This project will explore the relationship between white matter integrity and cognitive dysfunction in individuals with temporal lobe epilepsy (TIE). Although TLE is associated with deficits in multiple cognitive domains, the neurobiological basis underlying these deficits is unclear. A potential mechanism is epilepsy-induced abnormal connections (white matter tracts) between multiple brain regions that are involved in complex cognitive function. Diffusion tensor imaging (DTI) is a magnetic resonance sequence that measures the structural integrity of white matter tracts and thus is an extremely useful tool for investigating brain connections.
In Aim 1, I will use DTI to probe the integrity of white matter tracts in individuals with TLE.
In Aim 2, I will correlate DTI indices of white matter integrity with specific neuropsychological measures.
In Aim 3, I will prospectively examine the relationship between the changes in white matter integrity, as measured by DTI, and the development of cognitive deficits in children with TLE. Significant linkage between white matter integrity and cognitive function will support DTI as a useful biomarker for the development of cognitive deficits. This proposal utilizes advanced brain imaging techniques to uncover the biological basis of cognitive dysfunction in individuals with epilepsy. New insights from the study may enable us to target candidates for cognitive intervention and for potential prevention of epilepsy-related cognitive deficits. I am a dedicated Clinician/Scientist who is fully committed to a career in epilepsy research. I have received protected time and full support from the Neurology Department and the School of Medicine at the University of California, Irvine, a world-renowned center for neurosciences and a recognized center for basic and clinical epilepsy research. In the training portion of the proposal, I will receive training in clinical design, biostatics, bioethics, neuropsychological testing, as well as state-of-the-art neuroimaging techniques. My ultimate goal is to combine clinical and research efforts to understand the neurobiological basis of cognitive dysfunction in people with epilepsy and to develop potential preventive strategies. Relevance: Epilepsy is a brain disorder that affects 1% of the American population and is associated with significant cognitive (i.e. memory and language) problems. This proposal will use advanced brain imaging techniques to study the relationship between abnormal brain connections and cognitive problems. Better understanding of cognitive problems in individuals with epilepsy may lead to improved treatment options.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS060993-02
Application #
7904307
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fureman, Brandy E
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2010-08-01
Budget End
2011-07-31
Support Year
2
Fiscal Year
2010
Total Cost
$161,406
Indirect Cost
Name
University of California Irvine
Department
Neurology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Kam, J W Y; Szczepanski, S M; Canolty, R T et al. (2018) Differential Sources for 2 Neural Signatures of Target Detection: An Electrocorticography Study. Cereb Cortex 28:9-20
Zheng, Jie; Anderson, Kristopher L; Leal, Stephanie L et al. (2017) Amygdala-hippocampal dynamics during salient information processing. Nat Commun 8:14413
Jafarpour, Anna; Piai, Vitoria; Lin, Jack J et al. (2017) Human hippocampal pre-activation predicts behavior. Sci Rep 7:5959
Piai, Vitória; Anderson, Kristopher L; Lin, Jack J et al. (2016) Direct brain recordings reveal hippocampal rhythm underpinnings of language processing. Proc Natl Acad Sci U S A 113:11366-11371
Kellermann, Tanja S; Bonilha, Leonardo; Eskandari, Ramin et al. (2016) Mapping the neuropsychological profile of temporal lobe epilepsy using cognitive network topology and graph theory. Epilepsy Behav 63:9-16
Veenstra, Amy L; Riley, Jeffrey D; Barrett, Lauren E et al. (2016) The impact of bilingualism on working memory in pediatric epilepsy. Epilepsy Behav 55:6-10
Kellermann, Tanja S; Bonilha, Leonardo; Lin, Jack J et al. (2015) Mapping the landscape of cognitive development in children with epilepsy. Cortex 66:1-8
Garcia-Ramos, Camille; Lin, Jack J; Prabhakaran, Vivek et al. (2015) Developmental Reorganization of the Cognitive Network in Pediatric Epilepsy. PLoS One 10:e0141186
Riley, Jeffrey D; Fling, Brett W; Cramer, Steven C et al. (2015) Altered organization of face-processing networks in temporal lobe epilepsy. Epilepsia 56:762-71
Lin, Jack J; Dabbs, Kevin; Riley, Jeffrey D et al. (2014) Neurodevelopment in new-onset juvenile myoclonic epilepsy over the first 2 years. Ann Neurol 76:660-8

Showing the most recent 10 out of 20 publications