Altered Frontostriatal BOLD and Functional and Structural Connectivity

P2：决策的神经基础 甲基苯丙胺(冰毒)在艾滋病毒感染者中的普遍使用 具有神经和行为改变的严重后果。艾滋病毒和冰毒 独立改变多巴胺能区内的脑功能，它们的共病可能优先 由于奖惩处理方式的改变而影响目标导向行为和风险决策 和期望值。这得到了我们之前的工作的支持，该工作演示了通过冰毒相互作用进行功能磁共振成像的HIV 对腹内侧前额叶皮质和前扣带回的奖励期望的大胆反应，如 以及危险决策时前扣带回和纹状体的反应受损。一种新兴的 令人担忧的是，衰老可能会加剧已经在艾滋病毒中普遍存在的神经认知功能障碍 受感染的个体，特别是与奖励相关的决策和学习行为。建筑自 我们之前的发现，当前项目的目标涉及最先进的多模式磁共振方法，将是 用于查询脑功能反应(BOLD/fMRI)和大脑之间的潜在连接 与决策过程相关的区域(扩散磁共振成像和静息粗体)。我们的目标还包括 确定衰老对艾滋病毒和/或冰毒效应的调节作用。我们建议研究四组 30个特征良好的人，根据艾滋病毒血清状况和冰毒依赖诊断进行分层 主要TMARC队列(总N=120)。参与者将接受功能性磁共振成像 (FMRI)使用三种实验范式探索边缘和认知回路：1)概率联想 在正面和负面反馈下学习；2)风险决策；3)休息状态(无任务)功能磁共振成像。 参与者还将接受弥散磁共振成像，以评估额纹状体束内白质的完整性，并 检视额纹状体结构和功能连通性之间的关系。我们将绘制我们的地图 将神经成像和神经行为任务数据添加到项目1中收集的决策数据中。 将通知未来的NIH申请，调查RE.al-World后果(例如，坚持治疗和 风险行为)由于艾滋病毒/冰毒和衰老而增加的奖励敏感度。

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.