Milinski Linus, Nodal Fernando R, Emmerson Matthew K J, King Andrew J, Vyazovskiy Vladyslav V, Bajo Victoria M
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
PLoS One. 2024 Dec 4;19(12):e0304306. doi: 10.1371/journal.pone.0304306. eCollection 2024.
Subjective tinnitus is a phantom auditory perception in the absence of an actual acoustic stimulus that affects 15% of the global population. In humans, tinnitus is often associated with disturbed sleep and, interestingly, there is an overlap between the brain areas involved in tinnitus and regulation of NREM sleep. We used eight adult ferrets exposed to mild noise trauma as an animal model of tinnitus. We assessed the phantom percept using two operant paradigms sensitive to tinnitus, silent gap detection and silence detection, before and, in a subset of animals, up to six months after the mild acoustic trauma. The integrity of the auditory brainstem was assessed over the same period using auditory brainstem response recordings. Following noise overexposure, ferrets developed lasting, frequency-specific impairments in operant behaviour and evoked brainstem activity. To explore the interaction between sleep and tinnitus, in addition to tracking the behavioural markers of noise-induced tinnitus and hearing impairment after noise overexposure, we evaluated sleep-wake architecture and spontaneous and auditory-evoked EEG activity across vigilance states. Behavioural performance and auditory-evoked activity measurements after noise overexposure suggested distinct degrees of tinnitus and hearing impairment between individuals. Animals that developed signs of tinnitus consistently developed sleep impairments, suggesting a link between the emergence of noise-induced hearing loss and/or tinnitus and sleep disruption. However, neural markers of tinnitus were reduced during sleep, suggesting that sleep may transiently mitigate tinnitus. These results reveal the importance of sleep-wake states in tinnitus and suggest that understanding the neurophysiological link between sleep and tinnitus may provide a new angle for research into the causes of phantom percepts and inform future treatments.
主观性耳鸣是在没有实际声学刺激时出现的一种幻听,全球15%的人口受其影响。在人类中,耳鸣常与睡眠障碍相关,有趣的是,参与耳鸣的脑区与非快速眼动睡眠调节脑区存在重叠。我们使用八只成年雪貂暴露于轻度噪声创伤作为耳鸣动物模型。在轻度声学创伤前以及在一部分动物中,在创伤后长达六个月的时间里,我们使用对耳鸣敏感的两种操作性范式(静音间隙检测和静音检测)评估幻听感受。在同一时期,使用听觉脑干反应记录评估听觉脑干的完整性。噪声过度暴露后,雪貂在操作性行为和诱发的脑干活动方面出现了持续的、频率特异性的损伤。为了探究睡眠与耳鸣之间的相互作用,除了追踪噪声暴露后噪声诱发的耳鸣和听力损伤的行为标志物外,我们还评估了不同警觉状态下的睡眠 - 觉醒结构以及自发和听觉诱发的脑电图活动。噪声过度暴露后的行为表现和听觉诱发活动测量表明个体之间耳鸣和听力损伤程度不同。出现耳鸣迹象的动物始终出现睡眠障碍,这表明噪声诱发的听力损失和/或耳鸣的出现与睡眠中断之间存在联系。然而,耳鸣的神经标志物在睡眠期间减少,这表明睡眠可能会暂时减轻耳鸣。这些结果揭示了睡眠 - 觉醒状态在耳鸣中的重要性,并表明了解睡眠与耳鸣之间的神经生理联系可能为幻听成因的研究提供新视角,并为未来治疗提供参考。