The Impact of "Offset-Deafness" on Perception and Cortical Processing of Speech Sounds in Noise

在噪声环境中理解语音是人类听觉最困难也是最重要的任务之一。在噪声中对语音的准确感知不仅涉及耳朵内的听觉机制，还涉及大脑内的听觉机制。许多患有发育障碍的儿童和老年人在嘈杂的环境中感知言语有异常困难，即使他们的听力和在安静环境中感知言语的能力是正常的。这些噪音中言语感知的困难被认为至少部分是由听觉大脑的发育和年龄相关异常引起的，而不是耳朵。然而，在噪声环境中影响语音感知的听觉大脑异常的性质仍然知之甚少，我们最近发现，在小鼠模型中，听觉大脑对声音偏移（消失）的敏感性可能受损，而对声音起始（出现）的敏感性则不会。这种以前未被认识到的听力困难形式-“偏聋”-似乎是在大脑而不是耳朵中产生的。人类听力的标准临床测试几乎完全集中在对声音起始的敏感性上，甚至不会检测到听觉大脑对声音偏移的敏感性的特定缺陷，就像在小鼠模型中观察到的那样。然而，对声音偏移的敏感性被认为是关键的噪声中的语音知觉，因此，它是可能的，在人类的“偏移性耳聋”可能会产生困难的噪声中的语音知觉，尽管在临床测试中显然是正常的听力。我们建议测试这一假设，使用我们的小鼠模型自然发生的“偏置耳聋”，和正常小鼠，我们将诱导“偏置耳聋”实验抑制活动的声音偏置敏感细胞的听觉脑干。我们将测量小鼠在噪音中检测类似语音的声音变化的能力，同时我们将测量这些声音引起的听觉皮层活动。此外，我们将收集类似的行为和神经测量大脑对简单声音的敏感性，例如噪音中的短暂间隙和安静中的安静音调。通过比较有和没有“偏置耳聋”的小鼠之间的结果，我们将实现我们的主要目标：确定是否降低听觉大脑对声音偏置的敏感性会损害噪音中语音样声音的感知和皮层处理。其他目标将是确定是否可以从对噪声中短暂间隙的敏感性预测噪声中言语敏感性的异常;以及听觉脑干中的声音偏移敏感细胞如何影响感知。这些实验可能有助于我们理解为什么一些听力明显正常的人-特别是患有发育障碍的儿童和老年人-在嘈杂的环境中对言语的感知有异常的困难。如果“偏置性耳聋”确实会损害在嘈杂环境中的言语感知，那么引入简单的声音偏置敏感性临床测试可能有助于识别可能难以在噪声中感知言语的患者。此外，增强声音偏移感知的新型辅助听力设备可能会提高幼儿在嘈杂教室中有效听力的能力，以及老年人在老年时保持健康的社会互动水平的能力。

Understanding speech in noisy environments is one of the most difficult --- and important --- tasks of human hearing. Accurate perception of speech in noise involves not only mechanisms of hearing within the ear, but also mechanisms of hearing within the brain. Many children with developmental disorders and elderly adults have abnormal difficulty perceiving speech in noisy environments, even when their hearing and their ability to perceive speech in quiet environments is normal. These difficulties with speech-in-noise perception are thought to arise, at least in part, from developmental and age-related abnormalities in the auditory brain rather than the ear. However, the nature of the auditory brain abnormalities affecting perception of speech in noisy environments remains poorly understood.We have recently discovered, in a mouse model, that auditory brain sensitivity to sound offsets (disappearances) can be impaired while sensitivity to sound onsets (appearances) is not. This previously unrecognised form of hearing difficulty --- "offset-deafness" --- appears to arise in the brain rather than the ear. Standard clinical tests of human hearing focus almost exclusively on sensitivity to sound onsets, and would not even detect a specific deficit in auditory brain sensitivity to sound offsets like that observed in the mouse model. However, sensitivity to sound offsets is thought to be critical for speech-in-noise perception; therefore, it is possible that "offset-deafness" in humans could produce difficulties with speech-in-noise perception despite apparently normal hearing in clinical tests.The main objective of this research is to test the hypothesis that "offset-deafness" can disrupt perception and cortical processing of speech-like sounds in noise. We propose to test this hypothesis using both our mouse model of naturally occurring "offset-deafness", and normal mice in which we will induce "offset-deafness" experimentally by suppressing activity of sound-offset-sensitive cells in the auditory brainstem. We will measure the ability of the mice to detect changes in speech-like sounds in noise, and simultaneously we will measure auditory cortical activity evoked by those sounds. In addition, we will collect similar behavioural and neural measures of brain sensitivity to simpler sounds such as brief gaps in noise and quiet tones in silence. By comparing results between mice with and without "offset-deafness", we will achieve our main objective: to determine whether reduced auditory brain sensitivity to sound offsets impairs perception and cortical processing of speech-like sounds in noise. Additional objectives will be to determine whether abnormalities in speech-in-noise sensitivity can be predicted from sensitivity to brief gaps in noise; and how sound-offset-sensitive cells in the auditory brainstem influence perception.These experiments may help us to understand why some people with apparently normal hearing --- especially children with developmental disorders and elderly adults ---- have abnormal difficulty with perception of speech in noisy environments. If "offset-deafness" can indeed impair perception of speech in noisy environments, then the introduction of simple clinical tests for sound-offset sensitivity could help to identify patients likely to have to difficulty with speech-in-noise perception. Moreover, novel assisted-listening devices that enhance perception of sound offsets might improve the ability of young children to hear effectively in noisy classrooms, and of elderly adults to maintain healthy levels of social interaction into old age.