Developmental effects of early hearing loss on auditory information processing

描述（由申请人提供）：双耳听力是指协调使用双耳信息进行声音定位等听觉感知。本研究的目的是确定早期发育暴露于传导性听力损失（CHL）所产生的双耳听力行为缺陷的神经基础。早期经历过CHL的儿童，特别是单侧CHL，通常表现出双耳听力障碍，即使在CHL已经解决并且双耳听力灵敏度正常后，这种障碍仍然存在。双耳听觉增强了感知能力，可以在存在竞争声音的情况下，对特定来源（如语音）进行分离和选择性地关注。虽然双耳听力能力通常会恢复，但恢复正常听力可能需要几个月甚至几年的时间。因为语言是在嘈杂的混响环境中学习的，比如教室，持续的双耳障碍可能会导致语言和演讲的缺陷。在动物模型中对CHL的神经后果进行了数十年的研究，已经确定了在听觉系统的几个层次上，只有最基本的单耳和双耳神经元反应特性是如何改变的。然而，人类持续的双耳行为缺陷却无法根据这些基本反应特性来解释。本实验采用信息理论的新框架来验证以下假设：早期CHL持续改变下丘神经元携带声音线索信息到声音位置的能力，并且在CHL消退后，这种能力在暴露于正常听力后恢复。下丘，一个已知对双耳听力很重要的中脑核，在经历早期CHL的儿童中被认为是与双耳听力持续性损伤相关的神经缺陷的一个部位。本实验旨在确定下丘神经元反应的哪些方面受到实验诱导的CHL的影响，从而产生信息承载能力的降低，这反映在对定位线索的总体反应性、可靠性和一般敏感性的变化上。作为将这些结果与临床数据联系起来的一种方法，我们将把下丘神经元信息携带能力的变化与非侵入性测量的听觉脑干反应（ABR）的双耳相互作用成分的变化联系起来。在临床研究中，ABR的这些成分已被证明可预测CHL引起的持续性双耳听力障碍。行为分析将用于量化双耳听力缺陷及其恢复。总的来说，这项工作具有生物学和临床意义。从生物学的角度来看，我们将确定实验诱导的单侧CHL影响下丘神经元反应的哪些特定方面，从而导致信息承载能力降低。在临床意义上，我们将确定下丘神经信息处理的改变是否以及如何与双耳诱发电位和声音定位行为的属性相关。

DESCRIPTION (provided by applicant): Binaural hearing refers to the coordinated use of information from the two ears for auditory perceptions such as sound location. The goals of this study are to determine the neural bases for the behavioral deficits in binaural hearing produced by early developmental exposure to conductive hearing loss (CHL). Children that have experienced CHL early in life, particularly unilateral, often show impairments in binaural hearing abilities that persist even after the CHL has been resolved and hearing sensitivity in both ears is normal. Binaural hearing enhances the perceptual ability to separate and selectively attend to particular sources, such as speech, in the presence of competing sounds. While binaural hearing abilities often recover, a return to normal hearing can take months or even years. Because language is learned in noisy reverberant environments, like classrooms, persistent binaural impairments may contribute to deficits in language and speech. Decades of studies of the neural consequences of CHL in animal models have determined how only the most basic of monaural and binaural neuronal response properties are altered at several levels of the auditory system. Nevertheless, the persistent binaural behavioral deficits in humans have defied explanation based on these basic response properties. The proposed experiments use the novel framework of information theory to test the hypothesis that early CHL persistently alters the capacity of neurons in the inferior colliculus to carry information about the acoustical cues to sound location and that this capacity recovers with exposure to normal hearing after resolution of the CHL. The inferior colliculus, a midbrain nucleus known to be important for binaural hearing, has been implicated by clinical studies in children that have experienced early CHL as a site for the neural deficits associated with the persistent impairments in binaural hearing. The proposed experiments are designed to determine which aspects of responses of inferior colliculus neurons are affected by experimentally- induced CHL to produce the reduced information carrying capacities, reflected by changes in overall responsiveness, reliability, and general sensitivity to the localization cues. As one way to link these results to clinical data, we will correlate changes in the information carrying capabilities of inferior colliculus neurons with changes in the binaural interaction components of the non-invasively measured auditory brainstem response (ABR). These components of the ABR have proven to be predictive of the persistent binaural hearing impairments due to CHL in clinical studies. A behavioral assay will be used to quantify deficits in binaural hearing and its recovery. Overall this work has both biological and clinical significance. From a biological perspective, we will determine which particular aspects of responses of inferior colliculus neurons are affected by experimentally-induced unilateral CHL to produce the reduced information carrying capacities. Of clinical significance, we will determine whether and how the altered neural information processing in the inferior colliculus is correlated with attributes of the binaural evoked potentials and sound localization behavior.