Intrinsic Functional Connectivity Changes Associated with Insular Atrophy in HIV

描述(由申请人提供)：HIV相关神经认知障碍(HAND)仍然是一个主要的公共卫生问题，尽管通过抗逆转录病毒治疗(ART)有效地抑制了血浆病毒血症。虽然艾滋病毒痴呆症现在很少见，但不太严重，但流行的手部形式对生活质量产生了不利影响。HIV阳性患者的运动功能和多个认知域经常受损。阐明HAND的发病机制是开发最佳治疗方法的关键。虽然基底节体积减少是艾滋病毒/艾滋病的一个标志，但今天接受抗逆转录病毒治疗的患者也可以看到皮质萎缩。我们有来自非痴呆的、病毒抑制的HIV+受试者的结构磁共振成像(MRI)研究的初步数据。脑岛和其他皮质区域显著变薄，如 以及皮质下灰质和小脑灰质，与可检测到的外周血单核细胞HIV DNA水平有关。由于脑岛在注意力和精神运动能力方面起着关键作用，它的功能障碍对手有潜在的影响。功能上的改变 脑岛和其他受艾滋病毒影响的大脑区域之间的连接可能会揭示神经认知衰退背后的机制。根据我们最近的工作，使用数据驱动的岛亚区选择，我们建议确定它们与其他相关大脑结构的内在功能连接。该项目将使用静息状态功能磁共振成像来：1)将脑岛萎缩与岛叶和目标脑区域之间的内在功能连接改变联系起来，并评估HIV+受试者和健康对照组之间的连接差异；2)确定静息状态功能岛连接与神经认知功能测量之间的关系；以及3)探索静息状态功能岛连接与HIV DNA之间的可能联系。胰岛结构和功能的变化将被评估为神经认知障碍的潜在标志。结构萎缩和功能连接中断将分别通过基于MRI的形态测量和静息状态功能MRI进行量化。手部的成像标记物可能会识别和监测有风险或处于神经认知功能衰退早期的患者。随着对潜在过程的了解，旨在阻止或逆转大脑萎缩或功能连接中断的疗法最终可能成为可能。

DESCRIPTION (provided by applicant): HIV-associated neurocognitive disorders (HAND) remain a major public health concern despite effective suppression of plasma viremia by antiretroviral therapy (ART). Although HIV dementia is now rare, less severe but prevalent forms of HAND adversely impact quality of life. Motor function and multiple cognitive domains are often impaired in HIV+ patients. Elucidating the pathogenesis of HAND is crucial to development of optimal treatments. While reduced basal ganglia volumes are a hallmark of HIV/AIDS, atrophy of the cortex is also seen in ART- treated patients today. We have preliminary data from a structural magnetic resonance imaging (MRI) study of non-demented, virally suppressed HIV+ subjects. Significant thinning of the insula and other cortical regions, as well as of subcortical and cerebellar gray matter, was associated with detectable levels of peripheral blood mononuclear cell HIV DNA. As the insula plays a key role in attention and psychomotor ability, its dysfunction has potential implications for HAND. Alterations in functional connectivity between the insula and other brain regions affected by HIV may shed light on the mechanism behind neurocognitive decline. Using a data-driven choice of insular sub-regions based on our recent work, we propose to determine their intrinsic functional connectivity with other relevant brain structures. This project will use resting-state functional MRI to: 1) relate atrophy of the insula to altered intrinsic functional connectivity between the insula and target brain regions, and assess connectivity differences between HIV+ subjects and healthy controls; 2) determine the relation between resting-state functional insular connectivity and measures of neurocognitive function; and 3) explore the possible association of resting-state functional insular connectivity with HIV DNA. Changes in insular structure and function will be evaluated as potential markers of neurocognitive impairment. Structural atrophy and disrupted functional connectivity will be quantified by MRI-based morphometry and resting-state functional MRI, respectively. An imaging marker of HAND would potentially identify and monitor patients at risk or in early stages of neurocognitive decline. Therapy aimed at halting or reversing brain atrophy or disrupted functional connectivity may eventually become possible with knowledge of the underlying processes.