COGNITIVE CHANGE IN HIV: A FMRI STUDY

HIV感染通常伴随着认知、运动和行为的变化，从轻度的记忆力、注意力和运动减慢到HIV相关的痴呆。这些类型的变化类似于皮质下神经病理患者的神经心理学特征，包括帕金森氏病(PD)和亨廷顿病(HD)。研究还表明，HIV的病理与PD和HD相似，尸检、结构神经成像和静息代谢成像研究显示，主要损害基底节和丘脑。唯一报道的认知激活研究，使用正电子发射计算机断层扫描显示艾滋病毒阳性受试者在短期记忆任务中前额叶皮质功能障碍。所有这些证据表明，HIV感染者大脑中连接前额叶皮质、基底节和丘脑的回路功能障碍。然而，将艾滋病毒相关的认知障碍与任何大脑区域的功能直接联系起来的数据有限，包括额纹状体区域。这项研究的主要目的是将功能磁共振成像(FMRI)、神经心理学测量、免疫学标记物和日常功能测量相结合，以研究HIV相关的认知、运动和行为缺陷与大脑功能回路潜在变化的关系。数据将在150名艾滋病毒阳性的非痴呆受试者和50名艾滋病毒阴性的对照组受试者中收集。该建议的具体目的是：1)描述病毒载量、CD4+计数和脑功能之间的关系；2)使用功能磁共振成像来评估在执行认知任务时的脑功能，特别是那些与额纹状体功能有关的认知任务；3)研究脑功能、对艾滋病毒敏感的标准神经心理测试和日常功能之间的关系；4)分析这些关系是否受到抗逆转录病毒治疗的使用、年龄、种族、教育或病前智力等因素的调节。使用当前功能磁共振成像方法的机会是这项研究的主要优势，因为它允许在单个对象中检查大脑功能。由于艾滋病毒是一种非常不同的疾病，重要的是评估单个受试者内实验变量之间的关系，以更好地了解每个变量如何直接影响其他变量。最后，这项研究产生的数据可能会导致对艾滋病毒脑功能障碍的性质有更深入的了解，有助于开发治疗方法，通过瞄准受疾病最早影响的大脑区域来改善认知障碍。

HIV infection is often accompanied by cognitive, motor, and behavioral changes that range from mild impairments of memory, concentration and motor slowing to HIV-associated dementia. These types of changes resemble the neuropsychological profiles of individuals with subcortical neuropathology, including Parkinson's disease (PD) and Huntington's disease (HD). Studies have also shown HIV to have pathology similar to PD and HD, with post-mortem, structural neuroimaging, and resting metabolic imaging studies showing damage primarily to the basal ganglia and thalamus. The only reported cognitive activation study, used PET to show prefrontal cortex dysfunction in HIV-positive subjects during a short-term memory task. All of this evidence suggests dysfunction of the circuits linking the prefrontal cortex, basal ganglia, and thalamus in the brains of HIV-infected individuals. However, there is limited data that directly links HIV-related cognitive impairments with function in any brain areas, including frontostriatal regions. The main goal of this study is to integrate functional MRI (fMRI), neuropsychological measurements, immunological markers, and measures of everyday functioning to study the relationship between HIV-related cognitive, motor, and behavioral deficits and underlying changes in functional brain circuitry. Data will be collected in a group of 150 HIV-positive, non-demented subjects and 50 HIV-negative control subjects. The specific aims of the proposal are: 1) to characterize the relationship between viral load, CD4+ count and brain function, 2) to use fMRI to assess brain function during performance of cognitive tasks found to be impaired in HIV-infected individuals, especially those that are related to frontostriatal function, 3) to examine the relationship between brain function, standard neuropsychological tests that are sensitive to HIV, and everyday functioning and 4) to analyze whether such relationships are moderated by factors including antiretroviral therapy use, age, ethnicity, education, or premorbid intelligence. The opportunity to use current fMRI methodology is a major strength of this study as it permits examination of brain function in a single subject. As HIV is a very heterogeneous disorder, it will be important to evaluate the relationship between the experimental variables within single subjects to better understand how each variable directly impacts the others. Finally, data produced by this study may lead to a more sophisticated understanding of the nature of brain dysfunction in HIV, assisting in the development of therapies to ameliorate cognitive impairment by targeting brain regions affected earliest by the disease.