Yukhnovich Ekaterina A, Alter Kai, Sedley William
Newcastle University Medical School, Newcastle Upon Tyne, NE2 4HH, UK.
Faculty of Modern and Medieval Languages and Linguistics and the Languages Sciences Interdisciplinary Research Centre, University of Cambridge, Cambridge, UK.
J Assoc Res Otolaryngol. 2025 Feb;26(1):33-47. doi: 10.1007/s10162-024-00970-1. Epub 2024 Dec 16.
Due to the heterogeneous causes, symptoms and associated comorbidities with tinnitus, there remains an unmet need for a clear biomarker of tinnitus presence. Previous research has suggested a "final pathway" of tinnitus presence, which occurs regardless of the specific mechanisms that resulted in alterations of auditory predictions and, eventually, tinnitus perception. Predictive inference mechanisms have been proposed as the possible basis for this final unifying pathway. A commonly used measure of prediction violation is mismatch negativity (MMN), an electrical potential generated in response to most stimuli that violate an established regularity. This narrative review discusses 16 studies comparing MMN between tinnitus and non-tinnitus groups. Methods varied considerably, including type of deviant, type of paradigm and carrier frequency. A minority of studies matched groups for age, sex and hearing, with few measuring hyperacusis. Frequency deviants were the most widely studied; at frequencies remote from tinnitus, MMN was consistently smaller in tinnitus groups, though hyperacusis or altered distress or attention could not be ruled out as explanatory factors. Few studies have used tinnitus-related frequencies; these showed larger MMN to upward frequency deviants above the tinnitus frequency, and larger MMN to upward intensity deviants at or close to the tinnitus frequency. However, the latter appears a correlate of hyperacusis rather than tinnitus, and tinnitus groups without hyperacusis instead show larger MMN to downward intensity deviants than controls. Other factors that affect MMN amplitudes included age, attention, and the specific characteristics of the range of stimuli across a particular experiment paradigm. As such, MMN cannot presently be considered a specific biomarker of tinnitus, but showed potential to objectively characterise a number of auditory processing traits relevant to tinnitus and hyperacusis.
由于耳鸣的病因、症状及相关合并症具有异质性，目前仍缺乏明确的耳鸣存在生物标志物。先前的研究提出了耳鸣存在的“最终通路”，该通路的发生与导致听觉预测改变并最终引发耳鸣感知的具体机制无关。预测推理机制已被认为是这一最终统一通路的可能基础。一种常用的预测违背测量方法是失匹配负波（MMN），它是对大多数违背既定规律的刺激产生的一种电位。本叙述性综述讨论了16项比较耳鸣组和非耳鸣组MMN的研究。方法差异很大，包括偏差类型、范式类型和载波频率。少数研究对年龄、性别和听力进行了组间匹配，很少有研究测量听觉过敏。频率偏差是研究最广泛的；在远离耳鸣的频率上，耳鸣组的MMN始终较小，不过不能排除听觉过敏、痛苦或注意力改变作为解释因素。很少有研究使用与耳鸣相关的频率；这些研究表明，耳鸣频率以上的向上频率偏差会导致更大的MMN，耳鸣频率或接近耳鸣频率处的向上强度偏差也会导致更大的MMN。然而，后者似乎是听觉过敏的相关因素而非耳鸣，没有听觉过敏的耳鸣组对向下强度偏差的MMN反而比对照组更大。影响MMN振幅的其他因素包括年龄、注意力以及特定实验范式中刺激范围的具体特征。因此，目前MMN不能被视为耳鸣的特异性生物标志物，但显示出客观表征与耳鸣和听觉过敏相关的一些听觉加工特征的潜力。
