Presurgical Applications of FMRI in Epilepsy

描述(申请人提供)：脑外科手术是治疗顽固性癫痫患者的有效方法，最常见的癫痫手术类型是切除前颞叶(ATL)。然而，切除左侧ATL会导致认知副作用，特别是在大约一半的患者中，语言和记忆能力部分丧失。该项目的目标是确定决定哪些患者将经历这些副作用的因素，以便可以避免或将其降至最低。许多癫痫中心已经开始在手术前使用功能磁共振成像(FMRI)来绘制语言和记忆区的地图，但这些地图的含义尚不清楚。目前使用的大多数fMRI方法在检测ATL功能区方面并不可靠。更根本的是，目前尚不清楚被功能磁共振判断为“活跃”的区域是否对正常功能至关重要。由于在足够数量的患者中获得系统的术前和结果数据存在困难，因此在这一基本问题上进展甚微。该项目将创建一个由八个癫痫手术中心组成的联合体，拥有最先进的功能磁共振设备，被称为前颞叶癫痫手术(FATS)组的功能磁共振，以研究功能磁共振在癫痫手术中的作用。大约220名接受左侧ATL摘除手术的患者将在手术前后进行研究，使用神经心理测试、标准MRI、一种经过充分验证的语言优势的fMRI测量方法，以及一种在检测ATL的激活反应方面非常敏感的新fMRI方法。ATL的主要功能是快速提取和整合概念性(语义)知识，例如在句子理解和语篇过程中。这项研究将检验这一假说，即左ATL手术后的认知结果既取决于手术中ATL语义网络受损的程度，也取决于语言功能偏侧于左侧大脑半球的程度，因为后者表明左侧ATL语义系统与其他语言系统的耦合有多紧密。这一庞大的、系统的、前瞻性的数据集还将阐明许多其他因素在决定认知和癫痫发作结果方面的相对重要性，包括患者的认知状态和手术前癫痫发作相关的海马区损伤量、手术中切除的ATL组织的量以及海马区组织的摘除量。这些目标的实现将对顽固性癫痫患者的临床实践和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。这项研究将首次提供关于使用功能磁共振成像进行手术计划有效性的明确信息，将为进行此类验证研究提供一个新的模型，并将有助于实现这一应用的功能磁共振成像方案的标准化。

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.