The goal of this clinical trial is to investigate the efficacy and safety of vagus nerve stimulation (VNS) paired with rehabilitation for enhancing upper extremity motor function after ischemic stroke.

Researchers will compare the outcomes of active VNS paired with rehabilitation against sham VNS (the actual intensity is 0 mA) also paired with rehabilitation, in order to assess improvements in arm motor function post-stroke.

Participants in this study will undergo a surgical procedure to implant the VNS system and will subsequently recieve a 6 weeks in-clinic therapy, followed by an additional 6 weeks home exercise. During the final 6 weeks, participants will either recieve in-clinic therapy or maintain their home exercise, depending on their assigned group.

There are 6 follow-up timepoints in this trial:

1. Screening follow-up timepoint (V1): All participants will sign the informed consent form and receive pre-implant evaluation, including physical examination, brain magnetic resonance imaging, FMA-UE, WMFT, modified Ashworth sacle, BDI, ect.
2. Surgery follow-up timepoint (V2):All participants will be implanted with the VNS system, including the G115R IPG and L312 lead.
3. Baseline follow-up timepoint (V3): There is a baseline evaluation 7 to 14 days after the surgery, then participants will be randomly assigned to VNS group or Control group. The randomization will be stratified by baseline FMA-UE (20 to 35, 36 to 50), age (<50, ≥50) and research center (south centers, north centers).
4. Clinic rehabilitation follow-up timepoint (V4): Participants will receive standard clinic rehabilitation 3 days per week and lasting 6 weeks. Active VNS (VNS group) or sham VNS (Control group) will be paired with rehabilitation. Participants will be evaluated at the last day of this follow-up timepoint.
5. Home exercise follow-up timepoint (V5): Participants will take standard home exercise everyday in 6 weeks. Active VNS (VNS group) or sham VNS (Control group) will be paired with rehabilitation. At the last day, after evaluating, group assignment is unblinded.
6. Unmasking follow-up timepoint (V6): In this 6 weeks, all participants will receive active VNS. Participants in VNS group will still take standard home exercise, and participants in Control group will receive standard clinic rehabilitation again. Participants will be also evaluated at the last day of this follow-up timepoint.

Inclusion Criteria:

1. Age ≥22 years and <80 years, all gender is acceptable.
2. History of unilateral supratentorial ischemic stroke ≥ 9 months but < 10 years.
3. Upper Extremity motor section of the Fugl-Meyer Assessment score ≥20 and ≤50.
4. Right- or left-sided weakness of upper extremity.
5. Ability to communicate, understand, and give appropriate consent. Subjects can follow trial commands.
6. Subjects have good compliance and can complete the visits after surgery.

Exclusion Criteria:

1. History of hemorrhagic stroke.
2. Presence of ongoing dysphagia or aspiration difficulties.
3. Prior injury to vagus nerve, either bilateral or unilateral.
4. Subject receiving medication that may significantly interfere with actions of VNS on neurotransmitter systems at study entry, clinic rehabilitation follow-up timepoint, or home rehabilitation follow-up timepoint, such as centrally acting cholinoceptor blockers, centrally acting adrenoceptor blockers, norepinephrine re-uptake inhibitors, etc.
5. Botox injections within 4 weeks prior to enrollment through the unmasking follow-up timepoint (Visit 6).
6. Severe spasticity of the upper extremity (Modified Ashworth ≥ 3).
7. Significant sensory loss of the upper extremity (Upper Extremity sensory section of the Fugl-Meyer Assessment score < 6).
8. Severe depression (Beck Depression Scale > 29).
9. Current requirement, or likely future requirement, of diathermy.
10. Current use of any other stimulation device, such as a pacemaker or other neurostimulator.
11. Pregnancy or plans to become pregnant or to breastfeed during the study period.
12. Participated in any other clinical trials within the preceding 3 months.
13. Not considered to be applicable by the investigator.

The device can be set as active VNS or sham VNS (the actual intensity is 0 mA). An unmasking programmer not involved in treatments or assessments will be messaged the group of the participant and set appropriate stimulation setting at baseline follow-up timepoint. Other masking researchers, including therapists and assessors, as well as the participant will not know the stimulation setting.