The goal of this research study is to examine communication between brain and muscle in individuals with stroke and determine if applying non-invasive brain stimulation to different parts of the brain improves this communication and performance on a hand squeezing task.

The investigators will fit participants with an electroencephalography (EEG) cap and place electromyography (EMG) stickers on participants hand and arm muscles to record brain and muscle activity, respectively.

Participants will complete a single research visit lasting approximately 3 hours. During this visit, participants will receive two different types of non-invasive brain stimulation: [1] stimulation to the motor part of the brain and [2] stimulation to the visual part of the brain. Participants will be randomized so that half will receive stimulation to the motor part of the brain first followed by stimulation to the visual part of the brain second and vice versa. Participants will complete three blocks of hand squeezing trials using the stroke-affected (weak) hand. During the first block of squeezing trials, no brain stimulation will occur. During the second and third blocks, participants will receive stimulation just before each hand squeezing trial. The investigators will record participants' brain and muscle activity during these blocks of hand squeezing trials. Additionally, participants will also complete screening tests and exams looking at mood, motor function, and cognition.

The purpose of this pilot study is to investigate and modulate corticomuscular coherence (CMC) by using beta-burst repetitive transcranial magnetic stimulation (rTMS). The central hypothesis is that the enhancement of neural oscillatory rhythms in the beta frequency range (13-30 Hz), which supports corticomuscular circuit function, will strengthen CMC measurement. Prior research has indicated that CMC, a surrogate measure of functional connectivity between the brain and peripheral muscles, has clinical relevance as a potential biomarker for motor recovery following stroke. In this cross-over study, the investigators will enroll 20 participants with chronic (≥ 6 months) stroke to complete a single research visit. The investigator will examine corticomuscular circuit function in response to beta-burst repetitive transcranial magnetic stimulation (rTMS) delivery to either participants' ipsilesional motor hotspot (active site) or ipsilesional occipital cortex (control site). The sequence or order of brain stimulation to the active and control site will be randomized across participants (described further below).

Participants will perform three blocks of a precision grip task with their stroke-affected (weak) hand using a custom-built dynamometer device. Each block will contain 20 trials for a total of 60 trials. Participants will receive visual cues when to squeeze the dynamometer device and when to relax their hand. They will also receive visual feedback of their force output to a visual target, which corresponds to 20% of their maximum voluntary contraction force. Prior to the start of these three blocks, participants will be randomized to a rTMS sequence (AB or BA). The first block of 20 trials does not involve stimulation delivery. Participants randomized to the AB sequence will receive rTMS stimulation to a "decoy" or active control site (ipsilesional occipital cortex) during the second block of 20 trials followed by stimulation to the active site (ipsilesional motor hotspot around primary motor cortex, M1) during the third block of 20 trials. Those randomized to the BA sequence will start with stimulation to the active site (M1) during the second block followed by stimulation to the ipsilesional occipital cortex during the third block. Stimulation will occur as a "burst" delivered just prior to the start of each grip trial that is the time just before participant's receive the visual cue to initiate the squeeze.

The investigators will also determine how the degree of injury to the ipsilesional corticospinal tract impacts responsively to beta-burst rTMS. The investigators will assess corticospinal excitability using single transcranial magnetic stimulation pulses to measure the downstream motor-evoked potential (MEP) response. Lastly, investigators will also determine if beta-burst rTMS impacts motor performance as assessed by reaction time and grip precision. The hypotheses are as follows:

1. greater pre/post change in CMC following beta-burst rTMS to the active brain site (M1/motor hotspot region) compared to the active control site (ipsilesional occipital cortex)
2. those with greater corticospinal tract injury, as denoted by reduced MEP amplitude and increased MEP latency, will demonstrate less pre-post change in CMC
3. beta-burst rTMS to the active site (M1/motor hotspot region) will result in improved grip task performance based on reduced reaction times and improved grip precision in comparison rTMS delivery to the ipsilesional occipital cortex (active control site).

Inclusion Criteria:

• Chronic (≥ 6 months) unilateral cortical/subcortical ischemic or hemorrhagic stroke as confirmed by medical records
• Upper extremity weakness (hemiparesis) contralateral to the stroke
• Sufficient cognitive capacity (Montreal Cognitive Assessment ≥ 21 points), communication function, and English proficiency to understand and safely comply with all study procedures
• Ipsilesional motor-evoked potential response
• Able to perform isometric grip task by making a fist with their stroke-affected hand (hand contralateral to the stroke)

Exclusion Criteria:

• Contraindications to TMS (seizure activity within past 2 years, pregnancy, indwelling metal)
• Cognitive deficits (Montreal Cognitive Assessment < 21 points)
• Concurrent physical/occupational therapy and/or clinical trial participation related to stroke
• Injury or conditions that impact affected extremity-use beyond stroke (e.g., arthritis)
• Impaired vision despite use of aid (e.g. glasses, contacts, etc.)
• Cerebellar stroke
• Major medical/neurological/psychiatric condition impacting physical function in the opinion of the physician co-investigator
• Absent ipsilesional motor-evoked potential response

Deidentified individual data that support the results will be shared. Data will include: Corticomuscular Coherence Measures, Behavioral Tests/Measures, motor-evoked potential data.

Data will be shared no later than 6 months after publication submission with no end date.

Approved Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)'s Data and Specimen Hub (DASH).