A CLINICAL RESEARCH PROGRAM FOR THE PARTIAL EPILEPSIES

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The Clinical Neurophysiology Program (CNP) at UCLA makes use of the unique opportunities provided by an epilepsy surgery facility to carry out research on the human brain. In the past, emphasis was placed on clinical research directed toward improving the diagnosis and surgical treatment of epilepsy, although basic research has always been an important part of the program. More recently, resective surgery has become sufficiently accepted as a safe and effective mode of treatment for partial epilepsy to allow clinical activities of the CNP to be supported by hospital funds or supplemented by grants awarded to develop specific diagnostic techniques. In this research proposal we are requesting support only for basic research projects that take advantage of knowledge gained from animal studies and the clinical setting to investigate fundamental mechanisms of normal and abnormal human brain function. Information obtained from patients in our epilepsy surgery facility will be utilized by a multidisciplinary team of basic and clinical neuroscientists to define anatomical and physiological substrates of normal and epileptiform cerebral processes, and to determine how epilepsy related pathological processes might interfere with normal neuronal integration to disrupt behavior during, and between seizures. Specifically, we propose to examine alterations in cellular morphology in epileptogenic tissue and relate these findings to neurotransmitter function, to neuronal activity at the unit level, and to quantitative analysis of spontaneous and stimulation induced field potentials. We also propose to examine anatomical and physiological substrates of sensory processing, memory, and control of cardiorespiratory function. The long term objectives of the CNP are: a. to reveal mechanisms of epileptogenesis in order to suggest new medical, as well as surgical approaches to antiepileptic therapy; b. to better understand the neuronal basis of normal human behavior and mechanisms of pathological disruption that result in abnormal behavior, in order to prevent or more effectively treat behavioral disturbances associated with epilepsy and other neurological disorders; and c. to establish the most effective and efficient presurgical evaluation protocol for epileptic patients who are candidates for resective surgery, in order to allow the greatest number of patients to benefit from this procedure.