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.

摘要总结