The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits
Open accessAbstract
Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computational model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled this model with an anatomically realistic axon-cable model of motoneurons, interneurons, and myelinated afferent fibers for antagonistic ankle muscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruited neural structures revealed the lack of direct influence of EES on motoneurons and interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. The model also predicted the capacity of spatially distinct EES to modulate side-specific limb movements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walking after neurological disorders.
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“We previously showed that epidural electrical stimulation targeting the individual dorsal root entry zones of the lumbosacral spinal cord enables the modulation of specific leg motor pools9–12.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [9]
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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 [9]
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In the citing paper
“Epidural electrical stimulation of the spinal cord can modulate specific ensembles of motor pools through the recruitment of the dorsal root entry zones projecting to the spinal cord regions wherein these motor pools reside9,25.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [9]
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“A validated finite element model of EES of the lumbar spinal cord37,38 was used to estimate the proportion of afferent and efferent fibres recruited at a given stimulation amplitude.”
From The neurons that restore walking after paralysis (2022) · cites this paper as [37]
In the citing paper
“EES is known to enable walking through the recruitment of large-diameter afferents37,38.”
From The neurons that restore walking after paralysis (2022) · cites this paper as [37]
In the citing paper
“We performed computer simulations on a previously validated spiking neural network model37,38, reproducing the proprioceptive feedback circuits associated with a pair of antagonist muscles in the lumbar spinal cord of rodents.”
From The neurons that restore walking after paralysis (2022) · cites this paper as [37]
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Citations
Cites
1 retracted
Spinal cord stimulation for chronic pain
Mailis, A., Andrea D Furlan, M. P., Sandoval, J. A., & Taylor, R. S. (2004) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003783.pub2 · Cited by 193
RetractedThe NEURON Simulation Environment
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“2 (Hines and Carnevale, 1997) to develop a computational model of Group Ia/Ib fibers, Group II fibers, segmental interneurons, proprioceptive interneurons, commissural interneurons, and alpha motoneurons (Fig.”
BackgroundMethodInfluentialHarkema, 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 · cited 7×
“DOI:10.1523/JNEUROSCI.1688-13.2013 Copyright © 2013 the authors 0270-6474/13/3319326-15$15.00/0 and stimulation parameter modulates specific aspects of standing, stepping, and isolated movements (Minassian et al., 2004; Courtine et al., 2009; Harkema et al., 2011; Lyalka et al., 2011).”
BackgroundMethodInfluentialAlteration of proprioceptive messages induced by tendon vibration in man: a microneurographic study
Roll, J., Vedel, J. P., & Ribot, E. (1989) · Experimental Brain Research · doi:10.1007/bf00253639 · Cited by 989
Models of recruitment and rate coding organization in motor-unit pools.
Fuglevand, A. J., Winter, D. A., & Patla, A. E. (1993) · Journal of Neurophysiology · doi:10.1152/jn.1993.70.6.2470 · Cited by 988 · cited 3×
“To quantify the outputs of the model, we postulated the existence of direct relationships between the number of recruited axons and the overall muscle activation (Fuglevand et al., 1993).”
MethodInfluentialInterneuronal relay in spinal pathways from proprioceptors
Jankowska, E. (1992) · Progress in Neurobiology · doi:10.1016/0301-0082(92)90024-9 · Cited by 931 · cited 7×
“Computer simulations and pharmacological experiments provided evidence suggesting that these responses primarily emerged from the activation of interneurons via the direct recruitment of Group II fibers (Jankowska, 1992; Minassian et al., 2004; Gerasimenko et al., 2006).”
BackgroundInfluentialRestoring Voluntary Control of Locomotion after Paralyzing Spinal Cord Injury
van den Brand, R., Heutschi, J., Barraud, Q., DiGiovanna, J., Bartholdi, K., Huerlimann, M., Friedli, L., Vollenweider, I., Moraud, E. M., Duis, S., et al. (2012) · Science · doi:10.1126/science.1217416 · Cited by 767
Self-citationMcIntyre, C. C., Richardson, A. G., & Grill, W. M. (2002) · Journal of Neurophysiology · doi:10.1152/jn.00353.2001 · Cited by 764
Transformation of nonfunctional spinal circuits into functional states after the loss of brain input
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“DOI:10.1523/JNEUROSCI.1688-13.2013 Copyright © 2013 the authors 0270-6474/13/3319326-15$15.00/0 and stimulation parameter modulates specific aspects of standing, stepping, and isolated movements (Minassian et al., 2004; Courtine et al., 2009; Harkema et al., 2011; Lyalka et al., 2011).”
BackgroundMethodInfluentialSelf-citationAnalysis of Models for External Stimulation of Axons
Rattay, F. (1986) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.1986.325670 · Cited by 681 · cited 1×
“In fact, the external electrical excitability of cell membranes is proportional to the second spatial derivative along the direction of the membrane (Rattay, 1986).”
Background
Research works printed but not linked: 1
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Cited by
Sorted by citations
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
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
“Epidural electrical stimulation of the spinal cord can modulate specific ensembles of motor pools through the recruitment of the dorsal root entry zones projecting to the spinal cord regions wherein these motor pools reside 9,25 .”
BackgroundSelf-citationSpinal 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
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
Self-citationFormento, 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
Self-citation
Metadata
- Authors
- Capogrosso, M., Wenger, N., Raspopovic, S., Musienko, P., Beauparlant, J., Bassi Luciani, L., Courtine, G., & Micera, S.
- Affiliations
- Scuola Superiore Sant'Anna (IT)
- École Polytechnique Fédérale de Lausanne (CH)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-12-04
- Volume
- 33
- Issue
- 49
- Pages
- 19326-19340
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6618777
- OpenAlex
- W2127033470
- Cited by
- 435
- References
- 62
- Citations by year
- 2026: 36 · 2025: 56 · 2024: 45 · 2023: 44 · 2022: 47 · 2021: 57 · 2020: 40 · 2019: 24 · 2018: 28 · 2017: 20 · 2016: 13 · 2015: 16 · 2014: 9
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- CINECA IRIS Institutional Research Information System (Sant'Anna School of Advanced Studies) (submittedVersion)
- Funders
- National Science Foundation
- European Commission (258654)
- École Polytechnique Fédérale de Lausanne
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- FP7 Ideas: European Research Council (261247)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- epidural stimulation, spinal cord injury, lumbosacral spinal cord, sensorimotor circuits, motor neurons, interneurons, ankle muscles, standing and walking, rat model
- MeSH terms
- Algorithms, Animals, Computer Simulation, Electric Stimulation, Electrodes, Implanted, Epidural Space, Female, Interneurons, Models, Neurological, Motor Neurons, Nerve Fibers, Rats, Inbred Lew, Sensory Receptor Cells, Recruitment, Neurophysiological, Spinal Cord, Walking, Finite Element Analysis, Rats, Electrophysiological Phenomena
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