PROJECT SUMMARY ABSTRACT
Epilepsy affects 2.2 million adults in the United States, with 1 in 26 people developing epilepsy at some point in
their lives. Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy as medial structures, and
the hippocampus in particular, are prone to generating seizures. Selective temporal resection is effective in
curing TLE in 74-80% of patients, but puts patients at risk of impaired memory functioning. To minimize the
adverse impact of temporal lobe surgery on memory functioning, reliable pre-surgical guides are needed.
Clinical functional magnetic resonance imaging (fMRI) provides reliable, noninvasive guidance of language
functioning in the pre-surgical evaluation for epilepsy patients. FMRI of memory is also emerging as a useful
technology to predict adult outcomes and new AAN Practice Guidelines indicate moderate (Level B) evidence
for verbal memory fMRI in predicting verbal memory outcome, based on adult studies. However, no memory
fMRI studies exist in children with epilepsy. We will fill this gap by developing memory fMRI tasks that examine
how the functional anatomy of memory systems across development is affected by pediatric TLE. Our novel
approach links neuropsychological assessment with fMRI and MRI at standard and high-resolutions, and
through resting-state connectivity to characterize the developmental neural underpinnings of memory.
The aims of this proposal are to determine potential reorganization of memory function in children with TLE: 1)
at the whole brain level, 2) within the hippocampus, and 3) via connectivity. This project will establish an fMRI
protocol for the presurgical evaluation of memory in children with TLE. This protocol will improve surgical
intervention by establishing the optimal timing of surgery based on when critical windows for reorganization
occur. The Principal Investigator, Leigh Sepeta, PhD, is a neuropsychologist specializing in pediatric and adult
epilepsy, with a focus on fMRI for language and memory mapping in epilepsy. She has a strong background in
neurodevelopment, neuropsychology, and epilepsy. The proposed training plan will build upon her existing
knowledge and promote three goals: 1) to acquire expertise in advanced neuroimaging methods, 2) to develop
skills in high-resolution neuroimaging, hippocampal anatomy, and hippocampal subregion analysis, and 3) to
advance skills in biostatistical analysis. Dr. Sepeta has assembled a strong mentorship and consultant team
including William D. Gaillard, M.D., William H. Theodore, M.D., Chandan Y. Vaidya, PhD and Susan Y.
Bookheimer, PhD (secondary mentor). Their expertise in pediatric and adult epilepsy, neuroimaging,
hippocampal functioning, and neuropsychology are an ideal match for Dr. Sepeta's proposed research and
training plans. The research-training program Dr. Sepeta has designed for this K23 proposal will further her
overall goal of transitioning to an independent investigator focused on neuropsychological and neuroimaging
evaluation of memory in neurological disorders, such as epilepsy.