This NIH Mentored Patient-Oriented Research Career Development Award (K23) application is to support Dr. Jerzy Szaflarski's long-term career objective of improving the management of patients with medication resistant epilepsies. Among approximately 3 million patients with epilepsy in the U.S., 7-10% carry the diagnosis of juvenile myoclonic epilepsy (JME). JME is an epilepsy syndrome characterized by genetic predisposition, onset between the ages of 11 and 19, absence and generalized seizures, and massive myoclonic jerks. Although seizures are typically controlled with valproic acid (VPA) or other antiepileptic drugs (AED) in about 70-80% of patients with JME, many require frequent multiple AED trials to attain seizure freedom; 20-30% have persistent seizures. VPA-resistant JME is defined as persistent seizures despite adequate lifestyle adjustments and treatment trials including sufficient doses of VPA. Although resistance to VPA in patients with JME is a common occurrence, very little is known about the electroencephalographic differences between patients with VPA-resistant and VPA-responsive JME. The central focus of this study is to test the hypothesis that there is a correlation between localization and symmetry of the generalized spike and wave discharges and drug response in patients with JME. We aim to employ high-field EEC-triggered fMRI (EEG-fMRI) to localize the generators of SWD in both groups of patients and to answer the following question: Do patients with VPA-resistant JME have focal (e.g., cortical) seizure onset? If the expected correlations are confirmed, we will be able to design further studies evaluating treatments other than AEDs in patients with VPA-resistant JME. The objectives of this study are to: (Aim 1) Optimize simultaneous EEG and fMRI at 4T for use in patients with JME; (Aim 2) Record simultaneous EEG and fMRI data in two groups of JME patients; (Aim 3) Correlate SWD localization by EEG with that indicated by the activation maps constructed from the fMRI data in VPA-responsive and VPS-resistant patients with JME. The parallel training objective for Dr. Szaflarski is to develop skills necessary to become an independent clinical investigator in the area of neuroimaging in epilepsy, with independent research funding by the time the training is completed. [unreadable] [unreadable] [unreadable]