Human Cochlear Function: A Continuum of Maturation and Aging

 描述(由申请者提供)：在人的一生中，耳蜗功能在成熟和衰老的连续统一体中变化。耳声发射(OAE)提供了一个非侵入性的窗口，了解耳蜗和驱动这些变化的机制。在这里，我们应用耳声发射来绘制与年龄相关的耳蜗力学变化图，并探索新的听力探测的可能性。在目标1中，我们利用新生儿耳朵产生的强烈反射，并记录新生儿的刺激频率(SF)OAEs，这是一种反射源发射。单纯性耳声发射与耳蜗调谐和增益有关，但从未在新生儿中被表征，主要是因为他们需要令人望而却步的长协议来实现足够的信噪比。这个问题通过新的算法变得容易处理，允许将刺激快速呈现为扫频音调。我们将首次在一大批新生儿耳朵中描述SFOAE的特征，并调整创新的扫描音调算法，以在这一年龄段中进行最佳使用。目的2研究新生儿和成人耳蜗尖的部分，这一区域代表了我们可听频率范围的近一半，但在成熟过程中人们对此知之甚少，也完全没有被探索过。在新生儿耳朵中，已经观察到低频信号的非成人型DPOAE相；我们假设心尖频率-位置图中的细微不成熟可能解释了这些发现。在这里，从反射源和畸变源OAE中寻找聚合证据，记录和模拟DPOAE尖部相图，并对人类颞骨进行组织学分析，以将尖部解剖与OAE发育过程中的特征联系起来。耳蜗力学的变化在婴儿期后并没有停止；老化的耳朵经历了其感觉细胞健康和代谢环境的有案可查的变化，从而产生了改变的耳蜗效率。耳蜗性缺陷会导致老年人常见的知觉困难。在目标3中，我们假设其中一个这样的缺陷是老化耳朵中耳蜗非线性度的丧失，并定义了基于耳声发射的非线性度量从中年到衰老是如何变化的。此外，我们假设，随着年龄的增长，耳蜗会变得更加“粗糙”，这可能是因为尽管耳蜗健康状况每况愈下，它仍能产生反射发射。这三个目标应用了不同的实验和理论工具，并开辟了新的领域；他们将新生儿的SFOAEs描述为探索其作为新生儿听力筛查潜力的第一步，探索经常被忽视的人类耳蜗尖端半部分，在那里观察到了新生儿的不成熟，并定义了耳蜗非线性和耳声发射在老化的耳朵中如何发生变化。

 DESCRIPTION (provided by applicant): Cochlear function changes throughout the human lifespan in a continuum of maturation and aging. Otoacoustic emissions (OAE) provide a non-invasive window into the cochlea and the mechanisms driving these changes. Here, we apply OAEs to map age-related shifts in cochlear mechanics and explore the potential for new probes of hearing. In Aim 1 we exploit the robust reflection generated by neonatal ears and record stimulus frequency (SF) OAEs, a reflection-source emission, in newborns. SFOAEs have been linked to cochlear tuning and gain yet have never been characterized in newborns, mostly because of their need for prohibitively long protocols to achieve adequate signal-to-noise ratios. This problem is rendered tractable by novel algorithms allowing for the rapid presentation of stimuli as sweeping tones. We will characterize the SFOAE for the first time in a large cohort of newborn ears and adapt the innovative swept-tone algorithm for optimal use within this age group. Aim 2 studies the apical portion of the newborn and adult cochlea, a region representing nearly half of our audible frequency range, yet poorly understood and wholly unexplored during maturation. In newborn ears, non-adult-like DPOAE phase has been observed for low-frequency signals; we hypothesize that subtle immaturities in the apical frequency-place map may account for these findings. Here, seek converging evidence from reflection- and distortion-source OAEs, record and model DPOAE apical phase maps, and conduct histological analysis of human temporal bones to link apical anatomy to OAE features during development. Changes in cochlear mechanics do not cease after infancy; the aging ear experiences documented changes in the health of its sensory cells and in its metabolic environment, producing altered cochlear efficiency. Cochlear-based deficits contribute to perceptual difficulties common to older listeners. In Aim 3, we hypothesize that one such deficit is the loss of cochlear nonlinearity in the aging ear, and we define how OAE-based metrics of nonlinearity change from middle-age through senescence. Furthermore, we hypothesize that the cochlea becomes more "rough" with aging, possibly accounting for its ability to generate reflection emissions despite declining cochlear health. These three aims apply diverse experimental and theoretical tools and break new ground; they characterize SFOAEs in newborns as a first step in exploring their potential as a neonatal hearing screen, probe the oft-neglected apical half of the human cochlea where neonatal immaturities have been observed, and define how cochlear nonlinearities and OAE generation change in the aging ear.