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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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Muscle anatomy is reflected in the spatial organization of the spinal motoneuron pools
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“However, except for optimizing the treatment plan to alleviate the pain of patients as much as possible and reducing the occurrence of complications with SCI, there is no clinical method to promote the improvement of natural movements and sensory function in incomplete SCI (Rowald et al., 2022).”
MethodSchalk, G., Worrell, S., Mívalt, F., Belsten, A., Kim, I., Morris, J. M., Hermes, D., Klassen, B. T., Staff, N. P., Messina, S. A., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.932782 · Cited by 15
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“11,12,18 However, there is still a lack of research relating to the specific mechanisms underlying spinal nerve stimulation in preventing neuronal apoptosis and muscular atrophy.”
BackgroundSupraspinal control of motoneurons after paralysis enabled by spinal cord stimulationPreprint
Balaguer, J.-M., Prat-Ortega, G., Verma, N., Yadav, P., Sorensen, E., de Freitas, R., Ensel, S., Borda, L., Donadio, S., Liang, L., et al. (2023) · medRxiv · doi:10.1101/2023.11.29.23298779 · Cited by 13
“This interpretation could explain why, despite the well-known low specificity of SCS 11,17 , we can observe repeatable, strong clinical effects 4,5 .”
BackgroundSelf-citationAn open-access lumbosacral spine MRI dataset with enhanced spinal nerve root structure resolution
Liu, J., Zhang, W., Zhou, Y., Xu, L., Chu, Y., & Jia, F. (2024) · Scientific Data · doi:10.1038/s41597-024-03919-4 · Cited by 14
Nanofibrous Guidance Conduits with Multiple Gradient Cues for Spinal Cord Repair
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Dabbagh, A., Horn, U., Kaptan, M., Mildner, T., Müller, R., Lepsien, J., Weiskopf, N., Brooks, J. C. W., Finsterbusch, J., & Eippert, F. (2024) · Imaging Neuroscience · doi:10.1162/imag_a_00273 · Cited by 15
“Apart from a few notable exceptions ( Conrad et al., 2018; Martucci et al., 2019, 2021; Rowald et al., 2022; Stroman, 2002; Stroman et al., 2004), most spinal cord fMRI studies have focused on cross-sectional designs in healthy volunteers, that is, have not employed longitudinal designs or looked…”
BackgroundRussman, S. M., Cleary, D. R., Tchoe, Y., Bourhis, A. M., Stedelin, B., Martin, J. R., Brown, E. C., Zhang, X., Kawamoto, A., Ryu, W. H. A., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abq4744 · Cited by 13
“Last, we also believe that our microelectrode array could mediate SCI treatment by identifying and stimulating the root entry zones in patients with SCI, which has been shown recently to restore motor function (54).”
BackgroundAn optimization framework for targeted spinal cord stimulation
Mirzakhalili, E., Rogers, E. R., & Lempka, S. F. (2023) · Journal of Neural Engineering · doi:10.1088/1741-2552/acf522 · Cited by 14
“Patient-specific modeling has proven to be an important part of this application [71] and it can benefit from optimization for better clinical results.”
A Review of the Potential Use of Antioxidants in Spinal Cord Injuries
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“…53 walking without falling in people with late-stage Parkinson’s disease, 54 restoration of trunk and leg motor functions after complete paralysis, 55 recovery of over-ground walking, 56 restoration of walking after complete spinal cord injury, 57 and reduction of attack frequency in people with…”
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Evolution of Musculoskeletal Electronics
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Hvingelby, V. S., Carra, R. B., Terkelsen, M. H., Hamani, C., Capato, T., Košutzká, Z., Krauss, J. K., Moro, E., Pavese, N., & Cury, R. G. (2024) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.14143 · Cited by 12
“However, as SCS is an established therapy for other conditions, especially chronic pain, 13 but also recently as a potential restorative therapy for spinal cord injury, 14,15 indirect inferences can be attempted.”
Injectable Ventral Spinal Stimulator Evokes Programmable and Biomimetic Hindlimb Motion
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“Recovery of standing and walking ability in paraple-gics after esCs has been demonstrated by several research teams [17,22–24].”
Mukhametova, E., Militskova, A., Рамилевич, Б. А., Kharin, N. V., Семенова, Е. В., Александрович, С. О., Baltina, T., & Lavrov, I. A. (2023) · Mayo Clinic Proceedings Innovations Quality & Outcomes · doi:10.1016/j.mayocpiqo.2023.09.006 · Cited by 11
“30 The following critical step should elaborate advanced assessment of activated fi bers 33 and segment-speci fi c stimulation 66 for optimal activation of the spinal circuitry leading to further improvement.”
BackgroundResultInfluentialCombinatorial strategies for cell transplantation in traumatic spinal cord injury
Jagrit, V., Koffler, J. Y., & Dulin, J. N. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1349446 · Cited by 11
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“Recent breakthrough also demonstrates epidural electrical stimulation (EES)-based spinal cord neuromodulation can restore trunk and leg motor functions after complete paralysis [4].”
BackgroundRegional specialization of movement encoding across the primate sensorimotor cortex
Borgognon, S., Macellari, N., Hickey, A. M., Perich, M. G., Javaheri, H., Ornelas-Kobayashi, R., Delacombaz, M., Hitz, C., Fallegger, F., Lacour, S. P., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61172-8 · Cited by 14
“This concept may be particularly relevant to operate brain-controlled prostheses to regain walking after paralysis, since the control of these prostheses is primarily based on the extraction of the temporal structure of leg movements 56,57,78,80 – 82 .”
Self-citationGarcía-Moreno, A., Comerma-Montells, A., Tudela-Pi, M., Minguillón, J., Becerra-Fajardo, L., & Ivorra, A. (2022) · Journal of Neural Engineering · doi:10.1088/1741-2552/ac8dc4 · Cited by 12
“This approach has been successfully adopted for developing sensory neuroprostheses, such as cochlear implants for the deaf [1], for developing motor neuroprostheses, such as drop foot stimulators for improving gait in patients with hemiplegia [2], and for epidural electrical stimulators for restoring walking after par…”
MethodThe role of spinal cord neuroanatomy in the variances of epidural spinal recordings
Lam, D., Chin, J., Brucker-Hahn, M. K., Settell, M. L., Romanauski, B., Verma, N., Upadhye, A. R., Deshmukh, A., Skubal, A. C., Nishiyama, Y., et al. (2024) · Bioelectronic Medicine · doi:10.1186/s42234-024-00149-2 · Cited by 11
“Dorsal root activation is considered the primary goal concerning the control of spinal reflexes and complex motor functions like locomotion (Lavrov et al., 2008; Capogrosso et al. 2013; Rowald et al. 2022).”
BackgroundRestoration of complex movement in the paralyzed upper limb
Hasse, B. A., Sheets, D. E. G., Holly, N. L., Gothard, K. M., & Fuglevand, A. J. (2022) · Journal of Neural Engineering · doi:10.1088/1741-2552/ac7ad7 · Cited by 14
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Bakare, A. O., Stephens, K., Sanchez, K. R., Liu, V., Zheng, L., Goel, V., Guan, Y., & Sivanesan, E. (2024) · Regional Anesthesia & Pain Medicine · doi:10.1136/rapm-2024-105433 · Cited by 10
“11 12 Chemotherapy-induced gait impairment has been attributed to structural (eg, axonal degeneration) 3 and functional disorders (eg, sensorimotor disability associated with sensory processing dysfunction).”
BackgroundThe expanding horizon of neurotechnology: Is multimodal neuromodulation the future?
Micera, S., & Foffani, G. (2024) · PLoS Biology · doi:10.1371/journal.pbio.3002885 · Cited by 10
Self-citationRehabilitation of motor and sensory function using spinal cord stimulation: Recent advances
Iversen, M. M., Harrison, A. T., Stanley, C. T., & Dalrymple, A. N. (2024) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2024.100566 · Cited by 11
Soft sensory-neuromorphic system for closed-loop neuroprostheses
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Blueprints for healing: central nervous system regeneration in zebrafish and neonatal mice
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“Beyond regenerative approaches, recent studies have highlighted the potential of spinal cord electrical stimulation to restore neuronal function and walking following SCI in mouse models as well as human patients [24–31].”
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“Recent advances in closed-loop electrical stimulation systems—which integrate real-time motor intent decoding and adaptive stimulation parameter modulation— have further enhanced the spatiotemporal precision of CPG activation [86].”
Samejima, S., Shackleton, C., Malik, R. N., Hosseinzadeh, A., Rempel, L., Phan, A.-D., Williams, A. M. M., Nightingale, T. E., Ghuman, A., Elliott, S., et al. (2025) · Bioelectronic Medicine · doi:10.1186/s42234-025-00183-8 · Cited by 13
“These findings following long-term lumbosacral tSCS align with previous evidence supporting the restoration of motor functions with epidural spinal cord stimulation in individuals with motor-complete SCI (Rowald et al. 2022; Angeli et al. 2018; Darrow et al. 2019).”
Fast inference of spinal neuromodulation for motor control using amortized neural networks
Govindarajan, L. N., Calvert, J. S., Parker, S. R., Jung, M., Darie, R., Miranda, P., Shaaya, E. A., Borton, D. A., & Serre, T. (2022) · Journal of Neural Engineering · doi:10.1088/1741-2552/ac9646 · Cited by 10
“Additionally, previous clinical EES studies directly translated EMG data recorded at rest without ascending or descending input to use during spatiotemporal EES where stimulation is applied at specific time-locked portions of complex tasks such as locomotion [7, 18].”
BackgroundTiming‐dependent synergies between motor cortex and posterior spinal stimulation in humans
McIntosh, J. R., Joiner, E. F., Goldberg, J. L., Greenwald, P. L., Dionne, A. C., Murray, L. M., Thuet, E. D., Modik, O., Shelkov, E., Lombardi, J. M., et al. (2024) · The Journal of Physiology · doi:10.1113/jp286183 · Cited by 10
“…activation fits with human studies where volitional control was regained with epidural SCS despite severe damage to the neural pathway (Angeli et al., 2018; Carhart et al., 2004; Gill et al., 2018; Inanici et al., 2018, 2021; Powell et al., 2023; Rowald et al., 2022; Wagner et al., 2018).”
BackgroundOrtolá, I. C., Martínez-Rojas, B., Moreno‐Manzano, V., Castelló, M. G., Pradas, M. M., Martínez‐Ramos, C., & Estellés, J. M. (2022) · Biomedicines · doi:10.3390/biomedicines10112736 · Cited by 10
“Tissue engineering (TE) strategies have been gaining attention as an alternative approach in SCI injury treatment, with the aim of mimicking the native tissue both structurally and physiologically [12].”
MethodInfluentialExoskeleton gait training with spinal cord neuromodulation
Ivanenko, Y. P., Shapkova, E. Y., Petrova, D., Kleeva, D. F., & Lebedev, M. (2023) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2023.1194702 · Cited by 9
Scheffler, M. S., Martin, C. A., Dietz, V. A., Faraji, A. H., & Sayenko, D. G. (2024) · Clinical Neurophysiology · doi:10.1016/j.clinph.2024.06.015 · Cited by 9
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Real-time multicompartment Hodgkin-Huxley neuron emulation on SoC FPGA
Beaubois, R., Cheslet, J., Ikeuchi, Y., Branchereau, P., & Levi, T. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1457774 · Cited by 8
Advances in Neuromodulation and Digital Brain–Spinal Cord Interfaces for Spinal Cord Injury
Jaszczuk, P., Bratelj, D., Capone, C., Rudnick, M., Pötzel, T., Verma, R. K., & Fiechter, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136021 · Cited by 11
“By decoding motor intentions from cortical signals (e.g., via WIMAGINE’s 64-channel ECoG) and translating them into spatially selective epidural spinal stimulation (e.g., Courtine’s 32-channel arrays), BSIs enable physiological walking [12,27,55].”
Yang, C., Meng, Z., He, Z., Ma, P., Hou, Z., Kim, K., Lu, J., Yang, K., Wang, G., & Wang, X. (2024) · Engineered Regeneration · doi:10.1016/j.engreg.2024.02.001 · Cited by 9
Urbin, M. A. (2024) · The Journal of Physiology · doi:10.1113/jp285563 · Cited by 10
“Nevertheless, improvements that outlast the period of stimulation (Powell et al., 2023; Rowald et al., 2022) seem to point to a plasticity mechanism that is reliant on the interaction between currents injected into the spinal cord and the intrinsic neural activity underlying voluntary movement.”
Athanasiou, A., Mitsopoulos, K., Praftsiotis, A., Astaras, A., Antoniou, P. E., Pandria, N., Petronikolou, V., Kasimis, K., Lyssas, G., Terzopoulos, N., et al. (2022) · JMIR Research Protocols · doi:10.2196/41152 · Cited by 9
“…as spinal cord stimulation below the injury level, where novel findings suggest that reproducing natural central nervous system (CNS) input and output patterns below the injury level can lead to long-term functional improvement, even without stimulation, for select patients with chronic SCI [11].”
BackgroundSarica, C., Zemmar, A., Yousefi, O., Yang, A. C., Uzuner, A., Sheng, Z., Santyr, B. G., Samuel, N., Colditz, M., Vetkas, A., et al. (2023) · Stereotactic and Functional Neurosurgery · doi:10.1159/000531089 · Cited by 9
Thornton, W. A., Marzloff, G. E., Ryder, S. C., Best, A., Rasheed, K., Coons, D., & Smith, A. C. (2023) · Spinal Cord · doi:10.1038/s41393-023-00890-6 · Cited by 8
“Our findings may also suggest that those with no evidence of midsagittal tissue bridges should continue to emphasize compensatory strategies, and these individuals may require a more complex spatio-temporal neuromodulation intervention to drive motor output [14].”
BackgroundEvaluation of EMG patterns in children during assisted walking in the exoskeleton
Villani, M., Avaltroni, P., Scordo, G., Rubeca, D., Kreynin, P., Bereziy, E., Berger, D. J., Cappellini, G., Labini, F. S., Lacquaniti, F., et al. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1461323 · Cited by 8
Recent advances in potential mechanisms of epidural spinal cord stimulation for movement disorders
Zhang, T., Jia, Y., Wang, N., Chai, X., He, Q., Cao, T., Mu, Q., Lan, Q., Zhao, J., & Yang, Y. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115330 · Cited by 8
Rybka, V., Šedivá, K., Špačková, L., Kolář, P., Bradáč, O., & Kříž, J. (2025) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2025.1622033 · Cited by 9
Krenn, M. J., White, J. M., Stokić, D. S., & Tansey, K. E. (2022) · Experimental Brain Research · doi:10.1007/s00221-022-06521-5 · Cited by 9
“Thus, alternative stimulation strategies may be needed to distribute input across different spinal levels and phases of the gait cycle (Wagner et al. 2018; Rowald et al. 2022).”
BackgroundSpinal Cord Stimulation to Enable Leg Motor Control and Walking in People with Spinal Cord Injury
Seáñez, I., Capogrosso, M., Minassian, K., & Wagner, F. B. (2022) · Springer eBooks · doi:10.1007/978-3-031-08995-4_18 · Cited by 8
Self-citationPradat, P., Hayon, D., Blancho, S., Neveu, P., Khamaysa, M., & Guérout, N. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13060993 · Cited by 9
“Recently, this approach has been optimised with a new set of electrodes targeting all dorsal roots, computationally based electrode positioning, and software that supports the rapid configuration of activityspecific stimulation programs that reproduce the natural activation of underlying motor neurons for each activit…”
MethodJoshi, K., Rejc, E., Ugiliweneza, B., Harkema, S. J., & Angeli, C. (2023) · Bioengineering · doi:10.3390/bioengineering10091065 · Cited by 8
“Decreased lumbar curvature was observed when scES was applied targeting the erector spinae and quadratus lumborum muscles during repeated trunk flexion/extension in reaching and retrieving tasks and during four-point kneeling movement [25].”
MethodLiu, S., Wu, Q., Wang, L., Xing, C., Guo, J., Li, B., Ma, H., Zhong, H., Zhou, M., Zhu, S., et al. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114765 · Cited by 8
Khalili, M. R., Shadmani, A., & Sanie‐Jahromi, F. (2024) · Developmental Neurobiology · doi:10.1002/dneu.22949 · Cited by 8
“Rowald et al. (2022) has demonstrated context-specific modulation effects, where the cathode can more effectively modulate lower limb movements in spinal cord stimulation.”
Predictive modeling of ambulatory outcomes after spinal cord injury using machine learning
Draganich, C., Anderson, D., Dornan, G. J., Sevigny, M., Berliner, J., Charlifue, S. W., Welch, A., & Smith, A. C. (2024) · Spinal Cord · doi:10.1038/s41393-024-01008-2 · Cited by 8
“…would allow for improved ability to determine which individuals with AIS B and C SCIs would be less likely to ambulate, potentially allowing these individuals to be assigned to augmentative interventions, such as neuromodulatory interventions, earlier in their rehabilitation process [33 – 35].”
Characterization of a conductive hydrogel@Carbon fibers electrode as a novel intraneural interface
Giannotti, A., Santanché, R., Zinno, C., Carpaneto, J., Micera, S., & Riva, E. R. (2024) · Bioelectronic Medicine · doi:10.1186/s42234-024-00154-5 · Cited by 8
“…used to treat various conditions, restore the sense of touch in upper limb amputees (Raspopovic et al. 2014), support nerve reinnervation (Delgado-Martínez et al. 2017), and enable patients with spinal cord injuries to regain the use of lower limbs for assisted walking (Rowald et al. 2022).”
BackgroundSelf-citationSelective Activation of the Spinal Cord with Epidural Electrical Stimulation
Cuellar, C. A., Lehto, L. J., Islam, R., Mangia, S., Michaeli, S., & Lavrov, I. A. (2024) · Brain Sciences · doi:10.3390/brainsci14070650 · Cited by 7
“Spinal cord epidural electrical stimulation (EES) has been successfully applied to treat chronic pain [1] and to enable sensorimotor function in patients with spinal cord injury (SCI) [2–9].”
BackgroundGuo, X.-J., He, L., Chang, J.-Q., Su, W.-N., Feng, T., Gao, Y., Wu, Y., Zhao, C., & Rao, J. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.115112 · Cited by 7
Cervical spinal cord stimulation for treatment of upper limb paralysis: a narrative review
Lo, Y. T., Lam, J. L., Jiang, L., Lam, W. L., Edgerton, V. R., & Liu, C. Y. (2025) · Journal of Hand Surgery (European Volume) · doi:10.1177/17531934241307515 · Cited by 7
“…al., 2021; Mendell, 2014), has recently been employed to stimulate lumbosacral dorsal roots, yielding promising results in enabling independent walking and weight-bearing in individuals with tetraplegia (Angeli et al., 2014; Grahn et al., 2017; Rowald et al., 2022; Sea´ ~ nez and Capogrosso, 2021).”
Deep Brain Stimulation and Brain–Spine Interface for Functional Restoration in Spinal Cord Injury
Shiferaw, B. T., Jin, M. Y., Patel, M., Henjum, L. J., & Abd-Elsayed, A. A. (2025) · Biomedicines · doi:10.3390/biomedicines13030631 · Cited by 7
“In human studies, EES has significantly improved participants’ ability to stand and walk following SCI [19,20].”
Electric Stimulation Combined with Biomaterials for Repairing Spinal Cord Injury
Du, L., Zhang, L., Bao, S., Yan, F., Jiang, W., Wang, H., & Dong, C. (2025) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5c00615 · Cited by 7
Albano, L., Emedoli, D., Agnesi, F., Romeni, S., Losanno, E., Toni, L., Fossati, V., Ciucci, C., Gasperotti, F., Cociani, L., et al. (2025) · Med · doi:10.1016/j.medj.2025.100706 · Cited by 9
Self-citationVerma, N., Oh, J., Bedoy, E. H., Chetty, N., Steele, A. G., Park, S. J., Guerrero, J. R., Faraji, A. H., Weber, D. J., & Sayenko, D. G. (2025) · Journal of Neurophysiology · doi:10.1152/jn.00422.2024 · Cited by 9
“Segment-specific spinal stimulation that recruits afferent fibers is critical for engaging targeted motor pools and modulating descending and interneuronal pathways to enhance specific motor functions (12, 36–39).”
Sánchez-Martín, M. D. M., Giraldo, E., Alastrue‐Agudo, A., Mocholi, E. L., Pérez, S. M., Mannino, L., Paniagua, G., Sánchez, A. I. F., Monreal-Trigo, J., Haro, J. M. T., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.07.041 · Cited by 7
A computational roadmap to electronic drugs
Rowald, A., & Amft, O. (2022) · Frontiers in Neurorobotics · doi:10.3389/fnbot.2022.983072 · Cited by 7
“Patient-specific FEMs enable the approximation of electric fields in a patient’s anatomy (Frankemolle et al., 2010; Lempka et al., 2020; Rowald et al., 2022).”
BackgroundSelf-citationApplication of Vagus Nerve Stimulation in Spinal Cord Injury Rehabilitation
Fallahi, M. S., Azadnajafabad, S., Maroufi, S. F., Pour‐Rashidi, A., Khorasanizadeh, M., Sattari, S. A., Faramarzi, S., & Slavin, K. V. (2023) · World Neurosurgery · doi:10.1016/j.wneu.2023.02.101 · Cited by 7
Fasse, A., Newton, T., Liang, L., Agbor, U., Rowland, C. W., Kuster, N., Gaunt, R. A., Pirondini, E., & Neufeld, E. (2024) · Journal of Neural Engineering · doi:10.1088/1741-2552/ad4e6b · Cited by 6
“This makes it possible to personalize the choice of implant and its placement—the optimality of which has also been shown to be highly subject-specific [45].”
BackgroundInfluentialSelf-citationMapping Spinal Cord Stimulation-Evoked Muscle Responses in Patients With Chronic Spinal Cord Injury
Hoglund, B. K., Zurn, C. A., Madden, L. R., Hoover, C., Slopsema, J. P., Balser, D. Y., Parr, A. M., Samadani, U., Johnson, M. D., Netoff, T. I., et al. (2022) · Neuromodulation Technology at the Neural Interface · doi:10.1016/j.neurom.2022.10.058 · Cited by 7
Conductive PS inverse opals for regulating proliferation and differentiation of neural stem cells
Hu, Y., Zhang, H., Wei, H., Liao, M., Chen, X., Xing, J., Duan, L., Cheng, C., Lu, W., Yang, X., et al. (2023) · Engineered Regeneration · doi:10.1016/j.engreg.2023.03.001 · Cited by 7
Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulationPreprint
Capogrosso, M., Balaguer, J.-M., Prat-Ortega, G., Verma, N., Yadav, P., Sorensen, E., de Freitas, R., Ensel, S., Borda, L., Donadio, S., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3650257/v1 · Cited by 7
“This interpretation could explain why, despite the well-known low specificity of SCS 11,17 , we can observe repeatable, strong clinical effects 4,5 .”
BackgroundSelf-citationKeesey, R., Hofstoetter, U. S., Hu, Z., Lombardi, L., Hawthorn, R., Bryson, N. K., Rowald, A., Minassian, K., & Seáñez, I. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.26.603982 · Cited by 7
“Neural tissues were assigned anisotropic conductivity, calculated as per previously established methods 6 .”
MethodSelf-citationLuz, A., Rupp, R., Ahmadi, R., & Weidner, N. (2023) · Neurological Research and Practice · doi:10.1186/s42466-023-00241-z · Cited by 6
“[14] 3 T4 (AIS A); T3 (AIS A); T7 (AIS B); Overground walking with body-weight support after three days of ESCS; leg movements for cycling and swimming; improved trunk control Case series 4”
BackgroundChandrasekaran, S., Bhagat, N. A., Ramdeo, R., Ebrahimi, S., Sharma, P., Griffin, D. G., Stein, A., Harkema, S. J., & Bouton, C. E. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1210544 · Cited by 6
“Studies involving epidural stimulation of the spinal cord mediating restoration of voluntary motor control have shown the importance of targeted stimulation that can recruit specific motoneuron pools (Wagner et al., 2018; Rowald et al., 2022).”
BackgroundHingorani, S., Paniagua, G., Sánchez-Huertas, C., Villalba‐Riquelme, E., Mocholi, E. L., Martínez-Rojas, B., Alastrue‐Agudo, A., Dupraz, S., Montiel, A. V. F., & Moreno‐Manzano, V. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.03.038 · Cited by 7
An Update on Spinal Cord Injury and Current Management
Carroll, A. H., Fakhre, E., Quinonez, A., Tannous, O. O., & Mesfin, A. (2024) · JBJS Reviews · doi:10.2106/jbjs.rvw.24.00124 · Cited by 6
Gorgey, A. S., Trainer, R. J., Khalil, R. E., Deitrich, J. N., Rehman, M. U., Goetz, L. L., Lester, D. D., Klausner, A. P., Peterson, C. L., & Lavis, T. D. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14061829 · Cited by 7
“Multimodal neuromodulation intervention in conjunction with task-specific training provided promising outcomes in the restoration of motor behavior and overground locomotion in persons with SCI [22–32].”
An active electronic, high-density epidural paddle array for chronic spinal cord neuromodulation
Parker, S. R., Calvert, J. S., Darie, R., Jang, J., Govindarajan, L. N., Angelino, K., Chitnis, G. D., Iyassu, Y., Shaaya, E. A., Fridley, J., et al. (2025) · Journal of Neural Engineering · doi:10.1088/1741-2552/adba8b · Cited by 6
“To recruit more specific pools of neurons on the spinal cord, multipolar stimulation is applied in a current steering approach (Chandrasekaran et al 2020, Rowald et al 2022, Lorach et al 2023, Mishra et al 2023, Nanivadekar et al 2023), which requires access to multiple contacts in a confined…”
InfluentialPerilesional neuromodulation replaces lost sensorimotor function in persons with spinal cord injury
Calvert, J. S., Parker, S. R., Govindarajan, L. N., Darie, R., Shaaya, E. A., Solinsky, R. J., Valle, L. M. D., Miranda, P., Jang, J., Tiwari, E., et al. (2026) · Nature Biomedical Engineering · doi:10.1038/s41551-026-01627-5 · Cited by 6
Bowersock, C. D., Pisolkar, T., Ai, X., Zhu, C., Angeli, C., Harkema, S. J., Forrest, G. F., Agrawal, S. K., & Rejc, E. (2023) · Journal of Neurotrauma · doi:10.1089/neu.2023.0403 · Cited by 6
A 1280-Channel Neural Microelectrode Array With Complementary Wedge-Shaped 3-D Assembly Interfaces
Geng, L., Yang, Y., Chen, D., Xie, D., Xing, C., He, D., Xu, L., & Wu, F. H. (2024) · IEEE Sensors Journal · doi:10.1109/jsen.2024.3377920 · Cited by 6
“These neural microelectrodes can be used to understand brain function and to treat medical indications such as epilepsy [25], Parkinson’s disease [26], [27], spinal cord injuries [28], [29], and sequelae of strokes [30].”
BackgroundOrgan Neuroprosthetics: Connecting Transplanted and Artificial Organs with the Nervous System
Micera, S., Menciassi, A., Cianferotti, L., Gruppioni, E., & Lionetti, V. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202302896 · Cited by 5
Self-citationXi, P., Yao, Q., Liu, Y., He, J., Tang, R., & Lang, Y. (2024) · Cyborg and Bionic Systems · doi:10.34133/cbsystems.0131 · Cited by 6
“Currently, the available treatments in motion modulation include epidural electrical stimulation (EES) [1–4], surface neuromuscular electrical stimulation (NMES) [5–7], peripheral nerve stimulation (PNS) [8–14], transcranial direct current stimulation [15], and magnetic stimulation of spinal cord…”
BackgroundStrategies and safety simulations for ultrasonic cervical spinal cord neuromodulation
Xu, R., Bestmann, S., Treeby, B. E., & Martin, E. M. (2024) · Physics in Medicine and Biology · doi:10.1088/1361-6560/ad506f · Cited by 6
“The ultrasonic neuromodulation of the dorsal root ganglion appears to be viable at human scale (Hellman 2021), which may have exciting implications for targeted neuromodulation of motor control (Rowald 2022) and sensation (Hellman 2021).”
InfluentialBandres, M. F., Gomes, J. D. F., & McPherson, J. G. (2024) · Brain Communications · doi:10.1093/braincomms/fcae280 · Cited by 6
“At present, however, the majority of epidural stimulation paradigms to enhance movement use electrical current intensities supra-threshold for evoking contractions, 44,50,51 whereas epidural stimulation for pain management remains sub-threshold for motor unit recruitment.”
BackgroundSpinal cord injury: pathophysiology and principles of management
Roberts, S. B., & Tsirikos, A. I. (2024) · Orthopaedics and Trauma · doi:10.1016/j.mporth.2024.07.002 · Cited by 6
Liu, P., Cheng, Y., Xu, Z., Li, X., Chen, Z., & Duan, W. (2024) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.52281 · Cited by 6
Soft neural interface with color adjusted PDMS encapsulation layer for spinal cord stimulation
Wang, M., Zhang, Y., Wang, A., Gan, Z., Zhang, L., & Kang, X. (2025) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2025.110402 · Cited by 8
A Call for Reckoning and Reform in Interventional Pain Medicine and Neuromodulation Research
D'Souza, R. S., Schatman, M. E., & Hussain, N. (2025) · Journal of Pain Research · doi:10.2147/jpr.s552529 · Cited by 6
“34 However, these efforts remain exceptions.”
Xiao, G., Zhu, Y., Yang, Z., Wang, M., Feng, Y., Xu, X., & Li, Y. (2025) · European Spine Journal · doi:10.1007/s00586-025-09412-9 · Cited by 6
A digital bridge to reverse paralysis
Hachem, L. D., Balbinot, G. C., & Fehlings, M. G. (2023) · Cell Research · doi:10.1038/s41422-023-00845-9 · Cited by 6
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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