Oregon Hearing Research Center (OHRC), Department of Otolaryngology-Head & Neck Surgery, Oregon Health & Science University, Portland, Oregon, USA.
Veterans Affairs (VA) Rehabilitation Research & Development Service (RR&D) National Center for Rehabilitative Auditory Research (NCRAR), VA Portland Health Care System, Portland, Oregon, USA.
J Acoust Soc Am. 2022 Jan;151(1):561. doi: 10.1121/10.0009238.
Aging, noise exposure, and ototoxic medications lead to cochlear synapse loss in animal models. As cochlear function is highly conserved across mammalian species, synaptopathy likely occurs in humans as well. Synaptopathy is predicted to result in perceptual deficits including tinnitus, hyperacusis, and difficulty understanding speech-in-noise. The lack of a method for diagnosing synaptopathy in living humans hinders studies designed to determine if noise-induced synaptopathy occurs in humans, identify the perceptual consequences of synaptopathy, or test potential drug treatments. Several physiological measures are sensitive to synaptopathy in animal models including auditory brainstem response (ABR) wave I amplitude. However, it is unclear how to translate these measures to synaptopathy diagnosis in humans. This work demonstrates how a human computational model of the auditory periphery, which can predict ABR waveforms and distortion product otoacoustic emissions (DPOAEs), can be used to predict synaptic loss in individual human participants based on their measured DPOAE levels and ABR wave I amplitudes. Lower predicted synapse numbers were associated with advancing age, higher noise exposure history, increased likelihood of tinnitus, and poorer speech-in-noise perception. These findings demonstrate the utility of this modeling approach in predicting synapse counts from physiological data in individual human subjects.
衰老、噪声暴露和耳毒性药物会导致动物模型中的耳蜗突触丧失。由于哺乳动物物种的耳蜗功能高度保守，突触病也可能发生在人类身上。突触病预计会导致感知缺陷，包括耳鸣、听觉过敏和在噪声环境中理解言语的困难。由于缺乏在活人中诊断突触病的方法，因此阻碍了旨在确定噪声引起的突触病是否发生在人类、识别突触病的感知后果或测试潜在药物治疗的研究。几种生理测量方法对动物模型中的突触病敏感，包括听觉脑干反应 (ABR) 波 I 幅度。然而，目前尚不清楚如何将这些测量方法转化为人类突触病的诊断。这项工作表明，如何使用人类听觉外周的计算模型，该模型可以预测 ABR 波形和畸变产物耳声发射 (DPOAE)，可以根据个体参与者的测量 DPOAE 水平和 ABR 波 I 幅度来预测其突触损失。较低的预测突触数与年龄增长、噪声暴露史增加、耳鸣发生的可能性增加以及噪声环境中言语感知能力下降有关。这些发现证明了这种建模方法在从个体人类受试者的生理数据中预测突触数目的实用性。
