Cervical Spinal Cord Associative Plasticity

NCT07539025 | Recruiting DMC FDA Device

• 1 other identifier: AAAV2760-TD
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Associative plasticity has been used to promote functional recovery from conditions affecting movement. Prior work from the Carmel laboratory has shown that paired associative stimulation protocols timed to converge in the cervical spinal cord induce significantly larger upper limb motor responses than if timed to converge in the motor cortex. The goal of this prospective experimental study in typically developing adults is to test the effects of pairing sub-threshold hand motor cortical and median nerve stimulation targeted to induce plasticity in the cervical spinal cord, rather than in the motor cortex. Based on preliminary data, the investigators are performing a confirmatory study to test the physiological and behavioral effects of the paired brain and peripheral nerve protocol, called the SCAP-Nerve protocol. This study will first be conducted in typically developing adults to confirm the cervical spinal cord as the ideal target and verify the present stimulation parameters are sufficient to promote induction of associative plasticity of sensorimotor connections for manual dexterity. The outcomes from this study could then be translated to efficacy studies in people with spinal cord injury and cerebral palsy to promote clinically meaningful improvements in dexterity.

Conditions

Cervical Spinal Cord Plasticity

Keywords

cervical spinal cord; paired associative stimulation; motor evoked potential; spinal cord injury; cerebral palsy; manual dexterity; corticospinal; sensory afferent; SCAP; spinal cord associative plasticity

Outcome Measures

Primary Outcomes (1)

• Size of muscle response to brain stimulation after SCAP (percentage)

  Size of muscle response will be measured in response to brain stimulation. This value will be normalized to the equivalent measure taken before the SCAP protocol.

  30 minutes after SCAP

Secondary Outcomes (6)

• Size of muscle response to nerve stimulation during combined brain and nerve stimulation after SCAP (percentage)

  Immediately after intervention, up to 1 minute

• Size of muscle response to nerve stimulation during combined brain and nerve stimulation (percentage)

  Immediately after intervention, up to 1 minute

• Size of muscle response to nerve stimulation during combined brain and nerve stimulation after SCAP (percentage)

  30 minutes after SCAP

• Duration of effect of SCAP on subsequent responses to brain stimulation

  30 minutes after SCAP

• Pinch force variability

  30 minutes after SCAP

Study Arms (4)

SCAP

EXPERIMENTAL

With this session, participants will receive 90 trials of 0.1hz paired motor cortical stimulation and median nerve stimulation for 15 minutes at sub-threshold intensities, timed to converge in the cervical spinal cord simultaneously.

Other: SCAP

Cortical stimulation only

ACTIVE COMPARATOR

With this session, participants will receive 90 trials of 0.1hz motor cortical stimulation for 15 minutes at sub-threshold intensities.

Device: MagPro X100

Median nerve stimulation only

ACTIVE COMPARATOR

With this session, participants will receive 90 trials of 0.1hz median nerve stimulation for 15 minutes at sub-threshold intensities.

Device: Digitimer DS8R

Paired non-associative stimulation

ACTIVE COMPARATOR

With this session, participants will receive 90 trials of 0.1hz paired motor cortical stimulation and median nerve stimulation for 15 minutes at sub-threshold intensities, timed to be 40 milliseconds apart in the cervical spinal cord.

Other: Paired non-associative stimulation

Interventions

SCAP OTHER

This utilizes pairing of repetitive transcranial magnetic stimulation (rTMS) and peripheral nerve stimulation (rPNS) timed to converge in the cervical spinal cord.

SCAP

MagPro X100 DEVICE

This stimulator will be use to provide repetitive transcranial magnetic stimulation (rTMS).

Cortical stimulation only

Digitimer DS8R DEVICE

This stimulator will be used to provide repetitive peripheral nerve stimulation (rPNS).

Median nerve stimulation only

Paired non-associative stimulation OTHER

This utilizes pairing of repetitive transcranial magnetic stimulation (rTMS) and peripheral nerve stimulation (rPNS) timed to arrive at a pairing interval of 40 msec.

Paired non-associative stimulation

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willingness to participate in up to 4 sessions
• Maintenance of caffeine and exercise levels at time of sessions
• Ability to provide informed consent
• No known central or peripheral neurological disease or injury
• No known musculoskeletal injury of the tested arm or hand

You may not qualify if:

• Personal or family history of seizures
• Use of medications that lower seizure threshold
• History of implanted equipment including stimulators/pacemakers

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10040, United States

RECRUITING

Related Publications (7)

• Ling YT, Alam M, Zheng YP. Spinal Cord Injury: Lessons about Neuroplasticity from Paired Associative Stimulation. Neuroscientist. 2020 Jun;26(3):266-277. doi: 10.1177/1073858419895461. Epub 2019 Dec 31.

  PMID: 31889474 BACKGROUND

• Shulga A, Lioumis P, Zubareva A, Brandstack N, Kuusela L, Kirveskari E, Savolainen S, Ylinen A, Makela JP. Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients. Spinal Cord Ser Cases. 2016 Jul 14;2:16016. doi: 10.1038/scsandc.2016.16. eCollection 2016.

  PMID: 28053760 BACKGROUND

• Delvendahl I, Jung NH, Kuhnke NG, Ziemann U, Mall V. Plasticity of motor threshold and motor-evoked potential amplitude--a model of intrinsic and synaptic plasticity in human motor cortex? Brain Stimul. 2012 Oct;5(4):586-93. doi: 10.1016/j.brs.2011.11.005. Epub 2012 Feb 28.

  PMID: 22445536 BACKGROUND

• Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J. Induction of plasticity in the human motor cortex by paired associative stimulation. Brain. 2000 Mar;123 Pt 3:572-84. doi: 10.1093/brain/123.3.572.

  PMID: 10686179 BACKGROUND

• Murray LM, McIntosh JR, Goldsmith JA, Wu YK, Liu M, Sanford SP, Joiner EF, Mandigo C, Virk MS, Tyagi V, Carmel JB, Harel NY. Timing-dependent synergies between noninvasive motor cortex and spinal cord stimulation in chronic cervical spinal cord injury. medRxiv [Preprint]. 2025 Apr 27:2025.04.17.25326011. doi: 10.1101/2025.04.17.25326011.

  PMID: 40313296 BACKGROUND

• Murray LM, McIntosh JR, Goldsmith JA, Wu YK, Liu M, Sanford SP, Joiner EF, Mandigo C, Tyagi V, Virk MS, Carmel JB, Harel NY. Timing-dependent synergies between noninvasive motor cortex and spinal cord stimulation in chronic cervical spinal cord injury. Clin Neurophysiol. 2025 Dec;180:2111372. doi: 10.1016/j.clinph.2025.2111372. Epub 2025 Oct 10.

  PMID: 41106070 BACKGROUND

• Pal A, Park H, Ramamurthy A, Asan AS, Bethea T, Johnkutty M, Carmel JB. Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury. Brain. 2022 Dec 19;145(12):4531-4544. doi: 10.1093/brain/awac235.

  PMID: 36063483 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries; Cerebral Palsy

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Brain Damage, Chronic; Brain Diseases

Central Study Contacts

Shaker Dukkipati, MD, PhD

CONTACT

2123056616; sd3850@cumc.columbia.edu

Jason Carmel, MD, PhD

CONTACT

jbc28@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Weinberg Family Associate Professor of Neurology (in Orthopedic Surgery)

Model Details: All participants will undergo all arms of the study. They will first receive the SCAP protocol, which is the source of the primary investigation in this study. Then, they will receive the three comparator arms in randomized order over multiple sessions timed at least 24 hours apart to minimize carryover effects.

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: April 20, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

US (1)