Bridging the micro and macro scales of seizure dynamics

连接癫痫动力学的微观和宏观尺度

• 批准号: 10574151
• 负责人: Beth Ann Lopour
• 金额: $ 7.55万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574151
• 关键词: Address; Antiepileptic Agents; Area; Behavior; Biological Markers; Brain; Brain imaging; Characteristics; Clinical; Complex; Data; Data Collection; Electrodes; Electroencephalography; Electrophysiology (science); Epilepsy; Excision; Exhibits; Fellowship; Freedom; Frequencies; Future; Goals; High Frequency Oscillation; Implant; Implanted Electrodes; Intractable Epilepsy; Lead; Measurement; Measures; Methods; Microelectrodes; Modeling; Nature; Neurosciences; Operative Surgical Procedures; Outcome; Patient-Focused Outcomes; Patients; Pattern; Periodicity; Pharmaceutical Preparations; Phase; Physiological; Positioning Attribute; Procedures; Property; Quality of life; Reporting; Resolution; Seizures; Source; Structure; Testing; Time; Tissues; Travel; Variant; Work; brain electrical activity; brain tissue; childhood epilepsy; density; design; improved; improved outcome; mathematical model; millimeter; parent grant; spatiotemporal; temporal measurement; two-dimensional

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.

项目概要/摘要 在最严重的癫痫病例中，尽管进行了多次抗癫痫药物试验，癫痫发作仍持续存在， 患者可能会受益于手术切除引起癫痫发作的脑组织，在手术前放置电极。 通常直接植入患者的大脑，用于连续记录脑电 理想情况下，这能够捕获癫痫发作活动并确定其起源点。 然后，将这些信息与脑成像和其他测试的结果结合起来，以指导 虽然癫痫手术可能会导致癫痫发作消失，但 70-90% 的手术患者 继续服用抗癫痫药物，并且大约 50% 的患者继续出现癫痫发作。 在如此激烈的侵入性手术后，癫痫发作常常持续存在，这表明目前的定位方法 癫痫发作组织不足因此，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患者接受癫痫手术 然而，为了实现准确的、针对患者的癫痫定位和成功的手术， 许多研究报告称，迫切需要了解癫痫发作是如何发生和传播的。 癫痫发作的电生理特征，这些特征根据癫痫发作的空间尺度而变化 微电极阵列提供细胞水平的电生理细节，但仅限于 4mm x 范围内。 单个回上的 4 毫米面积提供了更广泛的空间覆盖范围，但它们缺乏。 准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 此外，当在这两个不同的尺度上测量时，其特征。 癫痫发作期间发生的复杂电活动本质上可能是矛盾的。 我们理解癫痫发作的一个重大障碍是我们无法弥合微观和宏观空间尺度。 为了解决这个问题，该提案的总体目标是量化和建模癫痫发作动态 具有高空间和时间分辨率的中间空间尺度，其基本原理是这将统一我们。 了解癫痫发作和在不同空间尺度上的传播，最终提高我们的能力 定位癫痫发作并通过手术治疗癫痫 为了实现总体目标，我们将记录患者的癫痫发作情况。 使用高密度硬膜下网格治疗难治性癫痫 使用这些数据，我们将进行以下具体研究。 目标：(1) 量化癫痫发作和扩散的中尺度皮质动力学。(2) 开发中尺度。 完成这些目标将提供非均匀捕获波传播的数学模型。 前所未有的毫米级癫痫动力学视图，弥合了现有研究的空间尺度差距 通过更详细地了解癫痫发作如何发生和发生，这将产生积极影响。 传播，这有可能为癫痫手术计划提供信息，这将导致更大的机会。 最严重癫痫患者的癫痫发作自由度和生活质量得到改善。