Bridging the micro and macro scales of seizure dynamics

项目摘要/摘要 在最严重的癫痫病例中，尽管多次试验抗癫痫药物，癫痫仍在发作， 患者可能受益于手术切除导致癫痫发作的脑组织。在手术前，电极是 通常被直接植入或植入患者的大脑中，用于连续记录脑电 连续几天的活动。理想情况下，这使临床医生能够捕捉癫痫发作活动并确定其起始点。 然后将这些信息与大脑成像和其他测试的结果结合起来，以指导 切除脑组织。虽然癫痫手术可能会导致癫痫发作自由，但70%-90%的手术患者 仍在服用抗癫痫药物，大约50%的患者仍有癫痫发作。事实是， 癫痫发作通常在如此剧烈的侵入性手术后持续存在，这表明目前的定位方法 导致癫痫发作的组织不足。因此，这项工作的长期目标是改善结果 通过开发更准确的方法来定位癫痫发作的产生，对接受癫痫手术的患者进行评估 组织。然而，为了实现准确的、针对患者的癫痫定位和成功的手术， 迫切需要了解癫痫发作是如何开始和传播的。许多研究都报告了 癫痫发作的电生理特征，这些特征取决于它们所处的空间尺度 都是经过测量的。微电极阵列提供细胞级别的电生理细节，但仅限于4 mm x 单个脑回面积为4 mm。标准的临床大电极提供了更广泛的空间覆盖，但它们缺乏 精确跟踪癫痫发作动态的空间分辨率，导致对波的高度可变的估计 来源和方向。此外，当在这两个不同的尺度上衡量时， 癫痫发作期间发生的复杂电活动在本质上可能看起来是矛盾的。因此，a 我们理解癫痫发作的重大障碍是我们无法在微观和宏观空间尺度上架起桥梁。 为了解决这个问题，这项建议的总体目标是量化和模拟癫痫发作的动态 具有高时空分辨率的中等空间比例尺。理由是这将统一我们的 了解癫痫发作的发生和在不同空间尺度上的传播，最终提高我们的能力 定位癫痫发作并手术治疗癫痫。为了达到总体目标，我们将记录患者的癫痫发作情况 使用高密度硬膜下格栅治疗难治性癫痫。使用这些数据，我们将实现以下具体目标 目的：(1)量化癫痫发作和扩散的中尺度皮层动力学。(2)发展中尺度 非均匀发作波传播的数学模型。完成这些目标将提供一个 前所未有的毫米级癫痫发作动力学视角，弥合了现有空间尺度的差距 学习。这将产生积极的影响，因为它可以更详细地了解癫痫发作的开始和 宣传，这有可能为癫痫手术计划提供信息。这将导致更大的机会 癫痫发作自由和改善最严重癫痫患者的生活质量。

PROJECT SUMMARY/ABSTRACT In the most severe cases of epilepsy, where seizures persist despite multiple trials of anti-seizure medications, patients may benefit from surgical removal of seizure-generating brain tissue. Prior to surgery, electrodes are often implanted directly into or onto the patient’s brain and are used to continuously record electrical brain activity over days. Ideally, this enables clinicians to capture seizure activity and determine its point of origin. Then this information is used in combination with the results of brain imaging and other testing to guide removal of brain tissue. While epilepsy surgery may lead to seizure freedom, 70-90% of surgery patients remain on anti-seizure medications and roughly 50% of patients continue to have seizures. The fact that seizures often persist after such a drastic, invasive procedure indicates that current methods for localization of seizure-generating tissue are insufficient. Therefore, the long-term goal of this work is to improve the outcomes of patients undergoing epilepsy surgery by developing more accurate methods to localize seizure-generating tissue. However, in order to achieve accurate, patient-specific seizure localization and successful surgery, there is a critical need to understand how seizures start and spread. Many studies have reported electrophysiological characteristics of seizures, and these vary depending on the spatial scale at which they are measured. Microelectrode arrays provide cellular-level electrophysiological detail, but only within a 4mm x 4mm area on a single gyrus. Standard clinical macroelectrodes provide broader spatial coverage, but they lack the spatial resolution to accurately track seizure dynamics, leading to highly variable estimates of wave sources and directions. Moreover, when measured at these two disparate scales, characteristics of the complex electrical activity that occurs during a seizure can appear contradictory in nature. Therefore, a significant barrier to our understanding of seizures is our inability to bridge the micro and macro spatial scales. To address this, the overall objective of this proposal is to quantify and model seizure dynamics at an intermediate spatial scale with high spatial and temporal resolution. The rationale is that this will unify our understanding of seizure onset and spread across different spatial scales, ultimately improving our ability to localize seizures and surgically treat epilepsy. To attain the overall objective, we will record seizures in patients with refractory epilepsy using high-density subdural grids. Using this data, we will pursue the following specific aims: (1) Quantify mesoscale cortical dynamics of seizure onset and spread. (2) Develop a mesoscale mathematical model of non-uniform seizure wave propagation. Completion of these aims will provide an unprecedented view of seizure dynamics at the millimeter scale, bridging the gap in spatial scales of existing studies. This will have a positive impact by providing a more detailed understanding of how seizures start and propagate, which has the potential to inform epilepsy surgical planning. This will lead to a greater chance of seizure freedom and improved quality of life for patients with the most severe cases of epilepsy.