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Séminaire impromptu - Fabien WagnerNeuroprosthetic technologies for restoring leg motor control after paralysis

Abstract :

 Spinal cord injury disrupts the neuronal connections between the brain and the spinal cord, resulting in the inability to activate the leg muscles required for walking.
I will present the development of neuroprosthetic technologies for enabling locomotion and enhancing activity-dependent plasticity in species ranging from rodents to non-human primates and eventually patients with spinal cord injury. These interventions act over two time scales. Immediately, electrical spatiotemporal neuromodulation of spinal circuits enables motor control of the paralyzed legs. In the long term, intense gait training enabled by these technologies promotes neuroplasticity and reestablishes voluntary control of movement.

We first developed, in animal models, spatially selective spinal implants that can modulate muscle synergies responsible for flexion and extension of the legs. To reproduce the natural muscle activation pattern during locomotion, we interfaced these implants with either kinematic feedback or brain activity recorded from intracortical microelectrode arrays.

In a non-human primate model of spinal cord injury, this brain-spine interface instantly restored robust locomotor movements of the paralyzed leg. We are now conducting a clinical feasibility study in patients with incomplete spinal cord injury to validate these concepts in humans. Spatiotemporal neuromodulation strategies during overground locomotion with robotic assistance resulted in considerable immediate facilitation of leg kinematics and muscle activity. In all participants, gait training during 5 months led to improvement of motor functions, even in the absence of stimulation. These preliminary results provide encouraging insights into the potential of this intervention to augment neural plasticity and functional recovery after spinal cord injury.

Selected publications

Capogrosso, M., Milekovic, T., Borton, D., Wagner, F., Moraud, E. M., Mignardot, J. B., ... & Courtine, G. (2016). A brain-spine interface alleviating gait deficits after spinal cord injury in primates. Nature, 539(7628), 284-288.

Wagner, F.B., Eskandar, E.N., Cosgrove, G.R., Madsen, J.R., Blum, A.S., Potter, N.S., Hochberg, L.R., Cash, S.S., and Truccolo, W. (2015). Microscale spatiotemporal dynamics during neocortical propagation of human focal seizures. Neuroimage 122, 114–130.

Dai, J., Ozden, I., Brooks, D.I., Wagner, F., May, T., Agha, N.S., Brush, B., Borton, D., Nurmikko, A.V., and Sheinberg, D.L. (2015). Modified toolbox for optogenetics in the nonhuman primate. Neurophotonics 2, 031202.

Van den Brand, R., Mignardot, J.-B., von Zitzewitz, J., Le Goff, C., Fumeaux, N., Wagner, F., Capogrosso, M., Martin Moraud, E., Micera, S., Schurch, B., et al. (2015). Neuroprosthetic technologies to augment the impact of neurorehabilitation after spinal cord injury. Ann Phys Rehabil Med.

Lu, Y., Truccolo, W., Wagner, F.B., Vargas-Irwin, C.E., Ozden, I., Zimmermann, J.B., May, T., Agha, N.S., Wang, J., and Nurmikko, A.V. (2015). Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex. J. Neurophysiol. 113, 3574–3587. Wagner, F.B., Truccolo, W., Wang, J., and Nurmikko, A.V. (2015). Spati

Scientific focus :

Closed-loop neuromodulation of spinal circuits underlying locomotion in non-human primates and patients with spinal cord injury (responsible for all stimulation-related aspects in clinical study).