The Epilepsy Connectome Project

 描述(由申请人提供)：据估计，美国有250万人患有癫痫，并与进行性认知和心理社会功能障碍的高风险以及巨大的社会经济和医疗保健利用成本有关。目前尚不清楚为什么一些患者对抗惊厥治疗反应良好，而另一些患者则出现无控制的癫痫发作和进行性脑功能障碍。目前已有强大的成像工具可用于定量描述组成癫痫网络的脑区之间的结构和功能连接，为理解、预测和治疗难治性癫痫提供了一种有前途的新途径。颞叶癫痫(TLE)是成人中最常见的癫痫形式，也是药物难治性癫痫发作中最大的一组。癫痫连接组项目(ECP)将收集200名特发性TLE患者的详细连接性测量，使用结构连接的扩散加权磁共振成像、动态网络相互作用的功能磁共振成像和以毫秒时间分辨率测量这些交互作用的脑磁图。这些方法将密切反映人类连接组项目(HCP)目前用于研究健康参与者网络连接性的方法，并且HCP数据将提供关键的基线，以与ECP连接组数据进行比较。这些比较基于用敏感的、最先进的方法研究的大量队列，将首次揭示TLE网络结构和功能异常的全面程度。数据将 被用来检验四个主要假说：1)多年反复发作导致TLE患者出现连接性异常，2)连接性异常导致TLE患者观察到的认知和心理社会功能障碍，3)连接性异常的严重程度预测认知和心理社会功能随后下降的风险，以及4)连接性异常的严重程度预测出现医学上难治性癫痫发作的风险。支持这些假说的证据将直接导致基于连接体定量成像的癫痫患者诊断和个体化治疗的新的临床工具。

 DESCRIPTION (provided by applicant): Epilepsy affects an estimated 2.5 million people in the United States and is associated with a high risk of progressive cognitive and psychosocial dysfunction, and enormous socioeconomic and health-care utilization costs. There is currently little understanding of why some patients respond well to anticonvulsant therapy whereas others develop uncontrolled seizures and progressive brain dysfunction. Powerful imaging tools are now available for quantitatively characterizing the structural and functional connections between brain regions that make up epileptic networks, providing a promising new approach for understanding, predicting, and treating refractory epilepsy. Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and the largest group among those with medically refractory seizures. The Epilepsy Connectome Project (ECP) will collect detailed connectivity measurements in 200 people with idiopathic TLE using diffusion-weighted magnetic resonance imaging of structural connections, functional magnetic resonance imaging of dynamic network interactions, and magnetoencephalography to measure these interactions with millisecond time resolution. The methods will closely mirror those currently used by the Human Connectome Project (HCP) to study network connectivity in healthy participants, and the HCP data will provide a critical baseline against which to compare the ECP connectome data. These comparisons, based on large cohorts studied with sensitive, state-of-the-art methods, will reveal for the first time the full extent of abnormal network structure and function in TLE. The data will be used to test four major hypotheses: 1) that recurring seizures over many years lead to connectivity abnormalities in TLE, 2) that connectivity abnormalities account for the cognitive and psychosocial dysfunction observed in people with TLE, 3) that the severity of connectivity abnormalities predicts the risk of subsequent decline in cognitive and psychosocial function, and 4) that the severity of connectivity abnormalities predicts the risk of developing medically refractory seizures. Evidence supporting these hypotheses would lead directly to novel clinical tools for diagnosis and individualized management of patients with epilepsy based on quantitative imaging of the connectome.