Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury.
Open accessAbstract
Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders.
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Krack, P., Batir, A., Blercom, N. V., Chabardès, S., Fraix, V., Ardouin, C., Koudsié, A., Limousin, P., Benazzouz, A., LeBas, J., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035275 · Cited by 2,208 · see citing works
Harkema, S., Gerasimenko, Y., Hodes, J., Burdick, J., Angeli, C., Chen, Y., Ferreira, C., Willhite, A., Rejc, E., Grossman, R. G., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60547-3 · Cited by 1,229 · see citing works
Closed-Loop Deep Brain Stimulation Is Superior in Ameliorating Parkinsonism
Rosin, B., Slovik, M., Mitelman, R., Rivlin-Etzion, M., Haber, S. N., Israel, Z., Vaadia, E., & Bergman, H. (2011) · Neuron · doi:10.1016/j.neuron.2011.08.023 · Cited by 793 · see citing works
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 · see citing works
Angeli, C. A., Edgerton, V. R., Gerasimenko, Y. P., & Harkema, S. J. (2014) · Brain · doi:10.1093/brain/awu038 · Cited by 750 · see citing works
Transformation of nonfunctional spinal circuits into functional states after the loss of brain input
Courtine, G., Gerasimenko, Y., van den Brand, R., Yew, A., Musienko, P., Zhong, H., Song, B., Ao, Y., Ichiyama, R. M., Lavrov, I., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2401 · Cited by 706 · see citing works
Self-citationProbing and regulating dysfunctional circuits using deep brain stimulation
Lozano, A. M., & Lipsman, N. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.020 · Cited by 665 · see citing works
Paz, J. T., Davidson, T. J., Frechette, E. S., Delord, B., Parada, I., Peng, K. K., Deisseroth, K. A., & Huguenard, J. R. (2012) · Nature Neuroscience · doi:10.1038/nn.3269 · Cited by 561 · see citing works
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 · see citing works
A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits
Capogrosso, M., Wenger, N., Raspopovic, S., Musienko, P., Beauparlant, J., Bassi Luciani, L., Courtine, G., & Micera, S. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1688-13.2013 · Cited by 435 · see citing works
Functional Electrical Stimulation
Lynch, C. L., & Popović, M. R. (2008) · IEEE Control Systems · doi:10.1109/mcs.2007.914689 · Cited by 342 · see citing works
Proprioception From a Spinocerebellar Perspective
Bosco, G., & Poppele, R. E. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.539 · Cited by 320 · see citing works
Edgerton, V. R., Courtine, G., Gerasimenko, Y., Lavrov, I. A., Ichiyama, R. M., Fong, A. J., Cai, L. L., Otoshi, C. K., Tillakaratne, N. J. K., Burdick, J. W., et al. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.09.002 · Cited by 316 · see citing works
Minassian, K., Jilge, B., Rattay, F., Pinter, M. M., Binder, H., Gerstenbrand, F., & Dimitrijevic, M. R. (2004) · Spinal Cord · doi:10.1038/sj.sc.3101615 · Cited by 307 · see citing works
Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's Disease
Fuentes, R., Petersson, P., Siesser, W. B., Caron, M. G., & Nicolelis, M. A. L. (2009) · Science · doi:10.1126/science.1164901 · Cited by 298 · see citing works
Coordinated reset has sustained aftereffects in Parkinsonian monkeys
Tass, P. A., Li, Q., Hauptmann, C., Doveró, S., Bézard, E., Boraud, T., & Meissner, W. G. (2012) · Annals of Neurology · doi:10.1002/ana.23663 · Cited by 264 · see citing works
Spinal circuitry of sensorimotor control of locomotion
McCrea, D. A. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0041b.x · Cited by 257 · see citing works
Field-Fote, E. C. (2001) · Archives of Physical Medicine and Rehabilitation · doi:10.1053/apmr.2001.23752 · Cited by 246 · see citing works
Ladenbauer, J., Minassian, K., Hofstoetter, U. S., Dimitrijevic, M. R., & Rattay, F. (2010) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2010.2054112 · Cited by 223 · see citing works
Gerasimenko, Y., Roy, R. R., & Edgerton, V. R. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.07.015 · Cited by 210 · see citing works
Minassian, K., Persy, I., Rattay, F., Pinter, M. M., Kern, H., & Dimitrijevic, M. R. (2007) · Human Movement Science · doi:10.1016/j.humov.2007.01.005 · Cited by 203 · see citing works
Heel and Toe Clearance Estimation for Gait Analysis Using Wireless Inertial Sensors
Mariani, B., Rochat, S., Büla, C., & Aminian, K. (2012) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2012.2216263 · Cited by 190 · see citing works
Borton, D., Micera, S., Millán, J. D. R., & Courtine, G. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005968 · Cited by 171 · see citing works
Epidural Stimulation Induced Modulation of Spinal Locomotor Networks in Adult Spinal Rats
Lavrov, I. A., Dy, C. J., Fong, A. J., Gerasimenko, Y., Courtine, G., Zhong, H., Roy, R. R., & Edgerton, V. R. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0080-08.2008 · Cited by 156 · see citing works
Евгеньевич, М. П., van den Brand, R., Märzendorfer, O., Roy, R. R., Gerasimenko, Y., Edgerton, V. R., & Courtine, G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5796-10.2011 · Cited by 153 · see citing works
Kinematic and EMG Determinants in Quadrupedal Locomotion of a Non-Human Primate (Rhesus)
Courtine, G., Roy, R. R., Hodgson, J. A., McKay, H. M., Raven, J., Zhong, H., Yang, H. S., Tuszynski, M. H., & Edgerton, V. R. (2005) · Journal of Neurophysiology · doi:10.1152/jn.01073.2004 · Cited by 149 · see citing works
A translational platform for prototyping closed-loop neuromodulation systems
Afshar, P., Khambhati, A. N., Stanslaski, S. R., Carlson, D., Jensen, R., Linde, D., Dani, S., Lazarewicz, M. T., Cong, P., Giftakis, J., et al. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2012.00117 · Cited by 146 · see citing works
Courtine, G., Harkema, S. J., Dy, C. J., Gerasimenko, Y. P., & Dyhre‐Poulsen, P. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.128447 · Cited by 145 · see citing works
On the Origin of Planar Covariation of Elevation Angles During Human Locomotion
Ivanenko, Y. P., d’Avella, A., Poppele, R. E., & Lacquaniti, F. (2008) · Journal of Neurophysiology · doi:10.1152/jn.01308.2007 · Cited by 143 · see citing works
Novel and Direct Access to the Human Locomotor Spinal Circuitry
Gerasimenko, Y., Gorodnichev, R., Machueva, E., Pivovarova, E. A., Semyenov, D., Savochin, A., Roy, R. R., & Edgerton, V. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.4751-09.2010 · Cited by 130 · see citing works
Beauparlant, J., van den Brand, R., Barraud, Q., Friedli, L., Musienko, P., Dietz, V., & Courtine, G. (2013) · Brain · doi:10.1093/brain/awt204 · Cited by 130 · see citing works
Improved efficacy of temporally non-regular deep brain stimulation in Parkinson's disease
Brocker, D. T., Swan, B. D., Turner, D. A., Gross, R. E., Tatter, S. B., Koop, M. M., Bronte-Stewart, H. M., & Grill, W. M. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.09.008 · Cited by 128 · see citing works
Degradation of neuronal function following a spinal cord injury: mechanisms and countermeasures
Dietz, V. H. (2004) · Brain · doi:10.1093/brain/awh255 · Cited by 120 · see citing works
Dominici, N., Keller, U., Vallery, H., Friedli, L., van den Brand, R., Starkey, M. L., Евгеньевич, М. П., Riener, R., & Courtine, G. (2012) · Nature Medicine · doi:10.1038/nm.2845 · Cited by 105 · see citing works
Multidirectional transparent support for overground gait training
Vallery, H., Lutz, P., Zitzewitz, J. V., Rauter, G., Fritschi, M., Everarts, C., Ronsse, R., Curt, A. E. P., & Bolliger, M. (2013) · International Conference on Rehabilitation Robotics · doi:10.1109/icorr.2013.6650512 · Cited by 85 · see citing works
Reanimating the arm and hand with intraspinal microstimulation
Zimmermann, J. B., Seki, K., & Andrew, J. O. (2011) · Journal of Neural Engineering · doi:10.1088/1741-2560/8/5/054001 · Cited by 85 · see citing works
Fénelon, G., Goujon, C., Gurruchaga, J.-M., Cesaro, P., Jarraya, B., Palfi, S., & Lefaucheur, J.-P. (2012) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2011.07.015 · Cited by 82 · see citing works
Braz, G. P., Russold, M., & Davis, G. M. (2009) · Neuromodulation Technology at the Neural Interface · doi:10.1111/j.1525-1403.2009.00213.x · Cited by 77 · see citing works
Real-time control of walking using recordings from dorsal root ganglia
Holinski, B. J., Everaert, D. G., Mushahwar, V. K., & Stein, R. B. (2013) · Journal of Neural Engineering · doi:10.1088/1741-2560/10/5/056008 · Cited by 58 · see citing works
Corticospinal neuroprostheses to restore locomotion after spinal cord injury
Borton, D. A., Bonizzato, M., Beauparlant, J., DiGiovanna, J., Moraud, E. M., Wenger, N., Евгеньевич, М. П., Minev, I. R., Lacour, S. P., Millán, J. D. R., et al. (2013) · Neuroscience Research · doi:10.1016/j.neures.2013.10.001 · Cited by 55 · see citing works
Principles of Force Gradation in Skeletal Muscles
Kernell, D. (2003) · Neural Plasticity · doi:10.1155/np.2003.69 · Cited by 48 · see citing works
Neuromodulation of motor-evoked potentials during stepping in spinal rats
Gad, P. N., Lavrov, I. A., Shah, P. K., Zhong, H., Roy, R. R., Edgerton, V. R., & Gerasimenko, Y. (2013) · Journal of Neurophysiology · doi:10.1152/jn.00169.2013 · Cited by 35 · see citing works
Lyalka, V. F., Hsu, L., Karayannidou, A., Zelenin, P. V., Orlovsky, G. N., & Deliagina, T. G. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00115.2011 · Cited by 24 · see citing works
Pharmacological Approaches to Chronic Spinal Cord Injury
Steuer, I., Rouleau, P., & Guertin, P. A. (2013) · Current Pharmaceutical Design · doi:10.2174/1381612811319240009 · Cited by 14 · see citing works
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Mathis, A., Mamidanna, P., Cury, K. M., Abe, T., Murthy, V. N., Mathis, M. W., & Bethge, M. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0209-y · Cited by 5,187 · see citing works
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 · see citing works
Self-citationWalking naturally after spinal cord injury using a brain–spine interface
Lorach, H., Galvez, A., Spagnolo, V., Martel, F., Karakas, S., Intering, N., Vat, M., Faivre, O., Harte, C., Komi, S., et al. (2023) · Nature · doi:10.1038/s41586-023-06094-5 · Cited by 631 · see citing works
A brain–spine interface alleviating gait deficits after spinal cord injury in primates
Capogrosso, M., Milekovic, T., Borton, D., Wagner, F., Moraud, E. M., Mignardot, J.-B., Buse, N., Gandar, J., Barraud, Q., Xing, D., et al. (2016) · Nature · doi:10.1038/nature20118 · Cited by 635 · see citing works
Self-citationGill, M. L., Grahn, P. J., Calvert, J. S., Linde, M. B., Lavrov, I. A., Strommen, J. A., Beck, L. A., Sayenko, D. G., Van Straaten, M. G., Drubach, D. I., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0175-7 · Cited by 574 · see citing works
Spinal cord repair: advances in biology and technology
Courtine, G., & Sofroniew, M. V. (2019) · Nature Medicine · doi:10.1038/s41591-019-0475-6 · Cited by 508 · see citing works
Self-citationRowald, A., Komi, S., Demesmaeker, R., Baaklini, E., Hernandez-Charpak, S. D., Paoles, E., Montanaro, H., Cassara, A., Becce, F., Lloyd, B., et al. (2022) · Nature Medicine · doi:10.1038/s41591-021-01663-5 · Cited by 455 · see citing works
Rat models of spinal cord injury: from pathology to potential therapies
Kjell, J., & Olson, L. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.025833 · Cited by 408 · see citing works
Formento, E., Minassian, K., Wagner, F., Mignardot, J. B., Le Goff-Mignardot, C. G., Rowald, A., Bloch, J., Micera, S., Capogrosso, M., & Courtine, G. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0262-6 · Cited by 370 · see citing works
Wenger, N., Moraud, E. M., Gandar, J., Musienko, P., Capogrosso, M., Baud, L., Le Goff, C. G., Barraud, Q., Pavlova, N., Dominici, N., et al. (2016) · Nature Medicine · doi:10.1038/nm.4025 · Cited by 369 · see citing works
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Grosenick, L., Marshel, J. H., & Deisseroth, K. A. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.034 · Cited by 384 · see citing works
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Prasanth, H., Caban, M., Keller, U., Courtine, G., Ijspeert, A., Vallery, H., & von Zitzewitz, J. (2021) · Sensors · doi:10.3390/s21082727 · Cited by 348 · see citing works
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Moseley, P., Florez, J. M., Sonar, H., Agarwal, G., Curtin, W. A., & Paik, J. K. (2015) · Advanced Engineering Materials · doi:10.1002/adem.201500503 · Cited by 276 · see citing works
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Chen, B., Li, Y., Yu, B., Zhang, Z., Brommer, B., Williams, P. R., Liu, Y., Hegarty, S. V., Zhou, S., Zhu, J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.005 · Cited by 254 · see citing works
Moraud, E. M., Capogrosso, M., Formento, E., Wenger, N., DiGiovanna, J., Courtine, G., & Micera, S. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.009 · Cited by 220 · see citing works
Hramov, A. E., Maksimenko, V., & Pisarchik, A. N. (2021) · Physics Reports · doi:10.1016/j.physrep.2021.03.002 · Cited by 218 · see citing works
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Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes
Wurth, S., Capogrosso, M., Raspopovic, S., Gandar, J., Federici, G., Kinany, N., Cutrone, A., Piersigilli, A., Pavlova, N., Guiet, R., et al. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.01.014 · Cited by 176 · see citing works
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Akan, Ö. B., Ramezani, H., Khan, T., Abbasi, N. A., & Kuşcu, M. (2016) · Proceedings of the IEEE · doi:10.1109/jproc.2016.2537306 · Cited by 178 · see citing works
Megía‐García, Á., Serrano‐Muñoz, D., Taylor, J., Avendaño‐Coy, J., & Gómez‐Soriano, J. (2019) · Neurorehabilitation and neural repair · doi:10.1177/1545968319893298 · Cited by 164 · see citing works
Battery-free, lightweight, injectable microsystem for in vivo wireless pharmacology and optogenetics
Zhang, Y., Castro, D. C., Han, Y., Wu, Y., Guo, H., Weng, Z., Xue, Y., Ausra, J., Wang, X. S., Li, R., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1909850116 · Cited by 158 · see citing works
Brain-controlled modulation of spinal circuits improves recovery from spinal cord injury
Bonizzato, M., Pidpruzhnykova, G., DiGiovanna, J., Shkorbatova, P., Pavlova, N., Micera, S., & Courtine, G. (2018) · Nature Communications · doi:10.1038/s41467-018-05282-6 · Cited by 149 · see citing works
Self-citationAdvanced Neurotechnologies for the Restoration of Motor Function
Micera, S., Caleo, M., Chisari, C., Hummel, F. C., & Pedrocchi, A. (2020) · Neuron · doi:10.1016/j.neuron.2020.01.039 · Cited by 140 · see citing works
Deep learning-based BCI for gait decoding from EEG with LSTM recurrent neural network
Tortora, S., Ghidoni, S., Chisari, C., Micera, S., & Artoni, F. (2020) · Journal of Neural Engineering · doi:10.1088/1741-2552/ab9842 · Cited by 134 · see citing works
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Moxon, K. A., & Foffani, G. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.036 · Cited by 125 · see citing works
Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics
Capogrosso, M., Wagner, F. B., Gandar, J., Moraud, E. M., Wenger, N., Milekovic, T., Shkorbatova, P. Y., Pavlova, N., Евгеньевич, М. П., Bézard, E., et al. (2018) · Nature Protocols · doi:10.1038/s41596-018-0030-9 · Cited by 123 · see citing works
Barra, B., Conti, S., Perich, M. G., Zhuang, K., Schiavone, G., Fallegger, F., Galan, K., James, N. D., Barraud, Q., Delacombaz, M., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01106-5 · Cited by 109 · see citing works
Bioelectronic Implantable Devices for Physiological Signal Recording and Closed‐Loop Neuromodulation
Oh, S., Jekal, J., Jia Liu, B., Kim, J., Park, J., Lee, T., & Jang, K. (2024) · Advanced Functional Materials · doi:10.1002/adfm.202403562 · Cited by 103 · see citing works
Pukos, N., Goodus, M. T., Sahinkaya, F. R., & McTigue, D. M. (2019) · Glia · doi:10.1002/glia.23702 · Cited by 94 · see citing works
Mechanisms of neuro-robotic prosthesis operation in leg amputees
Valle, G., Saliji, A., Fogle, E., Cimolato, A., Petrini, F. M., & Raspopović, S. (2021) · Science Advances · doi:10.1126/sciadv.abd8354 · Cited by 86 · see citing works
Minassian, K., McKay, W. B., Binder, H., & Hofstoetter, U. S. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0421-y · Cited by 89 · see citing works
A prototype closed-loop brain–machine interface for the study and treatment of pain
Zhang, Q., Hu, S., Talay, R. S., Xiao, Z., Rosenberg, D., Liu, Y., Sun, G., Li, A., Caravan, B., Singh, A., et al. (2021) · Nature Biomedical Engineering · doi:10.1038/s41551-021-00736-7 · Cited by 89 · see citing works
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Sartori, M., Yavuz, U. Ş., & Farina, D. (2017) · Scientific Reports · doi:10.1038/s41598-017-13766-6 · Cited by 85 · see citing works
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Brain-controlled neuromuscular stimulation to drive neural plasticity and functional recovery
Éthier, C., Gallego, J. Á., & Miller, L. E. (2015) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.03.007 · Cited by 82 · see citing works
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Go, G., Lee, Y., Seo, D., & Lee, T. (2022) · Advanced Materials · doi:10.1002/adma.202201864 · Cited by 83 · see citing works
Hachmann, J. T., Yousak, A., Wallner, J. J., Gad, P. N., Edgerton, V. R., & Gorgey, A. S. (2021) · Journal of Neurophysiology · doi:10.1152/jn.00020.2021 · Cited by 82 · see citing works
Closed-Loop Neuromodulation in Physiological and Translational ResearchPreprint
Zanos, S. P. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a034314 · Cited by 81 · see citing works
Gomes‐Osman, J., Cortes, M., Guest, J. D., & Pascual‐Leone, Á. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3812 · Cited by 79 · see citing works
Alam, M., García‐Alías, G., Jin, B., Keyes, J., Zhong, H., Roy, R. R., Gerasimenko, Y., Lu, D. C.-T., & Edgerton, V. R. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.02.006 · Cited by 76 · see citing works
A Fully Integrated Wireless SoC for Motor Function Recovery After Spinal Cord Injury
Lo, Y., Kuan, Y., Culaclii, S., Kim, B., Wang, P., Chang, C.-W., Massachi, J., Zhu, M., Chen, K., Gad, P. N., et al. (2017) · IEEE Transactions on Biomedical Circuits and Systems · doi:10.1109/tbcas.2017.2679441 · Cited by 78 · see citing works
Hofstoetter, U. S., Danner, S. M., Freundl, B., Binder, H., Mayr, W., Rattay, F., & Minassian, K. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00136.2015 · Cited by 75 · see citing works
Hybrid Human-Machine Interface for Gait Decoding Through Bayesian Fusion of EEG and EMG Classifiers
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Advances in Spinal Cord Stimulation
Lam, C. M., Latif, U., Sack, A., Govindan, S., Sanderson, M., Vu, D. T., Smith, G. V., Sayed, D., & Khan, T. W. (2023) · Bioengineering · doi:10.3390/bioengineering10020185 · Cited by 70 · see citing works
Minassian, K., & Hofstoetter, U. S. (2016) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12530 · Cited by 65 · see citing works
Surgical Neurostimulation for Spinal Cord Injury
Chari, A., Hentall, I. D., Papadopoulos, M. C., & Pereira, E. A. C. (2017) · Brain Sciences · doi:10.3390/brainsci7020018 · Cited by 62 · see citing works
Noninvasive Neuroprosthesis Promotes Cardiovascular Recovery After Spinal Cord Injury
Sachdeva, R., Nightingale, T. E., Pawar, K., Kalimullina, T., Mesa, A., Marwaha, A. S., Williams, A. M. M., Lam, T., & Krassioukov, A. V. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01034-5 · Cited by 61 · see citing works
Electrical Stimulation as a Tool to Promote Plasticity of the Injured Spinal Cord
Jack, A. S., Hurd, C., Martin, J. H., & Fouad, K. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2020.7033 · Cited by 58 · see citing works
Zhou, K., Wei, W., Yang, D., Zhang, H., Yang, W., Zhang, Y., Nie, Y., Hao, M., Wang, P., Ruan, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-44898-9 · Cited by 58 · see citing works
Mignardot, J.-B., Goff, C. G. L., van den Brand, R., Capogrosso, M., Fumeaux, N., Vallery, H., Anil, S., Lanini, J., Fodor, I., Eberle, G., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah3621 · Cited by 58 · see citing works
Implantable neurotechnologies: electrical stimulation and applications
Nag, S., & Thakor, N. V. (2016) · Medical & Biological Engineering & Computing · doi:10.1007/s11517-015-1442-0 · Cited by 55 · see citing works
Shah, P. K., Sureddi, S., Alam, M., Zhong, H., Roy, R. R., Edgerton, V. R., & Gerasimenko, Y. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2015.4256 · Cited by 51 · see citing works
22.2 A 176-channel 0.5cm3 0.7g wireless implant for motor function recovery after spinal cord injury
Lo, Y., Chang, C.-W., Kuan, Y., Culaclii, S., Kim, B., Chen, K., Gad, P. N., Edgerton, V. R., & Liu, W. (2016) · Digest of technical papers/Digest of technical papers - IEEE International Solid-State Circuits Conference · doi:10.1109/isscc.2016.7418067 · Cited by 50 · see citing works
Capogrosso, M., Gandar, J., Greiner, N., Moraud, E. M., Wenger, N., Shkorbatova, P. Y., Евгеньевич, М. П., Minev, I. R., Lacour, S. P., & Courtine, G. (2018) · Journal of Neural Engineering · doi:10.1088/1741-2552/aaa87a · Cited by 48 · see citing works
Rejc, E., & Angeli, C. (2019) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2018.12.009 · Cited by 45 · see citing works
Jangwan, N. S., Ashraf, G. M., Ram, V., Singh, V., Alghamdi, B. S. A., Abuzenadah, A. M., & Singh, M. F. (2022) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2022.1000495 · Cited by 51 · see citing works
Wang, Y., Xie, K., Yue, H., Chen, X., Luo, X., Liao, Q., Liu, M., Wang, F., & Shi, P. (2020) · Nanoscale · doi:10.1039/c9nr07583f · Cited by 42 · see citing works
Samejima, S., Henderson, R. P., Pradarelli, J. J., Mondello, S. E., & Moritz, C. T. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114178 · Cited by 41 · see citing works
Neurotechnologies to restore hand functions
Losanno, E., Mender, M. J., Chestek, C. A., Shokur, S., & Micera, S. (2023) · Nature Reviews Bioengineering · doi:10.1038/s44222-023-00054-4 · Cited by 42 · see citing works
Tinkhauser, G., & Moraud, E. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.734186 · Cited by 39 · see citing works
Progress in Neuroengineering for brain repair: New challenges and open issues
Panuccio, G., Semprini, M., Natale, L., Buccelli, S., Colombi, I., & Chiappalone, M. (2018) · Brain and Neuroscience Advances · doi:10.1177/2398212818776475 · Cited by 41 · see citing works
Spinal Epidural Stimulation Strategies: Clinical Implications of Locomotor Studies in Spinal Rats
Shah, P. K., & Lavrov, I. A. (2017) · The Neuroscientist · doi:10.1177/1073858417699554 · Cited by 37 · see citing works
Bonizzato, M., Hottin, R. G., Côté, S. L., Massai, E., Choinière, L., Macar, U., Laferrière, S., Sirpal, P., Quessy, S., Lajoie, G., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101008 · Cited by 37 · see citing works
Regulation of the JAK/STAT signaling pathway in spinal cord injury: an updated review
Guo, X., Jiang, C. Q., Chen, Z., Wang, X., Hong, F., & Hao, D. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1276445 · Cited by 37 · see citing works
An Accurate Wearable Foot Clearance Estimation System: Toward a Real-Time Measurement System
Arami, A., Raymond, N. S., & Aminian, K. (2017) · IEEE Sensors Journal · doi:10.1109/jsen.2017.2665624 · Cited by 33 · see citing works
Hofstoetter, U. S., Knikou, M., Guertin, P. A., & Minassian, K. (2017) · Current Pharmaceutical Design · doi:10.2174/1381612822666161214144655 · Cited by 33 · see citing works
Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration
Bryson, N. K., Lombardi, L., Hawthorn, R., Fei, J., Keesey, R., Peiffer, J. D., & Seáñez, I. (2023) · Journal of Neural Engineering · doi:10.1088/1741-2552/ace552 · Cited by 30 · see citing works
Neurorestorative interventions involving bioelectronic implants after spinal cord injury
Cho, N., Squair, J. W., Bloch, J., & Courtine, G. (2019) · Bioelectronic Medicine · doi:10.1186/s42234-019-0027-x · Cited by 31 · see citing works
Neuroprosthetic technologies to augment the impact of neurorehabilitation after spinal cord injury
van den Brand, R., Mignardot, J.-B., Zitzewitz, J. V., Goff, C. G. L., Fumeaux, N., Wagner, F. B., Capogrosso, M., Moraud, E. M., Micera, S., Schurch, B., et al. (2015) · Annals of Physical and Rehabilitation Medicine · doi:10.1016/j.rehab.2015.04.003 · Cited by 31 · see citing works
Neuromorphic neuromodulation: Towards the next generation of closed-loop neurostimulation
Contreras, L. F. H., Truong, N. D., Eshraghian, J. K., Xu, Z., Huang, Z., Bersani--Veroni, T., Aguilar, I., Leung, W. H., Nikpour, A., & Kavehei, O. (2024) · PNAS Nexus · doi:10.1093/pnasnexus/pgae488 · Cited by 30 · see citing works
Gogeascoechea, A., Kuck, A., van Asseldonk, E. H. F., Negro, F., Buitenweg, J. R., Yavuz, U. Ş., & Sartori, M. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00493 · Cited by 29 · see citing works
Zhang, H., Liu, Y., Zhou, K., Wei, W., & Liu, Y. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.749465 · Cited by 29 · see citing works
Siddiqui, A. M., Islam, R., Cuellar, C. A., Silvernail, J. L., Knudsen, B. E., Curley, D. E., Strickland, T., Manske, E., Suwan, P. T., Latypov, T. H., et al. (2021) · npj Regenerative Medicine · doi:10.1038/s41536-021-00176-6 · Cited by 33 · see citing works
Electroactive Scaffolds to Improve Neural Stem Cell Therapy for Spinal Cord Injury
Mutepfa, A. R., Hardy, J. G., & Adams, C. F. (2022) · Frontiers in Medical Technology · doi:10.3389/fmedt.2022.693438 · Cited by 29 · see citing works
Gill, M. L., Linde, M. B., Hale, R. F., Lopez, C., Fautsch, K. J., Calvert, J. S., Veith, D. D., Beck, L. A., Garlanger, K. L., Sayenko, D. G., et al. (2021) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2020.590231 · Cited by 29 · see citing works
Akan, O. B., Ramezani, H., Civas, M., Cetinkaya, O., Bilgin, B. A., & Abbasi, N. A. (2021) · IEEE Reviews in Biomedical Engineering · doi:10.1109/rbme.2021.3056455 · Cited by 28 · see citing works
Wang, S., Zhang, L.-C., Fu, H.-T., Deng, J., Fu, H., Li, T., Ji, X.-R., & Tang, P.-F. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.290905 · Cited by 27 · see citing works
Non-Invasive Brain Sensing Technologies for Modulation of Neurological Disorders
Alfihed, S., Majrashi, M. A., Ansary, M., Alshamrani, N., Albrahim, S. H., Alsolami, A., Alamari, H. A., Zaman, A., Almutairi, D., Kurdi, A., et al. (2024) · Biosensors · doi:10.3390/bios14070335 · Cited by 30 · see citing works
Paired Stimulation to Promote Lasting Augmentation of Corticospinal Circuits
Harel, N. Y., & Carmel, J. B. (2016) · Neural Plasticity · doi:10.1155/2016/7043767 · Cited by 26 · see citing works
Multimodal Technologies for Closed‐Loop Neural Modulation and Sensing
Li, L., Zhang, B., Zhao, W., Sheng, D., Yin, L., Sheng, X., & Yao, D. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202303289 · Cited by 25 · see citing works
Quantification of early learning and movement sub-structure predictive of motor performance
Jakkamsetti, V., Scudder, W., Kathote, G., Ma, Q., Angulo, G., Dobariya, A., Rosenberg, R. N., Beutler, B., & Pascual, J. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-93944-9 · Cited by 23 · see citing works
Closed-loop optogenetic neuromodulation enables high-fidelity fatigue-resistant muscle control
Herrera-Arcos, G., Song, H., Yeon, S. H., Ghenand, O., Gutierrez-Arango, S., Sinha, S., & Herr, H. (2024) · Science Robotics · doi:10.1126/scirobotics.adi8995 · Cited by 22 · see citing works
Preclinical upper limb neurorobotic platform to assess, rehabilitate, and develop therapies
Pasquini, M., James, N. D., Dewany, I., Coen, F.-V., Cho, N., Lai, S., Anil, S., Carpaneto, J., Barraud, Q., Lacour, S. P., et al. (2022) · Science Robotics · doi:10.1126/scirobotics.abk2378 · Cited by 21 · see citing works
Rehabilitative Soft Exoskeleton for Rodents
Florez, J. M., Shah, M., Moraud, E. M., Wurth, S. M., Baud, L., Zitzewitz, J. V., van den Brand, R., Micera, S., Courtine, G., & Paik, J. K. (2016) · IEEE Transactions on Neural Systems and Rehabilitation Engineering · doi:10.1109/tnsre.2016.2535352 · Cited by 21 · see citing works
Gad, P. N., Roy, R. R., Choe, J., Creagmile, J., Zhong, H., Gerasimenko, Y., & Edgerton, V. R. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00918.2014 · Cited by 19 · see citing works
Reddy, C. G., Miller, J., Abode-Iyamah, K. O., Safayi, S., Wilson, S., Dalm, B., Fredericks, D. C., Gillies, G. T., Howard, M. A., & Brennan, T. J. (2018) · Journal of Pain Research · doi:10.2147/jpr.s139843 · Cited by 20 · see citing works
Electrical Stimulation for Nervous System Injury: Research Progress and Prospects
Shan, Y., Feng, H., & Li, Z. (2020) · Acta Physico-Chimica Sinica · doi:10.3866/pku.whxb202005038 · Cited by 20 · see citing works
Mo, F., Zhang, Q., Zhang, H., Long, J., Wang, Y., Chen, G., & Ye, J. (2021) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2021.106270 · Cited by 19 · see citing works
Shon, A., Brakel, K., Hook, M. A., & Park, H. (2021) · IEEE Transactions on Biomedical Circuits and Systems · doi:10.1109/tbcas.2021.3072894 · Cited by 19 · see citing works
Spinally delivered ampakine CX717 increases phrenic motor output in adult rats
Thakre, P. P., Sunshine, M. D., & Fuller, D. D. (2021) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2021.103814 · Cited by 17 · see citing works
Spinal maps of motoneuron activity during human locomotion: neuromechanical considerations
Avaltroni, P., Cappellini, G., Labini, F. S., Ivanenko, Y. P., & Lacquaniti, F. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1389436 · Cited by 18 · see citing works
Shkorbatova, P. Y., Lyakhovetskii, V. A., Pavlova, N., Popov, A., Bazhenova, E. Y., Kalinina, D. S., Gorskii, O., & Евгеньевич, М. П. (2020) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2020.555593 · Cited by 18 · see citing works
Park, H., Oh, K., Prilutsky, B. I., & DeWeerth, S. P. (2016) · IEEE Biomedical Circuits and Systems Conference (BioCAS) · doi:10.1109/biocas.2016.7833733 · Cited by 18 · see citing works
Toward a personalized closed-loop stimulation of the visual cortex: Advances and challenges
Grani, F., Soto-Sánchez, C., Fimia, A., & Fernández, E. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.1034270 · Cited by 16 · see citing works
Tissue-like Bioelectronic Material Strategies for Personalized Closed-Loop Neuroprostheses
Kim, Y., Lee, H., Lee, J., Shin, M., & Son, D. (2025) · ACS Nano · doi:10.1021/acsnano.5c07150 · Cited by 15 · see citing works
Balaguer, J.-M., Prat-Ortega, G., Ostrowski, J., Borda, L., Verma, N., Yadav, P., Sorensen, E., de Freitas, R., Ensel, S., Donadio, S., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.08.023 · Cited by 17 · see citing works
Materials and System Design for Self‐Decision Bioelectronic Systems
Zeng, Q., Liu, H., Zhang, Y., Zheng, Y., Ding, X., Zhu, M., Shi, G., Wang, Y., Haick, H., & Zhang, M. (2026) · Advanced Materials · doi:10.1002/adma.202521164 · Cited by 21 · see citing works
Soloukey, S., de Rooij, J. D., Osterthun, R., Drenthen, J., Zeeuw, C. I. D., Huygen, F. J. P. M., & Harhangi, B. S. (2020) · Neuromodulation Technology at the Neural Interface · doi:10.1111/ner.13235 · Cited by 16 · see citing works
Katebi, M., Erfanian, A., Karami, M. A., & Sawan, M. (2024) · IEEE Access · doi:10.1109/access.2024.3432611 · Cited by 15 · see citing works
- Authors
- Wenger, N., Moraud, E. M., Raspopovic, S., Bonizzato, M., DiGiovanna, J., Musienko, P., Morari, M., Micera, S., & Courtine, G.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- ETH Zurich (CH)
- Translational Neural Engineering Lab, Center for Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
- International Paraplegic Foundation Chair in Spinal Cord Repair, Center for Neuroprosthetics and Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), Lausanne CH-1015, Switzerland.
- Scuola Superiore Sant'Anna (IT)
- Corresponding author
- Wenger, Nikolaus
- Moraud, Eduardo Martin
- Micera, Silvestro
- Courtine, Grégoire
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2014-09-24
- Volume
- 6
- Issue
- 255
- Pages
- 255ra133-255ra133
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W2105594224
- Cited by
- 209
- References
- 44
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 17 · 2023: 19 · 2022: 18 · 2021: 29 · 2020: 14 · 2019: 19 · 2018: 25 · 2017: 13 · 2016: 22 · 2015: 13 · 2014: 1
- FWCI
- 12.15
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- cc-by-nc-nd
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- PolyPublie (École Polytechnique de Montréal) (submittedVersion)
- CINECA IRIS Institutional Research Information System (Sant'Anna School of Advanced Studies) (submittedVersion)
- Funders
- National Science Foundation
- Fondation Bertarelli
- European Commission (258654)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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, feedback control, sensorimotor circuits, locomotion, leg kinematics, neural prostheses, feedforward control, movement feedback, personalized neuromodulation, paralysis, stair climbing
- MeSH terms
- Animals, Biomechanical Phenomena, Disease Models, Animal, Extremities, Female, Gait, Locomotion, Motor Neurons, Prosthesis Design, Rats, Inbred Lew, Spinal Cord Injuries, Spinal Nerves, Time Factors, Muscle Fatigue, Recovery of Function, Feedback, Sensory, Neural Prostheses, Neurofeedback
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