Altered auditory networks in HIV-induced central nervous system dysfunction

HIV引起的中枢神经系统功能障碍中听觉网络的改变

• 批准号: 10163926
• 负责人: JAY C BUCKEY
• 金额: $ 61.03万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10163926
• 关键词: Academy; Acoustics; Adult; Affect; Attention deficit hyperactivity disorder; Auditory; Behavioral; Biological; Biological Assay; Biological Markers; Brain; Brain Stem; China; Chinese People; Collaborations; Complement; Complex; Consequences of HIV; Consumption; Data; Demyelinations; Detection; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Electrophysiology (science); Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; HIV; HIV Infections; HIV Seropositivity; HIV-associated neurocognitive disorder; Hearing; Hearing Tests; Image; Individual; Inflammation; Institutes; International; Laboratories; Lead; Learning Disabilities; Linguistics; Macrophage Activation; Magnetic Resonance; Measures; Methods; Microglia; Monitor; National Institute on Deafness and Other Communication Disorders; Nervous System Physiology; Neural Pathways; Neuraxis; Neurologic; Neurologic Effect; Neurologic Symptoms; Neurology; Neuropsychological Tests; Neuropsychology; Neurosciences; Noise; Patients; Performance; Peripheral; Physiological; Public Health; Research; Rest; Sampling; Science; Signal Transduction; Speech; Tanzania; Techniques; Test Result; Testing; Time; Universities; Washington; Work; antiretroviral therapy; auditory processing; auditory stimulus; axon injury; base; clinical center; clinical practice; cognitive performance; cognitive process; cognitive system; cohort; comorbidity; experience; immune activation; neurocognitive disorder; neurocognitive test; neuroimaging; neurophysiology; normal hearing; novel; performance tests; relating to nervous system; response; sound; spectrograph; speech in noise

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.

摘要摘要 神经认知障碍是 HIV 感染的毁灭性后果，尽管活跃，但仍会发生这种情况 抗逆转录病毒治疗。中枢神经系统（CNS）可以作为艾滋病毒的储存库，并且继续 大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症状和 症状，包括 HIV 相关神经认知障碍 (HAND)。 HIV治疗也可能有 神经系统影响。 HIV 感染和治疗中 CNS 影响的可靠生物标志物对于 诊断并追踪艾滋病毒的这种令人衰弱的后果。传统上，使用神经认知测试电池， 这可能是耗时、劳动密集型的，有时还会给患者带来压力。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（多动症、学习障碍）而变得复杂。 残疾）。评估 HIV 感染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测定。在我们由 NIDCD 资助的坦桑尼亚和 中国上海我们已经证明艾滋病毒+个体有中枢听觉处理缺陷的迹象， 包括认知表现与理解言语的能力之间存在很强的负相关关系 背景噪音（尽管由听力阈值确定的周围听力正常），较高的差距 HIV+ 成人中的检测阈值（中枢听觉缺陷的另一个迹象），即使外周听力 完好无损，并且神经电生理测试发生变化（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、处理声音和 在噪声中解释语音是一项要求很高的中枢神经系统任务，涉及听觉网络及其与听觉网络的连接 其他电路和中心。这提供了评估艾滋病毒感染对中枢神经系统影响的可能性 使用中枢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 补充或增强当前的测试方法。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联 神经认知测试结果。上海公共卫生临床中心对 6000 多名艾滋病毒患者进行了追踪研究 积极的个体并具有广泛的神经影像能力。他们与达特茅斯学院合作 建立了制定详细的中枢听觉处理措施的能力。我们的研究将进行 HIV+ 感染者 (n=60) 和未感染者 (n=60) 的听觉网络及其连接的神经影像 HAND，包括静息态和基于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 HIV 组的结果进行比较。这些数据将表明中央听觉测试是否可以作为 评估艾滋病毒感染的中枢神经系统并发症的“窗口”。