Unbiased interrogation of whole brain circuits in spinal cord injury leading to the design of a clinically relevant therapy to improve locomotion

Spinal cord injury (SCI) remains a global problem, and despite decades of research there currently is no cure for this disease. Recently, significant advances in the use of neuroprosthetic rehabilitation to improve locomotor outcomes after SCI have been made both in preclinical models and in humans. More specifically, the administration of lumbar epidural electrical stimulation (EES) has been shown to improve lower limb function after SCI with long-term improvements when combined with locomotor training. There have been important strides in understanding the mechanisms of this strategy and the role of the spinal cord, but there remains a significant gap in understanding the role of the brain in the recovery of locomotion after SCI. The purpose of this thesis was to address this gap and to elucidate the circuits in the brain that potentially, when modulated, could improve functional recovery after SCI and augment current therapeutic paradigms.