Active and Nonlinear Models for Cochlear Mechanics

描述（由申请人提供）：流体流动刺激耳蜗内毛细胞（IHC）的毛束（HB），打开IHC的机电换能器（MET）通道。产生的电流使细胞体去极化，诱导神经递质释放，并最终刺激听觉神经。由外毛细胞（OHC）的运动性驱动的耳蜗的主动机制既调谐IHC HB的微流体激发又提供非线性压缩。然而，OHC体细胞和HB运动性对耳蜗中最终流体强迫的相对影响尚未最终分摊，也没有激发IHC HB的微流体流动。该补助金的具体目标是通过开发覆盖层下空间中流动的微流体表示并将这些模型耦合到耳蜗的宏观模型来开发IHC HB刺激模型。在具体目标2中，我们试图确定主动OHC力对Corti器官和流体力对IHC HB的张力依赖性和组合效应。本研究的首要目标是开发一个完整的流体-机械-电气模型，描述耳蜗对外部声刺激和内部电刺激的反应。如果成功的话，这个模型将增强我们对耳蜗故障机制的理解，回答关于耳蜗故障的形态要素及其原因的重要问题。这将改善听力的非侵入性诊断，因为响应措施中的异常可以与特定的病理联系起来。此外，由于我们的模型可以预测电刺激和声刺激的相互作用，因此它将能够预测组合声电假体（例如将 在仍然存在一些残余听力的方案中使用）。最后，耳蜗对整个频谱上的声音响应的数学模型将帮助我们了解耳蜗中如何处理重要的信号类别（例如语音和音乐），这可以导致更好的语音处理算法或耳蜗植入电刺激范例。

DESCRIPTION (provided by applicant): Fluid flow stimulates the hair bundles (HB) of the inner hair cells (IHC) of the cochlea opening the mechano-electric transducer (MET) channels of the IHCs. The resulting current depolarizes the cell body inducing neurotransmitter release and, ultimately, auditory nerve stimulation. The active machinery of the cochlea, driven by motility of outer hair cells (OHC), both tunes the microfluidic excitation of the IHC HBs and provides for nonlinear compression. However, the relative influence of OHC somatic and HB motility on this final fluidic forcing in the cochlea has yet to be conclusively apportioned nor has the microfluidi flow that excites the IHC HB. The specific aims of this grant are to develop models of IHC HB stimulation by developing a microfluidic representation of the flow in the subtectorial space and coupling these models to the macroscopic model of the cochlea. In specific aim 2 we seek to determine the tonotopic dependence and combined effect of active OHC forces on the organ of Corti and of the fluidic forces on the IHC HB. The overarching goal of this research is to develop a complete fluid-mechanical-electrical model that describes the response of the cochlea to both external acoustic and internal electrical stimulation. If successful, this model will enhance our understanding of failure mechanisms in the cochlea, answering important questions as to the morphological elements of the cochlea that fail and why. This will improve noninvasive diagnosis of hearing as abnormalities in the response measures can be linked to specific pathologies. Further, as our model can predict the interaction of electrical and acoustic stimulus it will enable a prediction of the effect of a combined acoustic-electric prosthesis (such as would be used in schemes where some residual hearing is still present). Finally, a mathematical model of the cochlear response to sound over the entire spectrum will help us to understand how important classes of signals are processed in the cochlea (such as speech and music) which can lead to better speech processing algorithms or cochlear implant electrical stimulation paradigms.