The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
A brain–spine interface alleviating gait deficits after spinal cord injury in primates
Open accessAbstract
Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.
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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 [13]
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Cites
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Hochberg, L. R., Bacher, D., Jarosiewicz, B., Masse, N. Y., Simeral, J. D., Vogel, J., Haddadin, S., Liu, J., Cash, S. S., van der Smagt, P., et al. (2012) · Nature · doi:10.1038/nature11076 · Cited by 2,719
High-performance neuroprosthetic control by an individual with tetraplegia
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Flexion‐reflex of the limb, crossed extension‐reflex, and reflex stepping and standing
Sherrington, C. (1910) · The Journal of Physiology · doi:10.1113/jphysiol.1910.sp001362 · Cited by 1,336
Restoring cortical control of functional movement in a human with quadriplegia
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Restoring Voluntary Control of Locomotion after Paralyzing Spinal Cord Injury
van den Brand, R., Heutschi, J., Barraud, Q., DiGiovanna, J., Bartholdi, K., Huerlimann, M., Friedli, L., Vollenweider, I., Moraud, E. M., Duis, S., et al. (2012) · Science · doi:10.1126/science.1217416 · Cited by 767
Self-citationAngeli, C. A., Edgerton, V. R., Gerasimenko, Y. P., & Harkema, S. J. (2014) · Brain · doi:10.1093/brain/awu038 · Cited by 750
Decoding the organization of spinal circuits that control locomotion
Kiehn, O. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.9 · Cited by 742
Decoding motor imagery from the posterior parietal cortex of a tetraplegic human
Aflalo, T., Kellis, S., Klaes, C., Lee, B., Shi, Y., Pejsa, K., Shanfield, K., Hayes-Jackson, S., Aisen, M., Heck, C., et al. (2015) · Science · doi:10.1126/science.aaa5417 · Cited by 649
Restoration of grasp following paralysis through brain-controlled stimulation of muscles
Ethier, C., Oby, E. R., Bauman, M. J., & Miller, L. E. (2012) · Nature · doi:10.1038/nature10987 · Cited by 485
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Sorted by citations
Yuk, H., Lu, B., & Zhao, X. (2018) · Chemical Society Reviews · doi:10.1039/c8cs00595h · Cited by 2,148
Targeted neurotechnology restores walking in humans with spinal cord injury
Wagner, F. B., Mignardot, J.-B., Le Goff-Mignardot, C. G., Demesmaeker, R., Komi, S., Capogrosso, M., Rowald, A., Seáñez, I., Caban, M., Pirondini, E., et al. (2018) · Nature · doi:10.1038/s41586-018-0649-2 · Cited by 1,087
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Spinal cord injury: molecular mechanisms and therapeutic interventions
Hu, X., Xu, W., Ren, Y., Wang, Z., He, X., Huang, R., Ma, B., Zhao, J., Zhu, R., & Cheng, L. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01477-6 · Cited by 840
Brain-Machine Interfaces: From Basic Science to Neuroprostheses and Neurorehabilitation
Lebedev, M., & Nicolelis, M. A. L. (2017) · Physiological Reviews · doi:10.1152/physrev.00027.2016 · Cited by 695
Metadata
- Authors
- Capogrosso, M., Milekovic, T., Borton, D., Wagner, F., Moraud, E. M., Mignardot, J.-B., Buse, N., Gandar, J., Barraud, Q., Xing, D., Rey, E., Duis, S., Jianzhong, Y., Ko, W. K. D., Li, Q., Detemple, P., Denison, T., Micera, S., Bezard, E., Bloch, J., & Courtine, G.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Brown University (US)
- Motac Neuroscience (United Kingdom) (GB)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Fraunhofer Institute for Microengineering and Microsystems (DE)
- Scuola Superiore Sant'Anna (IT)
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Courtine, Grégoire
- ORCID
- Venue
- Nature
- Published
- 2016-11
- Volume
- 539
- Issue
- 7628
- Pages
- 284-288
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5108412
- OpenAlex
- W2549361605
- Cited by
- 635
- References
- 35
- Citations by year
- 2026: 44 · 2025: 54 · 2024: 52 · 2023: 63 · 2022: 71 · 2021: 75 · 2020: 62 · 2019: 61 · 2018: 78 · 2017: 65 · 2016: 8
- FWCI
- 64.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (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)
- Funders
- National Science Foundation
- European Commission (331602, 258654)
- École Polytechnique Fédérale de Lausanne
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- FP7 Ideas: European Research Council (261247)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Life Sciences › Neuroscience › Cognitive Neuroscience › EEG and Brain-Computer Interfaces
- Keywords
- spinal cord injury, epidural stimulation, motor cortex, gait recovery, rhesus monkeys, corticospinal tract lesions, leg paralysis, locomotor recovery, intracortical microelectrode arrays, spinal cord stimulation, non-invasive brain-computer interface
- MeSH terms
- Animals, Disease Models, Animal, Electric Stimulation, Electric Stimulation Therapy, Gait, Leg, Locomotion, Lumbosacral Region, Macaca mulatta, Male, Microelectrodes, Motor Cortex, Paralysis, Spinal Cord, Spinal Cord Injuries, Reproducibility of Results, Gait Disorders, Neurologic, Neural Prostheses, Wireless Technology, Brain-Computer Interfaces
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