Spinal Cord Associative Plasticity Study

Conditions

• Cervical Myelopathy
• Cervical Spinal Cord Injury
• Tetraplegia/Tetraparesis

Eligibility Criteria

Sex

ALL

Age

18 Years - 80 Years

Healthy Volunteers

Accepted

Interventions

• Non-invasive pairing of cortical and spinal stimulation — PROCEDURE
  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.
• Intraoperative pairing of cortical and spinal stimulation — PROCEDURE
  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.
• Non-invasive repeated pairing of cortical and spinal stimulation (SCAP) — PROCEDURE
  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.
• Intraoperative repeated pairing of cortical and spinal stimulation (SCAP) — PROCEDURE
  Intraoperative: Spinal and cortical thresholds will be determined. Immediately prior to repetitive pairing, a set of 12 baseline cortical pulses and 12 baseline spinal pulses will be delivered at 120% threshold. SCAP protocol will be applied, both of which have been successful at inducing lasting effects in the rat. After pairing, cortical stimulation at 120% of threshold and spinal cord stimulation at 120% threshold will be repeated every 10 minutes for the duration of surgery. In a subset of patients repeated pairing will be conducted with a latency that investigator does not expect will induce SCAP, or with electrodes placed over the ventral epidural surface. The control intervention will include repeated pairing at a non-convergent latency, as well as pairing of cortical stimulation with ventral epidural stimulation.
• Intraoperative repeated pairing of cortical and spinal stimulation (SCAP) at or below myelopathic region — PROCEDURE
  As per the intervention 'Intraoperative repeated pairing of cortical and spinal stimulation (SCAP)' targeted at or below myelopathic region.

Study Details

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.

Key Dates

Start date

Sep 10, 2021

Status verified

May 2026

Primary completion

Jun 30, 2026

Completion

Jun 30, 2026

Study Design

Enrollment

92 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Arms

• Experimental: 1. Uninjured participants - Immediate and lasting effects of non-invasive paired stimulation
  Participants will take part in the following to examine the immediate effects of combining cortical and spinal stimulation: A) Non-invasive pairing of cortical and spinal stimulation; B) Non-invasive repeated pairing of cortical and spinal stimulation (SCAP).
• Experimental: 2. Intraoperative participants - Immediate effects of paired stimulation
  Participants will take part in the following if they have been scheduled for a clinically indicated cervical surgery to examine the immediate effects of combining cortical and spinal stimulation: A) Non-invasive pairing of cortical and spinal stimulation; B) Intraoperative pairing of cortical and spinal stimulation.
• Experimental: 3. Intraoperative participants - Lasting effects of SCAP
  Participants will take part in the following if they have been scheduled for a clinically indicated cervical surgery, to examine the lasting effects of repeated cortical and spinal stimulation: A) Non-invasive repeated pairing of cortical and spinal stimulation (SCAP); B) Intraoperative repeated pairing of cortical and spinal stimulation (SCAP).
• Experimental: 4. Chronic cervical SCI participants - Lasting effects of non-invasive SCAP
  Participants with chronic cervical SCI will take part in the following, to examine the lasting effects of repeated cortical and spinal stimulation: A) Non-invasive repeated pairing of cortical and spinal stimulation (SCAP).
• Experimental: 5. Intraoperative participants - Lasting effects of SCAP at or below myelopathic region
  Participants will take part in the following if they have been scheduled for a clinically indicated cervical surgery, to examine the lasting effects of repeated cortical and spinal stimulation: A) Non-invasive repeated pairing of cortical and spinal stimulation (SCAP); B) Intraoperative repeated pairing of cortical and spinal stimulation (SCAP) at or below myelopathic region.

Primary Outcome Measure

Size of hand muscle response to brain stimulation during combined brain and spinal stimulation [ Time Frame: Immediate ]

Central Contacts

• Jason B Carmel, M.D., Ph.D.
  917-301-1882
  [email protected]
• Noam Y Harel, M.D., Ph.D.
  212-241-7317
  [email protected]

Locations (3)

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