Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury
Open accessAbstract
Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited the therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here we developed stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real-time control software that modulate extensor and flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight-bearing capacity, endurance and skilled locomotion in several rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans.
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Recruiting dorsal root entry zones with preprogrammed spatiotemporal sequences replicates the physiological activation of leg motor pools underlying standing and walking.
“In turn, recruiting these dorsal root entry zones with preprogrammed spatiotemporal sequences replicates the physiological activation of leg motor pools underlying standing and walking4,5,11,13,14.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [11]
The Results (page unavailable) report that stimulation targeting dorsal roots produced hindlimb motoneuron-activation maps resembling those of intact rats during locomotion. They do not establish that the sequences replicated physiological activation during standing; the reported comparison concerns walking rats and describes resemblance, not exact replication. (LLM, conf=0.88)
Experimental — accuracy not yet measuredEpidural electrical stimulation targeting individual dorsal root entry zones of the lumbosacral spinal cord enables modulation of specific leg motor pools.
“We previously showed that epidural electrical stimulation targeting the individual dorsal root entry zones of the lumbosacral spinal cord enables the modulation of specific leg motor pools9–12.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [11]
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References 54 · Cited by 369
Research works printed but not linked: 1
- [46]Sayenko DG Angeli C Harkema SJ Edgerton VR Gerasimenko YP Neuromodulation of evoked muscle potentials induced by epidural spinal–cord stimulation in paralyzed individuals J Neurophysiol 2014 111 1088 1099 24335213 PMC3949232
- Authors
- Wenger, N., Moraud, E. M., Gandar, J., Musienko, P., Capogrosso, M., Baud, L., Le Goff, C. G., Barraud, Q., Pavlova, N., Dominici, N., Minev, I. R., Asboth, L., Hirsch, A., Duis, S., Kreider, J., Mortera, A., Haverbeck, O., Kraus, S., Schmitz, F., DiGiovanna, J., van den Brand, R., Bloch, J., Detemple, P., Lacour, S. P., Bézard, E., Micera, S., & Courtine, G.
- Affiliations
- Center for Stroke Research Berlin (DE)
- École Polytechnique Fédérale de Lausanne (CH)
- Scuola Superiore Sant'Anna (IT)
- Pavlov Institute of Physiology of the Russian Academy of Sciences (RU)
- Amsterdam Movement Sciences (NL)
- Fraunhofer Institute for Microengineering and Microsystems (DE)
- Centre Hospitalier Universitaire Vaudois (CH)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Courtine, Grégoire
- ORCID
- Venue
- Nature Medicine
- Published
- 2016-01-18
- Volume
- 22
- Issue
- 2
- Pages
- 138-145
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC5061079
- OpenAlex
- W2270484149
- Cited by
- 369
- References
- 54
- Citations by year
- 2026: 32 · 2025: 36 · 2024: 36 · 2023: 38 · 2022: 49 · 2021: 42 · 2020: 32 · 2019: 38 · 2018: 33 · 2017: 18 · 2016: 15
- FWCI
- 31.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- HAL (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Research Repository Saint Petersburg State University (Saint Petersburg State University) (submittedVersion)
- Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- CINECA IRIS Institutional Research Information System (Sant'Anna School of Advanced Studies) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- European Commission (258654)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Russian Science Foundation (14‐15‐00788)
- Berlin Institute of Health
- FP7 Ideas: European Research Council (261247)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Keywords
- spinal cord injury, neuromodulation, muscle synergies, locomotion, spinal implants, proprioceptive feedback, gait, weight bearing, electrode placement optimization, rodent models
- MeSH terms
- Animals, Biomechanical Phenomena, Computer Simulation, Female, Hindlimb, Kinetics, Locomotion, Motor Neurons, Rats, Inbred Lew, Spinal Cord, Spinal Cord Injuries, Spinal Nerve Roots, Time Factors, Muscle, Skeletal, Evoked Potentials, Motor, Rats, X-Ray Microtomography, Feedback, Sensory, Spinal Cord Stimulation
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