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: 10611979
• 负责人: Brian Nils Lundstrom
• 金额: $ 18.65万
• 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/10611979
• 关键词: Amplifiers; Animals; Award; Awareness; Behavioral; Biological Markers; Biometry; Brain; Brain region; Characteristics; Clinical; Clinical Data; Coupled; Coupling; Data; Electrodes; Electroencephalography; Enrollment; Environment; Epilepsy; Evaluation; Extramural Activities; Freedom; Frequencies; Generations; Glutamates; Goals; Grant; High Frequency Oscillation; Human; Hybrids; Impairment; Informatics; Instruction; Intractable Epilepsy; 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; Recurrence; Research; Research Design; Research Personnel; Resected; Scalp structure; Seizures; Sensitivity and Specificity; Signal Transduction; Sleep; Techniques; Time; Training; Work; Writing; biomarker development; career; career development; clinical application; cohort; density; epileptiform; gamma-Aminobutyric Acid; improved; inhibitory neuron; 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.

项目总结/摘要 大约20%的复发性癫痫患者患有局灶性耐药性癫痫。它仍然是 具有挑战性的定位癫痫区（EZ），定义为必须切除的大脑区域，或 调节以获得无癫痫发作。目前还没有精确的EZ定位， 起始区仍然是定义EZ的黄金标准。低频脑电活动（LFA）是相对 研究不足和先前的数据表明，LFA可以改善EZ定位。该提案的目标是充分 评估LFA用于EZ定位的潜力，并阐明LFA的病理生理机制。 为此，将对94例患者进行回顾性分析，以检查LFA的潜在疗效， 将前瞻性入组40例患者进行更详细的评估。临床 治疗患者的结局将用于回顾性确定EZ，该EZ可用于评估 LFA估计的EZ。前瞻性患者将同时接受临床EEG记录 宏电极以及研究级微电极，其使用DC- 能力的放大器。此外，磁共振波谱学的尖端技术将用于 确定这些大脑区域的神经递质水平。最后，非侵入性高密度脑电图， 结合侵入性EEG将用于评估非侵入性估计EZ的潜力。 我们希望，这一建议将导致更准确的非侵入性和侵入性定位的EZ， 会改善病人的治疗效果了解LFA的潜在机制将有助于 生物标志物的开发和临床应用，并可能影响治疗相关的决策。一个 非侵入性评估中基于LFA的信息丰富的EEG生物标志物意味着患者可能 避免侵入性脑电图监测。 对于这个指导奖，职业规划包括作为临床研究者独立的总体目标 研究癫痫的培训目标如下：（1）了解人类研究的研究设计，（2） 获得信息学和生物统计学的正式指导，（3）了解生物标志物的发展，（4）了解 微电极记录和MR光谱，（5）提高赠款写作技巧，（6）发展与 校外研究人员，（7）保持和提高对当前文献的认识。的环境 职业发展包括一个多学科团队，包括癫痫，神经放射学和生物统计学， 在微电极记录和EEG生物标志物开发方面具有实验室工作经验和支持。

项目成果

Cortical and thalamic electrode implant followed by temporary continuous subthreshold stimulation yields long-term seizure freedom: A case report.

• DOI: 10.1016/j.ebr.2020.100390
• 发表时间: 2020
• 期刊: Epilepsy & behavior reports
• 作者: Alcala-Zermeno JL;Gregg NM;Van Gompel JJ;Stead M;Worrell GA;Lundstrom BN
• 通讯作者: Lundstrom BN

Invasive neuromodulation for epilepsy: Comparison of multiple approaches from a single center.

• DOI: 10.1016/j.yebeh.2022.108951
• 发表时间: 2022-12
• 期刊: EPILEPSY & BEHAVIOR
• 影响因子: 2.6
• 作者: Alcala-Zermeno, Juan Luis;Gregg, Nicholas M.;Starnes, Keith;Mandrekar, Jayawant N.;Gompel, Jamie J. Van;Miller, Kai;Worrell, Greg;Lundstrom, Brian N.
• 通讯作者: Lundstrom, Brian N.

Case Report: Prolonged Effects of Short-Term Transcranial Magnetic Stimulation on EEG Biomarkers, Spectral Power, and Seizure Frequency.

• DOI: 10.3389/fnins.2022.866212
• 发表时间: 2022
• 期刊: FRONTIERS IN NEUROSCIENCE
• 影响因子: 4.3
• 作者: Starnes, Keith;Britton, Jeffrey W.;Burkholder, David B.;Suchita, Iffat A.;Gregg, Nicholas M.;Klassen, Bryan T.;Lundstrom, Brian Nils
• 通讯作者: Lundstrom, Brian Nils

Electroencephalogram (EEG) With or Without Transcranial Magnetic Stimulation (TMS) as Biomarkers for Post-stroke Recovery: A Narrative Review.

• DOI: 10.3389/fneur.2022.827866
• 发表时间: 2022
• 期刊: Frontiers in neurology
• 影响因子: 3.4
• 作者: Keser Z;Buchl SC;Seven NA;Markota M;Clark HM;Jones DT;Lanzino G;Brown RD Jr;Worrell GA;Lundstrom BN
• 通讯作者: Lundstrom BN

What Should We Expect for Real-World Outcomes of Deep Brain Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy?

我们应该对丘脑前核深部脑刺激治疗癫痫的现实结果有何期待？

• DOI: 10.1212/wnl.0000000000201455
• 发表时间: 2023
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Lundstrom,BrianNils;Gregg,NicholasM
• 通讯作者: Gregg,NicholasM