authors.lastname: Raspopovic
authors.affiliation: Translational Neural Engineering Lab, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Bonizzato
authors.affiliation: Translational Neural Engineering Lab, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, 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, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland. Pavlov Institute of Physiology, St. Petersburg RU-100034, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Musienko
authors.affiliation: Automatic Control Laboratory, Swiss Federal Institute of Technology (ETHZ), Zurich CH-8092, Switzerland.
authors.forename: Manfred
authors.initials: M
authors.lastname: Morari
authors.affiliation: Translational Neural Engineering Lab, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland. The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa IT-56025, 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, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland. gregoire.courtine@epfl.ch.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Courtine
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D004195:Disease Models, Animal; D005121:Extremities / Q000294:innervation*; D056228:Feedback, Sensory; D005260:Female; D005684:Gait; D008124:Locomotion; D009046:Motor Neurons; D018763:Muscle Fatigue; D058117:Neural Prostheses; D058765:Neurofeedback / Q000295:instrumentation*; D011474:Prosthesis Design; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D013127:Spinal Nerves / Q000503:physiopathology*; D013997:Time Factors