Zink Maggie E, Zhen Leslie, McHaney Jacie R, Klara Jennifer, Yurasits Kimberly, Cancel Victoria, Flemm Olivia, Mitchell Claire, Datta Jyotishka, Chandrasekaran Bharath, Parthasarathy Aravindakshan
bioRxiv. 2025 Jun 16:2024.08.01.606213. doi: 10.1101/2024.08.01.606213.
Middle age represents a critical period of accelerated brain changes and provides a window for early detection and intervention in age-related neurological decline. Hearing loss is a key early marker of such decline and is linked to numerous comorbidities in older adults. Yet, ∼10% of middle-aged individuals who report hearing difficulties show normal audiograms. Cochlear neural degeneration (CND) could contribute to these hidden hearing deficits, though its role remains unclear due to a lack of objective diagnostics and uncertainty regarding its perceptual outcomes. Here, we employed a cross-species design to examine neural and behavioral signatures of CND. We measured envelope following responses (EFRs) - neural ensemble responses to sound originating from the peripheral auditory pathway - in young and middle-aged adults with normal audiograms and compared these responses to young and middle-aged Mongolian gerbils, where CND was histologically confirmed. We observed near identical changes in EFRs across species that were associated with CND. Behavioral assessments revealed agerelated speech-in-noise deficits under challenging conditions, while pupil-indexed listening effort increased with age even when behavioral performance was matched. Together, these results demonstrate that CND contributes to speech perception difficulties and elevated listening effort in midlife, which may ultimately lead to listening fatigue and social withdrawal.
中年是大脑加速变化的关键时期,为与年龄相关的神经功能衰退的早期检测和干预提供了一个窗口。听力损失是这种衰退的一个关键早期指标,并且与老年人的多种合并症相关。然而,报告有听力困难的中年个体中约10%的人听力图正常。耳蜗神经变性(CND)可能导致这些隐匿性听力缺陷,尽管由于缺乏客观诊断方法以及其感知结果的不确定性,其作用仍不明确。在此,我们采用跨物种设计来研究CND的神经和行为特征。我们测量了听觉脑干反应(EFRs)——源自外周听觉通路的声音的神经集合反应——在听力图正常的年轻和中年成年人中,并将这些反应与年轻和中年蒙古沙鼠的反应进行比较,在蒙古沙鼠中组织学上证实存在CND。我们观察到跨物种的EFRs中与CND相关的几乎相同的变化。行为评估显示在具有挑战性的条件下与年龄相关的噪声中言语缺陷,而即使行为表现匹配,瞳孔指标化的听力努力也随年龄增加。总之,这些结果表明CND导致中年人的言语感知困难和听力努力增加,这最终可能导致听力疲劳和社交退缩。