Brain surgery is an effective treatment for people who suffer from intractable epilepsy, and the most common type of epilepsy surgery is removal of the anterior temporal lobe (ATL). Removal of the left ATL, however, causes cognitive side effects, particularly partial loss of language and memory ability, in about half of these patients. The goal of this project is to identify factors that determine which patients will experience these side effects so that they can be avoided or minimized. Many epilepsy centers have begun to use functional magnetic resonance imaging (fMRI) to "map" language and memory zones prior to surgery, but the meaning of these maps is unclear. Most of the fMRI methods in current use are not reliable at detecting functional areas in the ATL. More fundamentally, it is unknown whether areas judged to be "active" by fMRI are critically necessary for normal function. Little progress has been made on this fundamental issue because of the difficulty involved in obtaining systematic preoperative and outcome data in a sufficient number of patients. This project will create a consortium of eight epilepsy surgery centers with state of the art fMRI facilities, dubbed the FMRI in Anterior Temporal Epilepsy Surgery (FATES) group, to study the role of fMRI in epilepsy surgery. Roughly 220 patients who undergo left ATL removal will be studied before and after surgery, using neuropsychological tests, standard MRI, a well-validated fMRI measure of language dominance, and a novel fMRI method that is very sensitive at detecting activation responses in the ATL. The chief function of the ATL is to rapidly retrieve and integrate conceptual (semantic) knowledge, such as during sentence comprehension and discourse. The study will test the hypothesis that cognitive outcome after left ATL surgery depends on both the degree to which ATL semantic networks are damaged during surgery and on the degree to which language functions are lateralized to the left hemisphere, as the latter indicates how tightly the left ATL semantic system is coupled to other language systems. This large, systematic, prospective data set will also clarify the relative importance of many other factors in determining cognitive and seizure outcome, including the cognitive status of the patient and amount of seizure- related damage to the hippocampus prior to surgery, the amount of ATL tissue removed during surgery, and the amount of hippocampal tissue removed. The achievement of these aims will have a profound impact on clinical practice and optimal care for patients with intractable epilepsy. Current presurgical fMRI methods lack standardization and provide data of unclear significance. This research will provide the first definitive information about the validity of using fMRI for surgical planning, will provide a new model for the conduct of such validation studies, and will help bring about standardization of fMRI protocols for this application.

Public Health Relevance

This research will determine the usefulness of functional magnetic resonance imaging (fMRI), an advanced brain mapping tool, for predicting and preventing cognitive side effects from brain surgery. FMRI is used with increasing frequency to identify language and memory areas in patients undergoing brain surgery, but it is unknown whether it is reliable or able to distinguish critical from non-critical areas. This study will define the proper role of fMRI, bring about much needed standardization of this method, and help avoid the potential for wasteful expenditure of health care resources.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035929-11
Application #
8269714
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Fureman, Brandy E
Project Start
1997-09-01
Project End
2016-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
11
Fiscal Year
2012
Total Cost
$593,636
Indirect Cost
$113,968
Name
Medical College of Wisconsin
Department
Neurology
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Stewart, Christopher C; Swanson, Sara J; Sabsevitz, David S et al. (2014) Predictors of language lateralization in temporal lobe epilepsy. Neuropsychologia 60:93-102
Hamid, Hamada; Blackmon, Karen; Cong, Xiangyu et al. (2014) Mood, anxiety, and incomplete seizure control affect quality of life after epilepsy surgery. Neurology 82:887-94
Janecek, Julie K; Swanson, Sara J; Sabsevitz, David S et al. (2013) Naming outcome prediction in patients with discordant Wada and fMRI language lateralization. Epilepsy Behav 27:399-403
Janecek, Julie K; Swanson, Sara J; Sabsevitz, David S et al. (2013) Language lateralization by fMRI and Wada testing in 229 patients with epilepsy: rates and predictors of discordance. Epilepsia 54:314-22
Binder, Jeffrey R; Gross, William L; Allendorfer, Jane B et al. (2011) Mapping anterior temporal lobe language areas with fMRI: a multicenter normative study. Neuroimage 54:1465-75
Binder, Jeffrey R (2011) Preoperative prediction of verbal episodic memory outcome using FMRI. Neurosurg Clin N Am 22:219-32, ix
Binder, Jeffrey R (2011) Functional MRI is a valid noninvasive alternative to Wada testing. Epilepsy Behav 20:214-22
Binder, Jeffrey R; Swanson, Sara J; Sabsevitz, David S et al. (2010) A comparison of two fMRI methods for predicting verbal memory decline after left temporal lobectomy: language lateralization versus hippocampal activation asymmetry. Epilepsia 51:618-26
Binder, Jeffrey R; Desai, Rutvik H; Graves, William W et al. (2009) Where is the semantic system? A critical review and meta-analysis of 120 functional neuroimaging studies. Cereb Cortex 19:2767-96
Lee, Dongwook; Swanson, Sara J; Sabsevitz, David S et al. (2008) Functional MRI and Wada studies in patients with interhemispheric dissociation of language functions. Epilepsy Behav 13:350-6

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