Abstract
Epidural electrical stimulation (EES) of the spinal cord and real-time processing of gait kinematics are powerful methods for the study of locomotion and the improvement of motor control after injury or in neurological disorders. Here, we describe equipment and surgical procedures that can be used to acquire chronic electromyographic (EMG) recordings from leg muscles and to implant targeted spinal cord stimulation systems that remain stable up to several months after implantation in rats and nonhuman primates. We also detail how to exploit these implants to configure electrical spinal cord stimulation policies that allow control over the degree of extension and flexion of each leg during locomotion. This protocol uses real-time processing of gait kinematics and locomotor performance, and can be configured within a few days. Once configured, stimulation bursts are delivered over specific spinal cord locations with precise timing that reproduces the natural spatiotemporal activation of motoneurons during locomotion. These protocols can also be easily adapted for the safe implantation of systems in the vicinity of the spinal cord and to conduct experiments involving real-time movement feedback and closed-loop controllers.
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Acknowledgements
The illustration in Fig. 1 was created by C. Beach. N.W. is a participant in the Charité Clinical Scientist Program funded by the Charité–Universitätsmedizin Berlin and the Berlin Institute of Health. This work was supported by Medtronic, the European Community’s Seventh Framework Programme (CP-IP 258654, NeuWALK), the International Paraplegic foundation (IRP), a Consolidator Grant from the European Research Council (ERC-2015-CoG HOW2WALKAGAIN 682999), the Wyss Center in Geneva, the Russian Science Foundation (RSF grant 14-15-00788, P.M.), a Wings for Life Fellowship to G.C., Marie Curie COFUND EPFL fellowships to F.B.W. and T.M., and a Morton Cure Paralysis Fund fellowship to T.M., as well as by the Swiss National Science Foundation, including a Bonus of Excellence (310030B_166674), the National Center of Competence in Research (NCCR) Robotics, the Sino-Swiss Science and Technology Cooperation (IZLCZ3_156331), the NanoTera.ch program (SpineRepair) and the Sinergia program (CRSII3_160696).
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M.C., F.B.W., J.G., E.M.M., N.W., T.M. and G.C. developed the methods to control the stimulation and optimize the electrode placement. P.S., N.P., P.M., J.B. and G.C. developed the surgical procedures. M.C., F.B.W., J.G., E.M.M. and T.M. performed the experiments in monkeys. N.W., E.M.M., J.G. and M.C. performed the experiments in rats. E.B. and G.C. supervised the experiments and animal procedures. M.C., F.B.W., J.G., E.M.M., N.W. and T.M. analyzed the data. M.C., F.B.W. and J.G. created the figures. M.C., F.B.W. and G.C. wrote the manuscript.
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G.C., M.C., E.M.M., N.W., T.M., F.B.W., J.G. and J.B. hold various patents related to the present work. E.B. reports receipt of personal fees from Motac Neuroscience Ltd. UK and is a shareholder of Motac Holding, UK, and Plenitudes SARL, France. G.C. and J.B. are founders and shareholders of GTX Medical BV. The other authors declare no competing interests.
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1. Wenger, N. et al. Nat. Med. 22, 138–145 (2016) https://doi.org/10.1038/nm.4025
2. Capogrosso, M. et al. Nature 539, 284–288 (2016) https://doi.org/10.1038/nature20118
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Capogrosso, M., Wagner, F.B., Gandar, J. et al. Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics . Nat Protoc 13, 2031–2061 (2018). https://doi.org/10.1038/s41596-018-0030-9
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DOI: https://doi.org/10.1038/s41596-018-0030-9
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