Auditory Processing Deficits in Early-Onset Conductive Hearing Loss

项目总结 慢性耳部感染引起的儿童早期传导性听力损失(ECHL)可导致长期听力损失 听觉感知和语言处理方面的问题。当成长过程中面临环境挑战时，例如 依恋中断和社会经济地位低，这些孩子长期使用语言的风险更大 赤字。一种解释是，早期生活应激(ELS)和ECHL共同作用于神经 在听觉上产生复合缺陷的系统。虽然ELS对更高的 涉及注意力和学习的神经区，我们的证据表明ELS的一种新的听觉效应：改变 听觉皮层(ACX)的声音诱发反应。这将降低感官表征的保真度。 可用于受ELS影响的较高区域，并可能导致ELS的已知认知问题。是这样的 感觉退化会使ECHL引起的听觉感知问题复杂化。 这一建议的中心假设是ELS导致听觉知觉障碍，并恶化ECHL- 通过改变中央听觉系统中的感觉表征而导致的缺陷。我们将衡量以下方面的影响 ELS对听觉知觉和ACX敏感性的影响，并将确定听觉中是否存在改变的抑制 系统导致了可测量的赤字。声音中的幅度调制(AM)将用于确定 知觉和神经听觉敏感性，因为AM是语音和动物发声所固有的，以及 他们对ACX的准确感知涉及到ACX。在目标1中，我们测试ELS是否损害听觉和 使ECHL造成的损害更加严重。动物将被训练来检测具有不同参数的AM声音 (调制速率和深度)。这将通过识别AM参数来表征赤字的性质 对于动物来说，当用ELS和/或ECHL饲养时，都是具有挑战性的。在目标2中，我们测试知觉 ELS和ELS+ECHL引起的缺陷涉及ACX的感觉编码受损。神经反应时 动物被动地听AM的声音会表明感觉表征发生了变化。任务绩效已知 通过接触额外的非感觉区域，包括已知的认知区域，来增加ACX的敏感度 由ELS更改。我们将通过以下方式确定ELS是否损害了对听觉处理的非感官贡献 比较动物在学习和执行任务时的ACX反应与被动地听 同样的声音。在目标3中，我们将确定ELS和ELS+ECHL是否改变了ACX和其他皮质下的抑制 听觉区域，以及抑制性抢救是否改善ACX功能和知觉。这将确定 ELS-ECHL效应背后的机械性变化。总之，这些实验将揭示出在多大程度上 早期应激通过改变感觉和非感觉区域来损害听觉处理。这将扩大 我们对与听力损失相互作用的体验的理解，并为未来的实验提供了重点 更详细地确定ELS可能改变听觉功能的机制。

PROJECT SUMMARY Early conductive hearing loss (eCHL) in children, arising from chronic ear infections, can induce long-lasting problems in auditory perception and language processing. When raised with environmental challenges, such as disrupted attachment and low socio-economic status, these children are at greater risk for long-term language deficits. One explanation is that early-life stress (ELS) and eCHL in conjunction could interact in the nervous system to produce compounded deficits in auditory perception. While ELS has well-known effects on higher neural regions involved in attention and learning, our evidence suggests a novel auditory effect for ELS: altering sound-evoked responses in the auditory cortex (ACx). This would degrade the fidelity of sensory representations available to higher regions affected by ELS, and could contribute to known cognitive problems with ELS. Such sensory degradation would compound the auditory perceptual issues arising from eCHL. The central hypothesis of this proposal is that ELS causes deficits in auditory perception, and worsens eCHL- induced deficits, by altering sensory representations in the central auditory system. We will measure effects of ELS on auditory perception and ACx sensitivity, and will determine whether altered inhibition in the auditory system contributes to measured deficits. Amplitude modulations (AM) in sounds will be used to determine perceptual and neural auditory sensitivity, because AMs are intrinsic to speech and animal vocalizations, and their accurate perception involves ACx. In Aim 1, we test whether ELS impairs auditory perception and compounds impairments from eCHL. Animals will be trained to detect AM sounds with varying parameters (modulation rate and depth). This will characterize the nature of the deficits by identifying AM parameters that are challenging for animals to detect when raised with ELS, eCHL, or both. In Aim 2, we test whether perceptual deficits arising from ELS and ELS+eCHL involve impaired sensory encoding in ACx. Neural responses while animals listen passively to AM sounds will indicate altered sensory representations. Task performance is known to increase ACx sensitivity by engaging additional non-sensory areas, including cognitive regions known to be altered by ELS. We will determine whether ELS impairs non-sensory contributions to auditory processing, by comparing ACx responses while animals are learning and performing the task versus listening passively to the same sounds. In Aim 3, we will determine if ELS and ELS+eCHL alter inhibition in ACx and other subcortical auditory regions, and whether inhibitory rescue improves ACx function and perception. This will identify mechanistic changes underlying ELS-eCHL effects. Together, these experiments will reveal the extent to which early-life stress impairs auditory processing via changing sensory and non-sensory regions. This will broaden our understanding of experiences that interact with hearing loss, and provide a focus for future experiments to determine in greater detail the mechanisms by which ELS may alter auditory function.