A brain-spine interface alleviating gait deficits after spinal cord injury in primates.
Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. 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 locomotion. 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.
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.|Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.
Marco
M
Capogrosso
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Tomislav
T
Milekovic
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.|School of Engineering, Brown University, Providence, Rhode Island, USA.
David
D
Borton
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Fabien
F
Wagner
Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.
Eduardo Martin
EM
Moraud
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Jean-Baptiste
JB
Mignardot
Medtronic, Minneapolis, Minnesota, USA.
Nicolas
N
Buse
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Jerome
J
Gandar
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Quentin
Q
Barraud
School of Engineering, Brown University, Providence, Rhode Island, USA.
David
D
Xing
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Elodie
E
Rey
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Simone
S
Duis
Motac Neuroscience Ltd, Manchester, UK.
Yang
Y
Jianzhong
Motac Neuroscience Ltd, Manchester, UK.
Wai Kin D
WK
Ko
Motac Neuroscience Ltd, Manchester, UK.|Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.
Qin
Q
Li
Mainz Institute for Microtechnology, Fraunhofer Institute for Chemical Technology (ICT-IMM), Mainz, Germany.
Peter
P
Detemple
Medtronic, Minneapolis, Minnesota, USA.
Tim
T
Denison
Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL, Lausanne, Switzerland.|The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
Silvestro
S
Micera
Motac Neuroscience Ltd, Manchester, UK.|Institute of Lab Animal Sciences, China Academy of Medical Sciences, Beijing, China.|Institut des Maladies Neurodégénératives, University of Bordeaux, UMR 5293, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
Erwan
E
Bezard
Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Jocelyne
J
Bloch
Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.|Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Grégoire
G
Courtine
D000818:Animals; D062207:Brain-Computer Interfaces; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004599:Electric Stimulation Therapy / Q000295:instrumentation*; D005684:Gait / Q000502:physiology*; D020233:Gait Disorders, Neurologic / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*; D007866:Leg / Q000502:physiology; D008124:Locomotion / Q000502:physiology; D008161:Lumbosacral Region; D008253:Macaca mulatta; D008297:Male; D008839:Microelectrodes; D009044:Motor Cortex / Q000503:physiopathology; D058117:Neural Prostheses; D010243:Paralysis / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D015203:Reproducibility of Results; D013116:Spinal Cord / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*; D059015:Wireless Technology / Q000295:instrumentation