The proposed research study will explore the cortical dynamics of episodic memory processing in patients with temporal lobe epilepsy (TLE) by combining whole-head magnetoencephalography (MEG) and electroencephalography (EEG) with high-resolution structural MRI. The goals of this research are to elucidate 1) what brain regions are involved in memory processing in TLE, 2) when they are involved, and 3) whether or not MEG/EEG activation patterns can be used to predict memory dysfunction in TLE. These goals will be accomplished using the following methods. First, the time course and spatial extent of neural activations will be compared in patients with TLE and healthy controls during MEG/EEG tasks of verbal and nonverbal memory. Second, structural pathology will be quantified in patients with TLE using high-resolution MRI. Third, neurophysiological (MEG/EEG) and structural (MRI) data will be used to predict neuropsychological performances in TLE. This study has great clinical utility in that identifying the timing and distribution of brain regions involved in memory can assist with preoperative planning in TLE and possibly reduce morbidity associated with removal of eloquent cortex. The goals of this proposal are also aligned with the NIH/NINDS Benchmarks for Epilepsy Research, which encourage the use of improved technology for obtaining and analyzing detailed brain images of patients with epilepsy. This research project will be part of a programmatic, long-term line of MEG/EEG research in patients with temporal and extratemporal epilepsy that will eventually incorporate other cutting-edge multimodal imaging tools (i.e., MEG/fMRI) to understand cognitive dysfunction in epilepsy. The research plan described in this proposal will enable the applicant to 1) develop expertise in MEG/EEG and structural MRI data collection and analysis and 2) apply these newly learned skills to the study of cognitive dysfunction in an important clinical population. Epilepsy is a common neurological disease that costs the healthcare system approximately $12.5 billion annually and can negatively impact an individual's quality of life, employment, and health status. The current project has strong implications for public health because it strives to improve the presurgical evaluation of patients with epilepsy by using new, improved technology to identify regions of brain dysfunction in epilepsy. This information may facilitate surgical planning and reduce the potential for postoperative cognitive decline.

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 #
5K23NS056091-04
Application #
7681071
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fureman, Brandy E
Project Start
2006-09-01
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2009
Total Cost
$159,109
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Erkut Kucukboyaci, N; Girard, H M; Hagler Jr, D J et al. (2012) Role of frontotemporal fiber tract integrity in task-switching performance of healthy controls and patients with temporal lobe epilepsy. J Int Neuropsychol Soc 18:57-67
Butler, Tracy; Blackmon, Karen; McDonald, Carrie R et al. (2012) Cortical thickness abnormalities associated with depressive symptoms in temporal lobe epilepsy. Epilepsy Behav 23:64-7
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Kemmotsu, Nobuko; Girard, Holly M; Kucukboyaci, N Erkut et al. (2012) Age-related changes in the neurophysiology of language in adults: relationship to regional cortical thinning and white matter microstructure. J Neurosci 32:12204-13
Thesen, Thomas; Quinn, Brian T; Carlson, Chad et al. (2011) Detection of epileptogenic cortical malformations with surface-based MRI morphometry. PLoS One 6:e16430
Kemmotsu, Nobuko; Girard, Holly M; Bernhardt, Boris C et al. (2011) MRI analysis in temporal lobe epilepsy: cortical thinning and white matter disruptions are related to side of seizure onset. Epilepsia 52:2257-66
Leonard, Matthew K; Brown, Timothy T; Travis, Katherine E et al. (2010) Spatiotemporal dynamics of bilingual word processing. Neuroimage 49:3286-94
McDonald, Carrie R; Thesen, Thomas; Carlson, Chad et al. (2010) Multimodal imaging of repetition priming: Using fMRI, MEG, and intracranial EEG to reveal spatiotemporal profiles of word processing. Neuroimage 53:707-17
Blackmon, Karen; Barr, William B; Kuzniecky, Ruben et al. (2010) Phonetically irregular word pronunciation and cortical thickness in the adult brain. Neuroimage 51:1453-8

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