This Phase 3 study will evaluate whether lesion network mapping-guided continuous theta burst stimulation (cTBS) can improve recovery after acute ischemic stroke. The treatment uses each participant's brain imaging to identify individualized stimulation targets related to stroke symptoms. Participants will receive either active cTBS or a sham procedure in addition to standard stroke care. The study will assess whether this personalized brain stimulation approach improves functional recovery and is safe for patients after ischemic stroke.

Acute ischemic stroke often leads to persistent motor impairment despite standard medical treatment and rehabilitation. The early post-stroke period may represent an important window for modulating brain network plasticity and promoting recovery. Continuous theta burst stimulation (cTBS), a patterned form of repetitive transcranial magnetic stimulation, can modulate cortical excitability over a short stimulation period and may support recovery when applied to clinically relevant motor networks.

This study evaluates a personalized neuromodulation approach based on lesion network mapping. For each participant, the acute infarct lesion is identified on clinical brain imaging and mapped to a reference functional connectome to estimate lesion-associated networks. Candidate stimulation targets are selected from symptom-relevant cortical network nodes, with consideration of accessibility, safety, and electric-field modeling. Neuronavigation is used to guide coil placement and maintain targeting accuracy.

Active treatment consists of lesion network mapping-guided cTBS delivered to individualized cortical targets using a figure-8 coil under neuronavigation. Sham stimulation follows the same imaging-based target selection, electric-field modeling, positioning, and procedural workflow, but uses a sham coil designed to mimic the sensory and acoustic features of stimulation without delivering a therapeutic magnetic field. This approach is intended to maintain blinding while isolating the effect of active stimulation.

This Phase 3 trial evaluates the efficacy and safety of individualized lesion network mapping-guided cTBS for recovery after acute ischemic stroke.

Inclusion Criteria:

1. Age 18-80 years.
2. Ischemic stroke onset within the past 14 days.
3. Unilateral, supratentorial ischemic stroke confirmed by CT or MRI.
4. Pre-stroke modified Rankin Scale (mRS) score of 0-1.
5. NIH Stroke Scale (NIHSS) total score 6-25, with item 1a ≤ 1 point, and at least one of items 5a, 5b, 6a, or 6b ≥ 2 points.
6. Written informed consent signed by the patient or the patient's legally authorized representative.

Exclusion Criteria:

1. Contraindications to TMS (e.g. cranial metallic foreign bodies, cardiac pacemaker, implanted drug pump, cochlear implant).
2. History of epilepsy or seizure, intracranial hypertension, tumor, or other serious neurological disease.
3. Midline shift or parenchymal mass effect on cranial CT or other imaging.
4. CT or MRI evidence of bilateral acute cerebral infarction or infratentorial acute infarction (brainstem or cerebellum).
5. Evidence of acute intracranial hemorrhage, including spontaneous intracerebral hemorrhage, epidural hematoma, subdural hematoma, intraventricular hemorrhage, or subarachnoid hemorrhage.
6. Pre-stroke mRS ≥ 2.
7. Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg despite antihypertensive treatment.
8. Pregnant or breastfeeding women, or women planning pregnancy within 90 days.
9. Severe psychiatric disorders or dementia (or other conditions) precluding informed consent or follow-up.
10. Concomitant malignant tumor or severe systemic disease with life expectancy < 90 days.
11. Participation in any other interventional clinical study within 30 days before randomization, or currently enrolled in such a study.

Participants, care providers, investigators, and outcomes assessors are all blinded to treatment allocation. A separate, unblinded technician prepares and operates the stimulation device according to randomized codes but has no role in clinical assessments, data collection, or patient care beyond administering the sessions. Treatment codes remain concealed until database lock, except in predefined emergencies requiring unblinding for safety.