Toward a Biomarker for Spatial Hearing Ability

空间听力能力的生物标志物

• 批准号: 10472570
• 负责人: Zoe Owrutsky
• 金额: $ 3.2万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10472570
• 关键词: Acoustic Nerve; Acoustics; Auditory; Auditory Brainstem Responses; Basilar Membrane; Binaural; Biological Markers; Biological Process; Brain Stem; Brain region; Cell Nucleus; Characteristics; Child; Clinical; Clinical Research; Cochlear nucleus; Comparative Study; Complex; Computer Models; Conductive hearing loss; Contralateral; Correlation Studies; Cues; Dependovirus; Diagnosis; Ear; Elderly; Electrocardiogram; Electrophysiology (science); Environment; Etiology; Evoked Potentials; Fiber; Frequencies; Future; Generations; Gerbils; Goals; Halorhodopsins; Handedness; Hearing; Hearing Tests; Human; Ipsilateral; Knowledge; Lateral; Lesion; Light; Link; Mammals; Maps; Measurement; Measures; Medial; Methodology; Methods; Nature; Nerve Fibers; Neurons; Olives - dietary; Optics; Persons; Pharmacology; Population; Reporting; Research Design; Residual state; Restaurants; Sensory; Source; Stimulus; Sum; Synapses; Techniques; Testing; Time; Travel; aged; auditory pathway; auditory processing; auditory stimulus; autism spectrum disorder; base; binaural hearing; computer studies; design; diagnostic biomarker; diagnostic value; electrical measurement; experience; experimental study; hearing impairment; heart function; improved; indexing; infancy; interest; lateral superior olive; medial superior olive; neural circuit; normal hearing; novel; optogenetics; relating to nervous system; sound; trapezoid body

Project Summary Non-invasive measurement of electrical activity in the body has been used for over a century to assess biological function. For example, characteristics of the electrocardiogram (ECG) are widely used to assess very specific cardiac functions. This is possible because the mechanisms and sources of ECG waves are known. Similarly, stimulus evoked potentials are routinely used to assess sensory function. For example, auditory brainstem responses (ABRs) evoked by sound are used to assess function of one (monaural) or both (binaural) ears. Distinct peaks in ABR waveforms map roughly to specific nuclei or fiber tracts in the ascending auditory pathway and can be used to assess function at these different levels. While ABRs are widely used to assess monaural hearing, assessment of binaural hearing remains a major clinical challenge - no routine objective clinical measure currently exists to test for it. However, a derived component of the ABR, referred to as the binaural interaction component (BIC), has been shown over the past decades to correlate with binaural hearing capabilities in normal and hearing impaired listeners and thus represents a promising objective measure of binaural function. The most prominent BIC peak, termed DN1, has been shown to be reduced (or even absent) in populations with binaural hearing impairments including children who have experienced temporary conductive hearing loss or been diagnosed with central auditory processing or autism spectrum disorders, and the aged. Moreover, the amplitude and latency of DN1 vary systematically with binaural cues, interaural time and level differences, and can predict perceived laterality of an auditory stimulus. Despite the promise of BIC as a biomarker, in humans BIC DN1 is small and unreliably measured using typical clinical methodology. We posit that a better understanding of the brainstem source of DN1 may provide clues to why it is unreliably measured and also suggest avenues for more reliable measurement methods. Earlier attempts to resolve the circuitry of the BIC using pharmacological and lesioning approaches were inconclusive. However, several recent studies suggest that the lateral (LSO) and not the medial (MSO) superior olive of the brainstem as a likely candidate. However, these studies are correlational and thus do not prove the LSO is the source of the BIC. The LSO receives near-coincident excitatory and inhibitory input from the two ears which could theoretically underlie BIC DN1. The experiments comprising Aim 1 employ a novel combination of optogenetic and electrophysiological techniques to conclusively determine the brain region generating the BIC. Based in part on these results, Aim 2 will determine the optimal stimulus for evoking the BIC, with the goal of reducing variability in BIC measurements. These experiments will reveal the neural generator of the BIC DN1 and reduce sources of variability in BIC measurements by determining the optimal stimuli to elicit it. These findings will pave the way for future human studies designed to improve the diagnostic utility of the BIC as a biomarker for binaural hearing ability.

项目概要 一个多世纪以来，人们一直使用无创测量体内电活动来评估 生物学功能。例如，心电图 (ECG) 的特征被广泛用于评估非常严重的情况。 特定的心脏功能。这是可能的，因为心电图波的机制和来源是已知的。 同样，刺激诱发电位通常用于评估感觉功能。例如，听觉 由声音引起的脑干反应 (ABR) 用于评估其中一个（单耳）或两者的功能 （双耳）耳朵。 ABR 波形中的明显峰值大致映射到上行中的特定核或纤维束 听觉通路可用于评估这些不同水平的功能。虽然 ABR 被广泛用于 评估单耳听力，评估双耳听力仍然是一个主要的临床挑战 - 没有常规 目前存在客观的临床测量方法来对其进行测试。然而，ABR 的派生组件，称为 作为双耳交互成分（BIC），过去几十年已被证明与双耳交互相关 正常和听力受损听众的听力能力，因此代表了一个有希望的目标 双耳功能的测量。最突出的 BIC 峰（称为 DN1）已被证明已降低（或 甚至没有）在双耳听力障碍的人群中，包括经历过听力障碍的儿童 暂时性传导性听力损失或被诊断患有中枢听觉处理或自闭症谱系 疾病和老年人。此外，DN1 的幅度和潜伏期随双耳线索系统地变化， 耳间时间和电平差异，并且可以预测听觉刺激的感知偏侧性。尽管 BIC 作为生物标志物的前景，在人类中，BIC DN1 很小，并且使用典型的临床测量结果并不可靠 方法论。我们假设更好地了解 DN1 的脑干来源可能会提供线索 的测量不可靠，并且还提出了更可靠的测量方法的途径。早期的尝试 使用药理学和损伤方法解决 BIC 的电路尚无定论。然而， 最近的几项研究表明，脑干的外侧（LSO）而不是内侧（MSO）上橄榄 作为可能的候选人。然而，这些研究是相关的，因此并不能证明 LSO 是 BIC。 LSO 从两只耳朵接收几乎一致的兴奋性和抑制性输入，这可以 理论上是 BIC DN1 的基础。包括目标 1 的实验采用了光遗传学的新颖组合 和电生理学技术来最终确定产生 BIC 的大脑区域。总部设在 根据这些结果，目标 2 将确定引发 BIC 的最佳刺激，目标是减少 BIC 测量的可变性。这些实验将揭示 BIC DN1 的神经发生器和 通过确定引起 BIC 测量结果的最佳刺激来减少 BIC 测量结果的变异性来源。这些发现 将为未来旨在提高 BIC 作为生物标志物的诊断效用的人体研究铺平道路 对于双耳听力能力。