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: 9532039
• 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/9532039
• 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.

项目总结/文摘