We will investigate the therapeutic efficacy of EEG-synchronized noninvasive repetitive transcranial magnetic stimulation (rTMS) in the early subacute phase after ischemic stroke to improve upper limb motor rehabilitation. We hypothesize that synchronization of rTMS with the phase of the ongoing sensorimotor oscillation indicating high corticospinal excitability leads to significantly stronger improvement of paretic upper limb motor function than the same rTMS protocol non-synchronized to the ongoing sensorimotor oscillation or sham stimulation.

High-frequency rTMS will be applied to the ipsilesional motor cortex in 400 bursts of 100 Hz triplets with a mean inter-burst interval of 3 s (20 min treatment duration, 1,200 pulses per day) for 5 consecutive workdays (6,000 pulses total) at a stimulus intensity of 80% of resting motor threshold, in one of three conditions/arms, followed by 40 min task-specific hand/arm-physiotherapy.

Inclusion Criteria:

Subjects meeting all of the following criteria will be considered for admission to the trial:

1. Age ≥ 18 years at the time of signing the informed consent.

2. Cerebral ischemia identified by brain imaging (cerebral MRI or CT) occurred 1-14 days ago.

3. Subject understands and voluntarily signs an informed consent document prior to any study related assessments/procedures.

4. Stroke has resulted in a new arm-/hand motor deficit with ≤ 50 points in the FMA-UE.

5. Presence of motor evoked potentials (MEPs) in the paretic hand. MEPs has to be obtained in the resting muscle

   o If no MEPs can be obtained, MEP search procedure can be repeated later up to 14 days after stroke onset.

6. ● μ-oscillation (8-12 Hz) is recordable by EEG in the ipsilesional sensorimotor cortex with a sufficient signal-to-noise ratio of at least 3 dB

7. ● Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

Subjects presenting with any of the following criteria will not be included in the trial:

1. Hemorrhagic stroke (this refers to primary intracerebral hemorrhage only; hemorrhagic transformation of ischemic infarcts is not an exclusion criterion)
2. Estimated life expectancy < 12 months
3. Presence of intracranial ferromagnetic metal (extracranial stents ≥10 cm away from the TMS coil are acceptable) in accordance with current safety guidelines [18]
4. Intraocular metal, cochlear implants
5. If TMS might interact with sensors of active implants (e.g., intra-cardiac defibrillators).
6. If a cranial bone gap affects currents induced by TMS (such as after craniotomy).
7. History of seizures or epilepsy.
8. Treatment intervention can't be started within 14 days after onset of stroke.
9. Women during pregnancy and lactation.
10. Participation in other studies if they are MDR or AMG studies or there is otherwise a high risk of insurance law issues intervening between two studies. In case of uncertainty, competing insurances must be contacted prior to participation
11. persistent addiction disorder (except for nicotine dependence)
12. CNS malignoma
13. If there is any concern by the investigator regarding the safe participation of the subject in the study or for any other reason the investigator considers the subject inappropriate for participation in the study.
14. The ability to consent for patients who are unable to speak will be assessed on the basis of the NIHS-Score by an independent physician (details see chapter 21 and appendix).

The study is a multicenter randomized controlled double-blind three-arm parallel-group exploratory clinical trial. The subjects as well as the as the rater in the post- and the follow-up assessment will be blinded to the intervention condition the patient receives.