NEUROBEHAVIORAL FEATURES OF MESIAL TEMPORAL LOBE EPILEPSY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们正在提出首个前瞻性研究，旨在检测慢性早发性（小于14岁）颞叶癫痫（TLE）对大脑结构和功能的进行性不良影响。该研究将结合高分辨率定量MRI容积测量、综合神经心理学评估和功能磁共振成像记忆激活任务。本研究的目的是验证早发性TLE与脑结构和功能的普遍不良神经发育影响有关的假设。如果这被证明，这可能构成早期获得性神经生物学脆弱性进行性认知能力下降面对持续的慢性癫痫。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，这些受试者最初在4到5年前进行基线测试。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对象记忆任务。据预测：(1)与对照组相比，早发性TLE受试者在这4 - 5年期间的认知能力下降更大；(2)癫痫持续时间较长的患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、快速认知加工和非语言能力的测量结果也更为明显；(3)早发性TLE受试者的重测认知能力下降可通过时间脑组织总体积和重测间隔内脑组织损失的比例来预测；(4)癫痫慢性程度的增加与fMRI对象记忆任务中内侧颞叶激活程度的降低有关。额外的分析将检查特定癫痫病程变量、抑郁症和相关慢性医学疾病对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.