Courtine, GrégoireWagner, Fabien Bertrand PaulKomi, Salif Axel2021-10-282021-10-28202110.5075/epfl-thesis-8921https://infoscience.epfl.ch/handle/20.500.14299/182598Spinal cord injury (SCI) is a life-changing event. People who suffer from it lose their ability to move normally and are subject to life-threatening symptoms. When the insult is not too severe, partial recovery is possible. Otherwise, for severely affected people, the perspectives to ever retrieve normal functions is almost non-existent. A critically important window to promote plasticity 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 their limbs 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, SCI dramatically 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 a method to reactivate dormant neural networks innervated below the site of injury. It enables robust 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 intensive training. In human, its recent application indeed supported overground walking in chronically and severely injured people, but only showed limited plastic effects when compared to animals. Why? Recent advances support that continuous EES abolishes proprioceptive feedback that is essential to promote recovery. Moreover, late treatment of severe injuries consistently fail a promoting recuperation of functions. Alternatively, over the last decade, our laboratory developed a spatio-temporally patterned approach to EES. In addition to restore fine control over motor functions, this technique avoids the caveats of continuous EES, and hypothetically opens a window of opportunity for plasticity to happen. In this thesis, we propose a translation of this concept to humans. We first demonstrate that spatio-temporal EES restores robust and versatile locomotor control in people with chronic incomplete, though severe, SCI. Furthermore, the results support an aptitude of this approach to promote long lasting recovery of functions without stimulation after 5 months of intensive training. We then report on a patient-tailored technology, that includes personalized computational models enabling precise pre-operative planning strategies, a new electrode-lead and control softwares. This technology enables restoration of various motor functions in people with chronic and motor-complete injuries within few hours after beginning of therapy. Finally, we transfer this targeted approach to the control of blood pressure. We demonstrate that closed-loop stimulation protocols support a precise control over arterial blood pressure in rodents, non-humane primates and humans with severe SCI submitted to challenging cardiovascular conditions. Combined, the results presented in this manuscript open a clinically realistic perspective for the application of EES acutely after injury and to potentially promote robust recovery in severe SCI.enSpinal Cord InjuryEpidural Electrical Stimulationlocomotionmotor controlblood pressure controltrainingrecoverytranslational researchthesis::doctoral thesis