Presurgical Applications of FMRI in Epilepsy

描述（申请人提供）：脑外科手术是治疗难治性癫痫的有效方法，最常见的癫痫手术是切除颞叶（ATL）。然而，在大约一半的患者中，切除左侧ATL会导致认知方面的副作用，尤其是语言和记忆能力的部分丧失。这个项目的目标是确定决定哪些患者会经历这些副作用的因素，以便避免或尽量减少这些副作用。许多癫痫中心已经开始在手术前使用功能性磁共振成像（fMRI）来绘制语言和记忆区域的“地图”，但这些地图的意义尚不清楚。目前使用的大多数功能磁共振成像方法在检测ATL的功能区域时都不可靠。更根本的是，尚不清楚fMRI判断为“活跃”的区域是否对正常功能至关重要。由于难以在足够数量的患者中获得系统的术前和预后数据，因此在这一基本问题上进展甚微。该项目将建立一个由8个癫痫手术中心组成的联盟，这些中心拥有最先进的功能磁共振成像设备，被称为fMRI在颞叶前癫痫手术（FATES）小组，以研究功能磁共振成像在癫痫手术中的作用。大约220名接受左侧ATL切除术的患者将在手术前后进行研究，使用神经心理学测试，标准MRI，一种经过验证的功能磁共振成像测量语言优势，以及一种新的功能磁共振成像方法，该方法在检测ATL的激活反应方面非常敏感。ATL的主要功能是快速检索和整合概念（语义）知识，如在句子理解和话语中。该研究将验证左ATL手术后的认知结果取决于手术中ATL语义网络受损的程度，以及语言功能向左半球侧化的程度，因为后者表明左ATL语义系统与其他语言系统耦合的紧密程度。这个庞大的、系统的、前瞻性的数据集也将阐明许多其他因素在决定认知和癫痫结果方面的相对重要性，包括患者的认知状态、手术前与癫痫发作相关的海马体损伤量、手术期间移除的ATL组织量和移除的海马体组织量。这些目标的实现将对临床实践和对顽固性癫痫患者的最佳护理产生深远的影响。目前的术前功能磁共振成像方法缺乏标准化，提供的数据意义不明确。这项研究将提供关于fMRI在手术计划中的有效性的第一个明确的信息，将为此类验证研究的进行提供一个新的模型，并将有助于为该应用带来fMRI协议的标准化。

DESCRIPTION (provided by applicant): 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.