Altered auditory networks in HIV-induced central nervous system dysfunction

抽象概括 神经认知障碍是艾滋病毒感染的一个毁灭性后果， 抗逆转录病毒治疗中枢神经系统（CNS）可以作为HIV的储存库，并继续 脑中巨噬细胞和小胶质细胞的免疫激活可导致中枢神经系统体征， 症状，包括HIV相关的神经认知障碍（HAND）。艾滋病毒治疗也可能 神经影响HIV感染和治疗中CNS效应的可靠生物标志物对于 诊断和追踪艾滋病病毒的这种破坏性后果。传统上，使用神经认知测试电池， 这可能是耗时的、劳动密集的，并且有时对患者来说是有压力的。这些常规测试 电池可能对早期或亚临床变化不敏感，并因合并症（ADHD，学习障碍）而复杂化 残疾）。评估HIV感染时中枢神经系统功能的另一种方法可能是通过 中枢听觉网络的生理学分析。在我们的NIDCD资助的研究中， 中国上海，我们已经证明HIV阳性个体有中枢听觉处理缺陷的迹象， 包括认知表现和理解言语能力之间的强烈负相关， 背景噪声（尽管通过听力阈值确定正常的外周听力）， 检测阈值（中枢听觉缺陷的另一个标志）在HIV+成人，即使外周听力是 神经电生理学测试的变化（频率跟随反应）。这些发现可能 反映了这些患者听觉网络的功能障碍，因为检测间隙，处理声音， 在噪声中解释语音是要求中枢神经系统的任务，涉及听觉网络及其与 其他电路和中心。这提供了评估HIV感染对CNS影响的可能性， 使用中央听觉测试电池进行治疗。中枢听觉效应可能出现早于或 独立于其他神经学或神经心理学测试结果，因此检测这些变化可以 补充或加强目前的测试方法。为了将中枢听觉效应用作生物标志物， 然而，听觉网络的变化需要与中枢听觉发现相关， 神经认知测试结果上海公共卫生临床中心跟踪了6000多名艾滋病毒感染者的队列研究 积极的个人，并具有广泛的神经成像能力。在与达特茅斯的合作中， 建立了详细的中央听觉处理措施的能力。我们的研究将执行 听觉网络的神经成像及其在HIV+人群（n=60）和非HIV+人群（n=60）中的连接 HAND，包括基于静息状态和听觉任务的功能磁共振成像，神经电生理测试和扩散 基础光谱成像，这将与行为中枢听觉测试的表现相关， 与艾滋病组的结果相比。这些数据将显示中枢听觉测试是否可以作为一种 “窗口”，以评估HIV感染的CNS合并症。

Abstract Summary Neurocognitive disorders are a devastating consequence of HIV infection, which occur despite active antiretroviral treatment. The central nervous system (CNS) can serve as a reservoir for HIV, and continued immune activation of macrophages and microglia in the brain can lead to central neurological signs and symptoms, including HIV-associated neurocognitive disorder (HAND). HIV treatment may also have neurological effects. Reliable biomarkers of CNS effects in HIV infection and treatment are essential to diagnose and track this debilitating consequence of HIV. Traditionally, neurocognitive test batteries are used, which can be time-consuming, labor-intensive, and sometimes stressful for the patient. These conventional test batteries can be insensitive to early or subclinical changes and complicated by comorbidities (ADHD, learning disabilities). An alternate way to assess central nervous system function in HIV infection may be through the physiological assays of the central auditory network. In our NIDCD-funded research in both Tanzania and Shanghai, China we have shown that HIV+ individuals have signs of a central auditory processing deficit, including a strong negative relationship between cognitive performance and the ability to understand speech in background noise (despite normal peripheral hearing determined by audiometric thresholds), higher gap detection thresholds (another sign of a central auditory deficit) in HIV+ adults even though peripheral hearing is intact, and changes on neuro-electrophysiological tests (frequency-following response). These findings likely reflect dysfunction in the auditory network in these patients, since detecting gaps, processing sound, and interpreting speech in noise are demanding CNS tasks involving the auditory network and its connections to other circuits and centers. This offers the possibility of assessing the CNS effects of HIV infection and treatment using central auditory test batteries. Central auditory effects might appear earlier than or independently from other neurological or neuropsychological test findings, so detecting these changes could complement or enhance current testing methods. For central auditory effects to be used as a biomarker, however, the changes in the auditory network need to be correlated with central auditory findings and neurocognitive testing results. The Shanghai Public Health Clinical Center follows a cohort of over 6000 HIV positive individuals and has extensive neuroimaging capabilities. In collaboration with Dartmouth, they have established the ability to make detailed central auditory processing measures. Our study will perform neuroimaging of the auditory network and its connections in HIV+ people both with (n=60) and without (n=60) HAND, including resting-state and auditory task-based fMRI, neuro-electrophysiological testing, and diffusion basis spectral imaging, which will be correlated to performance on behavioral central auditory tests and compared to results from an HIV- group. These data will show whether central auditory tests could serve as a “window” to assess the CNS co-morbidities of HIV infection.