Hybrid peripheral-spinal neuromodulation therapies enable refined locomotion after paralysis by combining global and local control of leg movements

Electrical spatiotemporal neuromodulation of the lumbar spinal cord enabled controlling extension and flexion of paralyzed legs after spinal cord injury, both in animal models and humans. However, this stimulation protocol is not selective enough to modulate the distal musculature independently and efficiently, impeding a refined movement execution. Peripheral nerve stimulation selectively activates passing axons, which allowed precise control over agonist and antagonist muscles of the ankle in animal models. These results suggest that combined electrical stimulation of both spinal cord and peripheral nerves may provide a global and local control over leg movements, respectively. To evaluate this complementarity, we developed a hybrid neuroprosthetic system that targeted the spinal cord with epidural electrical stimulation and both sciatic nerves with intraneural electrodes in rat models of leg paralysis. Real-time control of peripheral nerve stimulation allowed the selective and graded tuning of distal leg movements, which was not possible with electrical spinal cord stimulation. This local stimulation enabled paralyzed rats to walk over ground and to climb a staircase. Preliminary results in humans suggested similar synergies between spatiotemporal neuromodulation of the lumbar spinal cord and peripheral nerve stimulation. These findings open promising perspectives for the development of hybrid neuroprosthetic systems to restore functional leg movements after spinal cord injury, and potentially other neurological disorders.

Authors
*S. M. WURTH1,2, J. GANDAR2, M. CAPOGROSSO2,3, A. CUTRONE4, S. RASPOPOVIC1,4, N. PAVLOVA2,5, P. SHKORBATOVA2,5, L. BAUD2, E. D’ANNA1, Q. BARRAUD2, K. MINASSIAN2, F. WAGNER2, S. MICERA1,4, G. COURTINE2;

1Bertarelli Fndn. Chair in Translational Neuroengineering, EPFL – Campus Biotech B3.04, Geneve, Switzerland; 2EPFL Ctr. for Neuroprosthetics and Brain Mind Inst., Geneva, Switzerland; 3Med., Fribourg Univ., Fribourg, Switzerland; 4The Biorobotics Institute, Scuola Superiore Sant’Anna, Pisa, Italy; 5Pavlov Inst. of Physiol., St Petersbourg, Russian Federation
Disclosures
S.M. Wurth: None. J. Gandar: None. M. Capogrosso: None. A. Cutrone: None. S. Raspopovic: None. N. Pavlova: None. P. Shkorbatova: None. L. Baud: None. E. D’Anna: None. Q. Barraud: None. K. Minassian: None. F. Wagner: None. S. Micera: None. G. Courtine: None.

Grant Support
FNS grant Dynamo [315230_149902]
Grant Support
FNS grant NeuGrasp [205321_170032]
Grant Support
ERC
Grant Support
Wyss Center for Bio and Neuroengineering
Grant Support
Bertarelli Foundation

LINK: Society for Neuroscience

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