Defining the Epileptogenic Network and Identifying which Components Generate Seizures

项目摘要 癫痫是一种严重的神经系统疾病，其特征是自发性癫痫发作和增加的风险。 死亡率，特别是对于三分之一的慢性癫痫患者，尽管有 最佳药物治疗目前，对耐药性癫痫发作最有效的治疗方法是切除手术 在颞叶癫痫（TLE）伴海马硬化的病例中，最常见的药物形式- 抗癫痫，手术可以减少或消除大多数患者的癫痫发作。然而，这并不能帮助所有人。 患者，特别是怀疑癫痫发作开始于颞叶但无MRI病变的患者，或 MRI显示双侧海马和新皮层或头皮EEG显示有病变。在这种情况下 致痫区（EZ）的范围，这是大脑区域，是必要的和足够的产生 癫痫发作和癫痫发作缓解所需的最小切除术是不确定的。人们对 癫痫网络（EN）的研究，即支持生成和传播的较大大脑区域 癫痫发作和癫痫表现，我们假设在困难的TLE病例中，EN知识 能帮我们定位“易”区即使最近的进展，从研究的EN，我们仍然不知道完整的 定义EN的大脑异常程度，什么部分是产生癫痫所必需的，或者有多少 需要移除EN以消除癫痫发作。这个项目解决了这些问题，我们已经制定了一个 全面的方法来研究它们，包括新的结构和扩散MRI和EEG功能 连接性测试，以及高频振荡（HFO）的研究，这是一个潜在的生物标志物， 的EZ。我们将把这种方法应用于需要侵入性脑电图测试的疑似TLE的手术前患者 作为他们标准诊断护理的一部分为了帮助我们在目标1中定义EN，我们将评估结构MRI， 灰质异常和脑区之间的形态学协方差;在目标2中，我们将评估 白色物质微结构和纤维束异常的扩散MRI;在目标3中，我们将使用一种新的方法 所谓的伽马事件耦合与单位和HFO记录相结合，以研究功能 包括EN的连通性，并确定其哪些部分正在产生缉获和传播;最后 在目标4中，我们将确定需要去除哪些EN组件以及需要去除多少EN组件 癫痫发作在本项目中，定义EN应提供有关结构和 产生癫痫发作的功能机制，最终这将有助于我们定位EZ，改善 诊断，推进手术和非手术治疗，开发新的治疗方法，并增加 癫痫发作自由。

Project Summary Epilepsy is a serious neurological disorder characterized by spontaneous seizures and increased risk of mortality, especially for one-third of the individuals with chronic seizures that cannot be controlled in spite of optimal drug therapy. Currently, the most effective treatment for drug-resistant seizures is resective surgery and in cases such as temporal lobe epilepsy (TLE) with hippocampal sclerosis, the most common form of drug- resistant epilepsy, surgery can reduce or eliminate seizures in most patients. However, it does not help all patients, particularly those with seizures suspected to begin in the temporal lobe but without a MRI lesion or MRI contains a lesion in hippocampus and neocortex or scalp EEG indicates bilaterally. In situations like these the extent of the epileptogenic zone (EZ), which is the brain area that is necessary and sufficient for generating seizures and minimum resection necessary for seizure relief, is uncertain. There is tremendous interest in studies of the epileptogenic network (EN), i.e. the larger brain region that supports the generation and spread of seizures and manifestation of epilepsy, and we hypothesize in difficult cases of TLE, knowledge of the EN could help us to localize the EZ. Even with recent progress from studies of the EN, we still do not know the full extent of brain abnormalities that define the EN, what part is necessary for generating seizures, or how much of the EN needs to be removed to eliminate seizures. This project addresses these issues and we have developed a comprehensive approach to study them, including novel structural and diffusion MRI and EEG functional connectivity tests, as well as studies of high frequency oscillations (HFOs), which are a potential biomarker of the EZ. We will apply this approach to presurgical patients with suspected TLE who require invasive EEG tests as part of their standard diagnostic care. To help us define the EN in Aim 1, we will evaluate structural MRI for gray matter abnormalities and morphological covariance between brain areas; in Aim 2, we will assess diffusion MRI for white matter microstructural and fiber tract anomalies; in Aim 3, we will use a new approach called gamma event coupling in combination with unit and HFO recordings to investigate the functional connectivity encompassing the EN and identify which parts of it are generating seizures and spread; and lastly in Aim 4, we will determine which components of the EN and how much of it needs to be removed to eliminate seizures. In this project, defining the EN should provide important information on the structural and functional mechanisms generating seizures, and ultimately this will help us to localize the EZ, improve diagnosis, advance surgical and non-surgical therapies, develop new therapies, and increase the likelihood for seizure freedom.