Hebbian-Type Associative Stimulation in Stroke Rehabilitation

NCT ID: NCT07085910

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2028-12-31

Brief Summary

Stroke remains the primary cause of long-term neurological disabilities. Effective rehabilitation solutions are essential to alleviate the burden poststroke survivors impose on hospitals and community services. Following unilateral stroke, interhemispheric balance is disrupted. Prior studies have extensively documented that exaggerated interhemispheric inhibitory flow from the contralesional to the ipsilesional hemisphere prevents maximal functional recovery in poststroke survivors. Therefore, we aimed to test the modulatory effects of a Hebbian-type plasticity induction paradigm using corticocortical paired associative stimulation (ccPAS) over the bilateral motor cortex. This approach aims to reverse the abnormal inhibitory flow from the contralesional to the ipsilesional hemisphere and assess its clinical benefits on upper extremity motor recovery in patients with stroke. In this randomized controlled trial, we hypothesize that Hebbian-type ccPAS would be more effective than sham ccPAS and conventional single-site inhibitory rTMS delivered to the contralesional hemisphere at improving hemiplegic upper limb motor functionality and modulating interhemispheric activity to an equilibrium state among patients with stroke. This approach seeks to address diseases related to brain network impairments, such as stroke. This project will provide insights into the recovery mechanisms activated following neurological diseases from the perspective of the Hebbian learning rules of associative plasticity.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Corticocortical paired associative stimulation (ccPAS)

The ccPAS will be applied using two MagPro X100 stimulators connected to two vertically oriented figure-of-eight coils designed for bilateral hemispheric stimulation. Each ccPAS session will involve the delivery of 90 paired pulses, stimulating the M1s over both the contralesional and ipsilesional hemispheres at a frequency of 0.05 Hz. Each session will be 30 minutes, and the interstimulus interval between paired pulses will be 8 ms to ensure that the ipsilesional M1 neurons are always activated before the firing of contralesional M1 neurons.

Group Type: EXPERIMENTAL

Transcranial magnetic stimulation - dual coil

Intervention Type: DEVICE

The dual coil stimulation will be applied using two MagPro X100 stimulators connected to two vertically oriented figure-of-eight coils designed for bilateral hemispheric stimulation.

Conventional single-site low frequency repetitive transcranial magnetic stimulation (rTMS)

LF rTMS will be performed using a TMS stimulator and the same stimulation coil (MC-B65-HO). The stimulation target will be set the contralesional M1 area, determined using motor hotspot hunting. In line with our recent trial, a total of 1200 pulses (20 mins) with a frequency of 1 Hz and an intensity of 120% of the RMT will be delivered to the contralesional M1

Group Type: ACTIVE_COMPARATOR

Transcranial magnetic stimulation

Intervention Type: DEVICE

Single coil TMS will be performed using a TMS stimulator and the same stimulation coil (MC-B65-HO).

Sham corticocortical paired associative stimulation (ccPAS)

The same dual-coil setup (MC-B65-HO) and stimulation intensity during sham stimulation as in the ccPAS group will be utilized. However, the inter-stimulus interval between paired pulses will be adjusted to 100 ms (a duration that prevents any STDP-like effects from being induced by repetitive paired-pulse stimulation)

Group Type: SHAM_COMPARATOR

Transcranial magnetic stimulation - dual coil

Intervention Type: DEVICE

The dual coil stimulation will be applied using two MagPro X100 stimulators connected to two vertically oriented figure-of-eight coils designed for bilateral hemispheric stimulation.

Interventions

Transcranial magnetic stimulation - dual coil

The dual coil stimulation will be applied using two MagPro X100 stimulators connected to two vertically oriented figure-of-eight coils designed for bilateral hemispheric stimulation.

Intervention Type: DEVICE

Transcranial magnetic stimulation

Single coil TMS will be performed using a TMS stimulator and the same stimulation coil (MC-B65-HO).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Diagnosis with monohemispheric ischemic subcortical stroke (with intact corpus callosum), with stroke onset ≥6 months,

2. Age 40-75 years.

3. Residual upper limb function between levels 3-6, according to the Functional Test for the Hemiplegic Upper Extremity (FTHUE), indicating mildly to moderately impaired upper limb motor function.

4. Capable of providing informed written consent.

Exclusion Criteria

1. any contraindications for TMS (screened using the safety checklist by Rossi)

2. Diagnosis of any concomitant neurological diseases other than stroke.

3. Signs of cognitive impairment, defined as a Montreal cognitive assessment Hong Kong version score <21/22 out of 30 .

4. Severe spasticity in the hemiparetic upper limb muscles, with a Modified Ashworth score >2.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hong Kong Polytechnic University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Jack Jiaqi Zhang, PhD

Role: CONTACT

jack-jiaqi.zhang@polyu.edu.hk

27666696

Other Identifiers

HSEARS20240927001

Identifier Type: -

Identifier Source: org_study_id