This research project will apply the emerging technology of functional magnetic resonance imaging (fMRI) to clinical problems faced by, and theoretical questions raised in, patients with mesial temporal lobe epilepsy (MTLE). Converging lines of evidence suggest that the mesial temporal lobe (MTL) is material specific; the dominant MTL is specialized for verbal memory and the non-dominant MTL is specialized for visuo-spatial memory. Patients with MTLE frequently exhibit subtle content-specific memory deficits related to the laterality of the epileptogenic focus, but generally maintain good overall memory function. This implies that patients with mesial temporal sclerosis reorganize normally lateralized memory functions to the contralateral MTL. This study will test the hypotheses that: (1) discrete, laterality-specific, activation of the left and right MTL may be seen in normals when engaging memory systems with content- specific tasks and (2) patients with temporal lobe epilepsy have particular reorganization of memory-activated regions of the temporal lobe based on the location of their epileptogenic foci. To test the hypotheses, we will develop verbal and non-verbal tasks that are able to selectively activate the dominant or non- dominant MTL in healthy volunteers. These paradigms will then be adapted for use in epilepsy patients who will be imaged as they perform the specific memory processing tasks. Patients will be studied both before and after temporal lobectomy, and correlation will be made to baseline memory deficits, intracarotid amytal testing, and post-operative outcome. Functional reorganization will be defined as a deviation from the expected laterality as observed in normals. The successful completion of this work will accomplish the dual goals of training the candidate in the new area of fMRI-an important new dimension to her research skills-and of furthering understanding of neuropsychological changes patients with MTLE.
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