Cochlear synaptopathy and tinnitus in veterans (Bramhall et al., 2023)

Purpose: Animal models and human temporal bones indicate that noise exposure is a risk factor for cochlear synaptopathy, a possible etiology of tinnitus. Veterans are exposed to high levels of noise during military service. Therefore, synaptopathy may explain the high rates of noise-induced tinnitus among Veterans. Although synaptopathy cannot be directly evaluated in living humans, animal models indicate that several physiological measures are sensitive to synapse loss, including the auditory brainstem response (ABR), the middle ear muscle reflex (MEMR), and the envelope following response (EFR). The purpose of this study was to determine whether tinnitus is associated with reductions in physiological correlates of synaptopathy that parallel animal studies.Method: Participants with normal audiograms were grouped according to Veteran status and tinnitus report (Veterans with tinnitus, Veterans without tinnitus, and non-Veteran controls). The effects of being a Veteran with tinnitus on ABR, MEMR, and EFR measurements were independently modeled using Bayesian regression analysis.Results: Modeled point estimates of MEMR and EFR magnitude showed reductions for Veterans with tinnitus compared with non-Veterans, with the most evident reduction observed for the EFR. Two different approaches were used to provide context for the Veteran tinnitus effect on the EFR by comparing to agerelated reductions in EFR magnitude and synapse numbers observed in previous studies. These analyses suggested that EFR magnitude/synapse counts were reduced in Veterans with tinnitus by roughly the same amount as over 20 years of aging.Conclusion: These findings suggest that cochlear synaptopathy may contribute to tinnitus perception in noise-exposed Veterans.Supplemental Material S1. Modeled population contrasts in mean auditory brainstem response wave I amplitude.Supplemental Material S2. Modeled population contrasts in mean middle ear muscle reflex magnitude.Supplemental Material S3. Modeled population contrasts in mean envelope following response magnitude.Bramhall, N. F., Theodoroff, S. M., McMillan, G. P., Kampel, S. D., & Buran, B. N. (2023). Associations between physiological correlates of cochlear synaptopathy and tinnitus in a veteran population. Journal of Speech, Language, and Hearing Research. Advance online publication. https://doi.org/10.1044/2023_JSLHR-23-00234

**研究目的**：动物模型与人类颞骨研究均证实，噪声暴露是耳蜗突触病（cochlear synaptopathy）的危险因素，而该病可能是耳鸣（tinnitus）的潜在致病机制。退伍军人在服役期间会暴露于高强度噪声环境，因此耳蜗突触病或可解释退伍群体中噪声诱导性耳鸣的高患病率。尽管无法直接在活体人类中评估耳蜗突触病，但动物实验显示多项生理学检测指标对突触丢失具有敏感性，包括听觉脑干反应（auditory brainstem response, ABR）、中耳肌反射（middle ear muscle reflex, MEMR）以及包络跟随反应（envelope following response, EFR）。本研究旨在探讨耳鸣是否与耳蜗突触病的生理学相关指标下降存在关联，且该关联与动物实验结果相符。

**研究方法**：将听力图（audiograms）正常的受试者按退伍军人身份及耳鸣报告情况分为三组：伴耳鸣退伍军人、不伴耳鸣退伍军人及非退伍军人对照组。采用贝叶斯回归分析（Bayesian regression analysis）分别建模伴耳鸣退伍军人身份对ABR、MEMR及EFR检测结果的影响。

**研究结果**：相较于非退伍军人对照组，伴耳鸣退伍军人的MEMR与EFR幅度的建模点估计值均出现下降，其中EFR的下降最为显著。为明确伴耳鸣退伍群体中EFR变化的临床参考价值，本研究采用两种不同分析方式，将EFR幅度的下降与既往研究中观察到的年龄相关性EFR幅度下降及突触数量减少进行对比。结果显示，伴耳鸣退伍军人的EFR幅度/突触数量下降幅度大致相当于超过20年衰老所带来的变化。

**研究结论**：本研究结果提示，耳蜗突触病可能是噪声暴露退伍军人出现耳鸣感知的潜在诱因之一。

**补充材料S1**：平均听觉脑干反应波I振幅的建模群体对比
**补充材料S2**：平均中耳肌反射幅度的建模群体对比
**补充材料S3**：平均包络跟随反应幅度的建模群体对比

Bramhall, N. F., Theodoroff, S. M., McMillan, G. P., Kampel, S. D., & Buran, B. N. (2023). 退伍军人群体中耳蜗突触病生理学相关指标与耳鸣的关联. 《言语、语言与听力研究杂志》, 预印在线发表. https://doi.org/10.1044/2023_JSLHR-23-00234