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

HIV 感染的重度饮酒者中与皮质 GABA 减少相关的认知和功能缺陷

• 批准号: 9753836
• 负责人: Eric Porges
• 金额: $ 16.07万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753836
• 关键词: Acute; Address; Adherence; Adult; Affect; Aging; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Area; Award; Baclofen; Basic Science; Behavioral; Biological; Brain; Brain region; Cerebrum; Clinical; Cognition; Cognitive; Collaborations; Contracts; Data; Decision Making; Development; Diagnosis; Dimensions; Disease; Enrollment; Ensure; Equipment and supply inventories; Exhibits; Experimental Designs; FDA approved; Florida; Foundations; Functional Magnetic Resonance Imaging; Funding; GABA Agonists; Gap Junctions; General Population; Grant; HIV; Health; Heavy Drinking; High Prevalence; Impairment; Individual; Intervention; Investigation; Knowledge; Lateral; Lead; Link; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mentors; Methodology; Motivation; Neurobiology; Neuropsychological Tests; Neuropsychology; Neurotransmitters; Outcome; Participant; Play; Population; Prevention; Problem Solving; Public Health; Quality of life; Research; Rodent Model; Role; Severities; Site; Testing; Therapeutic; Time; Training; Translating; Translational Research; Universities; Wisconsin; aged; alcohol consequences; alcohol research; antiretroviral therapy; behavioral pharmacology; brain dysfunction; career; career development; cognitive function; cognitive neuroscience; cognitive performance; cognitive process; cognitive testing; disease transmission; experience; flexibility; frontal lobe; frontal lobe function; gamma-Aminobutyric Acid; hazardous drinking; high risk behavior; high risk population; high risk sexual behavior; improved; innovation; neurophysiology; novel strategies; programs; recruit; skills; spasticity

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.

项目摘要/摘要 该项目将研究有关区域大脑γ-之间关系的重要假设 HIV+饮酒者中的氨基丁酸（GABA）浓度和认知灵活性。确保一个 独立职业邮政奖，将解决两个关键领域：1）行为和生物学 在艾滋病毒和2）衡量专业知识的发展中饮酒的后果 主要抑制性神经递质γ-氨基丁酸（GABA）使用磁共振成分 光谱法（MRS）。 PI是一种认知神经科学家，具有强大的衰老研究背景， 认知，实验设计，自主测量和磁共振成像（fMRI和MRI）。 K01将为PI提供受保护的时间和培训，以将其研究议程集中在酒精中 和艾滋病毒。具体而言，K01将使PI能够进行尖端非侵入性研究调查 据具有有版的行为，认知和健康改变的生物基础 艾滋病毒和大量饮酒。该培训将提供翻译PI基本所需的技能和知识 临床翻译应用的科学技能探讨了艾滋病毒+和大量饮酒之间的相互作用。 拟议的研究将调查：（a）GABA浓度与浓度之间的关系 艾滋病毒个体的饮酒，以及（b）GABA与认知灵活性之间的关系 患有艾滋病毒的人。调查这些研究问题，认知能力和皮质GABA 将检查浓度。全球有3500万人感染了艾滋病毒，超过120万人 在美国有艾滋病毒，每年有50,000多个新诊断。艾滋病毒+个人的速度几乎是 与普通人群相比，大量饮酒。艾滋病毒+成人的大量饮酒，影响 通过增加高风险行为的发生，与健康结果有关 脑功能障碍。这是艾滋病毒+的大量饮酒是一个主要的公共卫生问题。为了评估GABA， GABA浓度将在两个额叶区域中使用Mega-Press MRS测量 在认知灵活性和大脑后部区域实施。认知灵活性的度量将是 通过神经心理学测试测量。我们假设：1）较低的GABA浓度将相关 大量饮酒和艾滋病毒，有危险的饮酒艾滋病毒+成年人的浓度最低的GABA 2） 额叶区域的GABA浓度降低将与认知灵活性降低有关。