Long-lasting deficits induced by transient developmental hearing loss

短暂性发育性听力损失引起的长期缺陷

• 批准号: 8912226
• 负责人: MALCOLM N. SEMPLE
• 金额: $ 31.2万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912226
• 关键词: Abbreviations; Accounting; Acoustics; Address; Adolescent; Adult; Age; Animals; Auditory; Auditory Perception; Auditory area; Behavior; Behavioral; Benchmarking; Bilateral; CNS processing; Child; Childhood; Clinical Research; Cognitive deficits; Communication; Control Animal; Cues; Detection; Development; Earplug; Electrodes; Excision; Figs - dietary; Frequencies; Gerbils; Hearing; Impairment; Implant; Individual; Lead; Learning; Link; Measurement; Measures; Motivation; Neuraxis; Neurons; Neurophysiology - biologic function; Pattern; Perception; Performance; Preparation; Problem behavior; Procedures; Process; Property; Psychometrics; Psychophysics; Recording of previous events; Recovery; Research; Role; Sensory; Sensory Process; Sexual Maturation; Shapes; Site; Speech Perception; Stimulus; Synaptic Membranes; Task Performances; Testing; Training; awake; base; critical period; deafness; design; experience; hearing impairment; human TFRC protein; improved; language processing; novel; public health relevance; relating to nervous system; research study; response; sensory mechanism; skills; sound

 DESCRIPTION (provided by applicant): The emphasis of deafness research has been to establish the long-term consequences of permanent hearing loss. However, auditory processing deficits can be induced by transient hearing loss during childhood. These deficits in perception, speech, and language processing can persist long after normal audibility is restored. One explanation for the persistence of these deficits is that transient hearing loss causes irreversibl changes to CNS cellular properties that may lead to degraded stimulus encoding. Therefore, this proposal will evaluate the premise that transient, mild hearing loss during development induces behavioral deficits that are associated with sensory and non-sensory neural deficits. Auditory cortex responses from multiple sites will be recorded telemetrically from gerbils with a history of transient hearing loss as they train on, and perform, auditory psychophysical tasks. The core hypothesis: Perceptual deficits that accompany transient developmental hearing loss are attributable both to degraded sensory processing (e.g., encoding of acoustic parameters) and non-sensory mechanisms (e.g., increased neural response during task performance). Three aims test predictions emerging from this hypothesis: Aim 1 will determine whether there is a specific developmental epoch during which perceptual skills are vulnerable to transient hearing loss; animals will be reared with bilateral earplugs beginning during one of three age ranges. In all cases, psychometric performance will be assessed on two auditory tasks, amplitude (AM) or frequency modulation (FM) depth detection. Normal cochlear function will be confirmed with ABR measurements following earplug removal. Aim 2: To determine whether perceptual deficits induced by transient hearing loss are associated with a degraded sensory representation, an electrode array will be implanted in the primary auditory cortex, and neural responses will be recorded telemetrically as each animal is trained and tested on one of the tasks described in Aim 1. Neurometric functions will be compared directly to psychometric functions obtained during the same trials, permitting us to establish whether sensory encoding is impaired by transient hearing loss, and whether the magnitude of impairment could explain the perceptual deficits of individual animals. Aim 3: To determine whether the perceptual deficits induced by transient hearing loss is correlated with disruption of a non-sensory mechanism, we will compare neural responses to identical acoustic parameters as a function of listening state: during task performance versus during passive listening (i.e., a period when animals are not engaged in a task). This experiment will permit us to establish whether a non-sensory mechanism is correlated with the magnitude of perceptual deficits within individual animals. Together, these Aims will reveal whether there is a developmental period during which transient hearing loss disrupts the maturation of sensory and non-sensory mechanisms that support perceptual performance. The implication is that persistent neural processing deficits may present an enduring barrier to learning or improving on novel auditory perceptual skills.

 描述（由适用提供）：死亡研究的重点是确定永久性听力损失的长期后果。但是，听觉处理定义可以通过儿童期间的瞬时听力损失引起。在恢复正常可审核性之后，感知，语音和语言处理中的这些定义可能会持续很长时间。这些定义持久性的一种解释是，瞬时听力损失会导致CNS细胞特性的变化，这可能导致刺激编码的降解。因此，该提案将评估一个前提，即发育过程中短暂的轻度听力损失会导致行为定义与感觉和非感官中性定义相关的行为。来自多个站点的听觉皮层反应将从远程记录中记录在训练和执行听觉心理物理任务时具有瞬态听力损失史的史上记录。核心假设：感知定义涉及瞬时发育障碍的归因于降解的感觉处理（例如，声学参数的编码）和非敏感机制（例如，在任务绩效期间增加中性响应）。从这个假设中得出的三个目标测试预测：目标1将决定是否存在特定的发育时期，在此期间，感知技能容易受到短暂的听力损失的影响；动物将在三个年龄范围内开始饲养双侧耳塞。在所有情况下，心理测量表现都将在两个听觉任务，放大器（AM）或频率调制（FM）深度检测上进行评估。除耳塞后，将通过ABR测量确认正常的耳蜗功能。目的2：确定瞬态听力损失引起的感知定义是否与降解的感觉表示相关，电极阵列将在主要的听觉皮层中实现，并且在每只动物经过训练和测试时，将在远程培训中记录和测试神经函数的一项在AIM 1。瞬态听力损失受损，以及损害的幅度是否可以解释单个动物的感知缺陷。目的3：确定瞬态听力损失引起的感知是否与非感官机制的破坏相关，我们将比较对相同的声学参数的中性反应与听力状态的函数：在任务表现与被动聆听期间（即，在动物不参与任务的时期））。该实验将使我们能够确定一种非感官机制是否与单个动物内感知定义的大小相关。这些目标共同揭示了是否存在一个发育时期，在此期间，瞬时听力损失破坏了支持感知性能的感觉和非感官机制的成熟。这意味着持续的神经处理缺陷可能会带来学习或改善新型听觉感知技能的持久障碍。