Project Summary Over the last 20 years, upper limb rehabilitation intervention trials for severe and chronic post stroke hemiparesis have largely failed to find significant differences in functional improvement between intervention and control groups. This has resulted in a dearth of treatment options for at least 50% of stroke survivors who continue to experience deficits which limit their independence in activities of daily living. To remedy this shortcoming in field of neurorehabilitation, it is necessary to understand the neural mechanisms which are central to the motor recovery process following a stroke. We can then develop experiments to exploit these mechanisms with the goal of optimizing treatment efficacy and facilitating increased independence for the individual. Our lab recently published a pilot study on individuals with chronic stroke and moderate to severe impairments in the UL which suggests that bilateral motor priming in combination with task specific training is an effective treatment option that can benefit people with severe post-stroke hemiparesis. However, the neurophysiological mechanisms behind the positive behavioral changes remain unknown. This proposed research will use transcranial magnetic stimulation (TMS) data from an ongoing clinical trial to investigate the impact of bilateral motor priming on corticomotor excitability and transcallosal inhibition of the ipsilesional and contralesional hemispheres in people with chronic stroke (Aims 1 & 2) and determine the relationship between changes in neurophysiological and behavioral measures (Aim 3) to better understand how and why priming is effective. The proposed work will provide new insight into the mechanisms underlying priming and, more broadly, illuminate mechanisms of post stoke motor recovery. These results have the potential to improve functional restoration of the arm and hand thereby improving quality of life for stroke survivors. This research will be conducted in the Therapeutic Interventions for Neurological Disorders laboratory under the direction of Dr. Daniel Corcos at Northwestern University’s (NU) department of Physical Therapy and Human Movement Sciences (PTHMS). The facilities at NU PTHMS provide everything needed to complete this research successfully including expert personnel, state-of-the-art laboratories, and the necessary equipment. The training plan as outlined, will include formal and informal educational opportunities, training in data processing and analysis and support for manuscript preparation and dissemination of findings.