Speaking of Spikes: Connectivity and Language in Benign Epilepsy with Centrotemporal Spikes

说到尖峰：良性癫痫与中央颞叶尖峰的连通性和语言

• 批准号: 10115149
• 负责人: Fiona Mitchell Baumer
• 金额: $ 19.46万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10115149
• 关键词: Acute; Age; Area; Attention; Automobile Driving; Award; Benign; Biological; Blood flow; Brain; Brain region; Child; Childhood; Clinical; Clinical Research; Cognition; Cognitive; Complement; Coupled; Cross-Sectional Studies; Data; Development; Electroencephalogram; Electroencephalography; Ensure; Epilepsy; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Generations; Goals; Handedness; Inferior frontal gyrus; International; Knowledge; Laboratories; Language; Language Development; Language Disorders; Lead; Left; Link; Maps; Measurement; Mentors; Mentorship; Methodology; Methods; Motor; Motor Cortex; Neurologic; Neurosciences; Pathologic; Patients; Perception; Performance; Pharmaceutical Preparations; Physicians; Population; Positioning Attribute; Quality of life; Reporting; Research; Research Personnel; Rotation; Scientist; Seizures; Sleep; Specificity; Standardization; Structure; Superior temporal gyrus; Syndrome; Testing; Therapeutic; Training; Transcranial magnetic stimulation; Universities; Wakefulness; Work; childhood epilepsy; clinically significant; comorbidity; density; design; improved; innovation; language processing; magnetic field; minimally invasive; neurodevelopment; noninvasive brain stimulation; novel; patient oriented research; programs; recruit; response

PROJECT SUMMARY/ABSTRACT Children with benign epilepsy with centrotemporal spikes (BECTS), the most common pediatric epilepsy syndrome, have a mild seizure disorder but have moderate language difficulties, the pathophysiology of which is currently unknown. Many posit that interictal epileptiform discharges (IEDs) arising from one or both motor cortices disrupt language development, possibly by driving atypical connectivity between the motor and language networks. Supporting this, the candidate found that response of the motor cortex to transcranial magnetic stimulation (TMS) specifically correlates with performance on a language learning task in BECTS subjects. The aim of the proposed studies is to use a combination of high-density EEG (HD-EEG) alone and HD-EEG paired with TMS (TMS-EEG) to determine if IEDs disrupt language function by altering brain connectivity. The central hypothesis is that IEDs pathologically strengthen connectivity between the motor and language regions, thus inhibiting development of efficient connectivity within the language network. Aim 1 will define the immediate impact of IEDs on connectivity between the motor and language regions. Aim 2 will determine if children with BECTS have decreased connectivity within the language network compared to controls and whether disrupted connectivity predicts language dysfunction. We do not typically treat IEDs in BECTS as medications have limited efficacy and global neurologic impact. In contrast, repetitive trains of TMS (rTMS) have therapeutic potential for the treatment of IEDs as rTMS induces focal changes in cortical excitability. Thus, Aim 3 will determine if rTMS to the motor cortex reduces IED frequency and normalizes connectivity in children with BECTS. Dr. Baumer is a pediatric epileptologist at Stanford University who is establishing herself as an investigator in patient-oriented research. Her goal is to advance our mechanistic understanding of cognitive comorbidities in pediatric epilepsy. Dr. Baumer’s clinical training coupled with her background in TMS and clinical research make her ideally suited to contribute in this area. The training plan outlined in this application will allow Dr. Baumer to develop expertise in: (1) the conceptual and practical analysis of HD-EEG and TMS-EEG data with emphasis on connectivity analysis; (2) the design and implementation of pediatric TMS-EEG studies; and (3) the neurodevelopment and assessment of language processing. To achieve these goals, she has assembled a mentorship team of internationally recognized physician-scientists with expertise in the measurement and modulation of brain connectivity as well as the neuroscience of language development. She has recruited advisors with methodologic expertise in pediatric TMS, HD-EEG, and epilepsy research. Along with her mentors, Dr. Baumer has chosen laboratory rotations and courses that complement her research to ensure that she reaches her training goals. Upon conclusion of the award, Dr. Baumer will be optimally positioned to lead a pediatric neurostimulation research program that focuses on the interactions of epilepsy and cognition.

项目摘要/摘要 儿童良性癫痫伴中央-颞叶棘波(BECTS)，最常见的儿童癫痫 综合征，有轻度癫痫发作障碍，但有中度语言障碍，其病理生理学 目前还不得而知。许多人认为发作间期癫痫样放电(IED)源于一个或两个运动 大脑皮层干扰语言发展，可能是通过驱动运动和语言之间的非典型连接 网络。支持这一点的候选人发现，运动皮质对经颅磁的反应 在BECTS受试者中，刺激(TMS)与语言学习任务的表现特别相关。这个 建议研究的目的是使用高密度脑电(HD-EEG)单独和HD-EEG配对的组合 使用TMS(TMS-EEG)来确定IED是否通过改变大脑连接来扰乱语言功能。中环 假设IED在病理性上加强了运动区和语言区之间的连接，因此 抑制语言网络内有效连通性的发展。目标1将定义直接 简易爆炸装置对运动区和语言区之间连接性的影响。目标2将确定儿童是否患有 与对照相比，BECT在语言网络内的连通性降低，以及是否中断 连通性预示着语言功能障碍。我们通常不治疗BECTS中的IED，因为药物治疗有限 疗效和全球神经学影响。相比之下，重复序列的TMS(RTMS)有治疗潜力 将IEDS作为rTMS治疗可引起皮质兴奋性的局灶性变化。因此，目标3将确定rTMS是否 运动皮质可减少IED频率，并使BECTS儿童的连接正常化。 鲍默博士是斯坦福大学的一名儿科癫痫专家，她正在成为一名研究人员 以病人为中心的研究。她的目标是推进我们对认知并存的机械性理解 儿科癫痫。鲍默医生的临床培训，加上她在经颅医学和临床研究方面的背景，使 她非常适合在这一领域做出贡献。此申请中概述的培训计划将使Baumer博士能够 培养以下方面的专业知识：(1)HD-EEG和TMS-EEG数据的概念和实际分析，重点是 关于连接性分析；(2)儿科TMS-EEG研究的设计和实施；以及(3) 语言处理的神经发展和评估。为了实现这些目标，她组建了一个 由国际公认的医生-科学家组成的导师团队，在测量和 大脑连通性的调节以及语言发展的神经科学。她已经招募了 在儿科TMS、HD-EEG和癫痫研究方面具有方法论专长的顾问。和她的导师们一起， 鲍默博士选择了实验室轮换和课程来补充她的研究，以确保她 达到了她的训练目标。在奖项结束后，鲍默博士将处于领导一个 儿童神经刺激研究项目，重点研究癫痫和认知之间的相互作用。