Selective Attention: How does Neural Response Modulation in Auditory Cortex Enable Auditory Scene Analysis?

在拥挤的房间里听对话是听觉系统面临的最大挑战之一，也是英国1000万听力损失患者中许多人抱怨的最常见原因。例如，要完全理解你的朋友在餐厅里告诉你的八卦，你必须能够将他的声音与其他人的声音、玻璃杯的叮当声和背景音乐区分开来。你的大脑能够从所有其他声音中选择你朋友的声音--也许是根据他站的位置，或者他的声音的音调。正常的听力听者毫不费力地实现了这一壮举，尽管工程师们还没有创造出一种机器，能够在嘈杂的背景下成功地匹配这种信号分离。在这个提议中，我们试图理解大脑的神经机制如何能够提取感兴趣的声音，而忽略其他声音。我们的研究重点是大脑中一个叫做听觉皮质的区域；这一区域被认为是在上述复杂情况下倾听所必需的。我们的目标是了解听觉皮质神经元的反应如何代表多种相互竞争的声音，以及如何根据听者当前的需求塑造神经反应以最好地代表声音。在这个建议中，我们训练动物进行一系列听力任务，使我们能够对听觉皮质施加不同的要求。动物会从一系列非目标词中听一个目标词。在某些情况下，它们会在静默中进行，在另一些情况下，则会在背景噪音存在的情况下进行。在进一步的变化中，他们将听取两种语流，每种语流来自不同的说话者，并且来自不同的地点，并被要求有选择地注意一个说话者而不是另一个(相当于试图听你的朋友说话，而忽略她身后吵闹的男人)。当动物执行这些任务时，我们将从听觉皮质的神经元进行记录，以了解不同的任务要求如何改变声音唤起神经活动的方式。听觉皮质由多个按等级组织的区域组成，这些区域被认为执行不同的功能。我们将确定这一层次结构的早期区域是否与较高区域不同地受到注意力的影响。在这个项目的第二部分，我们将使用一种名为光遗传学的技术来选择性地抑制听觉皮质特定区域的神经活动。我们将检验这样一种假设，即听觉皮质的不同区域有助于不同类型的注意力--例如，根据声音在空间中的位置来区分声音，而不是根据音调、音色或特定说话者的声音。最后，我们将确定从高级听觉区域到初级听觉区域的反馈是否对主动倾听是必要的。这项工作将代表着我们对这些反馈投射的作用以及它们在积极倾听中所起作用的认识的根本性进步。我们的工作有可能开发出更复杂的、受生物启发的、用于助听器和人工耳蜗的信号处理设备--这两种设备在许多现实世界的听力条件下都表现不佳。听力通过听力图被评估为正常的听者在嘈杂的情况下仍可能难以听清--这个问题在老年听者中尤为严重。处理复杂声音的问题是中枢听觉处理障碍的基础，注意力障碍被认为是包括自闭症、注意力相关多动障碍以及痴呆症和其他神经精神疾病在内的各种发育障碍的基础。了解健康大脑中负责将注意力集中到声音场景中选定来源的神经机制，将为理解并可能治疗这些机制受损的情况奠定基础。

Listening to conversation in a crowded room is one of the greatest challenges that the auditory system faces, and the most common cause of complaint for many of the 10 million people in the UK who suffer hearing loss. For example, to fully appreciate the piece of gossip that your friend is telling you in a restaurant, you must be able to separate his voice from the voices of other people, the clatter of glasses, and the music playing in the background. Your brain is able to 'select' the voice of your friend over all these other sounds - perhaps on the basis of where he is standing, or the pitch of his voice. Normal hearing listeners achieve this feat effortlessly, although engineers have yet to create a machine that can successfully match such signal separation in noisy backgrounds. In this proposal we try to understand how the neural machinery of the brain is able to extract sounds of interest while ignoring others. Our work focuses on a brain area called the auditory cortex; an area that is thought to be necessary for listening in complex situations like the one described above. Our goal is to understand how the responses of neurons in auditory cortex represent multiple competing sounds, and how the neural responses can be shaped in order to best represent sounds according to the listener's current demands.In this proposal we train animals in a series of listening tasks that will enable us to impose different demands on auditory cortex. Animals will listen for a target word amongst a series of non-target words. In some cases they will do this in silence, in others in the presence of background noise. In further variations they will listen to two streams of speech, each from a different talker, and from different locations, and be asked to selectively attend to one talker over the other (equivalent to trying to listen to your friend while ignoring the loud man behind her). We will record from neurons in auditory cortex while animals perform these tasks in order to understand how the different task requirements change the way in which sounds evoke neural activity. Auditory cortex is made of multiple, hierarchically organised areas that are thought to perform different functions. We will determine whether areas early in this hierarchy are affected by attention differently from those in higher areas.In the second part of this project we will use a technique called optogenetics to selectively silence neural activity in particular regions of auditory cortex. We will test the hypothesis that different areas of Auditory Cortex facilitate different sorts of attention - for example separating sounds according to their location in space, as opposed to the pitch or timbre or a particular talker's voice. Finally we will determine whether feedback from higher auditory areas to primary auditory areas is essential for active listening. This work would represent a fundamental advance in our knowledge of the role of these 'feedback' projections and the role that they play in active listening.Our work has the potential to enable the development of more sophisticated, biologically inspired, signal processing devices for hearing aids and cochlear implants - both of which perform poorly in many real-world listening conditions. Listeners whose hearing is assessed via an audiogram as normal can still struggle with listening in noisy situations - this problem is particularly acute in aged listeners. Problems in processing complex sounds underlie Central Auditory Processing Disorder, and disorders of attention are thought to underpin a variety of developmental disorders including autism, attention related hyperactivity disorder, as well as dementia and other neuropsychiatric conditions. Understanding the neural mechanisms in the healthy brain responsible for engaging attention to select sources in a sound scene will lay the foundation for understanding, and potentially treating, conditions in which these mechanisms are impaired.