Non-Invasive Assays of Cochlear Synaptopathy - Candidates and Considerations
Non-Invasive Assays of Cochlear Synaptopathy - Candidates and Considerations
复制标题
DOI：
10.1016/j.neuroscience.2019.02.031
复制
发表时间：
2019-05-21
期刊：
影响因子：
3.3
通讯作者：
Shinn-Cunningham, Barbara G.
中科院分区：
文献类型：
--
作者：
Bharadwaj, Hari M.;Mai, Alexandra R.;Shinn-Cunningham, Barbara G.
在多个物种中的研究，包括在死后的人类组织中的研究，已经表明正常的老化和/或声学过度刺激可以导致支配耳蜗的传入突触的显著损失。假设，这种耳蜗突触病可能导致在具有挑战性的环境中的感知缺陷，并可能导致中枢神经效应，如耳鸣。然而，因为耳蜗突触病可以在听力阈值没有任何可测量的变化的情况下发生，所以突触病可以从标准临床诊断中保持隐藏。为了了解突触病的感知后遗症，并评估新兴疗法的疗效，需要建立个体患者水平的敏感和特异性非侵入性措施。在特定小鼠品系中进行的开创性实验有助于确定许多候选检测方法。这些包括听觉脑干反应，中耳肌反射，听力跟随反应和扩展高频听力图。不幸的是，由于这些非侵入性措施也可能受到突触病以外的外来因素的影响，因此它们在人类中的应用和解释并不简单。在这里，我们通过一系列相互关联的人体实验，系统地研究了六个外部因素，旨在了解它们的影响。使用的策略，可能有助于减轻这些外来因素的影响，我们然后表明，这些阈上生理检测表现出跨个体的相互关系，从一个共同的生理来源与耳蜗突触病一致的指示贡献。最后，我们讨论了应用这些检测两个关键的悬而未决的问题，并讨论了一些障碍，仍然remain.This文章是一个特殊的问题的一部分，题为：听力损失，耳鸣，听觉过敏，中央增益。(C)2019年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Studies in multiple species, including in post-mortem human tissue, have shown that normal aging and/or acoustic overexposure can lead to a significant loss of afferent synapses innervating the cochlea. Hypothetically, this cochlear synaptopathy can lead to perceptual deficits in challenging environments and can contribute to central neural effects such as tinnitus. However, because cochlear synaptopathy can occur without any measurable changes in audiometric thresholds, synaptopathy can remain hidden from standard clinical diagnostics. To understand the perceptual sequelae of synaptopathy and to evaluate the efficacy of emerging therapies, sensitive and specific non-invasive measures at the individual patient level need to be established. Pioneering experiments in specific mice strains have helped identify many candidate assays. These include auditory brainstem responses, the middle-ear muscle reflex, envelope-following responses, and extended high-frequency audiograms. Unfortunately, because these non-invasive measures can be also affected by extraneous factors other than synaptopathy, their application and interpretation in humans is not straightforward. Here, we systematically examine six extraneous factors through a series of interrelated human experiments aimed at understanding their effects. Using strategies that may help mitigate the effects of such extraneous factors, we then show that these suprathreshold physiological assays exhibit across-individual correlations with each other indicative of contributions from a common physiological source consistent with cochlear synaptopathy. Finally, we discuss the application of these assays to two key outstanding questions, and discuss some barriers that still remain.This article is part of a Special Issue entitled: Hearing Loss, Tinnitus, Hyperacusis, Central Gain. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.