PROJECT SUMMARY/ABSTRACT Cerebral palsy (CP) results from a perinatal brain injury and is one of the most prevalent and costly developmental disabilities in the United States. As persons with CP transition from adolescence into adulthood they continue to be faced with prominent mobility challenges. Despite the increased recognition of the mobility deteriorations, NIH funding related to transition aged persons with CP is remarkably low. Thus, research focused on enhancing the mobility of persons with CP during this critical transition period is sorely needed to help narrow the gap and eliminate this disparity. Over the last decade, there has been considerable interest in utilizing robotic exoskeletons in a therapeutic setting for improved mobility. This therapeutic approach is interesting because the exoskeleton can be used while the patient practices real-world tasks (i.e., stair and obstacle negotiation). However, the current therapeutic approaches used with these robotic exoskeletons are primarily focused on compensation (i.e., body weight support, passive leg facilitation), which might dampen motor learning since it can disengage the nervous system. This proposal opposes this treatment strategy in that we will use the exoskeleton as a treatment tool for perturbing the legs during locomotion, in order to generate heightened muscular activity and relevant motor errors in the context of real-world tasks. Our central hypothesis is that the heightened neuromuscular activity during our exoskeleton gait training will result in clinically relevant gait improvements that will be tightly connected with beneficial neuroplasticity in the spinal cord and key brain circuits that govern the leg motor actions. The Specific Aims of this project are: (1) To quantify the degree of mobility changes in transition aged persons (16- 25 years) with CP who undergo our innovative robotic exoskeleton gait training protocol, and (2) To identify whether transition aged persons with CP who undergo our robotic exoskeleton gait training protocol exhibit greater neurophysiological alterations in the key brain circuits and spinal cord dynamics that are involved in planning and executing leg motor actions. In brevity, the experimental design of this project involves transition aged persons with CP who will undergo 24 physical therapy sessions while wearing a robotic exoskeleton that will perturb the spatiotemporal gait kinematics during an overground therapeutic gait training protocol. Baseline and post-therapy measures will include clinical mobility assessments (Functional Gait Assessment, fast-as- possible 10-meter walk, 1-minute walk, time up and down stairs), magnetoencephalographic (MEG) brain imaging, and Hoffman reflex (i.e., H-reflex) assessments of the spinal cord interneuron dynamics. Clinical outcomes will be compared with a cohort of persons with CP that undergo standard gait training without using the exoskeleton. Beneficial outcomes from this clinical trial will c...