UNDERSTANDING SUPRATHRESHOLD HEARING DEFICITS

项目摘要/摘要 感音神经性听力损失(SNHL)可能是由于外毛细胞、内毛细胞、 听神经纤维或突触。然而，标准的临床技术在它们的能力方面是有限的 区分这些功能障碍是因为它们集中在阈值升高上，因此提供的 关于阈值上的听觉功能障碍的信息，其生态有效性高于阈值 立面。SNHL不会提高阈值，因此标准临床可能会遗漏 技术，有时被称为“隐性听力损失”(HHL)。最近的动物研究表明 噪声诱导的突触病变可能是HHL的基础，也可能是阈值上听力障碍的原因，如 因为在噪音中理解语音有困难。然而，支持HHL诊断的研究有限。 在人类中，Beyond报告称，一些人患有无法预测的阈值以上听力障碍 从他们的听力图来看。要了解人类的HHL，需要使用听觉测量 特定于听觉通路中功能障碍的位置的功能，包括特定的组 听神经纤维(低自发频率纤维与高自发频率纤维)是导致功能障碍的原因。长期目标 这项研究计划的目的是提高我们对阈值上听力障碍的理解，并发展 改善这些赤字的干预策略。这项提议的直接目标是建立一个 人类HHL诊断方法发展的理论框架。不幸的是，一枚“黄金” “标准”是不存在的，因为在人类身上不能直接观察到突触。因此，我们的 方法是开发HHL的统计模型，描述HHL之间的关系和相互依赖 被认为是HHL的听觉功能的特定行为和生理指标 以及反映沿听觉通路的位置的功能完整性的测量。目标一定会实现的 通过追求三个目标：(1)建立听力正常个体的HHL统计模型；(2)开发 噪声暴露所致临床听力损失个体的HHL统计模型，以及(3)验证 HHL的预测模型，并论证了它与噪声中的语音理解的关系。我们将建立一个 HHL的功能定义为受HHL影响的措施的可变性的一个组成部分，而不是由于 测听阈值。然后，我们将创建一个统计模型，将HHL的这一估计与以下指标相关联 沿着听觉通路反映出功能障碍的部位。通过AIMS，我们将检验HHL的假设 解释了听觉功能的阈值上测量的一些变异性。拟议的研究 将导致基于证据的阈值以上听力障碍模型，这些模型能够预测 听力障碍，提供了对阈值上听力障碍的进一步见解，并提高了我们对 听力和听力障碍的潜在机制。在临床上诊断HHL的能力将 为临床评估引入新的方法，并可能带来更好的听力损失补救技术。

PROJECT SUMMARY/ABSTRACT Sensorineural hearing loss (SNHL) can occur as a result of dysfunction of outer hair cells, inner hair cells, auditory-nerve fibers or synapses. However, standard clinical techniques are limited in their ability to differentiate these dysfunctions because they focus on threshold elevation and thus provide insufficient information about suprathreshold auditory dysfunction, which has greater ecological validity than threshold elevation. SNHL that does not elevate thresholds, and therefore would be missed by standard clinical techniques, is sometimes referred to as “hidden hearing loss” (HHL). Recent animal studies suggest that noise-induced synaptopathy may underlie HHL and may be the cause of suprathreshold hearing deficits, such as difficulty understanding speech in noise. However, there is limited research to support the diagnosis of HHL in humans beyond reports that some individuals have suprathreshold hearing deficits that cannot be predicted from their audiograms. Understanding HHL in humans will require the use of measurements of auditory function that are specific to the location of the dysfunction in the auditory pathway, including the specific group of auditory-nerve fibers (low vs. high spontaneous-rate fibers) underlying the dysfunction. The long-term goals of this research program are to improve our understanding of suprathreshold hearing deficits and to develop intervention strategies that ameliorate these deficits. The immediate goal of this proposal is to establish a theoretical framework for the development of diagnostic methods for HHL in humans. Unfortunately, a “gold standard” does not exist because synaptopathy cannot be directly observed in humans. Consequently, our approach is to develop a statistical model of HHL that describes the relationship and interdependence between specific behavioral and physiological measures of auditory function that are thought to be indicative of HHL and measures that reflect the functional integrity of sites along the auditory pathway. The goal will be achieved by pursuing three aims: (1) Develop a statistical model of HHL for individuals with normal hearing, (2) Develop a statistical model of HHL for individuals with clinical hearing loss caused by noise exposure, and (3) Validate a predictive model of HHL and demonstrate its relation to speech understanding in noise. We will establish a functional definition of HHL as a component of the variability in measures impacted by HHL that is not due to audiometric threshold. We will then create a statistical model that relates this estimate of HHL to measures that reflect sites of dysfunction along the auditory pathway. Through the aims, we will test the hypothesis that HHL accounts for some of the variability in suprathreshold measures of auditory function. The proposed research will lead to evidence-based models of suprathreshold auditory dysfunction that are capable of predicting hearing deficits, provide further insights into suprathreshold auditory deficits and improve our understanding of potential mechanisms underlying hearing and listening difficulties. The ability to diagnose HHL in the clinic will usher in new methods for clinical evaluation and may lead to better remediation techniques of hearing loss.