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

项目摘要/摘要 这个项目将调查关于局部脑γ- HIV阳性酗酒者的氨基丁酸(GABA)浓度和认知灵活性。要确保 独立职业岗位奖，将涉及两个关键的培训领域：1)行为和生物 酒精使用在艾滋病毒方面的后果和2)发展测量艾滋病毒的专门知识 主要抑制性神经递质γ-氨基丁酸的磁共振研究 波谱(MRS)。PI是一位认知神经学家，在衰老方面有很强的研究背景， 认知、实验设计、自主神经测量和磁共振成像(fMRI和MRI)。 K01将为PI提供受保护的时间和培训，以坚定地将他的研究议程集中在酒精上 和艾滋病病毒。具体地说，K01将使PI能够进行尖端的非侵入性研究 有充分证据的行为、认知和健康改变的生物学基础 艾滋病毒和酗酒。此培训将提供翻译PI基本知识所需的技能和知识 将科学技能转化为临床应用，探索艾滋病毒+与酗酒之间的相互作用。 这项拟议的研究将调查：(A)GABA浓度与体重之间的关系 HIV感染者的酒精使用，以及(B)GABA和认知灵活性之间的关系 艾滋病病毒携带者。为了研究这些研究问题，认知能力和皮质GABA 将对浓度进行检查。全球已有3500万人感染艾滋病毒，超过120万人 美国有艾滋病病毒感染者，每年有超过5万例新诊断病例。HIV+个体表现出几乎两倍于 与普通人群形成鲜明对比的是大量饮酒。HIV+成人中大量饮酒的影响 通过增加高危行为的发生来影响健康结果，并与增加的严重程度有关 大脑功能障碍。因此，在HIV+中大量饮酒是一个主要的公共卫生问题。为了评估GABA， GABA浓度将使用兆压MRS在两个额区测量，这两个区域已经 与认知灵活性和大脑后部区域有关。认知灵活性的衡量标准将是 通过神经心理测试进行测量。我们假设：1)较低的GABA浓度将与 大量饮酒和艾滋病毒，其中危险饮酒艾滋病毒+成年人的GABA 2浓度最低) 额叶区域GABA浓度降低将与认知灵活性降低相关。

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.