Active Filtering in the Cochlea

描述(由申请人提供)：我们的研究目标是弥合耳蜗学基础研究与耳科临床工具如耳声发射和人工耳蜗术之间的差距。我们将使用实验和理论技术相结合的方法来开发全面的耳蜗功能计算机模型。实验工作是专门为生成可用于模型参数估计和模型验证的详细数据集而设计的。我们的项目特别关注耳蜗电和机械特性，无论是主动的还是被动的，如何导致在内毛细胞(IHC)和听神经(AN)纤维中观察到的极其敏感的反应。将开发的模型将用于整合广泛的实验数据，以及模拟由于耳蜗病理学导致的耳声发射的变化，以及模拟人工耳蜗术后产生的电场。我们将解决四个基本问题：1)Corti器官的结构如何决定耳蜗的被动机械特性？2)外毛细胞(OHC)的机电特性如何导致耳蜗放大？3)什么机制驱动和分配离子电流通过耳蜗？4)耳声发射是在哪里以及如何在耳蜗中产生的？为了回答这些问题，我们将使用实验和理论相结合的技术来研究沙土鼠和人类耳蜗的机械和电学特性。我们将开发详细的耳蜗流体力学和电解剖有限元模型，以及结合耳蜗液力学特性和电解剖学特性的耳蜗放大器的集成有限差分模型。这些模型将使我们能够模拟导致临床重要场电位(如耳蜗微音响(CM)、总和电位(SP)和复合动作电位(CAP))的本征电流流动，并创建可用于预测人工电流的影响的工具，例如人工耳蜗植入物产生的电流。将要开发的模型也可以用来解释正常和疾病耳朵的排放数据。这项研究将对耳声发射等临床重要诊断指标的变化与潜在的耳蜗病理学之间的关系产生新的见解。它还将帮助设计和安装人工耳蜗。

DESCRIPTION (provided by applicant): The goal of our research is to bridge the gap between basic research in cochlear physiology and clinical tools in otology such as otoacoustic emissions and cochlear implants. We will use a combination of experimental and theoretical techniques to develop comprehensive computer models of cochlear function. The experimental work is specifically designed to generate detailed data sets that can be used for model parameter estimation and model validation. Our project specifically focuses on how the electrical and mechanical properties of the cochlea, both active and passive, result in the extremely sensitive responses observed in inner hair cells (IHC) and auditory-nerve (AN) fibers. The models to be developed will be used to integrate a wide range of experimental data as well as to simulate changes in otoacoustic emissions due to cochlear pathology and to simulate the electric fields produced by cochlear implants. We will address four fundamental questions: 1) How does the architecture of the organ of Corti determine the passive mechanical properties of the cochlea? 2) How do outer hair cell (OHC) electromechanical properties lead to cochlear amplification? 3) What are the mechanisms that drive and distribute ionic current flow throughout the cochlea? 4) Where and how are otoacoustic emissions produced in the cochlea? To answer these questions, we will use a combination of experimental and theoretical techniques to study the mechanical and electrical properties of the gerbil and the human cochlea. We will develop detailed finite element hydromechanical and electroanatomical models of the cochlea, as well as an integrated finite-difference model for the cochlear amplifier that incorporates both the hydromechanical properties and the electroanatomical properties of the cochlea. These models will allow us to simulate the intrinsic current flows that lead to clinically important field potentials such as the cochlear microphonic (CM), summating potential (SP) and the compound action potential (CAP), as well as to create tools that can be used to predict the effects of artificial currents such as those produced by cochlear implants. The models to be developed can also be used to interpret emission data from normal and diseased ears. This research will lead to new insights into the relationship between changes in clinically important diagnostic measures such as otoacoustic emissions and underlying cochlear pathologies. It will also aid in the design and fitting of cochlear implants.