Hebbian-Type Associative Stimulation in Stroke Rehabilitation

NCT07085910 | Not Yet Recruiting

• 1 other identifier: HSEARS20240927001
• Study Type: interventional
• Target: 108
• Locations: 0 countries
• Sites: N/A

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

Keywords

Stroke; Neuromodulation; Transcranial magnetic stimulation; Upper extremity; Rehabilitation and Occupational Therapy

Outcome Measures

Primary Outcomes (3)

• The Fugl-Meyer Assessment-Upper Extremity Scores

  The Fugl-Meyer Assessment-Upper Extremity Scores (FMA-UE) is the gold standard for assessing poststroke upper limb motor control. It is used to determine the movement, coordination, and reflex action of the affected upper limb in poststroke people.

  Baseline

• The Fugl-Meyer Assessment-Upper Extremity Scores

  The Fugl-Meyer Assessment-Upper Extremity Scores (FMA-UE) is the gold standard for assessing poststroke upper limb motor control. It is used to determine the movement, coordination, and reflex action of the affected upper limb in poststroke people.

  At 4 weeks

• The Fugl-Meyer Assessment-Upper Extremity Scores

  The Fugl-Meyer Assessment-Upper Extremity Scores (FMA-UE) is the gold standard for assessing poststroke upper limb motor control. It is used to determine the movement, coordination, and reflex action of the affected upper limb in poststroke people.

  At 3-month

Secondary Outcomes (3)

• Interhemispheric signal propagation (ISP) in TMS-evoked potential

  Baseline

• Interhemispheric signal propagation (ISP) in TMS-evoked potential

  At 4-week

• Interhemispheric signal propagation (ISP) in TMS-evoked potential.

  At 3-month

Study Arms (3)

Corticocortical paired associative stimulation (ccPAS)

EXPERIMENTAL

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.

Device: Transcranial magnetic stimulation - dual coil

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

ACTIVE COMPARATOR

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

Device: Transcranial magnetic stimulation

Sham corticocortical paired associative stimulation (ccPAS)

SHAM COMPARATOR

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)

Device: Transcranial magnetic stimulation - dual coil

Interventions

Transcranial magnetic stimulation - dual coil 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.

Corticocortical paired associative stimulation (ccPAS); Sham corticocortical paired associative stimulation (ccPAS)

Transcranial magnetic stimulation DEVICE

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

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

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis with monohemispheric ischemic subcortical stroke (with intact corpus callosum), with stroke onset ≥6 months,
• Age 40-75 years.
• 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.
• Capable of providing informed written consent.

You may not qualify if:

• any contraindications for TMS (screened using the safety checklist by Rossi)
• Diagnosis of any concomitant neurological diseases other than stroke.
• Signs of cognitive impairment, defined as a Montreal cognitive assessment Hong Kong version score \<21/22 out of 30 .
• Severe spasticity in the hemiparetic upper limb muscles, with a Modified Ashworth score \>2.

Sponsors & Collaborators

• The Hong Kong Polytechnic University: lead

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Jack Jiaqi Zhang, PhD

CONTACT

27666696; jack-jiaqi.zhang@polyu.edu.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: July 25, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): July 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 25, 2025

Record last verified: 2025-06