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.

项目摘要 非侵入性测量体内的电活动已有一个多世纪来评估 生物功能。例如，心电图（ECG）的特征被广泛用于评估 特定的心脏功能。这是可能的，因为已知ECG波的机理和来源。 同样，刺激诱发的电位通常用于评估感觉功能。例如，听觉 声音引起的脑干响应（ABR）用于评估一个（单声道）或两者兼而有之 （双耳）耳朵。 ABR波形中的不同峰值映射到上升的特定核或纤维区域 听觉途径可用于评估这些不同级别的功能。虽然ABR被广泛习惯 评估单声听力，双耳听证的评估仍然是一个重大的临床挑战 - 没有常规 目前存在客观的临床措施来测试它。但是，ABR的派生成分，称为 由于双耳相互作用分量（BIC）已在过去几十年中已显示与双耳相关 正常和听力受损的听众的听力能力，因此代表了一个有希望的目标 双耳功能的度量。最突出的BIC峰，称为DN1，已被证明已减少（或 甚至缺席）在患有双耳听力障碍的人群中，包括经历过的孩子 临时导电性听力损失或被诊断为中央听觉处理或自闭症谱系 疾病和年龄。此外，DN1的幅度和潜伏期随着双耳线索的系统变化， 播出时间和水平差异，可以预测听觉刺激的横向性。尽管有 BIC作为生物标志物的承诺，在人类中，BIC DN1很小，不可行地使用典型的临床测量 方法论。我们认为，更好地了解DN1的脑干来源可能会为为什么 是不可取的测量，还建议使用更可靠的测量方法的途径。较早的尝试 使用药理学和病变方法解决BIC的电路尚无定论。然而， 最近的一些研究表明，横向（LSO）而不是脑干的内侧（MSO）上橄榄 作为候选人。但是，这些研究是相关的，因此没有证明LSO是 Bic。 LSO从两只耳朵中获得接近偶然的兴奋性和抑制性输入 理论上是BIC DN1的基础。包含AIM 1的实验采用了新颖的光遗传学组合 和电生理技术以最终确定产生BIC的大脑区域。基于 在这些结果上，AIM 2将确定唤起BIC的最佳刺激，目的是减少 BIC测量的可变性。这些实验将揭示BIC DN1和 通过确定最佳刺激以引起BIC测量的可变性来源。这些发现 将为未来的人类研究铺平道路，旨在改善BIC作为生物标志物的诊断实用性 用于双耳听力能力。