Auditory Processing Deficits in Early-Onset Conductive Hearing Loss

项目摘要 由慢性耳部感染引起的儿童早期传导性听力损失（eCHL）， 听觉感知和语言处理的问题。面对环境挑战， 由于依恋中断和社会经济地位低下，这些儿童长期面临更大的风险， 语言缺陷一种解释是，早期生活压力（ELS）和eCHL结合在一起，可以相互作用， 神经系统产生复合缺陷的听觉感知。虽然ELS对 更高的神经区域参与注意力和学习，我们的证据表明ELS有一种新的听觉效应： 改变听觉皮层（ACx）的声音诱发反应。这将降低感官的保真度。 受ELS影响的更高区域可用的表征，并可能导致已知的认知问题 在ELS。这种感觉退化将加剧由eCHL引起的听觉感知问题。 该建议的中心假设是ELS导致听觉感知缺陷，并导致eCHL- 通过改变中枢听觉系统的感觉表征来诱发缺陷。我们将测量 ELS对听觉感知和ACx敏感性的影响，并将确定是否改变了听觉抑制 系统有助于衡量赤字。声音中的振幅调制（AM）将用于确定 感知和神经听觉灵敏度，因为AM是语言和动物发声的固有特性， 它们的准确感知涉及ACx。在目标1中，我们测试ELS是否会损害听觉感知， 从eCHL化合物损伤.将训练动物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参数来表征缺陷的性质， 当用ELS、eCHL或两者饲养时，动物很难检测到。在目标2中，我们测试是否 由ELS和ELS+eCHL引起的感知缺陷涉及ACx中受损的感觉编码。神经 当动物被动地听AM声音时的反应将指示改变的感觉表征。任务 已知性能通过接合额外的非感觉区域来增加ACx敏感性，包括 已知被ELS改变的认知区域。我们将确定ELS是否会损害非感官 通过比较动物在学习和表演时的ACx反应， 与被动地听同样的声音相比。在目标3中，我们将确定ELS和ELS+eCHL是否改变 ACx和其他皮质下听觉区域的抑制，以及抑制性补救是否改善ACx功能 和感知。这将确定ELS-eCHL效应背后的机制变化。所有这些 实验将揭示早期生活压力通过改变感觉来损害听觉处理的程度。 和非感官区域。这将拓宽我们对与听力损失相互作用的经历的理解， 并为未来的实验提供一个焦点，以更详细地确定ELS可能 改变听觉功能

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.