Balaguer, Josep-Maria
(2025)
Mechanisms of Spinal Cord Stimulation for the Recovery of Voluntary Motor Control after Paralysis.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Every year more than 4.5 million people in the world suffer from spinal cord injury and stroke. These diseases severely impact the quality of life. The most devastating impairment is some form of motor paralysis, with the restoration of walking and arm/hand movement being the main priorities for these people. While no clinical therapies currently exist, new neurostimulation treatments are emerging, offering hope for reversing the seemingly permanent condition of paralysis. Recently, epidural spinal cord stimulation (SCS) recovered the ability to regain motor control in patients with spinal cord injury and stroke. This exciting clinical evidence results from decades of scientific studies exploring the underlying mechanisms of SCS. However, these studies never considered the contribution of residual supraspinal inputs, thereby failing to explain the facilitation of voluntary movements. Indeed, residual supraspinal fibers are rarely completely abolished after a lesion and remain crucial in conveying voluntary commands. We believe that understating the transformation of artificial sensory inputs into voluntary motor function is the only approach to improve the design of stimulation protocols targeted to maximize residual volitional input, supporting the transition of SCS to all lesion severities and upper limb paralysis. In this thesis, we studied the role of residual supraspinal inputs in the recovery of voluntary motor control enabled by SCS. To do so, we inspected neural structures at postsynaptic, presynaptic and population levels. First, we investigated the integration of supraspinal and sensory postsynaptic potentials in the motoneuron membrane. By combining biophysical modelling, monkey and human experiments, we found that supraspinal inputs control motoneurons during specific combinations of SCS parameters. Second, we explored the effects of presynaptic mechanisms in the facilitation of supraspinal input during SCS. In anesthetized monkeys, we demonstrated that this facilitation is strongly contingent on presynaptic GABA. Third, we analyzed the impact of SCS on intraspinal population activity in monkeys. We showed that artificial pulsed stimulation impairs neural activity of functions unrelated to the stimulation target. Our results have direct clinical implications that can enhance SCS efficacy, thereby accelerating the transition of this technology into a clinical therapy.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
7 January 2025 |
| Date Type: |
Publication |
| Defense Date: |
1 August 2024 |
| Approval Date: |
7 January 2025 |
| Submission Date: |
17 September 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
271 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Swanson School of Engineering > Bioengineering |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
spinal cord stimulation, voluntary motor control, paralysis |
| Date Deposited: |
07 Jan 2025 21:01 |
| Last Modified: |
07 Jan 2025 21:01 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/46975 |
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