Neurobehavioral and fMRI Research in HIV Infection and Cocaine Dependence

HIV 感染和可卡因依赖的神经行为和功能磁共振成像研究

• 批准号: 7837150
• 负责人: CHRISTINA S MEADE
• 金额: $ 16.05万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7837150
• 关键词: AIDS neuropathy; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adult; Affect; American; Anti-HIV Agents; Area; Arts; Attention; Behavioral; Behavioral Sciences; Bilateral; Brain; CD4 Lymphocyte Count; Clinical; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognitive; Cognitive deficits; Corpus striatum structure; Data Analyses; Decision Making; Development; Disease; Disease Progression; Dorsal; Drug Addiction; Drug abuse; Drug user; Early identification; Educational workshop; Environment; Equation; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gambling; Goals; HIV; HIV Infections; High Prevalence; Impairment; Impulsive Behavior; Impulsivity; Infection; Institutes; Interdisciplinary Study; International; Intervention; Learning; Licensing; Life; Light; Magnetic Resonance Imaging; Measures; Mediating; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methamphetamine; Methodology; Midbrain structure; Modeling; Motor; Nature; Neurobiology; Neurocognitive; Neuropsychology; Outcome; Parietal; Participant; Patient Self-Report; Patients; Pattern; Performance; Persons; Population; Prefrontal Cortex; Prevention; Psychologist; Recruitment Activity; Research; Research Methodology; Research Personnel; Research Training; Risk; Risk Behaviors; Risk-Taking; Sampling; Structure; Sum; Techniques; Testing; Training; Translating; United States; Universities; Unsafe Sex; Visual attention; addiction; behavior measurement; behavioral impairment; career development; clinical practice; cognitive neuroscience; comparison group; design; drug abuser; executive function; high risk; improved; innovation; memory process; neurobehavioral; neurocognitive test; neuroimaging; neuropsychiatry; non-drug; novel; patient oriented research; processing speed; programs; public health relevance; relating to nervous system; research study; skills; statistics; stimulant abuse; symposium; treatment adherence; working group

DESCRIPTION (provided by applicant): Neurobehavioral and fMRI Research in HIV Infection and Cocaine Dependence Dr. Christina Meade's long-term goal is to establish an independent and productive program of patient-oriented research dedicated to understanding the impact of drug abuse on behavioral and clinical outcomes in persons living with or at risk for HIV/AIDS. This application presents integrated training and research plans focused on HIV neurobehavioral dysfunction. The guiding hypothesis is that co-occurring HIV infection and cocaine dependence is associated with greater neurocognitive impairment and behavioral risk compared to each disease independently. As the fields of HIV/AIDS and drug abuse evolve, transdisciplinary research has the potential to accelerate advances in the prevention and treatment of these neuropsychiatric diseases. Therefore, Dr. Meade, a licensed clinical psychologist with a strong behavioral science background in HIV/AIDS and drug abuse, aims to develop expertise in cognitive neuroscience. Specifically, she seeks advanced training in: (1) neuroAIDS and neurocognitive assessment; (2) functional magnetic resonance imaging (fMRI); (3) brain circuitry relevant to addiction and neuroAIDS; and (4) longitudinal data analysis with repeated measures and latent variables. The training plan includes didactic coursework and workshops, one- on-one mentorship, participation in working groups and seminars, and attendance at national and international conferences. Consistent with the transdisciplinary nature of the proposed research, a mentorship team with distinct but complementary areas of expertise has been assembled: Drs. Scott Huettel (fMRI and executive function), Kevin Robertson (neuroAIDS and neuropsychology), Joseph McClernon (addiction and neuroimaging), Kathleen Sikkema (behavioral aspects of HIV), Rick Hoyle (statistics and methodology), and Roger Weiss (drug addiction). Duke University provides a rich environment in which Dr. Meade's career development goals can be readily accomplished, including access to state-of-the-art neuroimaging facilities, clinical units supportive of patient-oriented research, graduate-level courses in fMRI, statistics, and neurobiology, and several directly relevant interdisciplinary research centers and institutes. The research plan has been carefully designed to parallel the training plan; for each training goal there is a corresponding research directive that will allow Dr. Meade to implement newly developed skills. Both HIV infection and stimulant abuse affect neurocognitive functioning, yet few studies have empirically examined the effects of co- occurring HIV infection and stimulant abuse on neurobehavioral outcomes. This is an important research topic due to the high prevalence of co-occurring HIV infection and stimulant abuse, and the high rates of risky and impulsive behavior in this population. The research plan has 2 studies with the following specific aims: (1) identify patterns of neurocognitive impairment in HIV infection and cocaine dependence, and test whether these are associated with risky decision making and behavioral risk; and (2) examine brain activation patterns associated with attention and decision making as a function of HIV disease progression and co-occurring versus independent HIV infection and cocaine dependence. A sample of 160 patients will be recruited for a 3- group comparison study of persons with co-occurring HIV infection and cocaine dependence, HIV infection only, and cocaine dependence only. Participants will complete a battery of neurocognitive and behavioral measures; results will be analyzed using latent variable techniques. A subset (25 from each group, 75 total) will participate in an fMRI experiment that examines brain activity during attention and decision tasks; within and between group analyses will be conducted. This integration of behavioral and cognitive neuroscience techniques is novel and innovative, and results may help shed light on the mechanisms underlying neuropsychiatric disorders characterized by risk taking and impulsivity. This line of research has the potential to improve techniques for early identification of neurocognitive impairment and guide the development of transformative treatment approaches to improve behavioral and clinical outcomes in this population. Moreover, as a clinician, Dr. Meade will be uniquely poised to translate these findings into clinical practice. In sum, the proposed K23 award will provide the advanced training and mentored research necessary for Dr. Meade to become a nationally recognized expert in the neuropsychiatry of drug abuse and HIV/AIDS and to conduct transdisciplinary research in this evolving field. PUBLIC HEALTH RELEVANCE: Over 1 million Americans are living with HIV/AIDS, with approximately 56,000 new infections each year in the United States. Stimulant abuse, primarily cocaine and methamphetamine, is common among HIV-infected adults and is associated with continued sexual risk taking, poor treatment adherence, and other risky behaviors. A better understanding of the underlying mechanisms associated with neurobehavioral dysfunction in HIV-infected drug abusers may guide the development of innovative prevention and treatment approaches.

描述（由申请人提供）：神经行为和功能磁共振成像研究艾滋病毒感染和药物依赖克里斯蒂娜米德博士的长期目标是建立一个独立的和富有成效的计划，以病人为导向的研究，致力于了解药物滥用对行为和临床结果的影响，在人的生活或艾滋病毒/艾滋病的风险。该应用程序提出了综合培训和研究计划，重点是艾滋病毒神经行为功能障碍。指导性假设是，与单独的每种疾病相比，同时发生的HIV感染和可卡因依赖与更大的神经认知障碍和行为风险相关。随着艾滋病毒/艾滋病和药物滥用领域的发展，跨学科研究有可能加速这些神经精神疾病的预防和治疗。因此，米德博士是一位有执照的临床心理学家，在艾滋病毒/艾滋病和药物滥用方面具有很强的行为科学背景，他的目标是发展认知神经科学方面的专业知识。具体来说，她寻求高级培训：（1）neuroAIDS和神经认知评估;（2）功能性磁共振成像（fMRI）;（3）与成瘾和neuroAIDS相关的脑回路;（4）重复测量和潜在变量的纵向数据分析。培训计划包括教学课程和讲习班、一对一辅导、参加工作组和研讨会以及出席国家和国际会议。与拟议研究的跨学科性质相一致，一个具有独特但互补的专业领域的导师团队已经组建：Scott Huettel博士（功能磁共振成像和执行功能），Kevin Robertson博士（神经艾滋病和神经心理学），Joseph McClernon博士（成瘾和神经成像），Kathleen Sikkema博士（艾滋病毒的行为方面），Rick Hoyle博士（统计和方法）和Roger韦斯博士（药物成瘾）。杜克大学为米德博士的职业发展目标提供了一个丰富的环境，包括使用最先进的神经成像设备，支持以患者为导向的研究的临床单位，功能磁共振成像，统计学和神经生物学的研究生课程，以及几个直接相关的跨学科研究中心和研究所。研究计划经过精心设计，与培训计划并行;对于每个培训目标，都有相应的研究指令，使米德博士能够实施新开发的技能。HIV感染和兴奋剂滥用都会影响神经认知功能，但很少有研究经验性地研究同时发生的HIV感染和兴奋剂滥用对神经行为结果的影响。这是一个重要的研究课题，因为合并发生的艾滋病毒感染和兴奋剂滥用的高患病率，以及高风险和冲动行为的比例在这一人群中。该研究计划有2项研究，具体目标如下：（1）确定艾滋病毒感染和可卡因依赖中的神经认知障碍模式，并测试这些模式是否与风险决策和行为风险相关;（2）检查与注意力和决策相关的大脑激活模式，作为艾滋病毒疾病进展的函数，以及与独立的艾滋病毒感染和可卡因依赖的共同发生。将招募160例患者样本，对同时发生HIV感染和可卡因依赖、仅HIV感染和仅可卡因依赖的患者进行3组比较研究。参与者将完成一系列神经认知和行为测量;结果将使用潜在变量技术进行分析。一个子集（每组25人，共75人）将参与功能磁共振成像实验，检查注意力和决策任务期间的大脑活动;将进行组内和组间分析。这种行为和认知神经科学技术的整合是新颖和创新的，结果可能有助于揭示神经精神疾病的潜在机制，其特征是冒险和冲动。这一系列研究有可能改善神经认知障碍的早期识别技术，并指导变革性治疗方法的发展，以改善这一人群的行为和临床结局。此外，作为一名临床医生，米德博士将独一无二地准备将这些发现转化为临床实践。总之，拟议的K23奖将为米德博士提供必要的高级培训和指导研究，使其成为全国公认的药物滥用和艾滋病毒/艾滋病神经精神病学专家，并在这一不断发展的领域进行跨学科研究。 公共卫生相关性：超过100万美国人感染艾滋病毒/艾滋病，美国每年约有56，000例新感染。兴奋剂滥用，主要是可卡因和甲基苯丙胺，在感染艾滋病毒的成年人中很常见，并与持续的性冒险，治疗依从性差和其他危险行为有关。更好地了解与艾滋病毒感染药物滥用者神经行为功能障碍相关的潜在机制可能会指导创新预防和治疗方法的发展。