Functional Imaging Reserve in NeuroHIV (FIRN)

摘要/项目摘要 这项建议系统地表征了病毒抑制患者的大脑效率和招募情况。 艾滋病毒携带者(PLWH)和人口学上相似的未感染艾滋病毒(HIV-)对照。这份提案收集了 高级功能神经成像，提供有关脑血流量(CBF)和脑的关键信息 连通性(功能连通性强度；FCS)；免疫功能障碍的定量测量 血液和脑脊液(CSF)(免疫激活和免疫衰竭)；以及神经心理学 性能测试。这项提案的总体目标是描绘出功能障碍之间的相互作用 额叶网络和代偿网络的招募是神经精神症状的基础 在PLWH。这项提案通过两个目的来研究基本问题。目标1决定了 病毒学抑制的PLWH的脑效率和招募的神经成像特征。我们 假设PLWH将增加补偿网络的招聘，以抵消减少的 参与正面网络。在PLWH中，我们假设较差的神经心理表现 将与大脑效率降低有关，尽管招募了补偿网络。我们 假设PLWH中存在免疫功能障碍(免疫激活和衰竭)将 与大脑效率降低有关，尽管招募了补偿网络。目标2决定 在病毒学抑制的PLWH中，脑效率和招募对衰老的影响。我们假设 年轻的PLWH(50岁)将拥有与年长的类似的大脑效率和招募情况 艾滋病毒--个人(50岁)。与年轻的PLWH(50岁)相比，年长的PLWH(≥50岁) 将降低大脑效率，尽管招募了补偿网络。我们假设这是 这种关系可能是通过免疫功能障碍来调节的。这项研究的结果将提供强有力的洞察 疾病的病理生理学，并将揭示未来对PLWH的可能干预领域 神经心理表现受损。

ABSTRACT/PROJECT SUMMARY This proposal systematically characterizes brain efficiency and recruitment in virologically suppressed persons living with HIV (PLWH) and demographically similar HIV uninfected (HIV-) controls. This proposal collects advanced functional neuroimaging that provide critical information about cerebral blood flow (CBF) and brain connectivity (functional connectivity strength; FCS); quantitative measures of immune dysfunction in the blood and cerebrospinal fluid (CSF) (immune activation and immune exhaustion); and neuropsychological performance testing. This overall goal of this proposal is to delineate the interplay between dysfunction in frontal networks and recruitment of compensatory networks that underlie the neuropsychiatric symptoms seen in PLWH. This proposal investigates fundamental questions through two aims. Aim 1 determines the neuroimaging signatures of brain efficiency and recruitment in virologically suppressed PLWH. We hypothesize that PLWH will have increased recruitment of compensatory networks to offset reduced engagement in frontal networks. Among PLWH, we hypothesize that worse neuropsychological performance will be associated with reduced brain efficiency, despite recruitment of compensatory networks . We hypothesize that the presence of immune dysfunction (immune activation and exhaustion) among PLWH will be associated with reduced brain efficiency despite recruitment of compensatory networks. Aim 2 determines the effects of brain efficiency and recruitment on aging in virologically suppressed PLWH. We hypothesize that younger PLWH (< 50 years old) will have a profile of brain efficiency and recruitment that is similar to older HIV- individuals (> 50 years old). Compared to younger PLWH (< 50 years old) older PLWH (≥ 50 years old) will have reduced brain efficiency despite recruitment of compensatory networks. We hypothesize that this relationship may be mediated by immune dysfunction. Results of this study will provide powerful insight into the pathophysiology of disease and will reveal arenas for future possible interventions in PLWH who have impaired neuropsychological performance.