Cognitive and functional deficits associated with reduced cortical GABA in HIV-infected heavy drinkers

项目概要/摘要 本项目将研究关于局部脑γ- 氨基丁酸（GABA）浓度和认知灵活性在HIV+重度饮酒者。以确保 独立的职业岗位奖，培训的两个关键领域将解决：1）行为和生物 2）在艾滋病毒背景下使用酒精的后果和2）在测量方面的专业知识的发展 γ-氨基丁酸（GABA），主要的抑制性神经递质，使用磁共振 波谱学（MRS）。PI是一位认知神经科学家，在衰老方面有很强的研究背景， 认知、实验设计、自主测量和磁共振成像（fMRI & MRI）。 K 01将为PI提供受保护的时间和培训，以将其研究议程牢牢地集中在酒精方面 和艾滋病病毒。具体而言，K 01将使PI能够进行尖端的非侵入性研究， 有据可查的行为、认知和健康改变的生物学基础， 艾滋病和酗酒。该培训将提供翻译PI基本 将科学技能转化为临床转化应用，探索HIV+和酗酒之间的相互作用。 拟议的研究将调查：（A）GABA浓度与重 （B）GABA与HIV患者认知灵活性之间的关系， 艾滋病毒携带者。为了调查这些研究问题，认知能力和皮质GABA 将检查浓度。全世界有3500万人感染艾滋病毒， 在美国，每年有超过50，000例新诊断。艾滋病毒阳性者的感染率几乎是 与一般人群相比，酒精消耗量很大。HIV+成人的大量饮酒，影响 通过增加高风险行为的发生率对健康结果产生影响，并与 脑功能障碍因此，HIV+患者大量饮酒是一个重大的公共卫生问题。为了评估GABA， 将使用MEGA-PRESS MRS在2个额叶区域测量GABA浓度， 与认知灵活性和大脑后部区域有关。认知灵活性的测量将是 通过神经心理学测试进行测量。我们假设：1）较低的GABA浓度将与 大量饮酒和艾滋病毒，危险饮酒艾滋病毒+成人具有最低浓度的GABA 2） 额叶区GABA浓度的降低与认知灵活性的降低有关。

Project Summary/Abstract This project will investigate important hypotheses regarding the relationship between regional cerebral γ- aminobutyric acid (GABA) concentrations and cognitive flexibility in HIV+ heavy drinkers. To ensure an independent career post award, two critical areas of training will be addressed: 1) Behavioral and biological consequences of alcohol use in the context of HIV and 2) the development of expertise in the measurement of γ-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter, using Magnetic Resonance Spectroscopy (MRS). The PI is a cognitive neuroscientist with a strong research background in aging, cognition, experimental design, autonomic measurement, and magnetic resonance imagining (fMRI & MRI). The K01 will provide protected time and training for the PI to focus his research agenda firmly in alcohol and HIV. Specifically, the K01 will enable the PI to conduct cutting edge non-invasive research investigating the biological foundations of the well documented behavioral, cognitive, and health alterations resulting from HIV and heavy drinking. This training will provide the skills and knowledge required to translate the PI's basic science skills into clinical translational applications exploring the interaction between HIV+ and heavy drinking. The proposed research will investigate: (A) the relationship between GABA concentrations and heavy alcohol use in individuals with HIV, and (B) the relationship between GABA and cognitive flexibility in individuals with HIV. To investigate these research questions, cognitive capabilities and cortical GABA concentrations will be examined. 35 million people have contracted HIV worldwide, more than 1.2 million people have HIV in the US, with more than 50,000 new diagnoses each year. HIV+ individuals exhibit almost twice the rate of heavy alcohol consumption in contrast to the general population. Heavy alcohol consumption in HIV+ adults, impacts on health outcomes by increasing the occurrences of high-risk behaviors and is associated with increased severity of brain dysfunction. Thus, heavy alcohol consumption in HIV+ is a major public health concern. To assess GABA, GABA concentrations will be measured using MEGA-PRESS MRS in 2 frontal regions that have been implicated in cognitive flexibility and a posterior region of the brain. Measures of Cognitive flexibility will be measured via neuropsychological testing. We hypothesize that: 1) Lower GABA concentrations will be related to heavy drinking and HIV, with hazardous drinking HIV+ adults having the lowest concentrations of GABA 2) Reduced GABA concentrations in frontal regions will be associated with reduced cognitive flexibility.