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（由申请人提供）：耳聋研究的重点是确定永久性听力损失的长期后果，但是，儿童时期的短暂性听力损失可能会导致听觉处理缺陷，这些缺陷会导致感知、言语和语言方面的缺陷。这些缺陷持续存在的一种解释是，短暂性听力损失会导致中枢神经系统细胞特性发生不可逆转的变化，从而可能导致刺激编码退化。因此，该提案将评估以下前提：发育过程中的轻度听力损失会导致与感觉和非感觉神经缺陷相关的行为缺陷，当沙鼠训练和执行听觉心理物理任务时，将通过遥测记录来自多个部位的听觉皮层反应。核心假设：伴随短暂性发育性听力损失的知觉缺陷可归因于感觉处理退化（例如，声学参数的编码）和非感觉机制（例如，任务期间神经反应增加）三个目标测试从该假设中得出的预测：目标 1 将确定是否存在一个特定的发育时期，在此期间感知技能容易受到短暂性听力损失的影响；动物将从三个年龄范围之一开始饲养。在所有情况下，将通过两项听觉任务、振幅 (AM) 或频率调制 (FM) 深度检测来评估心理测量表现，目的 2：确定耳塞是否正常。短暂性听力损失引起的知觉缺陷与感觉表征退化有关，将在初级听觉皮层植入电极阵列，并在每只动物接受目标 1 中描述的任务之一的训练和测试时，通过遥测方式记录神经反应神经测量功能将直接与在相同试验中获得的测量功能进行比较，使我们能够确定暂时性听力损失是否会损害感觉编码，以及损害的严重程度是否可以解释个体动物的知觉缺陷。短暂性听力损失引起的知觉缺陷是否与非感觉机制的破坏相关，我们将比较神经反应对相同的声学参数作为聆听状态的函数：在任务执行期间与被动聆听期间（即动物该实验将使我们能够确定非感觉机制是否与个体动物的知觉缺陷程度相关，这些目标将揭示是否存在短暂性听力损失的发育时期。扰乱了支持感知表现的感觉和非感觉机制的成熟，这意味着持续的神经处理缺陷可能会对学习或提高新的听觉感知技能造成持久的障碍。