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

Abstract

Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain–computer interfaces1–3 have directly linked cortical activity to electrical stimulation of muscles, which have 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, we showed in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion8–10. Here, we interfaced leg motor cortex activity with epidural electrical stimulation protocols to establish a brain–spinal interface that alleviated gait deficits after a spinal cord injury in nonhuman primates. Rhesus monkeys were implanted with an intracortical microelectrode array into the leg area of motor cortex; and 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–spinal interface in intact 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–spinal interface restored weight-bearing locomotion of the paralyzed leg on a treadmill and overground. The implantable components integrated in the brain–spinal 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.

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

“…There was evidence to support the NT‐3‐induced spinal circuitry plasticity to affect the changes necessary to promote the locomotor improvements. In a mature neuronal circuit, it is easy to establish the voluntary muscular contraction on one side of the organization by producing communication in the contralateral corticospinal motor pathway 48, 49, 50. With four canines in each group, we tested their CMEPs, and compared them with the CMEP before injury, 1 week and 4 weeks after graft.…”

Toward Bioelectronic Medicine—Neuromodulation of Small Peripheral Nerves Using Flexible Neural Clip

“…In case of NIT in the CNS applications, glial scar‐free neural recordings have been achieved using ultraflexible probes in the brains of rodents 10. Furthermore, the brain–spine interface was able to support the locomotion of monkeys using a multimodal neural interface, called e‐dura 11, 12…”

Viral-mediated optogenetic stimulation of peripheral motor nerves in non-human primates

“…FES is typically associated with electrical stimulation of muscles directly or through nerve stimulation. However, several groups have used brain-controlled electrical intraspinal [61] or epidural spinal [62] stimulation in NHPs for grasping and hindlimb locomotion, respectively. This mode of stimulation elicits muscle activation patterns either directly by stimulating pools of alpha motorneurons or indirectly by inducing motor patterns through interneurons following stimulation of dorsal roots.…”