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Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial

BACKGROUND: The seemingly simple tasks of standing and walking require continuous integration of complex spinal reflex circuits between descending motor commands and ascending sensory inputs. Spinal cord injury greatly impairs standing and walking ability, but both improve with locomotor training. H...

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Autores principales: Skiadopoulos, Andreas, Famodimu, Grace O., Solomon, Shammah K., Agrawal, Parul, Harel, Noam Y., Knikou, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949167/
https://www.ncbi.nlm.nih.gov/pubmed/36824823
http://dx.doi.org/10.21203/rs.3.rs-2527617/v1
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author Skiadopoulos, Andreas
Famodimu, Grace O.
Solomon, Shammah K.
Agrawal, Parul
Harel, Noam Y.
Knikou, Maria
author_facet Skiadopoulos, Andreas
Famodimu, Grace O.
Solomon, Shammah K.
Agrawal, Parul
Harel, Noam Y.
Knikou, Maria
author_sort Skiadopoulos, Andreas
collection PubMed
description BACKGROUND: The seemingly simple tasks of standing and walking require continuous integration of complex spinal reflex circuits between descending motor commands and ascending sensory inputs. Spinal cord injury greatly impairs standing and walking ability, but both improve with locomotor training. However, even after multiple locomotor training sessions, abnormal muscle activity and coordination persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits and potentiate neuronal activity based on need. Transcutaneous spinal cord (transspinal) stimulation alters motoneuron excitability over multiple segments by bringing motoneurons closer to threshold, a prerequisite for effectively promoting spinal locomotor network neuromodulation and strengthening neural connectivity of the injured human spinal cord. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after spinal cord injury is unknown. METHODS: Forty-five individuals with chronic spinal cord injury are receiving 40 sessions of robotic gait training primed with 30 Hz transspinal stimulation at the Thoracic 10 vertebral level. Participants are randomized to receive 30-minutes of active or sham transspinal stimulation during standing or active transspinal stimulation while supine followed by 30-minutes of robotic gait training. Over the course of locomotor training, the body weight support, treadmill speed, and leg guidance force are adjusted as needed for each participant based on absence of knee buckling during the stance phase and toe dragging during the swing phase. At baseline and after completion of all therapeutic sessions, neurophysiological recordings registering corticospinal and spinal neural excitability changes along with clinical assessment measures of standing and walking, and autonomic function via questionnaires regarding bowel, bladder and sexual function are taken. DISCUSSION: The results of this mechanistic randomized clinical trial will demonstrate that tonic transspinal stimulation strengthens corticomotoneuronal connectivity and dynamic neuromodulation through posture-dependent corticospinal and spinal neuroplasticity. We anticipate that this mechanistic clinical trial will greatly impact clinical practice because in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation. Additionally, by applying multiple interventions to accelerate motor recovery, we are employing a treatment regimen that reflects a true clinical approach. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04807764; Registered on March 19, 2021.
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spelling pubmed-99491672023-02-24 Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial Skiadopoulos, Andreas Famodimu, Grace O. Solomon, Shammah K. Agrawal, Parul Harel, Noam Y. Knikou, Maria Res Sq Article BACKGROUND: The seemingly simple tasks of standing and walking require continuous integration of complex spinal reflex circuits between descending motor commands and ascending sensory inputs. Spinal cord injury greatly impairs standing and walking ability, but both improve with locomotor training. However, even after multiple locomotor training sessions, abnormal muscle activity and coordination persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits and potentiate neuronal activity based on need. Transcutaneous spinal cord (transspinal) stimulation alters motoneuron excitability over multiple segments by bringing motoneurons closer to threshold, a prerequisite for effectively promoting spinal locomotor network neuromodulation and strengthening neural connectivity of the injured human spinal cord. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after spinal cord injury is unknown. METHODS: Forty-five individuals with chronic spinal cord injury are receiving 40 sessions of robotic gait training primed with 30 Hz transspinal stimulation at the Thoracic 10 vertebral level. Participants are randomized to receive 30-minutes of active or sham transspinal stimulation during standing or active transspinal stimulation while supine followed by 30-minutes of robotic gait training. Over the course of locomotor training, the body weight support, treadmill speed, and leg guidance force are adjusted as needed for each participant based on absence of knee buckling during the stance phase and toe dragging during the swing phase. At baseline and after completion of all therapeutic sessions, neurophysiological recordings registering corticospinal and spinal neural excitability changes along with clinical assessment measures of standing and walking, and autonomic function via questionnaires regarding bowel, bladder and sexual function are taken. DISCUSSION: The results of this mechanistic randomized clinical trial will demonstrate that tonic transspinal stimulation strengthens corticomotoneuronal connectivity and dynamic neuromodulation through posture-dependent corticospinal and spinal neuroplasticity. We anticipate that this mechanistic clinical trial will greatly impact clinical practice because in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation. Additionally, by applying multiple interventions to accelerate motor recovery, we are employing a treatment regimen that reflects a true clinical approach. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04807764; Registered on March 19, 2021. American Journal Experts 2023-02-16 /pmc/articles/PMC9949167/ /pubmed/36824823 http://dx.doi.org/10.21203/rs.3.rs-2527617/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Article
Skiadopoulos, Andreas
Famodimu, Grace O.
Solomon, Shammah K.
Agrawal, Parul
Harel, Noam Y.
Knikou, Maria
Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial
title Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial
title_full Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial
title_fullStr Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial
title_full_unstemmed Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial
title_short Priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial
title_sort priming locomotor training with transspinal stimulation in people with spinal cord injury: study protocol of a randomized clinical trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949167/
https://www.ncbi.nlm.nih.gov/pubmed/36824823
http://dx.doi.org/10.21203/rs.3.rs-2527617/v1
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