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 神经认知障碍是艾滋病毒感染的毁灭性后果，它发生目的地活动 抗逆转录病毒治疗。中枢神经系统（CNS）可以用作艾滋病毒的水库，并继续 大脑中巨噬细胞和小胶质细胞的免疫激活会导致中心神经系统体征和 症状，包括与HIV相关的神经认知障碍（手）。 HIV治疗也可能有 神经效应。 CNS感染和治疗中CNS效应的可靠生物标志物对于 诊断并跟踪艾滋病毒的这种衰弱的后果。传统上，使用神经认知测试电池 这可能是耗时的，劳动密集型的，有时对患者压力很大。这些常规测试 电池可能对早期或亚临床变化不敏感，并因合并症而复杂（ADHD，学习 残疾）。评估艾滋病毒感染中中枢神经系统功能的另一种方法可能是通过 中央听觉网络的生理评估。在我们在坦桑尼亚和NIDCD资助的研究中 中国上海，我们已经表明，艾滋病毒+个人有中央听觉加工防御的迹象， 包括认知表现与理解语音的能力之间的牢固的负面关系 背景噪声（尽管通过听觉阈值确定的外围听力正常），但较高的差距 即使外围听力是 完整以及神经循环生理测试的变化（频率跟随响应）。这些发现可能 反映这些患者听觉网络中功能障碍，因为检测差距，处理声音和 噪音中的解释语音要求CNS任务涉及听觉网络及其连接 其他电路和中心。这提供了评估HIV感染的中枢神经系统影响和 使用中央听觉测试电池进行处理。中央听觉效果可能比或 独立于其他神经或神经心理学测试结果，因此检测这些变化可能 补充或增强当前的测试方法。将中央听觉效应用作生物标志物， 但是，听觉网络的变化需要与中央听觉发现和 神经认知测试结果。上海公共卫生临床中心遵循6000多名HIV的队列 积极的个体，具有广泛的神经影像能力。与达特茅斯合作，他们有 建立了制定详细的中央听觉处理措施的能力。我们的研究将表演 听觉网络的神经影像学及其在HIV+人中的联系（n = 60）和没有（n = 60） 手，包括静止状态和基于任务的fMRI，神经电子生理测试和扩散 基本光谱成像，这将与行为中央听觉测试的性能相关 与HIV组的结果相比。这些数据将显示中央听觉测试是否可以用作 “窗口”评估CNS感染的CNS合并症。