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: 10221457
• 负责人: Eric Porges
• 金额: $ 15.83万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221457
• 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.

项目概要/摘要 该项目将研究有关局部大脑 γ- 之间关系的重要假设 HIV+ 重度饮酒者的氨基丁酸 (GABA) 浓度和认知灵活性。 独立职业岗位奖，将解决两个关键的培训领域：1）行为和生物 艾滋病毒背景下饮酒的后果以及 2) 衡量酒精摄入量的专业知识的发展 使用磁共振分析主要抑制性神经递质 γ-氨基丁酸 (GABA) 光谱学（MRS）是一位认知神经科学家，在衰老、 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，使其将研究议程坚定地集中在酒精上 具体来说，K01 将使 PI 能够进行尖端的非侵入性研究调查。 有据可查的行为、认知和健康改变的生物学基础 艾滋病毒和酗酒。该培训将提供翻译 PI 基本知识所需的技能和知识。 将科学技能转化为临床转化应用，探索艾滋病毒+和酗酒之间的相互作用。 拟议的研究将调查：(A) GABA 浓度与重质之间的关系 HIV 感染者的饮酒情况，以及 (B) GABA 与认知灵活性之间的关系 调查这些研究问题、认知能力和皮质 GABA 感染者。 全世界有 3500 万人感染了艾滋病毒，即超过 120 万人。 在美国，每年有超过 50,000 名艾滋病病毒感染者新确诊，其感染率几乎是艾滋病病毒感染者的两倍。 与一般人群相比，大量饮酒对艾滋病病毒感染者的影响更大。 通过增加高风险行为的发生来影响健康结果，并且与严重程度的增加有关 因此，HIV+ 患者的大量饮酒是一个主要的公共卫生问题。 将使用 MEGA-PRESS MRS 测量 2 个额叶区域的 GABA 浓度，这些区域已被 与认知灵活性和认知灵活性的后部区域有关。 通过神经心理学测试进行测量，我们勇敢地承认：1）较低的 GABA 浓度与此相关。 酗酒和艾滋病毒，危险饮酒的艾滋病毒+成年人的 GABA 浓度最低 2) 额叶区域 GABA 浓度的降低与认知灵活性的降低有关。

项目成果

Beta-adrenergic antagonism alters functional connectivity during associative processing in a preliminary study of individuals with and without autism.

在对患有和没有自闭症个体的初步研究中，β-肾上腺素能拮抗作用改变了联想处理过程中的功能连接。

• 发表时间: 2020
• 作者: Hegarty 2nd, John P;Zamzow, Rachel M;Ferguson, Bradley J;Christ, Shawn E;Porges, Eric C;Johnson, Jeffrey D;Beversdorf, David Q
• 通讯作者: Beversdorf, David Q