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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This recovery required wearable motion sensors to detect motor intentions from residual movements or compensatory strategies to initiate the preprogrammed stimulation sequences.
“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]
The ‘Recovery of independence in ecological settings’ section says participants could use open-loop sequences, clickers, or closed-loop control based on wearable sensors. The ‘Software App for configuration, optimization and evaluation of neurostimulation’ section likewise describes automatic looping and button-triggered sequences alongside sensor-detected movement. Wearable motion sensors were therefore an option, not a requirement for initiating stimulation. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe participant had previously participated in the STIMO clinical trial, which involved a five-month neurorehabilitation programme supported by targeted epidural electrical stimulation of the spinal cord.
“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]
The Study design and objectives section identifies STIMO as trial NCT02936453 and describes a five-month rehabilitation period with epidural electrical stimulation. Recovery of independence in ecological settings says the paper’s three participants underwent that programme. Our copy does not establish that the particular person referred to as “he” in the citing sentence was one of them; no page numbers are available in the indexed passages. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe 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.
“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]
The Main text (page not provided) says lumbosacral epidural electrical stimulation can restore walking after spinal cord injury. The Discussion reports restored leg and trunk functions in three people with complete paralysis, but the paper does not establish the claim's broader assertion that many individuals regained adaptive control of otherwise paralysed muscles. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe physiological principles underlying targeted epidural electrical stimulation of the spinal cord have now been validated in nine out of nine treated individuals with incomplete and complete injuries.
“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]
The Abstract and the section ‘Immediate recovery of walking after complete paralysis’ report successful targeted epidural stimulation in all three participants with complete sensorimotor paralysis. The Discussion mentions earlier findings in people with incomplete injuries, but this paper does not establish the claim’s nine-out-of-nine total. (LLM, conf=0.86)
Experimental — accuracy not yet measuredRecruiting 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 [5]
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 pools.
“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]
The STIMO programme enabled the participant to regain the ability to step with the help of a front-wheel walker.
“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]
The authors were able to configure stimulation programs that restored stepping within one day in three participants with complete sensorimotor paralysis.
“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]
This recovery has been documented in various independent studies, including in participants with complete sensorimotor paralysis.
“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]
A new paddle lead (ONWARD Medical) was specifically developed to target the dorsal roots involved in the control of trunk and leg movements.
“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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Spinal cord injury: molecular mechanisms and therapeutic interventions
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Self-citationEpidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis
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Multisite Hebbian Plasticity Restores Function in Humans with Spinal Cord Injury
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Is Graphene Shortening the Path toward Spinal Cord Regeneration?
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Neuromodulation Therapy for Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review
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Using a high-frequency carrier does not improve comfort of transcutaneous spinal cord stimulation
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First-in-human study of epidural spinal cord stimulation in individuals with spinal muscular atrophy
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Brain–computer interfaces in 2023–2024
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An implantable system to restore hemodynamic stability after spinal cord injury
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Self-citationCervical transcutaneous spinal stimulation for spinal motor mapping
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A Single Dermatome Clinical Prediction Rule for Independent Walking 1 Year After Spinal Cord Injury
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Soft Bioelectronics for Neuroengineering: New Horizons in the Treatment of Brain Tumor and Epilepsy
Yoo, S., Kim, M.-J., Choi, C., Kim, D., & Cha, G. D. (2023) · Advanced Healthcare Materials · doi:10.1002/adhm.202303563 · Cited by 18 · see citing works
REPORT-SCS: minimum reporting standards for spinal cord stimulation studies in spinal cord injury
Malik, R. N., Samejima, S., Shackleton, C., Miller, T., Pedrocchi, A., Rabchevsky, A. G., Moritz, C. T., Darrow, D., Field-Fote, E. C., Guanziroli, E., et al. (2024) · Journal of Neural Engineering · doi:10.1088/1741-2552/ad2290 · Cited by 18 · see citing works
Pain in the Context of Sensory Deafferentation
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Spinal maps of motoneuron activity during human locomotion: neuromechanical considerations
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- 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 › 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
- 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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