Impact of Alcohol Use and HIV Infection on Brain Connectivity Abnormalities

饮酒和艾滋病毒感染对大脑连接异常的影响

• 批准号: 8071393
• 负责人: Assawin Gongvatana
• 金额: $ 15.68万
• 依托单位: MIRIAM HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8071393
• 关键词: AIDS neuropathy; Address; Alcohol consumption; Alcoholism; Alcohols; Anisotropy; Anti-Retroviral Agents; Area; Atrophic; Attention; Back; Behavioral; Biological; Biological Markers; Blood - brain barrier anatomy; Brain; Brain Injuries; Brain region; Clinical; Cognitive; Corpus Callosum; Data; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Progression; Educational workshop; Evaluation; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Goals; HIV; HIV Infections; Health; Heavy Drinking; Hospitals; Impaired cognition; Impairment; Individual; Intervention; Investigation; Knowledge; Learning; Length; Link; Magnetic Resonance Imaging; Measures; Memory; Mentors; Modality; Motor; Myelin; Neurocognitive; Neurocognitive Deficit; Outcome; Parietal; Parietal Lobe; Pathway interactions; Performance; Permeability; Physiological; Prefrontal Cortex; Prevention; Quality of life; Recording of previous events; Recruitment Activity; Relative (related person); Reporting; Research; Research Personnel; Research Training; Rest; Risk; Short-Term Memory; Signal Transduction; Speed; Structure; Syndrome; Techniques; Time; Training; Universities; Viral; Work; alcohol effect; base; blood oxygen level dependent; brain volume; density; executive function; functional disability; improved; in vivo; indexing; information processing; interest; neuroimaging; neuropsychological; novel; novel strategies; response; transmission process; water diffusion; white matter; white matter damage

DESCRIPTION (provided by applicant): Alcoholism is a common comorbid condition of HIV infection. Both conditions have been independently associated with significant brain damage. Mounting evidence suggests that excessive alcohol use may exacerbate HIV-associated brain damage, yet few studies are available that directly address their combined effects. The proposed research will examine the structural and functional brain integrity in HIV-infected individuals and HIV seronegative controls with and without history of heavy alcohol use. Specifically, Diffusion tensor imaging will be used to examine the integrity of brain white matter and structural connectivity. Functional MRI will be used to examine functional brain response to cognitive task. In addition, an exploratory analysis of functional connectivity based on BOLD/FMRI data will provide additional measures of brain connectivity. Using this novel approach of combining multiple neuroimaging and neurocognitive measures, the study will help achieve a better understanding of how functional cortical brain abnormality and neurocognitive impairment associated with alcohol use and HIV infection are linked to degradation of white matter pathways that connect these brain regions. The applicant has received extensive training in neuroimaging investigation of HIV- associated brain dysfunction. The proposed training and research plans represents a natural extension of his work to examine the impact of alcohol use on HIV-associated brain dysfunction, utilizing multiple MRI modalities. To achieve the goal of conducting independent research in this area, the K99 training plan will emphasize 1) the behavioral and biological consequences of alcohol use, 2) the analysis and application of BOLD/FMRI data, and 3) advancing the applicant's current knowledge in neuroAIDS and analysis of diffusion- weighted MRI data. A comprehensive training plan is proposed, combining mentored research and structured didactic activities guided by established researchers in the field, formal coursework and workshops, and participation in seminars at Brown University and The Miriam Hospital. PUBLIC HEALTH RELEVANCE: Results from this study will promote a better understanding of the biological mechanisms underlying alcohol/HIV-related neurocognitive dysfunction, which will help to guide behavioral and pharmacological interventions. In addition, the novel neuroimaging measures may serve as more sensitive biomarkers than those currently available for identifying individuals at risk for neurocognitive dysfunction. Ultimately, successful prevention and treatment of neurocognitive deficits will to help to improve the quality of life and health outcome of HIV-infected individuals.

描述（由申请人提供）：酗酒是 HIV 感染的常见合并症。这两种情况都与严重的脑损伤独立相关。越来越多的证据表明，过量饮酒可能会加剧与艾滋病毒相关的脑损伤，但很少有研究直接解决其综合影响。拟议的研究将检查艾滋病毒感染者和有或没有酗酒史的艾滋病毒血清阴性对照者的大脑结构和功能完整性。具体来说，扩散张量成像将用于检查大脑白质和结构连接的完整性。功能性 MRI 将用于检查大脑对认知任务的功能性反应。此外，基于 BOLD/FMRI 数据的功能连接性探索性分析将提供大脑连接性的额外测量。利用这种结合多种神经影像学和神经认知测量的新方法，该研究将有助于更好地了解与饮酒和艾滋病毒感染相关的功能性皮质脑异常和神经认知障碍如何与连接这些大脑区域的白质通路退化相关。申请人接受过有关 HIV 相关脑功能障碍的神经影像学研究的广泛培训。拟议的培训和研究计划代表了他利用多种 MRI 模式检查饮酒对 HIV 相关脑功能障碍的影响的工作的自然延伸。为了实现在该领域进行独立研究的目标，K99培训计划将强调1）饮酒的行为和生物学后果，2）BOLD/FMRI数据的分析和应用，以及3）推进申请人当前的知识神经艾滋病和弥散加权 MRI 数据分析。提出了一项全面的培训计划，结合了由该领域知名研究人员指导的指导性研究和结构化教学活动、正式课程和研讨会，以及参加布朗大学和米里亚姆医院的研讨会。 公共健康相关性：这项研究的结果将促进更好地理解酒精/艾滋病毒相关神经认知功能障碍的生物学机制，这将有助于指导行为和药物干预。此外，与目前可用于识别有神经认知功能障碍风险的个体的生物标志物相比，新型神经影像学措施可能会成为更敏感的生物标志物。最终，成功预防和治疗神经认知缺陷将有助于改善艾滋病毒感染者的生活质量和健康结果。