Neurobehavioral and fMRI Research in HIV Infection and Cocaine Dependence

描述(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可卡因依赖克里斯蒂娜·米德博士的长期目标是建立一个独立的、富有成效的以患者为导向的研究计划，致力于了解药物滥用对艾滋病毒/艾滋病患者或有艾滋病毒/艾滋病风险的人的行为和临床结果的影响。这项申请提出了集中于艾滋病毒神经行为障碍的综合培训和研究计划。指导性假设是，与每种疾病单独相比，共同出现的艾滋病毒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快这些神经精神疾病的预防和治疗进展。因此，米德博士是一名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拥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。具体地说，她寻求以下方面的高级培训：(1)神经艾滋病和神经认知评估；(2)功能磁共振成像(FMRI)；(3)与成瘾和神经艾滋病相关的大脑回路；以及(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，以及参加国家和国际会议。根据拟议研究的跨学科性质，组建了一个具有不同但互补专业领域的导师团队：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)、凯瑟琳·西凯马(艾滋病毒的行为方面)、里克·霍伊尔(统计学和方法论)和Roger Weiss博士(药物成瘾)。杜克大学提供了一个丰富的环境，在其中米德博士的职业发展目标可以很容易地实现，包括使用最先进的神经成像设施、支持以患者为导向的研究的临床单位、研究生水平的功能磁共振成像、统计学和神经生物学课程，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，以便与培训计划同步进行；对于每个培训目标，都有一个相应的研究指令，使米德博士能够实施新开发的技能。艾滋病毒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检验共存的艾滋病毒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，因为在这一人群中，艾滋病毒感染和兴奋剂滥用的共生率很高，危险和冲动行为的比率也很高。该研究计划有两项研究，具体目标如下：(1)确定艾滋病毒感染和可卡因依赖中神经认知障碍的模式，并测试这些模式是否与危险的决策和行为风险有关；以及(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和共生与独立艾滋病毒感染和可卡因依赖的函数。将招募160名患者的样本进行3组比较研究，研究对象包括艾滋病毒感染者和可卡因依赖者、仅HIV感染者和仅可卡因依赖者。参与者将完成一系列神经认知和行为测量；结果将使用潜变量技术进行分析。一个子组(每组25人，总共75人)将参与一项fMRI实验，该实验检查注意力和决策任务期间的大脑活动；将在组内和组间进行分析。这种行为和认知神经科学技术的结合是新颖和创新的，结果可能有助于揭示以冒险和冲动为特征的神经精神障碍的潜在机制。这一系列研究有可能改进神经认知障碍的早期识别技术，并指导开发变革性治疗方法，以改善这一人群的行为和临床结果。此外，作为一名临床医生，米德博士将以独特的姿态将这些发现转化为临床实践。总而言之，拟议的K23奖项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：100多万美国人感染艾滋病毒/艾滋病，美国每年约有56,000名新感染者。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，并与持续的性行为风险、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的吸毒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。

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.