Early-onset epilepsy and genetics influence white matter tracts and cognition

描述（由申请人提供）：项目摘要：本项目将探讨白色物质完整性和认知功能障碍之间的关系，在个人与颞叶癫痫（TIE）。虽然TLE与多个认知领域的缺陷有关，但这些缺陷的神经生物学基础尚不清楚。一个潜在的机制是癫痫诱导的异常连接（白色物质束）之间的多个大脑区域，涉及复杂的认知功能。扩散张量成像（DTI）是一种磁共振序列，可测量白色物质束的结构完整性，因此是研究大脑连接的非常有用的工具。在目标1中，我将使用DTI探测TLE患者白色物质束的完整性。在目标2中，我将把白色物质完整性的DTI指数与特定的神经心理学测量相关联。在目标3中，我将前瞻性地研究白色物质完整性的变化（通过DTI测量）与TLE儿童认知缺陷发展之间的关系。白色物质完整性和认知功能之间的显着联系将支持DTI作为认知缺陷发展的有用生物标志物。该提案利用先进的脑成像技术来揭示癫痫患者认知功能障碍的生物学基础。这项研究的新见解可能使我们能够针对认知干预和潜在预防癫痫相关认知缺陷的候选人。我是一名敬业的临床医生/科学家，完全致力于癫痫研究的职业生涯。我得到了加州大学欧文分校神经病学系和医学院的保护时间和全力支持，这是一个世界知名的神经科学中心，也是公认的基础和临床癫痫研究中心。在计划书的培训部分，我将接受临床设计、生物静力学、生物伦理学、神经心理学测试以及最先进的神经成像技术的培训。我的最终目标是将联合收割机临床和研究工作结合起来，以了解癫痫患者认知功能障碍的神经生物学基础，并制定潜在的预防策略。相关性：癫痫是一种大脑疾病，影响1%的美国人口，并与显著的认知（即记忆和语言）问题有关。这项提案将使用先进的大脑成像技术来研究异常大脑连接和认知问题之间的关系。更好地了解癫痫患者的认知问题可能会改善治疗方案。

DESCRIPTION (provided by applicant): Project Summary: This project will explore the relationship between white matter integrity and cognitive dysfunction in individuals with temporal lobe epilepsy (TIE). Although TLE is associated with deficits in multiple cognitive domains, the neurobiological basis underlying these deficits is unclear. A potential mechanism is epilepsy-induced abnormal connections (white matter tracts) between multiple brain regions that are involved in complex cognitive function. Diffusion tensor imaging (DTI) is a magnetic resonance sequence that measures the structural integrity of white matter tracts and thus is an extremely useful tool for investigating brain connections. In Aim 1, I will use DTI to probe the integrity of white matter tracts in individuals with TLE. In Aim 2, I will correlate DTI indices of white matter integrity with specific neuropsychological measures. In Aim 3, I will prospectively examine the relationship between the changes in white matter integrity, as measured by DTI, and the development of cognitive deficits in children with TLE. Significant linkage between white matter integrity and cognitive function will support DTI as a useful biomarker for the development of cognitive deficits. This proposal utilizes advanced brain imaging techniques to uncover the biological basis of cognitive dysfunction in individuals with epilepsy. New insights from the study may enable us to target candidates for cognitive intervention and for potential prevention of epilepsy-related cognitive deficits. I am a dedicated Clinician/Scientist who is fully committed to a career in epilepsy research. I have received protected time and full support from the Neurology Department and the School of Medicine at the University of California, Irvine, a world-renowned center for neurosciences and a recognized center for basic and clinical epilepsy research. In the training portion of the proposal, I will receive training in clinical design, biostatics, bioethics, neuropsychological testing, as well as state-of-the-art neuroimaging techniques. My ultimate goal is to combine clinical and research efforts to understand the neurobiological basis of cognitive dysfunction in people with epilepsy and to develop potential preventive strategies. Relevance: Epilepsy is a brain disorder that affects 1% of the American population and is associated with significant cognitive (i.e. memory and language) problems. This proposal will use advanced brain imaging techniques to study the relationship between abnormal brain connections and cognitive problems. Better understanding of cognitive problems in individuals with epilepsy may lead to improved treatment options.