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.
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).
Extended data figures
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.