Neuroprosthetic Technologies to Evaluate and Train Leg Motor Control in Neurologically Impaired Individuals

Spinal cord injury (SCI) disrupts many essential sensorimotor and autonomic functions. Consequently, individuals with SCI can face decades with permanent disabilities. Advances in clinical management have decreased morbidity, but no clinical trial has yet demonstrated the efficacy of a repair strategy. In the past decade, Courtine lab has developed neurotechnologies that restored volitional control of locomotion in animal models of SCI. The intervention acts over two-time windows. In the short-term, the delivery of epidural electrical stimulation (EES) targeting the posterior lumbar roots with timing that mimics the natural activation of the spinal cord enables stepping in otherwise paralyzed rats. In the long-term, this targeted EES with intensive robot-assisted overground training triggers a reorganization of descending pathways that reestablished voluntary control of the paralyzed legs, even without EES. These results in animal models encouraged the transfer of these technologies and concepts to clinical applications. My contribution to this translational research program forms the core of my thesis.

The first section presents a software that I developed in order to enable a comprehensive yet semi-automated analysis of kinematics and muscle activity underlying locomotor functions in humans. This toolbox allows to evaluate gait features of people with neuromotor deficits, quantify locomotor performance compared to healthy people or to monitor changes in different experimental conditions or over the time course of interventions, and automatically generate comprehensive gait reports directly understandable by scientists and clinicians. The second section introduces a paradigm shift in robotic postural assistance: the gravity-assist. We demonstrated the detrimental impact of high levels of body weight support on gravity-dependent interactions during standing and walking. We developed a gravity-assist algorithm that fine-tunes the forward and upward body weight support to reestablish these interactions based on each patient’s residual capacities. We validated the personalized gravity-assist in 30 individuals with SCI or stroke. Compared to other conditions of support, the gravity-assist enabled all the patients to improve their locomotion performance. This platform establishes refined conditions to empower and train overground locomotion in a safe yet ecological environment. The third section reports the development of targeted EES in patients with chronic SCI, and the impact of an intensive 5-month rehabilitation with gravity-assist and targeted EES on the recovery of motor functions. The key findings can be summarized as follows: We established procedures to configure targeted EES that immediately enabled voluntary control of weak or paralyzed muscles; Targeted EES boosts the residual supraspinal inputs to the lumbar spinal cord, enabling all the patients to adapt their gait to specific tasks; Locomotor performance improved during the rehabilitation; All the patients regained voluntary control over previously paralyzed muscles without EES.

These combined results establish the proof-of-concept on the therapeutic potential of targeted EES and intensive, robot-assisted rehabilitation to restore locomotion after SCI. Together with similar results obtained in the US in patients with severe SCI, our findings are establishing a pathway towards the development of a viable treatment to support motor functions and improve recovery after SCI.