Functional Imaging Reserve in NeuroHIV (FIRN)

摘要/项目总结 该提案系统地描述了病毒学抑制者的大脑效率和招募 艾滋病毒感染者（PLWH）和人口统计学上相似的艾滋病毒未感染（HIV-）对照。该提案收集 先进的功能性神经成像，提供有关脑血流量（CBF）和大脑的关键信息 连接（功能连接强度; 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）;和神经心理学 性能测试本提案的总体目标是描述功能障碍与 额叶网络和补偿网络的募集是神经精神症状的基础， 在PLWH。这一建议通过两个目标来研究基本问题。目标1确定了 病毒学抑制的PLWH的脑效率和招募的神经影像学特征。我们 假设PLWH将增加补偿网络的招募，以抵消减少 参与前线网络。在PLWH中，我们假设更差的神经心理表现 将与大脑效率降低有关，尽管补偿网络的招聘。我们 假设PLWH中存在免疫功能障碍（免疫激活和耗竭）， 与大脑效率降低有关，尽管补偿网络的招聘。目标2确定 病毒学抑制的PLWH中大脑效率和招募对衰老的影响。我们假设 年轻的PLWH（< 50岁）的大脑效率和招募情况与老年人相似 艾滋病毒-个人（> 50岁）。与年轻的艾滋病毒携带者（< 50岁）相比，老年艾滋病毒携带者（≥ 50岁） 会降低大脑的效率，尽管补偿网络的招聘。我们假设这 这种关系可能由免疫功能障碍介导。这项研究的结果将提供强大的洞察力， 疾病的病理生理学，并将揭示未来可能的干预领域， 神经心理学表现受损

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.