A brain–spine interface alleviating gait deficits after spinal cord injury in primates

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Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1,2,3 have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis1,4. Theoretically, this strategy could also restore control over leg muscle activity for walking5. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges6,7. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8,9,10. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain–spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain–spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain–spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

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G.C. holds the International Foundation for Research in Paraplegia Chair in Spinal Cord Repair. S.M. holds the Bertarelli Foundation Chair in Translational Neuroengineering. We thank X. Rulin and C. Yunlong for providing support, taking care of the monkeys, performing behavioural training, and collecting data; E. Pirondini, N. Pavlova and P. Musienko for help with experiments; J. Courtine, I. Pitteloud, J. Rubattel, L. Dalang and R. Hasler for help with kinematic reconstruction; J. Courtine for the voice-over in video; J. Kreider for help with anatomy; and J. Laurens for discussions and photographs. The illustrations were created by Jemère Ruby. This work was supported by Medtronic, the European Community's Seventh Framework Program (CP-IP 258654, NeuWALK), the International Paraplegic foundation, a Starting Grant from the European Research Council (ERC 261247, Walk Again), the Wyss centre in Geneva, a Marie Curie Fellowship to D.B. (331602, e-WALK), Marie Curie COFUND EPFL fellowships to T.M. and F.W., a Morton Cure Paralysis Fund fellowship to T.M., and the Swiss National Science Foundation including the National Centre of Competence in Research in Robotics, the Sinergia program (CRSII3_160696), the Sino-Swiss Science and Technology Cooperation (IZLCZ3_156331), and the NanoTera.ch programme (SpineRepair).

Author information

Author notes

    • Marco Capogrosso
    • , Tomislav Milekovic
    •  & David Borton

    These authors contributed equally to this work.


  1. Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland

    • Marco Capogrosso
    • , Tomislav Milekovic
    • , David Borton
    • , Fabien Wagner
    • , Jean-Baptiste Mignardot
    • , Jerome Gandar
    • , Quentin Barraud
    • , Elodie Rey
    • , Simone Duis
    •  & Grégoire Courtine
  2. Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland

    • Marco Capogrosso
    • , Eduardo Martin Moraud
    •  & Silvestro Micera
  3. School of Engineering, Brown University, Providence, Rhode Island, USA

    • David Borton
    •  & David Xing
  4. Medtronic, Minneapolis, Minnesota, USA

    • Nicolas Buse
    •  & Tim Denison
  5. Motac Neuroscience Ltd, Manchester, UK

    • Yang Jianzhong
    • , Wai Kin D. Ko
    • , Qin Li
    •  & Erwan Bezard
  6. Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China

    • Qin Li
    •  & Erwan Bezard
  7. Mainz Institute for Microtechnology, Fraunhofer Institute for Chemical Technology (ICT-IMM), Mainz, Germany

    • Peter Detemple
  8. The BioRobotics Institute, Scuola Superiore Sant’Anna, Pisa, Italy

    • Silvestro Micera
  9. Institut des Maladies Neurodégénératives, University of Bordeaux, UMR 5293, Bordeaux, France

    • Erwan Bezard
  10. CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France

    • Erwan Bezard
  11. Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

    • Jocelyne Bloch
    •  & Grégoire Courtine


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M.C., T.M. and D.B. contributed equally to this work. F.W. and E.M.M. contributed equally to this work. S.M., E.B. and J.B. contributed equally to this work. M.C. developed the spinal cord stimulation protocols and the routines for the identification of flexion and extension hotspots. T.M. developed the brain decoder and the decoder calibration routines. D.B. developed the experimental platform. M.C., T.M., F.W. and E.M.M. performed all the behavioural experiments (with help from D.B., J.G., Y.J. and G.C.). M.C., T.M. and F.W. analysed the data (with input from E.M.M., J.-B.M. and D.X.). M.C., T.M., F.W., E.M.M. and J.G. developed the real-time software application. N.B. and T.D. developed the Neural Research Programmer (with input from M.C., D.B., T.M., F.W. and J.G.). Q.B. and E.R. processed the anatomical data. Y.J. trained all the monkeys. W.K.D.K., Q.L. and E.B. managed the experimental protocols and procedures. P.D. developed and produced the spinal implants (from designs by M.C., D.B., J.B. and G.C.). J.B., D.B., Q.L. and G.C. performed the surgeries. G.C., S.M., E.B., J.B. and P.D. secured funding for the study. G.C. conceived and supervised the study. G.C. wrote the paper with M.C., T.M. and F.W., and all the authors contributed to its editing.

Competing interests

G.C., D.B., M.C., S.M., E.M.M. and J.B. hold various patents related to the present work. T.D. and N.B. are Medtronic employees and contributed to the technical accuracy of the work but did not influence the results or the content of the manuscript. 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., S.M. and J.B. are founders and shareholders of G-Therapeutics BV.

Corresponding author

Correspondence to Grégoire Courtine.

Reviewer Information

Nature thanks A. Jackson, A. Prochazka, S. Scott and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Extended data

Supplementary information

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  1. 1.

    Supplementary Information

    This file contains Supplementary Text and Data and Supplementary Tables 1-3.


  1. 1.

    Technical design and therapeutic effects of the brain–spinal interface

    This video explains the design of the spinal cord stimulation system and brain decoding algorithms. The ability of the brain–spinal interface to modulate extension and flexion movements of the leg during continuous locomotion is then illustrated in intact monkeys. Finally, the video shows the recovery of functional leg movements during locomotion on a treadmill and overground in two monkeys with a spinal cord injury.


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