Localizing value and underlying mechanisms of low frequency EEG for focal epilepsy

低频脑电图对局灶性癫痫的定位价值和潜在机制

• 批准号: 10398927
• 负责人: Brian Nils Lundstrom
• 金额: $ 18.72万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10398927
• 关键词: Amplifiers; Animals; Award; Awareness; Behavioral; Biological Markers; Biometry; Brain; Brain region; Characteristics; Clinical; Clinical Data; Clinical Research; Coupled; Coupling; Data; Electrodes; Electroencephalography; Enrollment; Environment; Epilepsy; Evaluation; Extramural Activities; Freedom; Frequencies; Generations; Glutamates; Goals; Gold; Grant; High Frequency Oscillation; Human; Hybrids; Impairment; Informatics; Instruction; Intractable Epilepsy; Lead; Learning; Lesion; Link; Literature; Location; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mentors; Metabolism; Methods; Microelectrodes; Monitor; Neurons; Neurotransmitters; Outcome; Partial Epilepsies; Pathologic; Patient Care; Patient-Focused Outcomes; Patients; Process; Research; Research Design; Research Personnel; Resected; Scalp structure; Seizures; Sensitivity and Specificity; Signal Transduction; Sleep; Techniques; Time; Training; Work; Writing; base; biomarker development; career; career development; clinical application; cohort; density; gamma-Aminobutyric Acid; improved; innovation; laboratory experience; multidisciplinary; neuroimaging; non-invasive monitor; prospective; skills

Project Summary/Abstract Approximately 20% of patients with recurring seizures have focal drug-resistant epilepsy. It remains challenging to localize the epileptogenic zone (EZ), defined as the region of brain that must be resected or modulated to obtain seizure freedom. No precise localization for the EZ is currently available, and the seizure onset zone remains the gold standard for defining the EZ. Low Frequency EEG Activity (LFA) is relatively understudied and prior data suggests that LFA can improve EZ localization. This proposal’s objective is to fully evaluate the potential of LFA for EZ localization and to clarify pathophysiologic mechanisms that underlie LFA. To this end, a retrospective analysis of 94 patients will examine the potentially efficacy of LFA for estimating the EZ, and a cohort of 40 patients will be prospectively enrolled for more detailed assessments. Clinical outcomes from treated patients will be used to retrospectively determine the EZ, which can be used to evaluate the EZ as estimated by LFA. Prospective patients will receive simultaneous recordings from clinical EEG macroelectrodes as well as from research-grade microelectrodes, which record neuronal units using DC- capable amplifiers. In addition, cutting edge techniques for magnetic resonance spectroscopy will be used to determine neurotransmitter levels for these same brain regions. Finally, non-invasive high density EEG in conjunction with invasive EEG will be used to assess the potential for non-invasive estimation of the EZ. We expect that this proposal will lead to more accurate non-invasive and invasive localization of the EZ, which would lead to improved patient outcomes. Understanding the mechanisms underlying LFA will improve biomarker development and application to clinical use and could influence treatment-related decisions. An informative EEG biomarker based on LFA from non-invasive evaluations means patients could potentially avoid invasive EEG monitoring. For this mentored award, the career plan includes the overall goal of independence as a clinician investigator studying epilepsy with the following training objectives: (1) learn about study design for human research, (2) obtain formal instruction in informatics and biostatistics, (3) understand biomarker development, (4) learn about microelectrode recordings and MR spectroscopy, (5) improve grant writing skills, (6) develop relationships with extramural researchers, and (7) maintain and improve awareness of current literature. The environment for career development includes a multidisciplinary team including epilepsy, neuroradiology, and biostatistics with prior lab experience and support in microelectrode recordings and EEG biomarker development.

项目摘要/摘要 大约20％的经常性癫痫发作患者患有抗局灶性药物癫痫。它仍然存在 具有挑战性的定位癫痫发射区（EZ），定义为必须切除的大脑区域或 调制以获得癫痫发作自由。目前没有EZ的精确定位，并且癫痫发作 发作区仍然是定义EZ的金标准。低频脑电图活性（LFA）相对 研究并以前的数据表明LFA可以改善EZ定位。该提议的目标是完全 评估LFA对EZ定位的潜力，并阐明LFA构成的病理生理机制。 为此，对94名患者的回顾性分析将检查LFA估计的潜在有效性 EZ和40名患者的队列将被预期入学，以进行更详细的评估。临床 治疗患者的结果将用于追溯确定EZ，可用于评估 LFA估计的EZ。潜在的患者将从临床脑电图中同时收到记录 宏观电子以及研究级微电极，它们使用DC-记录神经元单元 功能强大的放大器。此外，用于磁共振光谱的尖端技术将用于 确定这些相同大脑区域的神经递质水平。最后，非侵入性高密度脑EEG 与侵入性脑电图的结合将用于评估EZ非侵入性估计的潜力。 我们希望该提案将导致EZ的更准确的非侵入性和侵入性本地化，这 将导致改善患者的预后。了解LFA的基础机制将有所改善 生物标志物开发和应用于临床使用，可能会影响与治疗相关的决策。一个 基于非侵入性评估的LFA的信息性脑电图生物标志物意味着患者可能有可能 避免侵入性脑电图监测。 对于此事项奖，职业计划包括独立的总体目标 使用以下培训目标研究发作：（1）了解人类研究的研究设计，（2） 获取有关信息和生物统计学的正式指示，（3）了解生物标志物的发展，（4）了解 微电极记录和MR光谱学，（5）提高赠款写作技巧，（6）与 外壁外研究人员以及（7）维持和提高对当前文献的认识。环境 职业发展包括一个多学科团队 微电极记录和脑电图生物标志物开发的先前实验室经验和支持。