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眨眼作为耳鸣之窗:猕猴耳鸣新动物模型。

The blinking eye as a window into tinnitus: A new animal model of tinnitus in the macaque.

机构信息

Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, Washington DC 20057, USA; Department of Medicine, University of Fribourg, Chemin du Musée 8, 1700, Fribourg, Switzerland.

Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road, Washington DC 20057, USA.

出版信息

Hear Res. 2022 Jul;420:108517. doi: 10.1016/j.heares.2022.108517. Epub 2022 May 11.

Abstract

Tinnitus is a highly prevalent, largely untreatable auditory disorder, characterized by the perception of phantom sound often in the form of incessant ringing or hissing. Despite longstanding research with animal models, its underlying pathophysiological causes remain poorly understood. Given recent data characterizing tinnitus as a disorder with a strong neurocognitive component, progress in the field might be hastened by testing a wider spectrum of animal models, including nonhuman primates, and by developing alternative measurement techniques of tinnitus, especially in animals. To provide fresh impetus, we developed a novel tinnitus-verification technique applicable to rhesus monkeys. Tinnitus was induced via salicylate administration in two monkeys, and was confirmed by applying a specific eyeblink procedure: Blinks, as monitored with EMG, were triggered via puffs of air towards the cheek, and their modulation was studied as a function of preceding tones under various frequency and intensity conditions. The advantage of a tactile reflex-inducing stimulus lies in its non-auditory modality, bypassing potential confounding factors of hearing loss and hyperacusis. Interference effects on the blink modulation pattern were interpreted as tinnitus, and the frequency of the preceding interfering tone as tinnitus frequency. A cross-validation in a sample of human tinnitus patients revealed interfering effects of the preceding tone in the specific frequency range corresponding to their own tinnitus frequency, as independently determined by audiologists. This interference effect increased as a function of individual tinnitus loudness. In conclusion, the present work demonstrates considerable transferability of a newly established tinnitus-verification technique from nonhuman primates to human tinnitus patients. The technique may be usable both for objective measurements of tinnitus in human patients as well as a potential alternative technique for routine tinnitus testing in animal models.

摘要

耳鸣是一种普遍存在、基本无法治疗的听觉障碍,其特征是感知到一种幻影声音,通常表现为持续不断的嗡嗡声或嘶嘶声。尽管对动物模型进行了长期研究,但它的潜在病理生理原因仍知之甚少。鉴于最近的数据将耳鸣描述为一种具有强烈神经认知成分的障碍,通过测试更广泛的动物模型,包括非人类灵长类动物,并开发替代的耳鸣测量技术,特别是在动物中,该领域的进展可能会加快。为了提供新的动力,我们开发了一种适用于恒河猴的新型耳鸣验证技术。通过给两只猴子注射水杨酸盐来诱导耳鸣,并通过应用特定的眨眼程序来确认:通过向脸颊吹气来触发肌电图监测到的眨眼,研究其在前导音的调制作为各种频率和强度条件下的函数。触觉反射诱导刺激的优点在于其非听觉模式,绕过了听力损失和听觉过敏的潜在混杂因素。对眨眼调制模式的干扰效应被解释为耳鸣,而前导干扰音的频率被解释为耳鸣频率。在一组人类耳鸣患者的交叉验证中,发现前导音在与他们自己的耳鸣频率相对应的特定频率范围内产生了干扰效应,该频率是由听力学家独立确定的。这种干扰效应随着个体耳鸣响度的增加而增加。总之,本工作表明,一种新建立的耳鸣验证技术从非人类灵长类动物到人类耳鸣患者具有相当大的可转移性。该技术可用于人类患者的耳鸣客观测量,也可作为动物模型常规耳鸣测试的潜在替代技术。

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