The Effects of Reversible Hearing Loss on the Development of Auditory Perception and Neural Coding

可逆性听力损失对听觉感知和神经编码发育的影响

• 批准号: 9241997
• 负责人: Melissa Lynne Caras
• 金额: $ 2.84万
• 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: 2015-03-16 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9241997
• 关键词: Address; Adult; Age; Animal Communication; Animals; Auditory; Auditory Brainstem Responses; Auditory Perception; Auditory area; Behavior; Behavioral; Bilateral; Child; Childhood; Chronic; Cochlea; Code; Cognitive; Communication; Comprehension; Cues; Detection; Development; Earplug; Electrodes; Excision; External auditory canal; Frequencies; Functional disorder; Goals; Hearing; Human; Impairment; Implant; Implanted Electrodes; Laboratory Study; Language Delays; Left; Measurement; Measures; Mediating; Mission; Monitor; National Institute on Deafness and Other Communication Disorders; Neuraxis; Otitis Media; Perception; Performance; Peripheral; Preparation; Process; Psychometrics; Recording of previous events; Recovery; Reporting; Risk; Sensory; Speech; Speech Delay; Stimulus; Telemetry; Testing; Time; Training; Treatment Efficacy; Wireless Technology; attenuation; auditory deprivation; auditory pathway; auditory processing; aversive conditioning; awake; base; behavioral impairment; comparison group; critical developmental period; critical period; deprivation; design; experimental study; falls; hearing impairment; improved; language impairment; language processing; neuromechanism; postnatal; public health relevance; relating to nervous system; response; restoration; sensory input; sound; speech processing; treatment group

 DESCRIPTION (provided by applicant): Childhood hearing loss disrupts central processing of spectral and temporal cues, and may contribute to perceptual deficits, including impaired speech and language processing. Though difficulties can persist even after normal auditory input is restored, earlier restoration is correlated with superior recovery. These findings suggest that there is a critical period of development during which the neural mechanisms subserving auditory processing are particularly vulnerable to sensory perturbations. The key goal of this proposal is to determine whether a brief period of developmental hearing loss disrupts the neural and perceptual detection of amplitude modulation (AM), a temporal cue necessary for speech comprehension and non-human animal communication. The core hypothesis is that transient hearing loss during a critical period disrupts the neural encoding of AM stimuli, thereby producing a perceptual impairment that persists after normal peripheral function is restored. This hypothesis will be explored in detail, with two experimental aims. Specific Aim 1 will determine whether there is a critical period during which temporary hearing loss impairs subsequent AM detection. Sound attenuation will be induced by the insertion of bilateral earplugs at various postnatal ages. After a period of restored auditory input (via earplug removal), animals will be trained and tested on an aversive conditioning paradigm designed to assess amplitude modulation detection capabilities. Behavioral performance will be quantified by calculating correct responses and false alarms. Detection thresholds will be estimated from psychometric functions and compared between earplug-reared animals and normally-reared littermates. These measures will reveal whether there is a critical period during which the maturation of AM detection is sensitive to hearing loss. Specific Aim 2 will examine the impact of temporary, developmental hearing loss on central sensory encoding in auditory cortex of awake-behaving animals performing the AM detection task described in Aim 1. Multi- and single-unit responses will be recorded wirelessly from chronically implanted electrode arrays in left auditory cortex. AM-evoked firing rates and power will be calculated and used to calculate neurometric curves that can be directly compared to behavioral psychometric functions. Additional analyses will assess the relationship between behavior and neural activity on trial-by-trial basis. Results will be compared between earplug-reared and normally-reared animals. The results of this experiment will elucidate whether behavioral deficits arising from developmental hearing loss can be explained by disrupted sensory coding, as is generally assumed, or whether non-sensory (e.g. cognitive) factors contribute to perceptual dysfunction. Together, these findings will reveal whether there is a discrete developmental critical period for the neural representation and perceptual detection of AM. Ultimately, these results may further our understanding of speech and language delays associated with childhood hearing loss, a goal directly relevant to the mission of NIDCD.

 描述（由申请人提供）：儿童听力损失破坏频谱和时间线索的中央处理，并可能导致知觉缺陷，包括言语和语言处理受损。虽然即使在恢复正常听觉输入后困难仍会持续，但早期恢复与上级恢复相关。这些发现表明 存在一个关键的发育时期，在此期间，促进听觉处理的神经机制特别容易受到感官扰动的影响。该提案的主要目标是确定短暂的发育性听力损失是否会破坏振幅调制（AM）的神经和感知检测，这是言语理解和非人类动物交流所必需的时间线索。核心假设是，在关键时期的短暂性听力损失破坏了AM刺激的神经编码， 产生在恢复正常外围功能后仍然存在的知觉损害。这个假设将被详细探讨，有两个实验目的。具体目标1将确定是否存在暂时性听力损失损害后续AM检测的关键时期。在出生后的不同年龄段，插入双侧耳塞会引起声音衰减。在恢复听觉输入（通过移除耳塞）一段时间后，将对动物进行训练，并在设计用于评估振幅调制检测能力的厌恶性条件反射范例上进行测试。行为表现将通过计算正确反应和错误警报来量化。将根据心理测量功能估计检测阈值，并在耳塞饲养的动物和正常饲养的同窝仔之间进行比较。这些措施将揭示是否有一个关键时期，在此期间，AM检测的成熟是敏感的听力损失。具体目标2将研究暂时性发育性听力损失对清醒行为动物听觉皮层中枢感觉编码的影响，这些动物执行目标1中描述的AM检测任务。将从左侧听觉皮层中长期植入的电极阵列无线记录多单位和单单位反应。将计算AM诱发的放电率和功率，并用于计算可直接与行为心理测量功能进行比较的神经测量曲线。其他分析将在逐个试验的基础上评估行为和神经活动之间的关系。将比较耳塞饲养和正常饲养动物的结果。本实验的结果将阐明是否发育性听力损失引起的行为缺陷可以解释为中断的感觉编码，一般认为，或是否非感官（如认知）因素有助于感知功能障碍。总之，这些发现将揭示是否有一个离散的发展关键期的神经表征 和AM的感知检测。最终，这些结果可能会进一步加深我们对与儿童听力损失相关的言语和语言延迟的理解，这一目标与NIDCD的使命直接相关。