Researchers at the University of Pittsburgh are conducting a research study to see how combining brain, nerve, and hand stimulation affect hand movement after stroke. The primary purpose of this study is to examine changes in the connection between the brain and the weak hand muscles after the combined brain, nerve, and hand stimulation. The primary hypothesis is that the combined brain, nerve, and hand stimulation will increase the the connection between the brain and the weak hand muscles. The secondary purpose of this study is to examine changes in weak hand's movement and function after the combined brain, nerve, and hand stimulation. The secondary hypothesis is that the combined brain, nerve, and hand stimulation will increase weak hand movement and function.

A total of 40 participants will be enrolled in this study. During the intervention sessions, Participants will receive three combinations of the brain, hand, and nerve stimulations.

Each participant will complete three intervention sessions for the short-term effect of the intervention. The time between sessions is 3-7 days. After data collection is completed for the short-term effect part of the study, 5 out of 40 participants will be randomly chosen to enroll in the long-term effect part of the intervention. Those participants will take part in 18 intervention sessions. The sessions will be administered three times a week for six weeks.

In the short-term effect part of the study, participants will complete the following three sessions:

1. Repeated brain, hand, and nerve stimulations while practicing a task. In this session, participants will receive 120 pairs of brain, hand, and nerve stimulation while repeatedly grasp and release a ball with the weak hand. The hand stimulation will help participants to release the ball.
2. Repeated brain and nerve stimulations during rest. In this session, participants will receive 120 pairs of brain and nerve stimulation while the weak hand is resting (or not performing a task).
3. Hand stimulation while practicing a task. In this session, participants will practice grasping and releasing the task 120 times with hand stimulation. The hand stimulation will help participants to release the ball.

In the long-term effect part of the study, participants will complete the following session (3/week for 6 weeks):

During the intervention, participants will receive repeated brain, hand, and nerve stimulations while practicing a task. They will receive 120 pairs of brain, hand, and nerve stimulation while repeatedly grasp and release a ball with the weak hand. The hand stimulation will help participants to release the ball. We will give rest breaks during the practice of the task.

Inclusion Criteria:

1. Age between 18-85 years
2. Diagnosis of first-ever subcortical stroke (single cerebrovascular accident)
3. Stroke onset of at least six months prior to the time of participation
4. A score of at least 1 out of 2 on the spherical grasping item of the Fugl-Meyer Upper Extremity Subscale to allow participants to grasp the ball
5. Cognitive skills to actively participate, as indicated by scores of > 23 on the Mini-Mental Status Examination
6. English speaking

Exclusion Criteria:

1. Inability to elicit a motor evoked potential (MEP) in the EDC muscle even with a 20% background muscle contraction
2. Presence of severe aphasia
3. Excessive spasticity of the wrist and finger muscles, defined as a Modified Ashworth Score >2
4. Diagnosis of neurological disorders other than stroke
5. History of seizure or epilepsy
6. Orthopedic/musculoskeletal conditions (e.g., arthritis) affecting the upper extremity
7. Presence of metallic implants in the head or neck
8. Currently or planning to become pregnant
9. Difficulty maintaining alertness or remaining still
10. Ferromagnetic metallic implants, pacemakers, other implanted devices, or ventilators for magnetic resonance imaging (MRI)
11. Bodyweight > 300 lbs due to MRI scanner dimensions (for subjects also undergoing MRI)
12. Psychiatric diagnosis according to the criteria of the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-V), or who are on psychotropic medication
13. Life expectancy less than the duration of the study
14. Excessive pain in the paretic hand, defined as a Visual Analog Scale Score >4
15. Participation in concurrent occupational therapy
16. Current use of recreational drugs and stimulants like cocaine and methylenedioxymethamphetamine (MDMA)