Transcranial Magnetic Stimulation Synchronized with Specific Tasks Intervention on Upper Limb Motor Dysfunction in Stroke Patients

The goal of this clinical trials is to investigate the effectiveness of individualized online repetitive transcranial magnetic stimulation (rTMS) in enhancing upper limb motor rehabilitation during the subacute and chronic phase of stroke. It will also learn about the safety of individualized online rTMS intervention methods. The main questions it aims to answer are:

1. Does rTMS synchronized with motor training improve motor rehabilitation in patients with the ability to induce motor evoked potentials(MEPs)？
2. Dose individualized rTMS synchronized with motor training improve motor rehabilitation in patients without the ability to induce MEPs?

Researchers will compare online rTMS to offline and sham stimulation in patients with MEPs to see if online rTMS works to alleviate motor dysfunction in preliminary trials. And compare individualized online rTMS to non-individualized online rTMS and sham in patients without MEPs to see if individualized online rTMS works to alleviate motor dysfunction in Randomized, double-blinded, and controlled trials.

Participants will:

1. randomized to one group acoording to the MEP condition of each person;
2. receive rTMS treatment for 10 days, with 5 working days per week for a total of two weeks;
3. receive magnetic resonance imaging (MRI) and electroencephalogram (EEG) evaluations before and after the entire treatment;
4. conduct scales and MEP assessment one day before the treatment, as well as one day, one month, and three months after the treatment.

In preliminary experiment, patients were be randomly assigned to three groups: online, offline and sham groups. if patients were able to induce MEPs, intensity of TMS will be 80% RMT; if not , inensity of TMS will be 70%\~80% of TMS output.

In RCT, patients without MEPs were randomly assigned to three groups: individualized, non-individualized, and sham groups. Patients were stimulated over 2 week period, 4 sessions of tasks were performed everyday. The patient will undergo a 2-week (10-day) stimulation protocol, with fourty tasks performed daily. This includes one session of 10 baseline tasks measurement and three sessions of 5 Hz rTMS synchronized with 10 motor tasks. rTMS will be applied to the ipsilesional motor cortex, delivering about 750 pulses per day, for a total of 7,500 pulses, at an intensity of 70\~80% of TMS output.

Eligibility Criteria:
Inclusion Criteria:

1. The patient is first diagnosed with stroke through neurological examination, CT or MRI scan.
2. The vital signs are stable and there is a certain degree of upper limb motor dysfunction.
3. The age is between 18 and 80 years old.
4. The cognitive ability is not significantly affected and the patient can cooperate with various examinations and assessments, with a MMSE score ≥ 20 points.
5. There are no serious complications (such as pneumonia, heart failure, urinary tract infection or malnutrition).
6. There is no pathological condition that is a contraindication for TMS in the medical history (for example, patients with metal in the brain, such as aneurysm clips, patients with a cardiac pacemaker, pregnant women, or those with a history of epileptic seizures).
7. The patient or guardian agrees to sign the informed consent form.

Exclusion Criteria:

1. Patients with severe heart, lung, liver, kidney diseases and malignant tumors;
2. Those with a history of aphasia, severe cognitive impairment or mental illness;
3. Patients who have had a history of epileptic seizures in the last month or are taking anti-epileptic drugs recently;
4. Those with severe visual or hearing impairments, unable to communicate normally;
5. People with metal implants, pacemakers, skull defects or other conditions that prevent them from undergoing TMS.