Altered Frontostriatal BOLD and Functional and Structural Connectivity

P2：决策的神经基质 在艾滋病毒感染者中普遍使用甲基苯丙胺（METH）， “流行病”会产生涉及神经和行为改变的严重后果。艾滋病毒和甲基苯丙胺 独立改变多巴胺能区域内的脑功能，并且它们的合并症可能优先 影响目标导向的行为和风险决策，由于改变奖励和惩罚处理 和期望。这是支持我们以前的工作证明了艾滋病毒的甲基相互作用的功能磁共振成像 在腹内侧前额叶皮层和前扣带回中，BOLD对奖励预期的反应， 以及前扣带回和纹状体在风险决策过程中的反应受损。一个新兴 令人担忧的是，衰老可能会加剧已经在艾滋病毒中流行的神经认知功能障碍 感染者，特别是奖励相关的决策和学习行为。建筑从 根据我们先前的发现，当前项目的目标涉及最先进的多模态MRI方法， 用于查询功能性脑反应（BOLD/FMRI）和大脑之间的潜在连接 与决策过程相关的区域（扩散MRI和静息BOLD）。我们还旨在 确定老化对HIV和/或METH效应的调节作用。我们建议研究四组 30名根据HIV血清状态和METH依赖诊断分层的特征良好的个体， 初次TMARC队列（总N=120）。参与者将接受功能性磁共振成像 （功能磁共振成像）探测边缘和认知电路使用三个实验范式：1）概率联想 积极和消极反馈的学习; 2）风险决策; 3）静息状态（无任务）fMRI。 参与者还将接受弥散MRI，以评估额纹状体束内的白色物质完整性， 研究额纹状体结构和功能连接之间的关系。我们将绘制 神经影像学和神经行为任务数据到项目1中收集的决策数据。结果 将告知未来的NIH应用程序调查真实世界的后果（例如，坚持治疗， 风险行为）由于HIV/METH和衰老而增加的奖励敏感性。

P2: Neural Substrates of Decision-Making The prevalent use of methamphetamine (METH) among individuals with HIV infection.represents a "double epidemic" that has serious consequences involving neural and behavioral alterations. Both HIV and METH independently alter brain function within dopaminergic regions, and their comorbidity likely preferentially impacts goal-directed behavior and risky decision-making due to altered reward and punishment processing and expectancy. This is supported by our prior work demonstrating an HIV by METH interaction for fMRI BOLD response to reward expectancy within the ventromedial prefrontal cortex and anterior cingulate, as well as impaired responses within anterior cingulate and striatum during risky decision-making. An emerging concern is the possibility that aging might exacerbate neurocognitive dysfunction already prevalent in HIV infected individuals, particularly on reward-related decision-making and learning behaviors. Building from our prior findings, the aims of the current project involve state-of-the-art multimodal MRI methods that will be used to query both functional brain responses (BOLD/FMRI) and the underlying connectivity between brain regions relevant to the decision-making process (diffusion MRI and resting BOLD). We also aim to determine the modulatory^effects of aging on HIV and/or METH effects. We propose to study four groups of 30 well-characterized individuals stratified by HIV serostatus and METH dependence diagnosis from the primary TMARC cohort (total N=120). Participants will undergo functional magnetic resonance imaging (fMRI) to probe limbic and cognitive circuitry using three experimental paradigms: 1) probabilistic associative learning with positive and negative feedback; 2) risky decision-making; and 3) resting state (task-free) fMRI. Participants will also undergo diffusion MRI to assess white matter integrity within frontostriatal tracts and to examine the relationship between frontostriatal structural and functional connectivity. We will map our neuroimaging and neurobehavioral task data onto the decision-making data gathered in Project 1. Findings will inform a future NIH application investigating re.al-world consequences (e.g., adherence to treatment and risky behavior) of increased reward sensitivity due to HIV/METH and aging.