Cortical control of intraspinal microstimulation to restore motor function after paralysis

Abstract

Spinal cord injury (SCI) is a devastating condition affecting the quality of life of many otherwise healthy patients. To date, no cure or therapy is known to restore functional movements of the arm and hand, and despite considerable effort, stem cell based therapies have not been proven effective. As an alternative, nerves or muscles below the injury could be stimulated electrically. While there have been successful demonstrations of restoration of functional movement using muscle stimulation both in humans and non-human primates, intraspinal microstimulation (ISMS) could bear bene􀄕ts over peripheral stimulation. An extensive body of research on spinal stimulation has been accumulated – however, almost exclusively in non-primate species. Importantly, the primate motor system has evolved to be quite different from the frog’s or the cat’s – two commonly studied species –, re􀄘ecting and enabling changes in how primates use their hands. Because of these functional and anatomical differences, it is fair to assume that also spinal cord stimulation will have different effects in primates. is question – what are the movements elicited by ISMS in the macaque – will be addressed in chapters  and . Chronic intraspinal electrode implants so far have been difficult to realise. In chapter  we describe a novel use of 􀄘oating microelectrode arrays (FMAs) as chronic implants in the spinal cord. Compared to implanted microwires or other arrays, these FMAs have the bene􀄕t of a high electrode density combined with different lengths of electrodes. We were able to maintain these arrays in the cord for months and could elicit movements at low thresholds throughout. If we could build a neural prosthesis stimulating the spinal cord, how would it be controlled? Remarkable progress has been recently achieved in the 􀄕eld of brain-machine interfaces (BMIs), for example enabling patients to control robotic arms with neural signals recorded from chronically implanted electrodes. Chapter  of this thesis examines an approach that combines ISMS with cortical control in a macaque model for upper limb paralysis for the 􀄕rst time and shows that there is a behavioural improvement. We have devised an experiment in which a monkey trained to perform a grasp-and-pull task receives a temporary cortically induced paralysis of the hand reducing task performance. At the same time, cortical recordings from a different area allow us to control ISMS at sites evoking hand movements – thus partially restoring function. Finally, in appendix A we describe a system we developed in order to introduce automated positive reinforcement training (aPRT) both at the breeding facility and in our animal houses. is system potentially reduces time spent on training animals, adds enrichment to the monkeys’ home environment, and allows for suitability screening of monkeys for behavioural neuroscience experiments.