PROJECT SUMMARY/ABSTRACT Drug-resistant epilepsy affects approximately 1 million people in the United States. Responsive neural stimulation (RNS) and deep brain stimulation (DBS) offer novel treatment options for refractory seizures. These neurostimulation therapies have significant advantages over surgical resection, though they are generally less effective. Treatment optimization has been challenging due to inter-patient variability, electrode placement, and the vast range of available stimulation parameters. This project aims to provide a more comprehensive description of the spatial and temporal dynamics that underlie neurostimulation and evaluate novel therapeutic effects that could prevent and modify the disease course in epilepsy. This proposal also outlines a five-year career development program focused on acquiring the skills necessary to perform an in-depth mechanistic analysis of neurostimulation in a rodent model of temporal lobe epilepsy. Washington University provides an excellent environment of collaborators and resources to develop skills necessary for investigating neurostimulation as a treatment modality for epilepsy. The outlined proposal builds on Dr. Foutz's prior research in deep brain stimulation and his clinical training in the field of epilepsy. Under the mentorship of Michael Wong, M.D., Ph.D. (basic scientist, clinical epileptologist), and Dominique Durand, Ph.D. (basic scientist, biomedical engineer), he will investigate the spatiotemporal dynamics underlying electrical neurostimulation and evaluate anti-epileptogenic effects. Dr. Foutz has a career goal to become a translational scientist focused on developing and optimizing device-based neuromodulatory treatments for patients with epilepsy. The career development plan outlines formal and informal training in animal models of epilepsy and neurostimulation. This work's potential impact is to optimize existing devices, guide the development of next- generation neurostimulation technology and discover novel therapeutic effects of neurostimulation in epilepsy.