While the cortex has long been recognized as a site of abnormal function in epilepsy, data from experimental models of epilepsy suggest that subcortical nuclei are important in modulating cortical excitability. This proposal describes a series of studies, using PET-FDG, EEG, and histopathological and brain imaging techniques, to investigate the subcortical-cortical functional relationships and underlying neuronal function in partial and generalized epilepsy in humans, and to extend the value of PET in clinical epilepsy. Studies in partial epilepsy will identify subcortical dysfunction by study of metabolism with PET, and characterize those alterations with regard to anatomical location of the cortical epileptogenic focus, which will be defined using electrophysiologic and histopathologic measures. Relationships between degree and location of subcortical metabolic derangement and seizure frequency, degree of seizure propagation, seizure duration, and degree of pathologic alteration will be determined. Studies to investigate patterns of metabolic derangement in an epileptogenic temporal lobe will determine precise electrophysiologic (using intracranial EEG) and histopathologic correlates of these metabolic patterns, define the effect of structural change on function, and extend the use of PET in localization for epilepsy surgery. Patients will be intensively studied with extra- and intra- cranial EEG, MRI, psychometrics, and pathology in resected specimens. Studies in primary generalized epilepsy will identify subcortical dysfunction by study of metabolism with PET, and characterize those alterations with regard to seizure type and seizure frequency so that subcortical-cortical interactions can be defined. The relationship of subcortical metabolism to successful and unsuccessful treatment will be determined exploring mechanisms of anticonvulsant action. Overall objectives are to better define pathophysiological mechanisms of human epilepsy so that more effective therapeutic measures can be taken.
