The Epilepsy Connectome Project

 描述（由申请人提供）：癫痫影响美国估计有250万人，并且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相关。目前还不清楚为什么有些患者对抗惊厥治疗反应良好，而另一些患者出现不受控制的癫痫发作和进行性脑功能障碍。强大的成像工具现在可用于定量表征构成癫痫网络的脑区域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方法。颞叶癫痫（TLE）是成人中最常见的癫痫形式，也是难治性癫痫发作的最大群体。癫痫连接组项目（ECP）将收集200名特发性TLE患者的详细连接测量结果，使用结构连接的弥散加权磁共振成像，动态网络相互作用的功能磁共振成像和脑磁图以毫秒时间分辨率测量这些相互作用。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的方法，HCP数据将提供一个关键的基线，以比较ECP连接组数据。这些比较，基于敏感的，国家的最先进的方法研究的大型队列，将首次揭示TLE异常网络结构和功能的全部范围。数据将 可以用来检验四个主要假设：1）多年反复发作导致TLE的连接异常，2）连接异常解释了TLE患者中观察到的认知和心理社会功能障碍，3）连接异常的严重程度预测了随后认知和心理社会功能下降的风险，和4）连接异常的严重性预测了发展医学难治性癫痫发作的风险。支持这些假设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管理的新临床工具。

 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.