NEUROBEHAVIORAL FEATURES OF MESIAL TEMPORAL LOBE EPILEPSY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。(来自CRISP网站)我们正在提出第一项前瞻性研究，旨在检测慢性早发性(14岁以下)颞叶癫痫(TLE)对大脑结构和功能的渐进性不良影响。这项拟议的研究将结合高分辨率定量MRI体积测量、全面的神经心理学评估和功能磁共振记忆激活任务。这项研究的目的是检验这一假说，即早发性TLE与对大脑结构和功能的普遍不利神经发育影响有关。如果这一点得到证实，这可能构成了在持续的慢性癫痫面前，进行性认知能力下降的早期获得性神经生物学脆弱性。我们将对80名早发性TLE受试者和80名年龄和性别匹配的对照组进行纵向检查，这些对照组最初是在四到五年前进行基线测试的。所有受试者将再次接受认知评估和全脑定量MRI体积测量，一部分受试者将接受fMRI目标记忆任务。据预测：(1)在这四-五年的时间间隔内，早发性TLE受试者的认知能力下降将比对照组更大；(2)癫痫病程较长的受试者的认知能力下降最为明显；与基于语言的任务相比，记忆功能、认知加工和非语言能力的测量结果将更加明显；(3)早发性TLE受试者表现出的重测认知能力下降将通过重测期间脑组织总体积和脑组织丢失比例的时间来预测；(4)癫痫慢性化程度的增加将与fMRI目标记忆任务中内侧颞叶激活的减少有关。其他分析将检查特定的癫痫病程变量、抑郁和相关的慢性内科疾病对TLE纵向变化的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (from CRISP website) We are proposing the first prospective investigation designed to detect progressive adverse effects of chronic early onset (less than age 14) temporal lobe epilepsy (TLE) on brain structure and function. This proposed study will combine high- resolution quantitative MRI volumetrics, comprehensive neuropsychological assessment, and an fMRI memory activation task. The purpose of this investigation is to test the hypothesis that early onset TLE is associated with a generalized adverse neurodevelopmental impact on both brain structure and function. If this is proven, that may constitute an early-acquired neurobiological vulnerability for progressive cognitive decline in the face of ongoing chronic epilepsy. We will do a longitudinal examination of 80 early onset TLE subjects and 80 age and gender matched controls that were initially seen for baseline testing four to five years earlier. All subjects will again undergo cognitive assessment and whole brain quantitative MRI volumetrics and a subset of subjects will undergo an fMRI object memory task. It is predicted that: (1) cognitive decline in this four-five year interval will be greater for early onset TLE subjects compared to controls, (2) decline will be most evident among those with longer duration of epilepsy, and for measures of memory function, speeded cognitive processing and non-verbal abilities compared to language based tasks, (3) test-retest cognitive decline shown by early onset TLE subjects will be predicted by time total brain tissue volume and proportional brain tissue lost over the test- retest interval, and (4) increasing chronicity of epilepsy will be associated with decreasing mesial temporal lobe activation on an fMRI object memory task. Additional analyses will examine the impact of specific epilepsy course variables, depression, and associated chronic medical illness on longitudinal changes in TLE.