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

项目概要/摘要 儿童良性癫痫伴中央颞区棘波（BECTS），最常见的小儿癫痫 综合征，有轻度癫痫发作障碍，但有中度语言困难，其病理生理学 目前尚不清楚。许多研究表明，发作间期癫痫样放电（IED）由一个或两个运动引起， 大脑皮层可能通过驱动运动和语言之间的非典型连接来破坏语言的发展 网络.支持这一点，候选人发现运动皮层对经颅磁刺激的反应， 刺激（TMS）与BECTS受试者的语言学习任务表现特别相关。的 所提出的研究的目的是使用单独的高密度EEG（HD-EEG）和HD-EEG配对的组合 通过TMS（TMS-EEG）来确定IED是否通过改变大脑连接来破坏语言功能。中央 假设简易爆炸装置在病理上加强了运动区和语言区之间连接， 抑制了语言网络内有效连接的发展。目标1将定义立即 简易爆炸装置对运动和语言区域之间连接的影响。目标2将确定是否有儿童 与对照组相比，BECTS语言网络内的连接性降低， 连通性预示着语言功能障碍。我们通常不会在BECTS中治疗IED，因为药物治疗有限 疗效和整体神经系统影响。相反，TMS的重复序列（rTMS）具有治疗潜力， 作为rTMS的IED治疗诱导皮质兴奋性的局灶性变化。因此，目标3将确定rTMS是否 运动皮层的神经刺激降低了IED频率，并使BECTS儿童的连接正常化。 博士鲍默是斯坦福大学的一名儿科癫痫病学家， 以病人为中心的研究。她的目标是推进我们对认知共病的机械理解， 小儿癫痫Baumer博士的临床培训加上她在TMS和临床研究方面的背景， 她非常适合在这个领域做出贡献。本申请中概述的培训计划将允许Baumer博士 培养以下方面的专业知识：（1）HD-EEG和TMS-EEG数据的概念和实践分析，重点是 连接分析;（2）儿科TMS-EEG研究的设计和实施;（3） 神经发育和语言处理评估。为了实现这些目标，她组织了一个 国际公认的医生-科学家的指导团队，具有测量和 大脑连接的调节以及语言发展的神经科学。她招募了 在儿科TMS、HD-EEG和癫痫研究方面具有方法学专业知识的顾问。沿着她的导师， 博士鲍默选择了实验室轮换和课程，以补充她的研究，以确保她 达到她的训练目标。在该奖项结束后，Baumer博士将处于最佳位置，领导一个 儿科神经刺激研究计划，重点是癫痫和认知的相互作用。

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.