Early onset temporal lobe epilepsy (TLE) typically is associated with cognitive deficits and quantitative volumetric magnetic resonance imaging (MRI) abnormalities. Impairment of episodic memory, or new learning, and hippocampal atrophy are the best characterized of these cognitive and structural deficits. In contrast, abnormalities of semantic memory, or factual knowledge, have been studied much less systematically, and the neuroanatomic correlates of impaired semantic memory in TLE have yet to be reported. In this application for a Mentored PatientOriented Research Career Development Award, the candidate proposes an organized program of training and supervised research focusing on semantic memory and its neural substrate in TLE. While the applicant has experience in clinical neuropsychology, the proposal provides for additional training in research ethics, experimental cognitive neuropsychology, quantitative volumetric MRI processing, MRI diagnostics, clinical epilepsy, language development, and advanced statistical analysis. This training will be integrated with a research project that will: 1) Compare TLE patients and healthy controls on a comprehensive battery of semantic memory measures, 2) quantify MRI volumetric abnormalities in sub-regions of the temporal lobe, and 3) determine the relationship between the cognitive measures and lateral versus mesial (i.e., hippocampal) temporal lobe volumetrics. These findings will lead to improved detection of semantic knowledge deficits in clinical neuropsychological assessment and an advance understanding of the neural substrate of semantic memory. Finally, this award would provide the applicant with the background and training for an independent research career dedicated to elucidating the relationships in TLE patients among semantic memory, other cognitive abilities, and brain structure, and characterizing the implications of these relationships for social, educational, and occupational functioning.
