Hebbian-Type Associative Stimulation in Stroke Rehabilitation

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

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.

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.