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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Epidural electrical stimulation targeting individual dorsal root entry zones of the lumbosacral spinal cord enables modulation of specific leg motor pools.
“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]
In “Evaluation of EES selectivity during standing and walking in spinal rats” (page unavailable), the paper reports that stimulation at L2 and S1 preferentially modulated different hindlimb muscles and motor pools. It describes electrodes on the lateral aspect of those spinal segments, but does not establish that they targeted individual dorsal root entry zones; that anatomical detail is more specific than the evidence supports. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOptimized 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 pools.
“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]
The ‘Computer and experimental evaluation of EES selectivity’ section (page unavailable) reports that electrode position affected selective recruitment of limb muscles and flexor and extensor motor pools. But the ‘Coupling between FEM and NEURON models’ section describes monopolar cathodal stimulation, not optimized configurations of anodes and cathodes steering fields toward subsets of dorsal root entry zones. The paper also says selectivity under static conditions was limited. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEpidural electrical stimulation of the spinal cord can modulate specific ensembles of motor pools through recruitment of dorsal root entry zones projecting to the spinal cord regions wherein these motor pools reside.
“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]
EES is known to enable walking through the recruitment of large-diameter afferents.
“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]
A validated finite element model of epidural electrical stimulation of the lumbar spinal cord was used to estimate the proportion of afferent and efferent fibres recruited at a given stimulation amplitude.
“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]
Computer simulations were performed on a previously validated spiking neural network model reproducing proprioceptive feedback circuits associated with a pair of antagonist muscles in the lumbar spinal cord of rodents.
“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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- 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 › Pathology and Forensic Medicine › 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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