Active and Nonlinear Models for Cochlear Mechanics

描述(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。由此产生的电流使细胞体去极化，诱导神经递质释放，最终刺激听神经。在外毛细胞(OHC)运动的驱动下，耳蜗的活动机械既调节IHC HBs的微流体兴奋，又提供非线性压缩。然而，OHC体细胞和Hb运动对耳蜗内这一最终的流体强迫的相对影响尚未得到最终的分配，也没有刺激IHC Hb的微流体流。这笔赠款的具体目标是开发IHC HB刺激的模型，方法是开发覆盖下空间的流动的微流体表示，并将这些模型与耳蜗宏观模型相耦合。在特定的目标2中，我们试图确定主动的OHC力对Corti器官的依赖和联合作用，以及流体力对IHC Hb的影响。这项研究的首要目标是开发一个完整的流体-机械-电学模型，描述耳蜗对外部声学和内部电刺激的反应。如果成功，这个模型将加强我们对耳蜗失败机制的理解，回答关于失败的耳蜗形态要素和原因的重要问题。这将改善听力的非侵入性诊断，因为反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和声刺激的相互作用，因此它将能够预测组合的声电假体(例如 用于仍存在一些剩余听力的方案中)。最后，整个频谱上的耳蜗对声音的反应的数学模型将帮助我们理解如何在耳蜗中处理重要的信号类别(如语音和音乐)，这可以导致更好的语音处理算法或人工耳蜗电刺激范例。

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.