Postnatal Cochlear Maturation and Sources of Immaturity

描述（由申请人提供）：本项目的长期目标是：(1)研究出生后早期人类耳蜗功能的最终成熟阶段；(2)研究新生儿耳蜗功能不成熟的机制或来源。这种理解将为更精确地识别耳蜗功能障碍和支持听觉假体的开发和改进提供一个框架。这也将阐明特定的耳蜗元素对听力和听力成熟的重要性。第一个目标将通过研究产后早期失真产物耳声发射（dpoae）的抑制和幅度增长来实现。最近的结果清楚地表明，DPOAE抑制的不成熟和抑制生长持续超过足月分娩，因此迫使研究者检查出生后的时间来定义成熟的时间过程。第二个目标将通过研究这种基于dpoae的不成熟的三个潜在来源来实现：外毛细胞功能、内侧传出系统功能和中耳功能。实验1是一项纵向实验，记录DPOAE同侧抑制和振幅增长，作为新生儿从出生到6个月大的两个f2频率（1500和6000 Hz）和三个主要音调水平下耳蜗功能和非线性的测量。早产儿和足月出生的受试者将被包括在内，以检查这两组的成熟过程是否相似。从出生到6个月，随着新生儿年龄的增长，将分析抑制调谐曲线宽度、斜率、尖端和抑制生长斜率的措施，以及DPOAE I/O功能的特征。实验2将相同的DPOAE模式（如上所述）应用于已知或诱导外毛细胞功能障碍的受试者和新生儿。新生儿DPOAE抑制数据将与OHC功能障碍组的数据进行比较，以验证OHC不成熟导致新生儿不成熟DPOAE抑制的假设。在实验3中，对侧dpoae的抑制将作为对听力正常的成人和新生儿内侧耳蜗（MOC）系统功能的测试。将在这些受试者中建立MOC响应强度的连续统（从“弱”到“强”），并研究DPOAE抑制特性与MOC功能之间的相关性。该分析将验证未成熟MOC功能有助于新生儿未成熟DPOAE抑制的假设。实验4包括测量所有新生儿中耳功能的声能反射。能量反射率的测量已被证明可以有效地预测OAE水平的变化，并且对中耳不成熟和病理敏感。我们将研究能量反射率变化与DPOAE抑制和振幅变化之间的相关性，以阐明不成熟的中耳系统对DPOAE抑制不成熟的贡献。

DESCRIPTION (provided by applicant): The long-term goals of this project are: (1) to investigate the final maturational stages of human cochlear function during early postnatal life and (2) to investigate the mechanism or sources underlying immaturity of cochlear function in neonates. This understanding will provide a framework for more precise identification of cochlear dysfunction and support for development and refinement of auditory prostheses. It will also elucidate the importance of specific cochlear elements to hearing and hearing maturation. The first goal will be accomplished by studying suppression and amplitude growth of distortion product otoacoustic emissions (DPOAEs) during early postnatal life. Recent results have clearly shown an immaturity in DPOAE suppression and suppression growth persists beyond term birth, thus compelling investigators to examine the postnatal period to define maturational time course. The second goal will be accomplished by investigating three potential sources of this DPOAE-based immaturity: outer hair cell function, medial efferent system function and middle ear function. Experiment 1 is a longitudinal experiment to record DPOAE ipsilateral suppression and amplitude growth as measures of cochlear function and non-linearity in neonates from birth through 6 months of age at two f2 frequencies (1500 and 6000 Hz) and three primary tone levels. Prematurely born and term-born subjects will be included to examine whether maturation proceeds similarly in these two groups. Measures of suppression tuning curve width, slope, tip and suppression growth slope, as well as characteristics of the DPOAE I/O function, will be analyzed for session effects as neonates increase in age from birth through 6 months. Experiment 2 applies the same DPOAE paradigms (as described above) to subjects with known or induced outer hair cell dysfunction and to neonates. Neonatal DPOAE suppression data will be compared to data from groups with OHC dysfunction to test the hypothesis that OHC immaturity contributes to immature DPOAE suppression in neonates. In Experiment 3 contralateral suppression of DPOAEs, as a test of medial olivocochlear (MOC) system function, will be measured in normal hearing adults and neonates. A continuum of MOC response strength (from "weak" to "strong") will be established in these subjects and correlations between DPOAE suppression characteristics and MOC function will be examined. This analysis will test the hypothesis that immature MOC function contributes to immature DPOAE suppression in neonates. Experiment 4 includes the measurement of acoustic energy reflectance as a test of middle ear function in all neonatal subjects. Measures of energy reflectance have been shown to effectively predict variance in OAE level and are sensitive to middle ear immaturity and pathology. Correlations between variance in energy reflectance and variance in DPOAE suppression and amplitude will be examined to elucidate the contribution of an immature middle ear system to immaturities in DPOAE suppression.