Does cathodal HD-tDCS-preconditioned iTBS over the contralesional dorsal premotor cortex improve upper limb motor function in patients with severe ischaemic stroke? A study protocol for a single-centre, participant-blinded and outcome assessor-blinded randomised controlled trial

Abstract

Introduction The contralesional dorsal premotor cortex (cPMd) is a potential target for motor recovery in severe stroke. However, interindividual heterogeneity and the limited efficacy of standalone repetitive transcranial magnetic stimulation may restrict its clinical benefit. This study aims to investigate whether cathodal high-definition transcranial direct current stimulation (HD-tDCS) preconditioning enhances the effects of intermittent theta-burst stimulation (iTBS) over the cPMd on upper limb function in patients with severe ischaemic stroke. Methods and analysis This participant-blinded and outcome assessor-blinded, randomised controlled trial will enrol 90 patients with severe ischaemic stroke, defined as a Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score ≤22. Participants will be randomly assigned in a 1:1:1 ratio to one of three groups: (1) the HD-tDCS+iTBS group, receiving cathodal HD-tDCS preconditioning over the cPMd followed by iTBS; (2) the sham HD-tDCS+iTBS group, receiving sham HD-tDCS preconditioning over the cPMd followed by iTBS; and (3) the sham HD-tDCS+sham iTBS group, receiving sham HD-tDCS preconditioning over the cPMd followed by sham iTBS. Cathodal HD-tDCS will be delivered at 1.5 mA for 20 min and iTBS at 80% of the active motor threshold. Stimulation sessions will be administered once daily, 5 days per week for four consecutive weeks. All participants will also receive conventional rehabilitation therapy during the intervention period. The primary outcome is the FMA-UE. Secondary outcomes include the Arm Subscore of the Motricity Index, the Hong Kong edition of the Functional Test for the Hemiplegic Upper Extremity, the Modified Barthel Index and the Modified Ashworth Scale. Functional MRI and diffusion tensor imaging will be performed. All clinical and imaging outcome measures will be evaluated at baseline and after the intervention. Ethics and dissemination The study has been approved by the Ethics Committee of the First Affiliated Hospital with Nanjing Medical University (2025-SR-1066). The findings will be published in peer-reviewed journals and presented at international rehabilitation conferences. Trial registration number ChiCTR2600119646.