DESCRIPTION (provided by applicant): Upper extremity dysfunction is an important part of the disability caused by stroke, the leading cause of long term disability in adults. An evolving body of research suggests that specific rehabilitation interventions can improve functioning in an impaired arm even after sustained loss of function. We and others have shown that robot assisted rehabilitation can reduce arm impairment compared to baseline. We have now shown that robot assisted rehabilitation can reduce arm impairment in a randomized, single-blind trial compared to conventional occupational therapy. Studies of robotic training and also constraint-induced therapy suggest that specific training on functional tasks may enhance to translation of training gains into improved function. We propose to study the value of adding a functional training session (which we refer to as transition to task training or TTT) to robotic training. One published study suggests that robotic training induces changes in cortical motor maps. We will conduct studies of cortical motor excitability in our patients before and after training to investigate this issue. Criteria for determining the maximum benefit of robotic training have not yet been developed. One approach would be to conduct conventional upper extremity evaluations during the course of therapy but that would significantly increase therapist time. The robots record the assistance provided to patients during each training session and we will examine whether that data might be used on an ongoing basis to evaluate patient benefit. Primary hypothesis: TTT immediately following each robotic training session leads to greater functional improvement than robot- assisted training alone for patients with chronic upper extremity dysfunction due to hemi-paretic stroke. Secondary mechanistic hypothesis: Robotic training results in alterations in cortical motor excitability as detected by transcranial magnetic stimulation. Secondary clinical hypothesis: Robot kinematic data will reflect the functional changes seen in the training and that this information can be used clinically to determine when a patient has reached maximum benefit from robotic training. In order to test these hypotheses we propose a randomized, single-blind trial comparing 36-60 minute robotic training sessions with 36 training session consisting of 45 minutes of robotic training and 15 minutes of TTT training. Outcomes will include upper arm functional assessments, the results of transcranial magnetic stimulation and robot generated kinematic data. Page 1 PUBLIC HEALTH RELEVANCE: Relevance to the VHA Care Mission Stroke is the leading cause of permanent disability in the United States with 780,000 strokes occurring each year (1). Improvement in the management of its care is one area targeted by the VA. Stroke can lead to permanent, sometimes progressive, neurological impairment with upper extremity involvement often seen in more severely impaired patients. The majority of veterans with stroke each year receive inpatient rehabilitation. Yet many of individuals remain severely limited in their participation in life tasks because of decreased functional use of the affected upper extremity (33). The problem of upper extremity dysfunction due to stroke has a disproportionate effect on the VHA health care system; the chronicity and disability frequently causes patients to become unemployed, loose their health insurance and to deplete their own resources so that they are forced to seek care through the VHA system. In addition, the incidence of stroke increases with age and the VHA enrolled population is older than the general population. Approximately 75,000 stroke survivors are cared for by the VHA system and more than half of those patients have significant loss of upper extremity function. While the VHA enrolled population is actually decreasing (as WWII vets expire), the demand for rehabilitation services is expected to in the coming decades due to increased longevity. Upper extremity neuro-rehabilitation has the potential for improving the VA systems delivery of care in several ways. The delivery of more efficient and effective therapy for upper extremity use and carry-over to the home environment has the potential to reduce long-term costs of care (need for nursing home care, and hospital readmissions). If robot training combined with transition to task training is found to be significantly more effective in improving function, then adopting this combination will improve the standard of care. Robotic therapy also provides new, objective measures to assist in diagnosis of movement deficits, evaluate progress, and customize therapy through robot adaptation and control (42). Finally, perhaps even more important, stroke can be a model for other brain disorders that are more difficult to study. Traumatic brain injury, multiple sclerosis, and Parkinsonism have prominent motor impairments that result from brain lesions. There is a possibility that further understanding of the neural mechanisms of therapy-related to recovery of stroke may be applicable to these other disorders (42). Particularly for individuals with traumatic brain injury, which may affect younger veterans, expanding the range and specificity of rehabilitation therapies will have a positive impact on veterans' health and quality of life over the course of a lifetime. Page 1

Relevance to the VHA Care Mission Stroke is the leading cause of permanent disability in the United States with 780,000 strokes occurring each year (1). Improvement in the management of its care is one area targeted by the VA. Stroke can lead to permanent, sometimes progressive, neurological impairment with upper extremity involvement often seen in more severely impaired patients. The majority of veterans with stroke each year receive inpatient rehabilitation. Yet many of individuals remain severely limited in their participation in life tasks because of decreased functional use of the affected upper extremity (33). The problem of upper extremity dysfunction due to stroke has a disproportionate effect on the VHA health care system; the chronicity and disability frequently causes patients to become unemployed, loose their health insurance and to deplete their own resources so that they are forced to seek care through the VHA system. In addition, the incidence of stroke increases with age and the VHA enrolled population is older than the general population. Approximately 75,000 stroke survivors are cared for by the VHA system and more than half of those patients have significant loss of upper extremity function. While the VHA enrolled population is actually decreasing (as WWII vets expire), the demand for rehabilitation services is expected to in the coming decades due to increased longevity. Upper extremity neuro-rehabilitation has the potential for improving the VA systems delivery of care in several ways. The delivery of more efficient and effective therapy for upper extremity use and carry-over to the home environment has the potential to reduce long-term costs of care (need for nursing home care, and hospital readmissions). If robot training combined with transition to task training is found to be significantly more effective in improving function, then adopting this combination will improve the standard of care. Robotic therapy also provides new, objective measures to assist in diagnosis of movement deficits, evaluate progress, and customize therapy through robot adaptation and control (42). Finally, perhaps even more important, stroke can be a model for other brain disorders that are more difficult to study. Traumatic brain injury, multiple sclerosis, and Parkinsonism have prominent motor impairments that result from brain lesions. There is a possibility that further understanding of the neural mechanisms of therapy-related to recovery of stroke may be applicable to these other disorders (42). Particularly for individuals with traumatic brain injury, which may affect younger veterans, expanding the range and specificity of rehabilitation therapies will have a positive impact on veterans' health and quality of life over the course of a lifetime. Page 1