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 #
5K23NS060993-04
Application #
8310030
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fureman, Brandy E
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$166,841
Indirect Cost
$12,359
Name
University of California Irvine
Department
Neurology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Bonilha, Leonardo; Tabesh, Ali; Dabbs, Kevin et al. (2014) Neurodevelopmental alterations of large-scale structural networks in children with new-onset epilepsy. Hum Brain Mapp 35:3661-72
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
Jackson, Daren C; Lin, Jack J; Chambers, Karlee L et al. (2014) Birth weight and cognition in children with epilepsy. Epilepsia 55:901-8
Addis, Laura; Lin, Jack J; Pal, Deb K et al. (2013) Imaging and genetics of language and cognition in pediatric epilepsy. Epilepsy Behav 26:303-12
Lin, Jack J; Riley, Jeff D; Hsu, David A et al. (2012) Striatal hypertrophy and its cognitive effects in new-onset benign epilepsy with centrotemporal spikes. Epilepsia 53:677-85
Riley, Jeffrey D; Moore, Stephanie; Cramer, Steven C et al. (2011) Caudate atrophy and impaired frontostriatal connections are linked to executive dysfunction in temporal lobe epilepsy. Epilepsy Behav 21:80-7
Jackson, Daren C; Irwin, William; Dabbs, Kevin et al. (2011) Ventricular enlargement in new-onset pediatric epilepsies. Epilepsia 52:2225-32
Riley, Jeffrey D; Franklin, David L; Choi, Vicky et al. (2010) Altered white matter integrity in temporal lobe epilepsy: association with cognitive and clinical profiles. Epilepsia 51:536-45