The purpose of this research study is to find out the optimal intensity and frequency of Low Intensity Focused Ultrasound (LIFU) that is safe and tolerable in people who have had a stroke.

Aim 1 is to determine the optimal intensity of Low Intensity Focused Ultrasound stimulation (LIFUS) in stroke patients in terms of safety. We will investigate the optimal spatial-peak temporal-average intensity/ISPTA in the range of 0(or sham) W/cm2 to 8 W/cm2. Safety will be investigated by assessing clinically detectable signs and symptoms by monitoring vital signs and surveying subjects with a questionnaire before and after each stimulation session, and additionally by detecting subclinical neuronal injury using MRI/DWI. Aim 1 requires up to 36 subjects.

Aim 2 is to determine the optimal frequency of LIFU stimulation in stroke patients in terms of cortical excitability. Stroke subjects undergo each of the 5 frequency levels (0.35 MHz; 0.5 MHz; 0.75 MHz, 1.0 MHz and 1.5 MHz) on 5 different days with at least one day washout. The intensity (ISPTA) will set up at the level that is determined from Aim 1. Cortical excitability is measured by the amplitude of motor evoked potentials (MEPs) induced by Transcranial Magnetic Stimulation (TMS) from the Abductor Pollicis Brevis (ABP) muscle of the affected side. MEPs will be recorded pre- and post-stimulation to determine the optimal intensity for maximal cortical excitability from the hemisphere where the lesion is located. Aim 2 requires 18 subjects.

Inclusion Criteria:

1. ≥ 21 years old of any gender and race;
2. Clinical ischemic stroke or hemorrhagic (confirmed by CT or MRI) that occurred >= 2 months ago
3. Predominantly unilateral motor impairment with FM-UE score ≤ 62/66;
4. MEPs are inducible from a hand muscle on the affected side (i.e. Abductor Pollicis Brevis (APB) muscle).

Exclusion Criteria:

1. Any concomitant neurological disorder affecting arm function;
2. Documented history of severe dementia with or without medication before stroke;
3. Subject is unable to do the motor learning practice at the baseline;
4. Presence of any MRI/TMS/ultrasonic stimulation risk factors: an electrically, magnetically, or mechanically activated metal or nonmetal implant including cardiac pacemaker, intracerebral vascular clips, or any other electrically sensitive support system; non-fixed metal in any part of the body; pregnancy (the effect of TMS/ultrasonic stimulation on the fetus is unknown); no history of seizure before or after the stroke; preexisting scalp lesion or wound or bone defect or hemicraniectomy.

we will follow the American Heart Association/American Stroke Association data sharing policy per grant requirement