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.

项目总结/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， 患者可受益于手术切除产生肿瘤的脑组织。在手术之前， 通常直接植入患者的大脑中或大脑上， 活动日。理想情况下，这使临床医生能够捕获癫痫发作活动并确定其起源点。 然后将这些信息与大脑成像和其他测试的结果相结合， 移除脑组织虽然癫痫手术可能导致癫痫发作的自由，70-90%的手术患者， 继续服用抗癫痫药物，大约50%的患者继续癫痫发作。的事实 在如此剧烈的侵入性手术后，癫痫发作通常会持续存在，这表明目前的癫痫定位方法 造瘤组织不足。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生， 组织.然而，为了实现准确的、患者特异性的癫痫发作定位和成功的手术， 迫切需要了解癫痫发作如何开始和蔓延。许多研究报告说， 癫痫发作的电生理特征，这些变化取决于空间尺度，他们 都是经过测量的。微电极阵列提供细胞水平的电生理细节，但仅在4 mm x 在单个脑回上有4 mm的区域。标准的临床宏电极提供更广泛的空间覆盖，但它们缺乏 精确跟踪癫痫发作动态的空间分辨率，导致波动的高度可变估计 来源和方向。此外，当在这两个不同的尺度上测量时， 在癫痫发作期间发生的复杂电活动在本质上可能表现为矛盾。因此 我们理解癫痫发作的一个重要障碍是我们无法在微观和宏观空间尺度上架起桥梁。 为了解决这一问题，本提案的总体目标是在一个 具有高空间和时间分辨率中等空间尺度。理由是，这将统一我们的 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， 局部癫痫发作和手术治疗癫痫。为了达到整体目标，我们会记录病人的癫痫发作情况， 用高密度硬膜下网格来治疗难治性癫痫利用这些数据，我们将进行以下具体工作： 目的：（1）定量研究癫痫发作和蔓延的中尺度皮层动力学。(2)发展中尺度 非均匀癫痫发作波传播的数学模型。这些目标的实现将提供一个 在毫米尺度上对癫痫发作动力学的前所未有的看法，弥合了现有空间尺度上的差距， 问题研究这将产生积极的影响，使人们更详细地了解癫痫发作是如何开始的， 传播，这有可能为癫痫手术规划提供信息。这将导致更大的机会， 癫痫发作的自由和改善生活质量的患者最严重的情况下癫痫。