Electrical spinal cord stimulation protocols to regulate neurological functions after spinal cord injury

Spinal cord injury (SCI) is a life-changing event. People who suffer from it lose their abilityto move normally and are subject to life-threatening symptoms. When the insult is not toosevere, partial recovery is possible. Otherwise, for severely affected people, the perspectives toever retrieve normal functions is almost non-existent. A critically important window to promoteplasticity is in the acute phase after the trauma (weeks to months). However, at this stage,people cannot take active part in rehabilitation programs due to their incapacity to activate theirlimbs and to the apparition of severe autonomic symptoms such as orthostatic hypotension.Hence, current activity-based treatments are of little help for this population. Consequently, SCIdramatically affects their autonomy and quality of life on the life-long term.Continuous Epidural Electrical Stimulation (EES) of the spinal cord has been proposed as amethod to reactivate dormant neural networks innervated below the site of injury. It enablesrobust control over locomotion and autonomic functions. In animal models of severe lesion,continuous EES promoted long lasting recovery of motor abilities when coupled with an intensivetraining. In human, its recent application indeed supported overground walking in chronicallyand severely injured people, but only showed limited plastic effects when compared to animals.Why? Recent advances support that continuous EES abolishes proprioceptive feedback thatis essential to promote recovery. Moreover, late treatment of severe injuries consistently fail apromoting recuperation of functions. Alternatively, over the last decade, our laboratory developeda spatio-temporally patterned approach to EES. In addition to restore fine control over motorfunctions, this technique avoids the caveats of continuous EES, and hypothetically opens a windowof opportunity for plasticity to happen. In this thesis, we propose a translation of this concept tohumans. We first demonstrate that spatio-temporal EES restores robust and versatile locomotorcontrol in people with chronic incomplete, though severe, SCI. Furthermore, the results supportan aptitude of this approach to promote long lasting recovery of functions without stimulationafter 5 months of intensive training. We then report on a patient-tailored technology, thatincludes personalized computational models enabling precise pre-operative planning strategies, anew electrode-lead and control softwares. This technology enables restoration of various motorfunctions in people with chronic and motor-complete injuries within few hours after beginningof therapy. Finally, we transfer this targeted approach to the control of blood pressure. Wedemonstrate that closed-loop stimulation protocols support a precise control over arterial bloodpressure in rodents, non-humane primates and humans with severe SCI submitted to challengingcardiovascular conditions. Combined, the results presented in this manuscript open a clinicallyrealistic perspective for the application of EES acutely after injury and to potentially promoterobust recovery in severe SCI.