Neural mechanisms underlying the recovery of voluntary control of motoneurons after paralysis with spinal cord stimulation
Spinal cord stimulation (SCS) improves motor control after paralysis. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Here, we demonstrate that this hypothesis is not supported by experimental evidence. Instead, we show that residual supraspinal inputs modulate motoneurons' membrane potential to transform subthreshold SCS pulses into suprathreshold action potentials, thereby entraining motoneuron activity to SCS. Despite this entrainment, residual supraspinal inputs can control motoneuron firing rates by modulating the number of subthreshold SCS pulses transformed into action potentials, resulting in volitional modulation of motor output for a restricted set of SCS parameters. Furthermore, we predict that residual supraspinal inhibitory drive can silence unwanted suprathreshold motoneuron activity, enlarging the functional set of SCS parameters. Finally, we demonstrate that this set of functional stimulation parameters is further restricted by lesion severity, highlighting an intrinsic limitation of SCS in cases of severe injury.
Authors
- Luigi Borda (ORCID: https://orcid.org/0009-0003-4670-8530)
- Scott Ensel (ORCID: https://orcid.org/0000-0003-0264-3686)
- Josep-Maria Balaguer (ORCID: https://orcid.org/0000-0002-7792-6376)
- Arianna Damiani (ORCID: https://orcid.org/0009-0002-8521-865X)
- Roberto de Freitas (ORCID: https://orcid.org/0000-0001-6237-1040)
- Erynn Sorensen (ORCID: https://orcid.org/0000-0003-0988-4132)
- Jorge Alvaro Gonzalez-Martinez (ORCID: https://orcid.org/0000-0002-9936-7034)
- Julia Ostrowski
- Elvira Pirondini (ORCID: https://orcid.org/0000-0002-8078-3951)
- Douglas J. Weber (ORCID: https://orcid.org/0000-0002-9782-3497)
- Lee E. Fisher (ORCID: https://orcid.org/0000-0002-9072-3119)
- Serena Donadio (ORCID: https://orcid.org/0000-0002-2425-6145)
- Lucy Liang (ORCID: https://orcid.org/0009-0003-5462-832X)
- Peter Carlos Gerszten (ORCID: https://orcid.org/0000-0002-1483-6090)
- Genís Prat-Ortega (ORCID: https://orcid.org/0000-0002-3401-3569)
- Daryl P. Fields (ORCID: https://orcid.org/0000-0002-4594-2996)
- Marco Capogrosso (ORCID: https://orcid.org/0000-0002-0975-316X)
- Erinn M. Grigsby (ORCID: https://orcid.org/0000-0002-8378-6488)
- Prakarsh Yadav (ORCID: https://orcid.org/0000-0002-1170-6290)
- Nikhil Verma (ORCID: https://orcid.org/0009-0004-5533-6887)
- Jonathan Ho (ORCID: https://orcid.org/0009-0007-9463-6884)
Institutions
- University of Pittsburgh (US)
- Center for the Neural Basis of Cognition (US)
- Neurological Surgery (US)
- Carnegie Mellon University (US)
Publication Details
- Journal
- Neuron
- Published
- 2025-09-22
- DOI
- https://doi.org/10.1016/j.neuron.2025.08.023
- Citations
- 3
- Primary Topic
- Spinal Cord Injury Research
- Type
- article
- Field-Weighted Citation Impact
- 4.41