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NCT Number: NCT07085910

Hebbian-Type Associative Stimulation in Stroke Rehabilitation

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.

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Key information

Conditions

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

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

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.

Transcranial Magnetic Stimulation

Device

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

Primary outcomes

  1. The Fugl-Meyer Assessment-Upper Extremity Scores

    Time frame: Baseline

    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.

  2. The Fugl-Meyer Assessment-Upper Extremity Scores

    Time frame: At 4 weeks

    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.

  3. The Fugl-Meyer Assessment-Upper Extremity Scores

    Time frame: At 3-month

    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.

Secondary outcomes

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

    Time frame: Baseline

    ISP measured using concurrent TMS-evoked potential is set as another outcome for measuring the interhemispheric inhibitory flow between the bilateral M1s. TMS-evoked activity will be defined as the local mean field power (LMFP) of six channels surrounding the M1 (Left: C1, C3, C5, CP1, CP3, CP5; Right: C2, C4, C6, CP2, CP4, CP6) in a specific time frame. Because of the approximately 10 ms of transcallosal conduction, the LMFP from 50 to 130 ms is rectified for the stimulated M1 and from 60 to 140 ms for the non-stimulated M1. A higher ISP value indicates a higher inhibitory flow from the non-stimulated M1 to the stimulated M1.

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

    Time frame: At 4-week

    ISP measured using concurrent TMS-evoked potential is set as another outcome for measuring the interhemispheric inhibitory flow between the bilateral M1s. TMS-evoked activity will be defined as the local mean field power (LMFP) of six channels surrounding the M1 (Left: C1, C3, C5, CP1, CP3, CP5; Right: C2, C4, C6, CP2, CP4, CP6) in a specific time frame. Because of the approximately 10 ms of transcallosal conduction, the LMFP from 50 to 130 ms is rectified for the stimulated M1 and from 60 to 140 ms for the non-stimulated M1. A higher ISP value indicates a higher inhibitory flow from the non-stimulated M1 to the stimulated M1.

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

    Time frame: At 3-month

    ISP measured using concurrent TMS-evoked potential is set as another outcome for measuring the interhemispheric inhibitory flow between the bilateral M1s. TMS-evoked activity will be defined as the local mean field power (LMFP) of six channels surrounding the M1 (Left: C1, C3, C5, CP1, CP3, CP5; Right: C2, C4, C6, CP2, CP4, CP6) in a specific time frame. Because of the approximately 10 ms of transcallosal conduction, the LMFP from 50 to 130 ms is rectified for the stimulated M1 and from 60 to 140 ms for the non-stimulated M1. A higher ISP value indicates a higher inhibitory flow from the non-stimulated M1 to the stimulated M1.

Study contacts

Contact information is provided by the study sponsor or research team.

Jack Jiaqi Zhang, PhD

CONTACT

[email protected]

27666696

Sponsors and collaborators

Lead sponsor

The Hong Kong Polytechnic University

Other

Registry information

Official study title

Modulating Interhemispheric Interactions Using Hebbian-Type Associative Stimulation to Promote Upper Extremity Motor Recovery Following Stroke

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Jul 25, 2025
Registry last updated
Jul 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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