There is much evidence that the hippocampus and surrounding structures in the medial temporal lobe (MTL) are involved in memory. Exactly what role these structures play and whether or not they can be divided into functionally distinct subunits is unclear and the subject of much controversy in the current literature. The investigators propose to investigate the functional role of the hippocampus in memory processes. The hypothesize that the hippocampus can be subdivided into distinct functional regions that show dependence on both the type of mnemonic task undertaken (encoding versus retrieval), and the characteristics of the memory process being encoded or retrieved (spatial versus temporal, verbal versus visual). The hippocampus is a difficult structure to image with either PET or functional MRI. The investigators have developed a high-resolution fMRI approach, which compensates for signal loss in regions of high magnetic field inhomogeneity such as that found in the MTL. This susceptibility effect has limited the power of previous fMRI experiments and made it particularly difficult to image the anterior MTL region. This technical difficulty is likely the source of conflicting findings between earlier PET and fMRI studies that employed similar tasks. The new imaging approach to generate robust activation maps over the entire length of the hippocampal formation in studies on both normal volunteers will be use, and on MTL patients who present with intractable epilepsy. Such patients are often treated by surgical resection of the epileptogenic foci. The investigators will functionally image these patients both pre- and post- surgery allowing us to validate the pre-surgical fMRI maps through behavioral studies postsurgery, and through cortical stimulation experiments with depth electrodes prior to tissue resection. Functionally mapping the hippocampal formation before and after resection provides a unique opportunity to determine if the remaining MTL structures can compensate for tissue loss and if so identifies the specific structures responsible. This project will increase our understanding of the role of the hippocampus in memory, as well as lead to intelligent paradigms for pre-surgical mapping of patients who are candidates for temporal lobotomy. This work will have significant impact in both the neuroscience and medical communities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040497-03
Application #
6540332
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Fureman, Brandy E
Project Start
2000-07-10
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$237,160
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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