Using Non-invasive Brain and Spinal Cord Stimulation to Improve Arm and Hand Function After Spinal Cord Injury

Combining Non-invasive Brain and Spinal Cord Stimulation for Improving Arm and Hand Function Following Spinal Cord Injury.

Cervical spinal cord injury (SCI) disrupts communication between the brain and spinal circuits, affecting voluntary movement control and contributing to arm and hand impairments, the top recovery priority for people with tetraplegia. Although rehabilitation and emerging neuromodulation approaches can support meaningful gains, many individuals experience persistent limitations in reaching and grasping. Current noninvasive stimulation strategies typically target the brain OR the spinal cord alone, despite strong reciprocal interactions between these structures. Cervical transcutaneous spinal cord stimulation (tSCS) can enhance upper limb function. Cerebellar stimulation, given its key role in sensorimotor integration and modulation of corticospinal excitability, represents a promising but underexplored therapeutic target. Theta burst stimulation (TBS), a rapid form of repetitive transcranial magnetic stimulation (TMS), induces lasting changes in cortical excitability and may promote associative plasticity when paired with spinal cord stimulation. This double-blind, randomized, sham-controlled pilot trial (n=24) will evaluate the feasibility, preliminary efficacy, and mechanisms of combined cerebellar TBS + cervical tSCS in people with chronic cervical SCI (AIS B, C or D). Participants will either receive cerebellar TBS + cervical tSCS, tSCS only, or sham stimulation while engaging in functional task practice such as pinching and grasping 3x/week for 8 weeks. Feasibility outcomes include adherence, retention, and safety. Efficacy will be assessed using the GRASSP strength sub-score and KINARM-based measures of sensorimotor control. Mechanistic outcomes will assess changes in cortical and spinal cord functional connectivity using resting state fMRI, corticospinal excitability using motor evoked potentials, and spinal excitability using the H reflex. Findings will establish whether combined cerebellar TBS and cervical tSCS is feasible, safe, and capable of enhancing upper limb recovery.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Cord Injuries and Disorders (SCI/D)
• Intervention / Treatment: Device: Cerebellar theta burst stimulation; Device: Cervical transcutaneous spinal cord stimulation; Behavioral: Functional task practice

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Raza Malik, PhD; Phone Number: 604-827-3369; Email: boyd.lab@ubc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z3
      • University of British Columbia
      • Contact: Jordan Lab Manager; Phone Number: 604-822-6886; Email: brocato@mail.ubc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At least 19 years of age and no older than 75 years at the time of enrollment. Previous research has demonstrated the safety and efficacy of stimulation-based interventions in adults up to 75 years of age. The lower age limit reflects the legal age for independent informed consent in British Columbia.7,8
2. Non-progressive cervical SCI from C2-C8 inclusive
3. AIS classification B, C or D
4. Indicated for upper extremity training procedures by the participant's treating physician, occupational therapist, or physical therapist
5. GRASSP-Prehension score ≥10 or GRASSP-Strength score ≥30
6. Minimum 12 months after injury (i.e., chronic SCI)
7. If prescribed anti-spasticity or pain medications, must be at a stable dose for at least 4 weeks before commencing study procedures
8. Stable management of spinal cord related clinical issues (e.g., spasticity management, autonomic dysreflexia)
9. Capable of providing informed consent

Exclusion Criteria:

1. Has any unstable or significant medical condition that is likely to interfere with study procedures or likely to confound study endpoint evaluations, such as severe neuropathic pain, depression, mood disorders or other cognitive disorders
2. Has been diagnosed with autonomic dysreflexia that is severe, unstable and uncontrolled
3. History of additional neurologic disease, such as stroke, multiple sclerosis and traumatic brain injury
4. History of seizures (e.g. epilepsy).
5. Any implanted metal (other than dental implants) in the skull or presence of pacemakers, stimulators, or medication pumps in the trunk.
6. Participant has undergone electrode implantation surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cerebellar TBS + Cervical tSCS; Participants will recieve 60 min of active cervical transcutaneous spinal cord stimulation with intermittent bouts of active Cerebellar theta burst stimulation 3x/week for 8 weeks, alongside functional task practice.	Device: Cerebellar theta burst stimulation; Theta burst stimulation (TBS) is a pattern of repetitive transcranial magnetic stimulation that will be delivered over the lateral hemisphere of the cerebellum. Sham TBS will be delivered using a sham coil over the cerebellum.; Device: Cervical transcutaneous spinal cord stimulation; Non-invasive electrical stimulation at 30Hz will be delivered through 2 round electrodes placed over the cervical vertebrae to target the cervical spinal cord. Sham cervical tSCS will involve briefly increasing stimulation intensity to the sensory threshold, followed by reducing the intensity to zero for the remainder of the session; Behavioral: Functional task practice; All participants will complete 60-minute sessions of functional task practice three times per week for eight weeks, delivered concurrently with either real or sham stimulation. Following functional task practice guidelines, training will consist of repetitive, goal-directed upper-limb activities designed to promote functional independence in everyday tasks.
Active Comparator: Cervical tSCS only; Participant will recieve 60 min of active cervical transcutaneous spinal cord stimulation only 3x/week for 8 weeks, alongside functional task practice.	Device: Cervical transcutaneous spinal cord stimulation; Non-invasive electrical stimulation at 30Hz will be delivered through 2 round electrodes placed over the cervical vertebrae to target the cervical spinal cord. Sham cervical tSCS will involve briefly increasing stimulation intensity to the sensory threshold, followed by reducing the intensity to zero for the remainder of the session; Behavioral: Functional task practice; All participants will complete 60-minute sessions of functional task practice three times per week for eight weeks, delivered concurrently with either real or sham stimulation. Following functional task practice guidelines, training will consist of repetitive, goal-directed upper-limb activities designed to promote functional independence in everyday tasks.
Sham Comparator: Sham Cerebellar TBS + Sham Cervical tSCS; Participants will recieve 60 min of sham cervical transcutaneous spinal cord stimulation with intermittent bouts of sham Cerebellar theta burst stimulation 3x/week for 8 weeks, alongside functional task practice.	Device: Cerebellar theta burst stimulation; Theta burst stimulation (TBS) is a pattern of repetitive transcranial magnetic stimulation that will be delivered over the lateral hemisphere of the cerebellum. Sham TBS will be delivered using a sham coil over the cerebellum.; Device: Cervical transcutaneous spinal cord stimulation; Non-invasive electrical stimulation at 30Hz will be delivered through 2 round electrodes placed over the cervical vertebrae to target the cervical spinal cord. Sham cervical tSCS will involve briefly increasing stimulation intensity to the sensory threshold, followed by reducing the intensity to zero for the remainder of the session; Behavioral: Functional task practice; All participants will complete 60-minute sessions of functional task practice three times per week for eight weeks, delivered concurrently with either real or sham stimulation. Following functional task practice guidelines, training will consist of repetitive, goal-directed upper-limb activities designed to promote functional independence in everyday tasks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility outcomes	Feasibility, which will be assessed through adherence, recruitment, retention, and adverse event rates across all groups. We will specifically document session numbers, dates and times, as well as the frequency and severity of skin irritations, abnormal blood pressure responses (e.g., autonomic dysreflexia), cardiac responses (e.g., tachycardia, bradycardia) and any symptoms. Participant safety will be monitored throughout the intervention via regular skin integrity checks and cardiovascular recordings (blood pressure and heart rate) throughout each session.	From enrollment to the end of stimulation at 8 weeks
Upper limb strength	Change in upper limb strength from pre- to post-intervention using the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP) strength sub-score. The GRASSP evaluates three domains: strength manual muscle testing of key upper limb muscles), sensibility (light touch and pinprick discrimination), and prehension, which includes both a qualitative analysis of grasp patterns and a performance-based component (GRASSP-Prehension Performance) that assesses functional use of the hand during object manipulation tasks. Strength will be the primary dependent measure from this measure.	Baseline and after 8 weeks of stimulation
Sensorimotor network connectivity	Change in functional connectivity strength of the cortical sensorimotor network from pre- to post- intervention using resting-state functional MRI (fMRI). We will use a Philips Ingenia Elition 3.0T MRI scanner with a 32-channel sensitivity head coil to scan brain and a separate 20 channel dStream head/neck coil for cervical spinal cord. We will collect T1 and resting state functional MRI scans of both brain and cervical spinal cord at baseline and post-intervention. Resting state functional MRI will be acquired to characterize functional reorganization of the brain and/or spinal cord driven by cerebellar TBS + cervical tSCS (or tSCS alone) alongside functional task practice. Brain and spinal cord functional connectivity: We will characterize properties of the sensorimotor network, particularly global efficiency, which represents the overall capacity that the network has to transfer information (i.e., quantifies the extent to which nodes of the network are integrated).	Baseline and after 8 weeks of stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm and hand sensorimotor control	Arm and hand sensorimotor control will be indexed using Kinarm standard tests. Specifically, by the task score and path: length ratio during a four target visually guided reaching task using the Kinarm End-Point Lab (BKIN Technologies Ltd., Kingston, ON, Canada). These metrics take into account the spatial and temporal components of reaching, providing nuanced information regarding motor control strategies. We will also characterize proprioceptive sense by using an arm position matching task on the Kinarm and quantifying absolute matching error.	Baseline and after 8 weeks of stimulation
Corticospinal excitability (Motor Evoked Potentials [MEPs]):	To characterize cortical excitability, we will index resting motor threshold for corticospinal tracts. We will use single-pulse TMS delivered using a figure-of-eight coil connected to the Magstim SuperRapid2 Plus-1 stimulator (Magstim Rapid II System , Magstim Company Ltd., GB, Class II License No 69773). MEPs will be recorded from the first dorsal interosseous (FDI) muscle (Bagnoli™, Delsys Inc., Natick, USA). The motor hotspot, which is the region where a single-pulse stimulation elicits the largest and most consistent MEP in the most-affected hand, will be identified and recorded. A neuronavigation system, will be used to ensure the consistent targeting of the hotspot across sessions. Resting motor threshold is the stimulator output that elicits an MEP >50μV in 5 of 10 trials at rest. We will quantify MEP amplitudes and latencies to evaluate corticospinal excitability.	Baseline and after 8 weeks of stimulation
Cerebellar-brain inhibition (CBI)	Cerebellar influences on motor evoked potentials can be assessed using a dual TMS coil approach. CBI will be elicited by applying a conditioning pulse (CS) over the lateral cerebellum (midpoint between the inion and the mastoid targets the lateral cerebellum)16 using a double-cone coil before a test stimulus (TS) over the contralateral motor cortex using a figure-of-eight coil (Magstim Rapid II System , Magstim Company Ltd., GB, Class II License No 69773). The interstimulus interval between CS and TS will be 5ms-7ms to maximize the inhibitory effect. TS intensity will be set to the minimum intensity that elicits MEPs with an average peak-to-peak amplitude of 0.5-1 mV. CS intensity will be set to 100% RMT, with a maximum intensity cut-off at 80% maximum stimulator output (MSO) to avoid discomfort. Ten conditioned and 15 unconditioned MEPs will be collected. The amplitude of the conditioning MEPs will be expressed as a ratio of the mean unconditioned stimuli.	Baseline and after 8 weeks of stimulation
Spinal reflex excitability (H-reflex):	H-reflex testing will be conducted by obtaining surface EMG responses (Bagnoli™, Delsys Inc., Natick, USA, not a medical device [research purposes only]) from the upper limb muscles (e.g., extensor/flexor carpi radialis, FDI) in response to median/radial nerve stimulation (Bio-logic aep system - stimulator, facial digitimer ds7a, natus medical incorporated dba excel-tech ltd (xltek), Oakville, Canada, Class II License No 85645). To generate a H-Reflex recruitment curve (input-output curve), square-wave pulses will be delivered starting at sub-threshold intensities for eliciting an H-reflex. Stimulations of progressively higher intensity will be delivered until a plateau in the peak-to-peak amplitude of the M-Wave is observed. We will calculate Hmax/Mmax ratio to index the percentage of the motoneuron pool that is activated.	Baseline and after 8 weeks of stimulation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurological function and injury severity	Neurological evaluations of participants with SCI will be performed using the ISNCSCI exam. The level and severity of damage to motor and sensory pathways will be determined by a trained team member using the standard ISNCSCI examination (2019 revision). In brief, this examination includes the assessment of motor function of key muscles in the upper and lower extremities using an established scale (muscle power graded as 0-5; for a total of 20 muscles in the four limbs) and sensory evaluation to light touch and pin prick in 28 dermatomes of the body. Sensory scores for each dermatome are assigned as 0=absent, 1=abnormal, and 2=normal. With this coding system, participants who perceive a pinprick as minimally sharp touch are assigned the same score as those who perceive it as almost normal. Perception of light touch stimuli is graded similarly.	Baseline and after 8 weeks of stimulation
Short-form (36) Health Survey (SF-36):	The SF-36 is the most commonly used generic measure of QoL. The SF-36 consists of 8 domains pertaining to the respondents' experiences in the last 4 weeks. Each of the 8 summed scores is linearly transformed onto a scale from 0 (negative health) to 100 (positive health) to provide a score for each subscale. The SF-36 is widely used to measure QOL in patients with SCI.	Baseline and after 8 weeks of stimulation
Autonomic Dysfunction following SCI (ADFSCI) questionnaire:	The ADFSCI assesses self-reported frequency and severity of autonomic related symptoms. The OH part of the questionnaire includes 8 items, each using a 5-point scale to score the frequency and severity of hypotensive symptoms, such as dizziness, nausea, confusion, etc., under different circumstances.	Baseline and after 8 weeks of stimulation

Collaborators and Investigators

• Sponsor: University of British Columbia

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): February 28, 2031

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Neuroimaging; Spinal cord injury; Neurophysiology; Transcutaneous Spinal Cord Stimulation; Cerebellar Theta Burst Stimulation; Arm and Hand Function; Upper Limb Motor Control
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Trauma, Nervous System; Spinal Cord Diseases; Pathological Conditions, Signs and Symptoms; Disease; Spinal Cord Injuries
• Other Study ID Numbers: H25-02621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the results reported in publications arising from this study will be made available to qualified researchers upon reasonable request. Requests will be subject to approval by the study investigators, completion of a data-use agreement, and compliance with participant consent and institutional ethics approvals. Data will be available beginning after publication of the primary study results. Requests should be directed to the study principal investigator.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No