This research career development proposal is a multidisciplinary mentored program allowing the investigator, Dr. Wu, to develop expertise in quantitative electroencephalography (EEC) and magnetoencephalography (MEG) in pediatric epilepsy. Dr. Wu will apply this expertise to further the understanding of the clinical significance of an EEC and MEG finding, paroxysmal fast activity (PFA), and determine its potential as a localizing and predictive surrogate marker of the seizure-generating cortex. Dr. Wu is a pediatric neurologist and epileptologist with clinical expertise in pediatric epilepsy and clinical neurophysiology, and plans to develop a program of combined EEC and MEG research on PFA for improved understanding of drug-resistant epilepsy and improved seizure outcome after epilepsy surgery. She will be mentored by neurosurgeon and epileptologist Dr. Mathern, who brings a unique expertise in both pediatric epilepsy surgery and clinical neurophysiology as well as access to the support and resources necessary for development of a MEG laboratory at UCLA. Co-mentor Dr. Sutherling, epileptologist with MEG expertise, will supervise a customized MEG fellowship and will be a critical resource for the development of a MEG laboratory at UCLA. Taking advantage of the already existing infrastructure that evaluates children for epilepsy and epilepsy surgery with EEC at UCLA and MEG at Scripps Institute, Dr. Wu will prospectively examine the co-localizing value of PFA to the seizure-generating brain region, as well as examine the value of PFA in predicting, preoperatively, which children undergoing epilepsy surgery are at high risk for having recurrent seizures postoperatively. Epilepsy is a common group of disorders in children, a significant portion of whom will continue to have debilitating seizures despite new anticonvulsants and despite surgical resection of epileptogenic cortex. Why seizures continue unabated despite the best current medical and surgical therapy is unclear. In keeping with the NINDS agenda to identify markers of epileptogenesis and to """"""""cure epilepsy"""""""", this proposal seeks to establish PFA as a potential surrogate marker, first by establishing its value in localizing the seizure-generating region in all children receiving prolonged video EEG and MEG (Hypothesis 1), and second by establishing its value in predicting who, and particularly which brain region, will have seizures postoperatively in all children undergoing epilepsy surgery (Hypothesis 2). The results from this proposal will lead to the questions of: what is the underlying neurophysiologic mechanism of this potential surrogate marker?; is PFA able to identify who is at risk for seizures in high-risk populations (such as stroke, trauma, Tuberous Sclerosis), before their seizures occur?; would complete resection of the PFA-generating region lead to more seizure-free children after surgery? Studies to help answer all three questions are some of the long-term plans of this candidate.
