Epilepsy and Electrical Stimulation of the STN

DESCRIPTION (provided by applicant): This application is for a Mentored Clinical Scientist Development Award (K08) for Fred Lado, MD PhD. Dr. Lado obtained clinical training in neurology at the Cornell University Medical College and subsequently completed a fellowship in Clinical Neurophysiologywith emphasis in EEG and Epilepsy at the Albert Einstein College of Medicine. His current faculty appointment in the Department of Neurology at the Albert Einstein College of Medicine began in 1999. He previously received a PhD for his investigation of human subjects using magnetoencepahalography, but he is currently learning in vivo experimental methods using animals, as these are best suited to his longterm career goals. His goals are to study subcortical structures that regulate and propagate seizure activity, and to develop therapies targeting these regions in order to control human epilepsy. The Albert Einstein College of Medicine and the Montefiore Medical Center, the main teaching hospital of the College, offer broad strengths in basic neuroscience and clinical epileptology. Laboratory space, equipment, office space and access to established scientists across multiple disciplines are readily available. Opportunities for didactic instruction are also available through the medical college and through specialized summer courses. The environment and support available to the candidate are ideally suited to promoting and fostering Dr. Lado's longterm professional goals. Dr. Lado proposes to investigate the anticonvulsant effects of electrical stimulation of the subthalamic nucleus. The goals of these investigations are fourfold. (1) To investigate a novel treatment of seizures of adults using deep brain electrical stimulation of the subthalamic nucleus (STN). (2) To investigate the mechanisms of anticonvulsant action of STN stimulation and further development of our basic understanding of intrinsic anticonvulsant networks in the brain. (3) To determine whether anticonvulsant deep brain stimulation produces detrimental effects. And (4), to determine whether deep brain stimulation at the STN has an antiepileptogenic or neuroprotective effect. In the course of the proposed work, Dr. Lado will learn methods of intracranial injection, induction of chemical and electrical seizures, in vivo electrophysiology to record single unit and population activity, 2deoxyglucose autoradiography to map metabolic activation, neuroanatomical methods to detect synaptic reorganization and neuronal injury, and biostatistics. The proposed studies are designed to translate the insights and results obtained from animal research into improved treatments of human epilepsy. Moreover, the work described in this proposal will provide the investigator with an opportunity to acquire the necessary intellectual and technical skills be an independent investigator in translational i epilepsy research.