Imaging the Impact of Childhood Epilepsy on Memory Development

项目总结摘要 在美国，癫痫影响着220万成年人，每26人中就有1人在 他们的生活。颞叶癫痫(TLE)是局灶性癫痫最常见的内侧结构形式， 尤其是海马体，容易导致癫痫发作。选择性颞叶切除术对 治愈74-80%的TLE患者，但会使患者面临记忆功能受损的风险。要最小化 颞叶手术对记忆功能的不利影响，需要可靠的术前指导。 临床功能磁共振成像(FMRI)提供可靠的、无创的语言指导 癫痫患者术前功能评价。记忆的功能磁共振成像也正在成为一种有用的 预测成人结局的技术和新的AAN实践指南表明中等(B级)证据 基于成人研究的言语记忆功能磁共振成像在预测言语记忆结果中的作用。然而，没有记忆 患有癫痫的儿童存在功能磁共振研究。我们将通过开发检查以下内容的记忆功能磁共振任务来填补这一空白 儿童TLE如何影响发育过程中记忆系统的功能解剖。我们的小说 方法将神经心理评估与标准和高分辨率的fMRI和MRI联系起来，以及 通过静息状态的连接来表征记忆的发育神经基础。 这项建议的目的是确定TLE儿童记忆功能的潜在重组：1) 在整个大脑水平上，2)在海马体内，以及3)通过连接。该项目将建立一个功能磁共振成像 TLE儿童的术前记忆评估方案。这一方案将改进外科手术 根据重组的关键时间窗确定最佳手术时机进行干预 发生。首席研究员Leigh Sepeta博士是一位专门研究儿童和成人的神经心理学家 癫痫，重点是用于癫痫的语言和记忆映射的功能磁共振成像。她在…方面有很强的背景 神经发育、神经心理学和癫痫。拟议的培训计划将建立在她现有的基础上 知识和促进三个目标：1)获得先进神经成像方法的专业知识，2)开发 具备高分辨率神经成像、海马区解剖和海马区分析的技能，以及3) 生物统计分析方面的高级技能。塞佩塔博士组建了一支强大的导师和顾问团队 包括William D.Gaillard，M.D.，William H.Theodore，M.D.，ChanY.Vaidya，PhD和Susan Y. 布克海默，博士(二级导师)。他们在儿童和成人癫痫、神经成像、 海马体功能和神经心理学是Sepeta博士提议的研究和 训练计划。Sepeta博士为K23计划设计的研究-培训计划将进一步促进她 过渡到专注于神经心理学和神经成像的独立调查员的总体目标 对癫痫等神经性疾病的记忆评估。

PROJECT SUMMARY ABSTRACT Epilepsy affects 2.2 million adults in the United States, with 1 in 26 people developing epilepsy at some point in their lives. Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy as medial structures, and the hippocampus in particular, are prone to generating seizures. Selective temporal resection is effective in curing TLE in 74-80% of patients, but puts patients at risk of impaired memory functioning. To minimize the adverse impact of temporal lobe surgery on memory functioning, reliable pre-surgical guides are needed. Clinical functional magnetic resonance imaging (fMRI) provides reliable, noninvasive guidance of language functioning in the pre-surgical evaluation for epilepsy patients. FMRI of memory is also emerging as a useful technology to predict adult outcomes and new AAN Practice Guidelines indicate moderate (Level B) evidence for verbal memory fMRI in predicting verbal memory outcome, based on adult studies. However, no memory fMRI studies exist in children with epilepsy. We will fill this gap by developing memory fMRI tasks that examine how the functional anatomy of memory systems across development is affected by pediatric TLE. Our novel approach links neuropsychological assessment with fMRI and MRI at standard and high-resolutions, and through resting-state connectivity to characterize the developmental neural underpinnings of memory. The aims of this proposal are to determine potential reorganization of memory function in children with TLE: 1) at the whole brain level, 2) within the hippocampus, and 3) via connectivity. This project will establish an fMRI protocol for the presurgical evaluation of memory in children with TLE. This protocol will improve surgical intervention by establishing the optimal timing of surgery based on when critical windows for reorganization occur. The Principal Investigator, Leigh Sepeta, PhD, is a neuropsychologist specializing in pediatric and adult epilepsy, with a focus on fMRI for language and memory mapping in epilepsy. She has a strong background in neurodevelopment, neuropsychology, and epilepsy. The proposed training plan will build upon her existing knowledge and promote three goals: 1) to acquire expertise in advanced neuroimaging methods, 2) to develop skills in high-resolution neuroimaging, hippocampal anatomy, and hippocampal subregion analysis, and 3) to advance skills in biostatistical analysis. Dr. Sepeta has assembled a strong mentorship and consultant team including William D. Gaillard, M.D., William H. Theodore, M.D., Chandan Y. Vaidya, PhD and Susan Y. Bookheimer, PhD (secondary mentor). Their expertise in pediatric and adult epilepsy, neuroimaging, hippocampal functioning, and neuropsychology are an ideal match for Dr. Sepeta's proposed research and training plans. The research-training program Dr. Sepeta has designed for this K23 proposal will further her overall goal of transitioning to an independent investigator focused on neuropsychological and neuroimaging evaluation of memory in neurological disorders, such as epilepsy.