Advances in Neuromodulation and Digital Brain–Spinal Cord Interfaces for Spinal Cord Injury
Abstract
1. Introduction
1.1. Fundamentals of Key Technologies
1.2. Overview of the Important Challenges and Potential Gains of Bringing Brain–Spine Interfaces from Bench to Bedside
- Integration of BSIs in SCI rehabilitation.
- Comparative analysis of leading implantable brain–computer interfaces (iBCIs);
- Advances in ESCS and adaptation of spinal neuromodulation technologies.
- Surgical complexity and need for specialized neurosurgical training.
- Regulatory hurdles for clinical translation of technologies and device approval.
- Signal degradation and long-term reliability of neural implants.
- Potential to restore walking in patients with complete SCI.
- Scalable solutions for low-resource settings using minimally invasive systems.
- Frameworks for personalized neurorehabilitation combining artificial intelligence (AI), BSIs, and physical therapy.
2. Scientific Considerations
3. Neurosurgical Considerations
4. Advancements in Implanted Brain–Computer Interfaces
4.1. Neurorestore WIMAGINE-Based Brain–Spine Interface
Device | SCI-Specific Application | Decoding Accuracy | Complication Profile | Regulatory Status | Scalability | 5-Year Leadership Prediction | Prediction for Adoption (Based on Current Parameters) | References |
---|---|---|---|---|---|---|---|---|
Neurorestore WIMAGINE-based BSI | Proven efficacy in restoring locomotion; integrates with spinal stimulation for walking and stepping in chronic tetraplegia | 80–90% | Zero device-related adverse events; 1–2% craniotomy-related risks (e.g., CSF leakage, gliosis) | Approved for European trials (NCT02550522); potential FDA Breakthrough by 2027 | High, but limited by invasive craniotomy | Likely to lead due to ongoing trials and regulatory progress | Strong contender, but may be surpassed by less invasive options | [27,31,32] |
Neuralink N1 Implant | Limited SCI data; focused on upper limb prosthetics, potential for future SCI applications | 95% (preclinical) | 5% electrode detachment, 1% infection risk | Early-stage, faces ethical and transparency hurdles | High potential via robotic implantation, but SCI data lacking | Unlikely to lead without SCI-specific trials | Potential if ethical/regulatory issues resolved | [34,35] |
Synchron Stentrode | Growing SCI relevance; prosthetic arm control, pending locomotion trials | 85% | 3% thrombosis, 2% signal degradation | FDA Breakthrough Device designation (2021) | High due to minimally invasive endovascular approach | Competitive, but limited by precision | Could lead if scalability and precision improve | [36,37,38] |
Blackrock Utah Array | Reliable for hand/arm function; limited SCI locomotion data | 90% | 4% infection, 5% electrode degradation | FDA-approved for investigational use | Low due to invasiveness and cost | Unlikely to lead due to scalability issues | Outdated for scalable SCI solutions | [38,39,40,41,42,43] |
4.2. Neuralink N1 Implant
4.3. Synchron Stentrode
4.4. Blackrock Neurotech Utah Array
4.5. FDA-Approved Pathways for Clinical Adoption of Implanted Cortical Devices
- Expanded Access Programs: Use FDA’s Expanded Access pathway to provide WIMAGINE to SCI patients outside trials, generating real-world evidence while awaiting full approval [44].
- Modular Approval Strategy: Seek FDA approval for WIMAGINE’s cortical component separately from spinal stimulators, leveraging existing approvals for epidural devices (e.g., Medtronic’s Intellis) to streamline the BSI system [8].
- Collaborative Trials: Partner with US institutions (e.g., Shirley Ryan AbilityLab) to conduct multicenter trials, diversifying patient cohorts and accelerating FDA data requirements [31].
5. Spinal Surgical Considerations
6. Advancements in Spinal Stimulation Technology
6.1. Courtine Group Epidural Spinal Electrode Arrays
6.2. Medtronic Intellis Spinal Cord Stimulation Platform
6.3. Abbott Eterna Spinal Cord Stimulation System
6.4. Boston Scientific Spectra WaveWriter SCS System
6.5. Comparative Analysis and Industry Leadership Predictions
6.6. FDA-Approved Pathways for Clinical Adoption for Spinal Arrays
- Expanded Access Programs: Use FDA’s Expanded Access pathway to provide arrays to SCI patients outside trials, generating real-world evidence to support full approval [42].
- Multicenter US Trials: Partner with US institutions (e.g., Craig H. Neilsen Rehabilitation Hospital) to conduct diverse trials, accelerating FDA data requirements [31].
7. The Bridge
8. Neurological Considerations
9. Postsurgical Multimodal Neurorehabilitation
10. Bench-to-Bedside Medicine and Surgery: Technology for Patients
11. Discussion
12. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Anderson, M.A.; O’Shea, T.M.; Burda, J.E.; Ao, Y.; Barlatey, S.L.; Bernstein, A.M.; Kim, J.H.; James, N.D.; Rogers, A.; Kato, B.; et al. Required growth facilitators propel axon regeneration across complete spinal cord injury. Nature 2018, 561, 396–400. [Google Scholar] [CrossRef] [PubMed]
- Courtine, G.; Sofroniew, M.V. Spinal cord repair: Advances in biology and technology. Nat. Med. 2019, 25, 898–908. [Google Scholar] [CrossRef]
- Angeli, C.A.; Boakye, M.; Morton, R.A.; Vogt, J.; Benton, K.; Chen, Y.; Ferreira, C.K.; Harkema, S.J. Recovery of overground walking after chronic motor complete spinal cord injury. N. Engl. J. Med. 2018, 379, 1244–1250. [Google Scholar] [CrossRef] [PubMed]
- Anderson, M.A.; Squair, J.W.; Gautier, M.; Hutson, T.H.; Kathe, C.; Barraud, Q.; Bloch, J.; Courtine, G. Natural and targeted circuit reorganization after spinal cord injury. Nat. Neurosci. 2022, 25, 1584–1596. [Google Scholar] [CrossRef]
- Asboth, L.; Friedli, L.; Beauparlant, J.; Martinez-Gonzalez, C.; Anil, S.; Rey, E.; Baud, L.; Pidpruzhnykova, G.; Anderson, M.A.; Shkorbatova, P.; et al. Cortico–reticulo–spinal circuit reorganization enables functional recovery after severe spinal cord contusion. Nat. Neurosci. 2018, 21, 576–588. [Google Scholar] [CrossRef]
- Audet, J.; Yassine, S.; Lecomte, C.G.; Mari, S.; Soucy, F.; Morency, C.; Merlet, A.N.; Harnie, J.; Beaulieu, C.; Gendron, L. Spinal sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered thoracic lateral hemisections but cannot restore posture and interlimb coordination during quadrupedal locomotion in adult cats. eNeuro 2023, 10, ENEURO.0191-23.2023. [Google Scholar] [CrossRef]
- Hu, X.; Xu, W.; Ren, Y.; Wang, Z.; He, X.; Huang, R.; Ma, B.; Zhao, J.; Zhu, R.; Cheng, L. Spinal cord injury: Molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther. 2023, 8, 245. [Google Scholar] [CrossRef] [PubMed]
- Harkema, S.; Gerasimenko, Y.; Hodes, J.; Burdick, J.; Angeli, C.; Chen, Y.; Ferreira, C.; Willhite, A.; Rejc, E.; Grossman, R.G.; et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: A case study. Lancet 2011, 377, 1938–1947. [Google Scholar] [CrossRef] [PubMed]
- Schalk, G.; Brunner, P.; Allison, B.Z.; Chan, A.M.; Guan, C.; Denison, T.; Rao, J.; Miller, K.J. Translation of neurotechnologies. Nat. Rev. Bioeng. 2024, 2, 637–652. [Google Scholar] [CrossRef]
- Leibinger, M.; Zeitler, C.; Paulat, M.; Gobrecht, P.; Hilla, A.; Andreadaki, A.; Gutoff, R.; Fischer, D. Inhibition of microtubule detyrosination by parthenolide facilitates functional CNS axon regeneration. eLife 2023, 12, RP88279. [Google Scholar] [CrossRef]
- Alam, M.; Ling, Y.T.; Rahman, M.A.; Wong, A.Y.L.; Zhong, H.; Edgerton, V.R.; Zheng, Y.-P. Restoration of Over-Ground Walking via Non-Invasive Neuromodulation Therapy: A Single-Case Study. J. Clin. Med. 2023, 12, 7362. [Google Scholar] [CrossRef] [PubMed]
- 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. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature 2018, 563, 65–71. [Google Scholar] [CrossRef]
- Formento, E.; Minassian, K.; Wagner, F.; Mignardot, J.B.; Le Goff-Mignardot, C.G.; Rowald, A.; Bloch, J.; Micera, S.; Capogrosso, M.; Courtine, G. Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury. Nat. Neurosci. 2018, 21, 1728–1741. [Google Scholar] [CrossRef] [PubMed]
- Rosenzweig, E.S.; Courtine, G.; Jindrich, D.L.; Brock, J.H.; Ferguson, A.R.; Strand, S.C.; Nout, Y.S.; Roy, R.R.; Miller, D.M.; Beattie, M.S.; et al. Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nat. Neurosci. 2010, 13, 1505–1510. [Google Scholar] [CrossRef]
- Takeoka, A.; Vollenweider, I.; Courtine, G.; Arber, S. Muscle spindle feedback directs locomotor recovery and circuit reorganization after spinal cord injury. Cell 2014, 159, 1626–1639. [Google Scholar] [CrossRef]
- Courtine, G.; Song, B.; Roy, R.R.; Zhong, H.; Herrmann, J.E.; Ao, Y.; Qi, J.; Edgerton, V.R.; Sofroniew, M.V. Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat. Med. 2008, 14, 69–74. [Google Scholar] [CrossRef] [PubMed]
- Capogrosso, M.; Milekovic, T.; Borton, D.; Wagner, F.; Moraud, E.M.; Mignardot, J.B.; Buse, N.; Gandar, J.; Barraud, Q.; Xing, D.; et al. A brain–spine interface alleviating gait deficits after spinal cord injury in primates. Nature 2016, 539, 284–288. [Google Scholar] [CrossRef]
- Capogrosso, M.; Wenger, N.; Raspopovic, S.; Musienko, P.; Beauparlant, J.; Luciani, L.B.; Courtine, G.; Micera, S. A computational model for epidural electrical stimulation of spinal sensorimotor circuits. J. Neurosci. 2013, 33, 19326–19340. [Google Scholar] [CrossRef]
- Willett, F.R.; Kunz, E.M.; Fan, C.; Avansino, D.T.; Wilson, G.H.; Choi, E.Y.; Kamdar, F.; Glasser, M.F.; Hochberg, L.R.; Druckmann, S.; et al. A high-performance speech neuroprosthesis. Nature 2023, 620, 1031–1036. [Google Scholar] [CrossRef]
- Soekadar, S.R.; Witkowski, M.; Gómez, C.; Opisso, E.; Medina, J.; Cortese, M.; Cempini, M.; Carrozza, M.C.; Cohen, L.G.; Birbaumer, N.; et al. Hybrid EEG/EOG-based brain/neural hand exoskeleton restores fully independent daily living activities after quadriplegia. Sci. Robot. 2016, 1, eaag3296. [Google Scholar] [CrossRef]
- Benabid, A.L.; Costecalde, T.; Eliseyev, A.; Charvet, G.; Verney, A.; Karakas, S.; Foerster, M.; Lambert, A.; Morinière, B.; Abroug, N.; et al. An exoskeleton controlled by an epidural wireless brain-machine interface in a tetraplegic patient: A proof-of-concept demonstration. Lancet Neurol. 2019, 18, 1112–1122. [Google Scholar] [CrossRef] [PubMed]
- Minev, I.R.; Musienko, P.; Hirsch, A.; Barraud, Q.; Wenger, N.; Moraud, E.M.; Gandar, J.; Capogrosso, M.; Milekovic, T.; Asboth, L.; et al. Electronic dura mater for long-term multimodal neural interfaces. Science 2015, 347, 159–163. [Google Scholar] [CrossRef] [PubMed]
- Macaya, D.; Spector, M. Injectable hydrogel materials for spinal cord regeneration: A review. Biomed. Mater. 2012, 7, 012001. [Google Scholar] [CrossRef] [PubMed]
- Collinger, J.L.; Kryger, M.A.; Barbara, R.; Betler, T.; Bowsher, K.; Brown, E.H.; Clanton, S.T.; Degenhart, A.D.; Foldes, S.T.; Gaunt, R.A.; et al. Collaborative approach in the development of high-performance brain-computer interfaces for a neuroprosthetic arm: Translation from animal models to human control. Clin. Transl. Sci. 2014, 7, 52–59. [Google Scholar] [CrossRef]
- Ghafoor, U.; Rupp, R.; Weidner, N.; Luz, A. Epidural spinal cord stimulation for motor function recovery after spinal cord injury: A systematic review. Neurol. Res. Pract. 2023, 5, 61. [Google Scholar]
- Klein, E.; Brown, T.; Sample, M.; Truitt, A.R.; Goering, S. Engineering the Brain: Ethical Issues and the Introduction of Neural Devices. Hastings Cent. Rep. 2015, 45, 26–35. [Google Scholar] [CrossRef]
- Lorach, H.; Galvez, A.; Spagnolo, V.; Martel, F.; Karakas, S.; Intering, N.; Vat, M.; Faivre, O.; Harte, C.; Komi, S.; et al. Walking naturally after spinal cord injury using a brain–spine interface. Nature 2023, 618, 126–133. [Google Scholar] [CrossRef]
- Burns, A.S.; Marino, R.J.; Kalsi-Ryan, S.; Middleton, J.W.; Tetreault, L.A.; Dettori, J.R.; Mihalovich, K.E.; Fehlings, M.G. Type and timing of rehabilitation following acute and subacute spinal cord injury: A systematic review. Glob. Spine J. 2017, 7, 175S–194S. [Google Scholar] [CrossRef]
- Mestais, C.; Charvet, G.; Sauter-Starace, F.; Foerster, M.; Ratel, D.; Benabid, A.L. WIMAGINE: Wireless 64-channel ECoG recording implant for long-term clinical applications. IEEE Trans. Neural Syst. Rehabil. Eng. 2015, 23, 10–21. [Google Scholar] [CrossRef]
- Kathe, C.; Skinnider, M.A.; Hutson, T.H.; Regazzi, N.; Gautier, M.; Demesmaeker, R.; Komi, S.; Ceto, S.; James, N.D.; Cho, N.; et al. The neurons that restore walking after paralysis. Nature 2022, 611, 540–547. [Google Scholar] [CrossRef]
- Moraud, E.M.; Capogrosso, M.; Formento, E.; Wenger, N.; DiGiovanna, J.; Courtine, G.; Micera, S. Mechanisms underlying the neuromodulation of spinal circuits for correcting gait and balance deficits after spinal cord injury. Neuron 2016, 89, 814–828. [Google Scholar] [CrossRef]
- Borton, D.; Micera, S.; Millan, J.d.R.; Courtine, G. Personalized neuroprosthetics. Sci. Transl. Med. 2013, 5, 210rv2. [Google Scholar] [CrossRef] [PubMed]
- Gill, 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. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat. Med. 2023, 29, 1124–1132. [Google Scholar] [CrossRef] [PubMed]
- Fiani, B.; Reardon, T.; Ayres, B.; Cline, D.; Sitto, S.R. An Examination of Prospective Uses and Future Directions of Neuralink: The Brain-Machine Interface. Cureus 2021, 13, e14192. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Waisberg, E.; Ong, J.; Lee, A.G. Ethical Considerations of Neuralink and Brain-Computer Interfaces. Ann. Biomed. Eng. 2024, 52, 1937–1939, Erratum in Ann. Biomed. Eng. 2024, 52, 1940. [Google Scholar] [CrossRef] [PubMed]
- Mitchell, P.; Lee, S.C.M.; Yoo, P.E.; Morokoff, A.; Sharma, R.P.; Williams, D.L.; MacIsaac, C.; Howard, M.E.; Irving, L.; Vrljic, I.; et al. Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients: The Stentrode with Thought-Controlled Digital Switch (SWITCH) Study. JAMA Neurol. 2023, 80, 270–278. [Google Scholar] [CrossRef]
- Ongard, J.; El-Hajj, G.; Verma, O.; Ghazy, S.; Kadirvel, R.; Kalmes, D.F.; Brinjikji, W. Advances in endovascular brain computer interface: Systematic review and future implications. J. Neurosci. Methods 2025, 420, 110471. [Google Scholar] [CrossRef]
- Oxley, T.J.; Yoo, P.E.; Rind, G.S.; Ronayne, S.M.; Lee, C.M.; Bird, C.; Hampshire, V.; Sharma, R.P.; Morokoff, A.; Williams, D.L.; et al. Motor neuroprosthesis implanted with neurointerventional surgery improves capacity for activities of daily living tasks in severe paralysis: First in-human experience. J. Neurointerv. Surg. 2021, 13, 102–108. [Google Scholar] [CrossRef]
- Ajiboye, A.B.; Willett, F.R.; Young, D.R.; Memberg, W.D.; Murphy, B.A.; Miller, J.P.; Walter, B.L.; Sweet, J.A.; Hoyen, H.A.; Keith, M.W.; et al. Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: A proof-of-concept demonstration. Lancet 2017, 389, 1821–1830. [Google Scholar] [CrossRef]
- Collinger, J.L.; Wodlinger, B.; Downey, J.E.; Wang, W.; Tyler-Kabara, E.C.; Weber, D.J.; McMorland, A.J.; Velliste, M.; Boninger, M.L.; Schwartz, A.B. High-performance neuroprosthetic control by an individual with tetraplegia. Lancet 2013, 381, 557–564. [Google Scholar] [CrossRef]
- Chen, X.; Wang, F.; Kooijmans, R.; Klink, P.C.; Boehler, C.; Asplund, M.; Roelfsema, P.R. Chronic stability of a neuroprosthesis comprising multiple adjacent Utah arrays in monkeys. J. Neural Eng. 2023, 20, 036039. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Bullard, A.J.; Hutchison, B.C.; Lee, J.; Chestek, C.A.; Patil, P.G. Estimating Risk for Future Intracranial, Fully Implanted, Modular Neuroprosthetic Systems: A Systematic Review of Hardware Complications in Clinical Deep Brain Stimulation and Experimental Human Intracortical Arrays. Neuromodulation 2020, 23, 411–426. [Google Scholar] [CrossRef] [PubMed]
- 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. Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 2012, 485, 372–375. [Google Scholar] [CrossRef]
- Lottes, A.E.; Cavanaugh, K.J.; Chan, Y.Y.; Devlin, V.J.; Goergen, C.J.; Jean, R.; Linnes, J.C.; Malone, M.; Peat, R.; Reuter, D.G.; et al. Navigating the Regulatory Pathway for Medical Devices-a Conversation with the FDA, Clinicians, Researchers, and Industry Experts. J. Cardiovasc. Transl. Res. 2022, 15, 927–943. [Google Scholar] [CrossRef]
- 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. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury. Nat. Med. 2016, 22, 138–145. [Google Scholar] [CrossRef] [PubMed]
- Donati, A.R.C.; Shokur, S.; Morya, E.; Campos, D.S.F.; Moioli, R.C.; Gitti, C.M.; Augusto, P.B.; Tripodi, S.; Pires, C.G.; Pereira, G.A.; et al. Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces Partial Neurological Recovery in Paraplegic Patients. Sci. Rep. 2016, 6, 30383. [Google Scholar] [CrossRef] [PubMed]
- Vansteensel, M.J.; Pels, E.G.M.; Bleichner, M.G.; Branco, M.P.; Denison, T.; Freudenburg, Z.V.; Gosselaar, P.; Leinders, S.; Ottens, T.H.; Van Den Boom, M.A.; et al. Fully Implanted Brain-Computer Interface in a Locked-In Patient with ALS. N. Engl. J. Med. 2016, 375, 2060–2066. [Google Scholar] [CrossRef]
- Kirshblum, S.; Snider, B.; Eren, F.; Guest, J. Characterizing Natural Recovery after Traumatic Spinal Cord Injury. J. Neurotrauma 2021, 38, 1267–1284. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Fishman, M.; Cordner, H.; Justiz, R.; Provenzano, D.; Merrell, C.; Shah, B.; Naranjo, J.; Kim, P.; Calodney, A.; Carlson, J.; et al. Twelve-Month results from multicenter, open-label, randomized controlled clinical trial comparing differential target multiplexed spinal cord stimulation and traditional spinal cord stimulation in subjects with chronic intractable back pain and leg pain. Pain Pract. 2021, 21, 912–923. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Darrow, D.; Balser, D.; Netoff, T.I.; Krassioukov, A.; Phillips, A.; Parr, A.; Samadani, U. Epidural spinal cord stimulation facilitates immediate restoration of dormant motor and autonomic supraspinal pathways after chronic neurologically complete spinal cord injury. J. Neurotrauma 2019, 36, 2325–2336. [Google Scholar] [CrossRef]
- Carter, M.L. Spinal cord stimulation in chronic pain: A review of the evidence. Anaesth. Intensive Care 2004, 32, 11–21. [Google Scholar] [CrossRef] [PubMed]
- Deer, T.R.; Russo, M.; Grider, J.S.; Pope, J.; Hagedorn, J.M.; Weisbein, J.; Abd-Elsayed, A.; Benyamin, R.; Raso, L.J.; Patel, K.V.; et al. The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Best Practices for Cervical Neurostimulation. Neuromodulation 2022, 25, 35–52, Erratum in Neuromodulation 2022, 25, 482. [Google Scholar] [CrossRef] [PubMed]
- Deer, T.R.; Grigsby, E.; Weiner, R.L.; Wilcosky, B.; Kramer, J.M. A prospective study of dorsal root ganglion stimulation for the relief of chronic pain. Neuromodulation 2013, 16, 67–71; discussion 71–72. [Google Scholar] [CrossRef] [PubMed]
- North, J.; Loudermilk, E.; Lee, A.; Sachdeva, H.; Kaiafas, D.; Washabaugh, E.; Sheth, S.; Scowcroft, J.; Mekhail, N.; Lampert, B.; et al. Outcomes of a Multicenter, Prospective, Crossover, Randomized Controlled Trial Evaluating Subperception Spinal Cord Stimulation at ≤1.2 kHz in Previously Implanted Subjects. Neuromodulation 2020, 23, 102–108. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Rowald, A.; Komi, S.; Demesmaeker, R.; Baaklini, E.; Hernandez-Charpak, S.D.; Paoles, E.; Montanaro, H.; Cassara, A.; Becce, F.; Lloyd, B.; et al. Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis. Nat. Med. 2022, 28, 260–271. [Google Scholar] [CrossRef] [PubMed]
- Pradat, P.F.; Hayon, D.; Blancho, S.; Neveu, P.; Khamaysa, M.; Guerout, N. Advances in Spinal Cord Neuromodulation: The Integration of Neuroengineering, Computational Approaches, and Innovative Conceptual Frameworks. J. Pers. Med. 2023, 13, 993. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Nanda, G.; Jain, P.; Suman, A.; Mahajan, H. Role of diffusion tensor imaging and tractography in spinal cord injury. J. Clin. Orthop. Trauma 2022, 33, 101997. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Flesher, S.N.; Downey, J.E.; Weiss, J.M.; Hughes, C.L.; Herrera, A.J.; Tyler-Kabara, E.C.; Boninger, M.L.; Collinger, J.L.; Gaunt, R.A. A brain–computer interface that evokes tactile sensations improves robotic arm control. Science 2021, 372, 831–836. [Google Scholar] [CrossRef]
- Behrman, A.L.; Argetsinger, L.C.; Roberts, M.T.; Stout, D.; Thompson, J.; Ugiliweneza, B.; Trimble, S.A. Activity-based therapy targeting neuromuscular capacity after pediatric-onset spinal cord injury. Top. Spinal Cord. Inj. Rehabil. 2019, 25, 132–149. [Google Scholar] [CrossRef]
- Edgerton, V.R.; Courtine, G.; Gerasimenko, Y.P.; Lavrov, I.; Ichiyama, R.M.; Fong, A.J.; Cai, L.L.; Otoshi, C.K.; Tillakaratne, N.J.; Burdick, J.W.; et al. Training locomotor networks. Brain Res. Rev. 2008, 57, 241–254. [Google Scholar] [CrossRef]
- Estes, S.; Zarkou, A.; Hope, J.M.; Suri, C.; Field-Fote, E.C. Combined Transcutaneous Spinal Stimulation and Locomotor Training to Improve Walking Function and Reduce Spasticity in Subacute Spinal Cord Injury: A Randomized Study of Clinical Feasibility and Efficacy. J. Clin. Med. 2021, 10, 1167. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Stolbkov, Y.K.; Gerasimenko, Y.P. Neurorehabilitation based on spinal cord stimulation and motor training. Neurosci. Behav. Physiol. 2024, 54, 737–748. [Google Scholar] [CrossRef]
- Baniya, M.; Rana, C.; Dhakal, R.; Makower, S.G.; Halpin, S.J.; Hariharan, R.; Sivan, M.; Allsop, M.J. The Experience of Limited Access to Care for Community-Based Patients with Spinal Cord Injury and Stroke in Nepal and the Potential of Telerehabilitation: A Qualitative Study. Inquiry 2023, 60, 469580221146830. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Fudan University Media Center. Fudan’s AI Empowered BSI Enables Paralyzed Patients to Walk. 5 March 2025. Available online: https://www.fudan.edu.cn/en/2025/0305/c344a144344/page.htm (accessed on 25 May 2025).
- Insausti-Delgado, A.; López-Larraz, E.; Nishimura, Y.; Ziemann, U.; Ramos-Murguialday, A. Non-invasive brain-spine interface: Continuous control of trans-spinal magnetic stimulation using EEG. Front. Bioeng. Biotechnol. 2022, 10, 975037. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- National Commission for the Protection of Human Subjects of Biomedical Behavioral Research. The Belmont Report: Ethical Principles Guidelines for the Protection of Human Subjects of Research; US Department of Health, Education, and Welfare: Bethesda, MD, USA, 1979. Available online: https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html (accessed on 7 May 2025).
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Jaszczuk, P.; Bratelj, D.; Capone, C.; Rudnick, M.; Pötzel, T.; Verma, R.K.; Fiechter, M. Advances in Neuromodulation and Digital Brain–Spinal Cord Interfaces for Spinal Cord Injury. Int. J. Mol. Sci. 2025, 26, 6021. https://doi.org/10.3390/ijms26136021
Jaszczuk P, Bratelj D, Capone C, Rudnick M, Pötzel T, Verma RK, Fiechter M. Advances in Neuromodulation and Digital Brain–Spinal Cord Interfaces for Spinal Cord Injury. International Journal of Molecular Sciences. 2025; 26(13):6021. https://doi.org/10.3390/ijms26136021
Chicago/Turabian StyleJaszczuk, Phillip, Denis Bratelj, Crescenzo Capone, Marcel Rudnick, Tobias Pötzel, Rajeev K. Verma, and Michael Fiechter. 2025. "Advances in Neuromodulation and Digital Brain–Spinal Cord Interfaces for Spinal Cord Injury" International Journal of Molecular Sciences 26, no. 13: 6021. https://doi.org/10.3390/ijms26136021
APA StyleJaszczuk, P., Bratelj, D., Capone, C., Rudnick, M., Pötzel, T., Verma, R. K., & Fiechter, M. (2025). Advances in Neuromodulation and Digital Brain–Spinal Cord Interfaces for Spinal Cord Injury. International Journal of Molecular Sciences, 26(13), 6021. https://doi.org/10.3390/ijms26136021