Hebbian-Type Associative Stimulation in Stroke Rehabilitation

The Hong Kong Polytechnic University

Status: Not yet enrolling

Conditions: Stroke

Treatments: Device: Transcranial magnetic stimulation - dual coil; Device: Transcranial magnetic stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT07085910

HSEARS20240927001

Details and patient eligibility

About

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.

Enrollment: 108 estimated patients

Sex: All

Ages: 40 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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108 participants in 3 patient groups

Corticocortical paired associative stimulation (ccPAS)

Experimental group

Description:

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.

Treatment:

Device: Transcranial magnetic stimulation - dual coil

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

Active Comparator group

Description:

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

Treatment:

Device: Transcranial magnetic stimulation

Sham corticocortical paired associative stimulation (ccPAS)

Sham Comparator group

Description:

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)

Treatment:

Device: Transcranial magnetic stimulation - dual coil