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.

项目摘要/摘要 在最严重的癫痫病例中，癫痫发作持续了目的地多次试验抗癫痫药物， 患者可以通过手术去除癫痫发作的脑组织受益。手术前，电极是 通常直接植入患者的大脑中，并用于继续记录电动大脑 几天的活动。理想情况下，这使临床医生能够捕获癫痫发作并确定其起源点。 然后，将这些信息与脑成像和其他测试的结果结合使用以指导 去除脑组织。尽管癫痫手术可能导致癫痫发作自由，但有70-90％的手术患者 保留抗塞氏菌药物，大约50％的患者继续癫痫发作。事实 在如此剧烈的侵入性过程之后，癫痫发作通常持续存在，表明当前的定位方法 生成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，接受癫痫手术的患者 组织。但是，为了实现准确的，特定于患者的癫痫发作定位和成功手术， 迫切需要了解癫痫发作是如何开始和传播的。许多研究报道 癫痫发作的电生理特征，这些特征因其空间量表而异 测量。微电极阵列提供细胞级的电生理细节，但仅在4mm x内 单个回的4mm区域。标准的临床宏观电极提供更广泛的空间覆盖范围，但缺乏 精确跟踪癫痫动力学的空间分辨率，导致波浪的高度估计值 来源和方向。此外，当在这两个不同的尺度上测量 在癫痫发作期间发生的复杂电活动在本质上可能显得矛盾。因此， 我们对癫痫发作的理解的重大障碍是我们无法弥合微型和宏空间尺度。 为了解决这个问题，该提案的总体目的是量化和模拟癫痫发作动力学 具有高空间和临时分辨率的中间空间尺度。理由是，这将统一我们 了解癫痫发作和分布在不同的空间尺度上，最终提高了我们的能力 局部癫痫发作并通过手术治疗癫痫。为了达到整体目标，我们将记录患者的癫痫发作 使用高密度下硬膜网格的难治性癫痫。使用这些数据，我们将追求以下特定的特定 目的：（1）量化癫痫发作和扩散的中尺度皮质动力学。 （2）发展中尺度 非均匀癫痫波传播的数学模型。这些目标的完成将提供 以毫米尺度上癫痫发作动力学的前所未有的观点，在现有的空间尺度上弥合了差距 研究。通过对癫痫发作的开始和 繁殖，有可能告知癫痫手术计划。这将导致更大的机会 癫痫病例最严重的患者的癫痫发作自由和改善的生活质量。