Spinal Cord Injuries
Conditions
Keywords
spinal cord injury, spinal cord stimulation, rehabilitation, neuromodulation
Brief summary
Spinal cord injury leads to long-lasting paralysis and impairment. Re-enabling movement of paralyzed areas is challenging and more information is needed about neurological recovery. The purpose of this study is to understand the contribution of individual neural tracts to movements facilitated by transcutaneous spinal cord stimulation (SCS).
Detailed description
Spinal cord injury leads to long-lasting motor impairment and paralysis that currently is not curable. Electrical spinal cord stimulation (SCS) is beginning to be used as a neuromodulation technique to re-enable movement of paralyzed areas, however the mechanisms of neurorecovery induced by electrical neuromodulation of the spinal cord remain poorly understood. The goal of this project is to generate evidence-based knowledge of changes in the short-term excitability of corticospinal and reticulospinal neural structures that may mediate immediate improvements in motor function enabled by SCS. The proposed study will: (1) determine which kinds of SCS-facilitated movements are mediated by the corticospinal tract. (2) determine which kinds of SCS-facilitated movements are mediated by the reticulospinal tract. Having a better understanding of the neural mechanisms that are enhanced by SCS can allow the development of therapies that directly target the excitability and plasticity states of these structures towards improved and accelerated recovery.
Interventions
Kinematics and cortical spinal motor excitability
Kinematics and reticular spinal motor excitability
Motor task combined with real or sham stimulation
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
After baseline evaluations of the effect of transcutaneous SCS on single pulse responses, motor function, and a familiarization phase on a body-machine interface, participants will be randomly assigned to one of two arms in the study. Arm 1: Participants will receive interventions A and B and transcranial magnetic stimulation is used to evaluate the excitability of the corticospinal tract. Arm 2: Participants will receive interventions A and B and a loud auditory stimuli is used to evaluate the excitability of the reticulospinal tract. Arms 1 and 2 will run in parallel. Participants will perform interventions A and B in a randomized cross-over design. In both interventions A and B, participants will use their legs to control a computer cursor as transcutaneous spinal cord stimulation is delivered. Intervention A, participants perform a range-of-motion task, while in intervention B, participants perform a precision-control task.
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy volunteers * Age between 16-65 * Healthy individuals with no major conditions of any organ system
Exclusion criteria
Healthy volunteers * Not willing or able to provide consent * Any acute or chronic pain condition * Any acute or chronic disease of a major organ system * Use of analgesics within 24 hours prior to study appointment * Use of caffeine with 3 hours of study appointment * History of epilepsy * Implanted metal * Active medical problems Inclusion criteria: Participants with spinal cord injury (SCI) * Age between 16-65 * Traumatic SCI C4-T9 level, complete (ASIA A) or incomplete (ASIA B, C or D) * at least 1 year post injury * Stable medical condition * difficulty independently performing leg movements in routine activities * able to follow simple commands * able to speak and respond to questions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Corticospinal Tract Excitability After Training | 30 minutes before and 30 minutes into intervention | This primary outcome is a measure of changes in corticospinal tract excitability as quantified by changes in the amplitude size of motor evoked potentials. Data for this arm were not collected due to early study termination. |
| Reticulospinal Tract Excitability During Different Types of Movements | During intervention, *1 Day*. | This primary outcome measures changes in reticulospinal tract excitability (RST) during training as quantified by changes in reaction time after a startling auditory stimulus. RST contrubution was evaluated for dorsiflexion, plantarflexion, hip flexion movements during precision and range of motion control tasks under three conditions: with transcutaneous spinal cord stimulation or without stimulation. All conditions/evaluations were performed in the same session. 30 repetitions were performed per condition during a single session and averaged for each participant. RST is a ratio calculated by = (visual - startle)/(visual - auditory), where: visual represents the reaction time to a visual cue, auditory represents the reaction time to an auditory cue, startle represents the reaction time to a startling cue. A RST ratio value greater than 1 would indicate a significant contribution of the reticulospinal tract for a given task. A value equal or lower than 1 would suggest |
Countries
United States
Participant flow
Recruitment details
Participants enrolled from flyers and word of mouth at Washington University in St. Louis. The first participant was enrolled on 06/23/2022, the last participant was enrolled on 03/06/2023.
Pre-assignment details
Recruitment was only perform for the second arm of the study: evaluating reticulospinal tract contributions during different types of movements. Participants performed range-of-motion and precision-control tasks in randomized order during the same session. As this study was terminated early based on change in funding, no participants were assigned to the Evaluation of Motor Evoked Potentials arm, and no data could be provided for this outcome measure.
Participants by arm
| Arm | Count |
|---|---|
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements This arm will receive the loud auditory stimuli to evaluate the excitability of the reticulospinal tract first then the arm will receive the transcranial magnetic stimulation to excite the corticospinal tract second
Electrophysiology assessment - reticulospinal tract: Kinematics and reticular spinal motor excitability
Training with some stimulation: Motor task combined with real or sham stimulation | 20 |
| Evaluation of Motor Evoked Potentials During Non-invasive Spinal Cord Stimulation and Leg Movements Evaluation of motor evoked potentials during non-invasive spinal cord stimulation and leg movements
This arm will receive the transcranial magnetic stimulation to evaluate the excitability of the corticospinal tract first then the arm will receive the loud auditory stimuli to evaluate the excitability of the reticulospinal track second.
Electrophysiology assessment - corticospinal tract: Kinematics and cortical spinal motor excitability
Training with some stimulation: Motor task combined with real or sham stimulation | 0 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Evaluation of Motor Evoked Potentials During Non-invasive Spinal Cord Stimulation and Leg Movements |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 0 Participants |
| Age, Continuous | 25.8 years STANDARD_DEVIATION 8.67 | 25.8 years STANDARD_DEVIATION 8.67 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | — |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 18 Participants | — |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Asian | 9 Participants | 9 Participants | — |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | — |
| Region of Enrollment United States | 20 participants | 20 participants | — |
| Sex: Female, Male Female | 6 Participants | 6 Participants | — |
| Sex: Female, Male Male | 14 Participants | 14 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 0 |
| other Total, other adverse events | 0 / 20 | 0 / 0 |
| serious Total, serious adverse events | 0 / 20 | 0 / 0 |
Outcome results
Primary
Changes in Corticospinal Tract Excitability After Training
This primary outcome is a measure of changes in corticospinal tract excitability as quantified by changes in the amplitude size of motor evoked potentials. Data for this arm were not collected due to early study termination.
Time frame: 30 minutes before and 30 minutes into intervention
Primary
Reticulospinal Tract Excitability During Different Types of Movements
This primary outcome measures changes in reticulospinal tract excitability (RST) during training as quantified by changes in reaction time after a startling auditory stimulus. RST contrubution was evaluated for dorsiflexion, plantarflexion, hip flexion movements during precision and range of motion control tasks under three conditions: with transcutaneous spinal cord stimulation or without stimulation. All conditions/evaluations were performed in the same session. 30 repetitions were performed per condition during a single session and averaged for each participant. RST is a ratio calculated by = (visual - startle)/(visual - auditory), where: visual represents the reaction time to a visual cue, auditory represents the reaction time to an auditory cue, startle represents the reaction time to a startling cue. A RST ratio value greater than 1 would indicate a significant contribution of the reticulospinal tract for a given task. A value equal or lower than 1 would suggest
Time frame: During intervention, *1 Day*.
Population: The average across all participants is reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Plantar flexion - range of motion - No stimulation | 1.443 arbitrary units | Standard Error 0.325 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Plantar flexion - precision control - No stimulation | 1.455 arbitrary units | Standard Error 0.258 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Dorsiflexion - precision control - No stimulation | 1.364 arbitrary units | Standard Error 0.377 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Hip flexion - range of motion - stimulation | 1.497 arbitrary units | Standard Error 0.569 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Hip flexion - precision control - stimulation | 1.689 arbitrary units | Standard Error 0.667 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Plantar flexion - range of motion - stimulation | 1.465 arbitrary units | Standard Error 0.667 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Hip flexion - range of motion - No stimulation | 1.405 arbitrary units | Standard Error 0.285 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Hip flexion - precision control - No stimulation | 1.480 arbitrary units | Standard Error 0.325 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Dorsiflexion - range of motion - No stimulation | 1.544 arbitrary units | Standard Error 0.578 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Plantar flexion - precision control - stimulation | 1.376 arbitrary units | Standard Error 0.285 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Dorsiflexion - range of motion - stimulation | 1.363 arbitrary units | Standard Error 0.225 |
| Reaction Time Evaluation During Non-invasive Spinal Cord Stimulation and Leg Movements | Reticulospinal Tract Excitability During Different Types of Movements | RST: Dorsiflexion - precision control - stimulation | 1.294 arbitrary units | Standard Error 0.189 |
Comparison: Reticulospinal tract (RST) contribution computed as RST = (visual - startle)/(visual - auditory) reaction times, where a RST value greater than 1 would indicate a significant contribution of the reticulospinal tract for a given task.~A one sample t-test (or Wilcoxon signed-rank test for non-normally distributed data) was used to test the hypothesis that the RST contribution for a given movement was significantly greater than 1.p-value: <0.05t-test, 2 sided