The effects of age on temporal coding in the auditory system

听力能力随着年龄的增长而恶化，导致沟通困难和生活质量下降。其中一些变化在听力图中很明显，听力图是听力灵敏度的标准临床测量，它描述了耳朵对不同频率的纯音的灵敏度。然而，除了使用标准临床技术可以检测到的变化之外，从动物和人类研究中越来越清楚地发现，听觉功能的退化可能发生在听音图测量的对低水平声音的敏感性显著下降之前，或者独立于此。临床上听力正常的听者在嘈杂环境中理解语言的能力可能会随着年龄的增长而下降，而这种能力对现实世界的交流至关重要。有人认为，这可能部分是由于神经纤维无法以同步的激活模式来表现声音的快速波动。这种“时间编码”与年龄相关的缺陷最近在人类身上得到了证实，该技术通过将电极附着在头皮上来记录听觉大脑中神经纤维的电活动。时间编码对于语音识别本身可能很重要，但它被认为对于将语音与干扰声音分开尤其重要。特别是，我们依赖于细粒度的时间信息，根据它们的空间位置来分离声音（例如，几个人在嘈杂的聚会上说话）。与年龄相关的时间编码下降的神经基础尚不清楚，但有两个潜在的候选人。首先，动物研究和对人耳的尸检表明，听觉神经纤维随着年龄的增长而逐渐丧失，尤其是那些代表中高水平信息的纤维。因此，这种损失可以在不降低对安静声音敏感度的情况下发生。其次，时间编码的缺陷可能是由于神经纤维之间的同步性丧失。这可能是因为年龄与神经纤维周围的脂肪鞘的斑状变性有关，并增加了神经冲动的传递速度。拟议的研究将结合最先进的电生理学和听力测试技术，以全面了解人类与年龄相关的时间编码下降的神经基础和感知后果。我们的重点将放在临床听力正常的听者身上，这样我们就可以将这些影响与与临床听力损失相关的内耳毛细胞和其他结构的功能障碍的影响分开研究。通过测试一大批不同年龄段的志愿者的神经纤维功能和实验室和“真实世界”声音的听力能力，我们将能够建立联系和推断，这是在不那么雄心勃勃的研究中不可能实现的。特别是，我们将确定与年龄相关的时间编码缺陷是由于神经纤维的损失，神经纤维传输速度的降低，还是两者兼而有之。我们还将能够确定时间编码的缺陷如何与现实世界的听力能力有关，例如噪音中的语音检测和音乐音高感知。结果将为诊断测试提供基础，可以识别神经功能障碍。在听音图显示出任何缺陷之前对损伤进行早期诊断，将允许临床医生提供个性化的医疗保健建议，例如，避免任何会使问题复杂化的情况，例如暴露于娱乐噪音中。这项研究还将为未来可能纠正这些缺陷的干预措施铺平道路，例如，带有定向麦克风的助听器可以促进语音接收，以及药物和干细胞疗法可以恢复神经功能。

Hearing ability deteriorates with age, leading to communication difficulties and a reduced quality of life. Some of these changes are apparent in the audiogram, the standard clinical measure of hearing sensitivity, which describes the sensitivity of the ear to pure tones at different frequencies. However, in addition to the changes that can be detected using standard clinical techniques, it is becoming increasing clear from animal and human studies that a deterioration in auditory function may occur before, or independently from, a significant decline in sensitivity to low-level sounds as measured by the audiogram. Listeners with clinically normal hearing may experience an age-related decline in their ability to understand speech in noisy environments, an ability that is vital for real-world communication. It has been suggested that this may be due, in part, to a deficit in the ability of nerve fibres to represent the rapid fluctuations in sounds in terms of their synchronised patterns of activation. An age-related deficit in this "temporal coding" has been demonstrated recently in humans using techniques that record the electrical activity of nerve fibres in the auditory brain by attaching electrodes to the scalp. Temporal coding may be important for speech identification per se, but it is thought to be particularly important for segregating speech from interfering sounds. In particular, we rely on fine-grained timing information to separate sounds on the basis of their spatial locations (for example, several people talking at a noisy party).The neural bases for the age-related decline in temporal coding are unclear, but there are two potential candidates. First, animal studies and post-mortem examinations of human ears suggest that there is a progressive loss in auditory nerve fibres with age, particularly those fibres that represent information at medium-to-high levels. Hence, this loss can occur without a reduced sensitivity to quiet sounds. Second, it is possible that the deficit in temporal coding may be due to a loss of synchrony between nerve fibres. This may occur because age is associated with a patchy degeneration of the fatty sheaths that surround nerve fibres and increase the speed of transmission of nerve impulses.The proposed research will use a combination of state-of-the-art electrophysiological and listening-test techniques to provide a comprehensive understanding of the neural bases and perceptual consequences of the age-related decline in temporal coding in humans. Our focus will be on listeners with clinically normal hearing, so that we can study these effects in isolation from the effects of dysfunction of the hair cells and other structures in the inner ear that are associated with clinical loss. By testing a large cohort of volunteers across the age range with measures of nerve-fibre function and listening ability with laboratory and "real world" sounds, we will be able to make connections and inferences that are not possible with less ambitious studies. In particular, we will determine whether the age-related temporal coding deficits are due to a loss in nerve fibres, a reduction in nerve fibre transmission speed, or both. We will also be able to determine how the deficit in temporal coding is related to real-world hearing ability on tasks such as speech detection in noise, and musical pitch perception. The results will provide the basis for a diagnostic test that can identify the neural dysfunction. Early diagnosis of damage, before any deficit is apparent in the audiogram, will allow clinicians to provide personalised healthcare advice, for example, to avoid any situations that will compound the problems, such as exposure to recreational noise. The research will also pave the way for future interventions that may correct for the deficits, for example hearing aids with directional microphones to facilitate speech reception, and drug and stem cell therapies to restore neural function.