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Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis
Open accessAbstract
Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial ( www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.
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“However, this recovery required wearable motion sensors to detect motor intentions from residual movements or compensatory strategies to initiate the preprogrammed stimulation sequences5.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [5]
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“He had previously participated in the STIMO clinical trial (clinicaltrials.gov, NCT02936453), which involved a five-month neurorehabilitation programme supported by targeted epidural electrical stimulation of the spinal cord4,5.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [5]
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“The delivery of epidural electrical stimulation over the lumbar spinal cord has enabled many individuals with spinal cord injury to regain adaptive control over the activity of otherwise paralysed muscles.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [5]
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“First, the physiological principles underlying targeted epidural electrical stimulation of the spinal cord have now been validated in nine out nine treated individuals with incomplete4 and complete5 injuries6.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [5]
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“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 [5]
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“In turn, optimized configurations of anodes and cathodes can steer electric fields towards specific subsets of dorsal root entry zones to modulate well-defined ensembles of motor neuron pools5,9,25.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [5]
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“This programme enabled him to regain the ability to step with the help of a front-wheel walker.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [5]
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“Indeed, we were able to configure stimulation programs that restored stepping within one day in three participants with complete sensorimotor paralysis5.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [5]
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“This recovery has been documented in various independent studies, including in participants with complete sensorimotor paralysis5,6,30–34.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [5]
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“The last three participants were implanted with a new paddle lead that was specifically developed to target the dorsal roots involved in the control of trunk and leg movements18 (ONWARD Medical).”
From The neurons that restore walking after paralysis (2022) · cites this paper as [18]
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Citations
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“35 In this scenario, a generalised improvement in motor control might be the consequence of directed motor practice layered on top of this unmasked corticospinal system capacity.”
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Editorial: Neuroplasticity in Rehabilitation
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“…purpose, stimulation electrode types can range from microelectrodes to macroelectrodes, and the required stimulation current may vary from hundreds of nanoamperes ( nA ) in preclinical animal model studies [3] to tens of milliamperes ( mA ) in high-current applications such as DBS and SCS [1], [2].”
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Metadata
- Authors
- Rowald, A., Komi, S., Demesmaeker, R., Baaklini, E., Hernandez-Charpak, S. D., Paoles, E., Montanaro, H., Cassara, A., Becce, F., Lloyd, B., Newton, T., Ravier, J., Kinany, N., D’Ercole, M., Paley, A., Hankov, N., Varescon, C., McCracken, L., Vat, M., Caban, M., Watrin, A., Jacquet, C., Bole-Feysot, L., Harte, C., Lorach, H., Galvez, A., Tschopp, M., Herrmann, N., Wacker, M., Geernaert, L., Fodor, I., Radevich, V., Van Den Keybus, K., Eberle, G., Pralong, E., Roulet, M., Ledoux, J.-B., Fornari, E., Mandija, S., Mattera, L., Martuzzi, R., Nazarian, B., Benkler, S., Callegari, S., Greiner, N., Fuhrer, B., Froeling, M., Buse, N., Denison, T., Buschman, R., Wende, C., Ganty, D., Bakker, J., Delattre, V., Lambert, H., Minassian, K., van den Berg, C. A. T., Kavounoudias, A., Micera, S., Van De Ville, D., Barraud, Q., Kurt, E., Kuster, N., Neufeld, E., Capogrosso, M., Asboth, L., Wagner, F. B., Bloch, J., & Courtine, G.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- ETH Zurich (CH)
- Foundation for Research on Information Technologies in Society (CH)
- Scuola Superiore Sant'Anna (IT)
- École Polytechnique Fédérale de Lausanne (CH)
- University Medical Center Utrecht (NL)
- Centre National de la Recherche Scientifique (FR)
- Medtronic (United States) (US)
- Technical University of Munich (DE)
- Medical University of Vienna (AT)
- Radboud University Medical Center (NL)
- University of Fribourg (CH)
- Corresponding author
- Bloch, Jocelyne
- Courtine, Grégoire
- ORCID
- Rowald, Andreas
- Komi, Salif
- Demesmaeker, Robin
- Baaklini, Edeny
- Hernandez-Charpak, Sergio Daniel
- Montanaro, Hazael
- Cassara, Antonino
- Becce, Fabio
- Lloyd, Bryn
- Newton, Taylor
- Kinany, Nawal
- Hankov, Nicolas
- Varescon, Camille
- McCracken, Laura
- Caban, Miroslav
- Lorach, Henri
- Fodor, Isabelle
- Eberle, Grégoire
- Ledoux, Jean-Baptiste
- Fornari, Eleonora
- Mandija, Stefano
- Martuzzi, Roberto
- Nazarian, Bruno
- Callegari, Simone
- Greiner, Nathan
- Fuhrer, Benjamin
- Froeling, Martijn
- Buschman, Rik
- Minassian, Karen
- Kavounoudias, Anne
- Micera, Silvestro
- Van De Ville, Dimitri
- Barraud, Quentin
- Kurt, Erkan
- Kuster, Niels
- Neufeld, Esra
- Capogrosso, Marco
- Asboth, Leonie
- Wagner, Fabien B.
- Bloch, Jocelyne
- Courtine, Grégoire
- Venue
- Nature Medicine
- Published
- 2022-02
- Volume
- 28
- Issue
- 2
- Pages
- 260-271
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W4210917455
- Cited by
- 455
- References
- 72
- Citations by year
- 2026: 83 · 2025: 113 · 2024: 94 · 2023: 93 · 2022: 72
- FWCI
- 62.99
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.library.uu.nl
- Licence
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- CINECA IRIS Institutional Research Information System (Sant'Anna School of Advanced Studies) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Keywords
- epidural stimulation, spinal cord injury, complete paralysis, dorsal root stimulation, neurorehabilitation, swimming, standing
- MeSH terms
- Humans, Leg, Paralysis, Spinal Cord, Spinal Cord Injuries, Walking, Spinal Cord Stimulation
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