This study will validate a predictive model that uses demographics, functional status, neurophysiology, neuroanatomy, and other potential biomarkers to predict the likelihood of a clinically significant change in impairment at the end of a robot assisted therapy intervention.The study will include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS), and an arm exercise program consisting of robot-assisted exercise combined with functional arm exercise called transition to task training (TTT).

After informed consent, a baseline neurological exam, medical records review, MRI of the brain, TMS, questionnaires, cognitive testing, robot evaluations, and arm function testing will occur. Baseline testing will occur in the first 4-6 weeks of participation including two separate sessions approximately 1 week a part to examine arm strength, range of motion, and ability to perform functional tasks, with one additional session if needed to verify stability between results. Additionally, one robot evaluation will be completed.

The intervention phase consists of 12 weeks of robot and transition to task arm exercise training (TTT). Interventions will occur approximately 3 times per week for 12 weeks for a total of 36 visits. Additional time and visits will be allowed with visits occurring 4 times per week or up to 6 additional weeks (not to exceed 18 weeks) if scheduling conflicts arise. The intervention sessions will be one hour in duration.

During the hour-long intervention, 45 minutes of robotic intervention will be followed by 15 minutes of TTT. The training will be sequential with 12 sessions focused on the wrist, followed by 12 sessions on the shoulder-elbow and the final 12 sessions alternating between the wrist and elbow-shoulder.

After the final training session, subjects will return after a 12 week retention period. At various time points during and after the intervention phase there will be additional arm function testing, robot evaluations, questionnaires, MRI and TMS sessions for re-assessment.

Inclusion Criteria:

• Clinically defined, unilateral, hemiparetic stroke with radiologic exclusion of other possible diagnosis
• Stroke onset at least 6 months before enrollment
• Present with Mild/Moderate to Severe arm dysfunction (based on Fugl-Meyer scores of 10 to 45)
• Be medically stable to participate in the study
• Be English speaking

Exclusion Criteria:

• Unable to give informed consent
• Have a serious complicating medical illness that would preclude participation.
• Contractures or orthopedic problems limiting range of joint motion in the potential study arm
• Visual loss such that the subject would not be able to see the test patterns on the robot computer monitor
• Botulinum toxin to study arm within four months of study enrollment or if received during the study period
• Unable to comply with requirements of the study
• Participants with a history of a seizure will not be precluded from the study, but will not be enrolled in the TMS portions
• Participants with electromagnetic exclusions (metal implants in the cranium, implanted electronic devices etc.) will not be precluded from the study but will be excluded from the MRI and TMS portions
• Have a serious complicating medical illness that would preclude participation

A de-identified, anonymized dataset will be created and shared. Where practicable, sharing should take place under a written agreement prohibiting the recipient from identifying or re-identifying (or taking steps to identify or reidentify) any individual whose data are included in the dataset. However, it is permissible for final datasets in machine-readable format to be submitted to and accessed from PubMed Central (and similar sites) provided that care is taken to ensure that the individuals cannot be re-identified using other publicly available information.

Datasets will be made available to the public following appropriate approvals for disclosure criteria.

Every effort will be made to protect personal privacy and the confidentiality of private information collected for research purposes. This particular dataset will be de-identified and the minimum amount of information necessary to achieve the objectives of the research proposed will be collected and shared.

5 months