Spinal Cord Associative Plasticity Study
Columbia University
Summary
Spinal cord associative plasticity (SCAP) is a combined cortical and spinal electrical stimulation technique developed to induce recovery of arm and hand function in spinal cord injury. The proposed study will advance understanding of SCAP, which is critical to its effective translation to human therapy. The purpose of the study is to: 1. Determine whether signaling through the spinal cord to the muscles can be strengthened by electrical stimulation. 2. Improve our understanding of the spinal cord and how it produces movement. 3. Determine whether spinal surgery to relieve pressure on the spinal cord can improve its function. Aim 1 is designed to advance mechanistic understanding of spinal cord associative plasticity (SCAP). Aim 2 will determine whether SCAP increases spinal cord excitability after the period of repetitive pairing. In rats, SCAP augments muscle activation for hours after just 5 minutes of paired stimuli. Whereas Aims 1 and 2 focused on the effects of paired stimulation in the context of uninjured spinal cord, Aim 3 assesses whether paired stimulation can be effective across injured cord segments. Aim 3 will incorporate the experiments from Aim 1 and 2 but in people with SCI, either traumatic or pre-operative patients with myelopathy in non-invasive experiments, or targeting myelopathic segments in intraoperative segments.
Description
For people with cervical spinal cord injury (SCI), regaining hand function is their highest priority. Currently there are no effective treatments for people living with paralysis or profound weakness after SCI. The goal of this project is to translate a promising therapy for improving arm and hand function after partial spinal cord injury to humans. The approach promotes repair of residual brain to spinal cord connections using combined motor cortex and spinal cord stimulation. The direct brain to spinal cord connection is critical for skilled hand movement in health, and for the loss of move…
Eligibility
- Age range
- 18–80 years
- Sex
- All
- Healthy volunteers
- Yes
NON-INVASIVE Inclusion Criteria: (All participants) * Age between 18-80 years. * Must have stable prescription medication for 30 days prior to screening * Must be able to: abstain from alcohol, smoking and caffeine consumption on the day of each experiment; abstain from recreational drugs for the entirety of the study; commit to study requirements (i.e., 7 visits); provide informed consent. (Able-bodied participants) * No known central or peripheral neurological disease or injury. (SCI participants - including patients scheduled for intraoperative procedures) * Score of 1-4 (out of 5) o…
Interventions
- ProcedureNon-invasive pairing of cortical and spinal stimulation
Transcranial magnetic stimulation (TMS) threshold, Transcutaneous spinal cord stimulation (TSCS) threshold, and peripheral and central motor conduction times will be determined. In the active intervention, two TMS pulse intensities will be tested: 90% and 120% of motor threshold. Two conditioning TSCS pulse intensities will be tested: 50% and 90% of response threshold. Single TSCS pulses will be delivered timed to arrive in the cervical spinal cord at a range of intervals from 30ms before to 30ms after the TMS pulse. The control conditions will include TMS only TSCS only and non-convergent pairing latency pairing stimulation.
- ProcedureIntraoperative pairing of cortical and spinal stimulation
The surgeon will position spinal cord electrodes on the epidural surface one level rostral (typically C4/C5) to the site of myelopathy. Spinal and cortical thresholds will be determined. Investigator will then test the immediate effects of paired stimulation by stimulating the cortex at 120% of threshold and the spinal cord at 90% of threshold at various latencies relative to the time of synchronous convergence. The control intervention will include cortical only (120%) spinal only (90%) and non-convergent latency pairing stimulation.
- ProcedureNon-invasive repeated pairing of cortical and spinal stimulation (SCAP)
Thresholds will be determined as above. Immediately prior to repetitive pairing, a set of 12 TMS pulses will be delivered at 120% threshold to measure the baseline cortical MEP. Likewise, a set of 12 TSCS pulses will be delivered at 120% of threshold to establish the baseline spinal MEP. For each session, baseline maximal pinch dynamometry will be determined. Immediately after the SCAP protocol is completed, response to TMS, TSCS, and maximal pinch dynamometry will be measured again every 10 minutes over the subsequent hour. The control conditions will include TMS only TSCS only and non-convergent pairing latency pairing stimulation.
Locations (3)
- Bronx Veterans Medical Research Foundation, IncNew York, New York
- Columbia University Irving Medical CenterNew York, New York
- Weill Cornell MedicineNew York, New York