OBJECTIVE MEASURE OF LOW-FREQUENCY INNER EAR FUNCTION

低频内耳功能的客观测量

• 批准号: 8431863
• 负责人: Jeffery Lichtenhan
• 金额: $ 15.2万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-13 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8431863
• 关键词: Acoustic Nerve; Action Potentials; Acute; Address; Affect; Animal Model; Animals; Apical; Auditory; Auditory Brainstem Responses; Auditory Threshold; Characteristics; Chronic; Cochlea; Cochlear Nerve; DNQX; Diagnosis; Diffusion; Ear; Edema; Endolymph; Endolymphatic Hydrops; Exposure to; Fiber; Foundations; Frequencies; Functional disorder; Generations; Goals; Hair Cells; Hearing; Hearing Aids; Human; Individual; Infant; Intralymphatic Injections; Iontophoresis; Knowledge; Labyrinth; Low Frequency Deafness; Maps; Masks; Measures; Meniere' s Disease; Microinjections; Minor; Modeling; Monitor; Nerve Fibers; Noise; Pathology; Perilymph; Pharmacologic Substance; Physiological; Physiology; Relative (related person); Scala Tympani; Severities; Specificity; Speech; Staging; Stimulus; Symptoms; Techniques; Testing; Tetrodotoxin; Time; Vasopressins; Work; afferent nerve; hearing impairment; in vivo; nanolitre; novel; otoacoustic emission; relating to nervous system; research study; response; salicylate; seal; sound

DESCRIPTION (provided by applicant): The scientific goal of this work is to understand low-frequency function of the cochlea. The projects will utilize a novel functional measure - the auditory nerve overlapped waveform (ANOW) - which is thought to originate from apical cochlear nerve fibers in response to low-frequency stimuli of low- to moderate-level. In Aim 1 we will compare the cochlear frequency-place specificity of ANOW to several conventionally used functional measures of higher cochlear frequency places (e.g., otoacoustic emissions, compound action potentials) by inducing highly localized regions of cochlear dysfunction. This approach will utilize another novel technique in which nanoliter volumes of toxic pharmaceuticals are introduced into scala tympani from a pipette sealed into the scala wall. When delivered in this manner, the distribution with time and distance is dominated by diffusion that is slow, highly predictable, and can be calculated. Functional measures from individual ears during induced local dysfunction will demonstrate whether ANOW evoked from less than 1 kHz stimuli originates from neural fibers associated with apical turns. Origins of conventionally used measures at both higher frequencies were their generation region is well known and at their low-frequency limit (~1 to 2 kHz) where their generation regions are less specific will be compared. Additionally, we will quantify auditory sensitivity as frequency is lowered from mid-frequencies down to infrasonic frequencies using low-frequency biasing paradigms. In Aim 2 we will use ANOW to objectively quantify, for the first time, low-frequency auditory sensitivity of animal models of endolymphatic hydrops. Low-frequency hearing loss is a primary symptom of human Meniere's disease, of which endolymphatic hydrops is the underlying pathology. A battery of measures will be used to assess function in three different animal models of hydrops and our focus will be to quantify low-frequency sensitivity. We hypothesize that our new ANOW measure will detect changes to low-frequency function in the early stages of endolymphatic hydrops when conventional measures of higher-frequency function do not. These studies will provide a scientific foundation for a better understanding of apical cochlear function. PUBLIC HEALTH RELEVANCE: This proposal addresses a long standing problem of the lack of non-behavioral measures of low-frequency auditory function. Presently available objective tests cannot adequately quantify hearing loss in low-frequency regions associated with speech vowels. An objective test to quantify low-frequency hearing loss would help to accurately fit infant hearing aids and to assist in the diagnosis of Meniere's disease.

描述（由申请人提供）：这项工作的科学目标是了解耳蜗的低频功能。这些项目将利用一种新型的功能度量 - 听觉神经重叠波形（ANOW） - 被认为起源于对低至中等水平的低频刺激的顶端耳蜗神经纤维。在AIM 1中，我们将通过诱导高度高度的人工耳蜗功能障碍区域来比较Anow的耳蜗频率位置与几种常规使用的较高耳蜗频率位置（例如耳声发射，复合动作电位）的常规功能度量。这种方法将利用另一种新型技术，其中从密封到Scala壁的移液器中将有毒药物的纳米素体积引入了Scala Tympani中。当以这种方式传递时，与距离和距离的分布是由缓慢，高度可预测的扩散所支配的，并且可以计算。诱导局部功能障碍期间，来自单个耳朵的功能测量将证明是否从小于1 kHz刺激中引起的肛门是否源自与顶端转弯相关的神经纤维。在两个较高频率上的常规使用措施的起源都是其产生区域众所周知，并且在其低频极限（〜1至2 kHz）中，将比较其发电区域的特异性较低。此外，我们将量化听觉灵敏度，因为使用低频偏置偏见范式从中间频率降低到频率的频率。在AIM 2中，我们将使用ANOW对内淋巴水流动物模型的低频听觉敏感性进行客观量化。低频听力损失是人类梅尼尔氏病的主要症状，其中内淋巴水滴是潜在的病理学。一系列措施将用于评估三种不同动物模型的功能，我们的重点是量化低频灵敏度。我们假设我们的新的AnOW度量将在内淋巴水杂交早期的早期阶段检测到低频功能的变化。这些研究将为更好地理解根尖耳蜗功能提供科学基础。 公共卫生相关性：该提案解决了一个长期存在的问题，即缺乏低频听觉功能的非行为措施。目前可用的客观测试无法充分量化与语音元音相关的低频区域的听力损失。量化低频听力损失的客观测试将有助于准确适应婴儿助听器，并有助于诊断梅尼尔氏病。