An integrative approach to uncovering the neural basis of pitch perception.

当声波进入你的耳朵后，你大脑中成千上万的神经元的活动将这个信号转化为感知体验。我们赋予声音的音调质量，称为它们的“音高”，是这种体验最重要的特征之一。音高感知使我们能够识别熟悉的音乐旋律，狮子的低吼，或者某人声音中好奇的音调。许多动物物种也使用音高来交流和解释他们的世界。例如，母猴在呼唤幼崽时会提高音调，就像人类母亲对孩子说话一样。随着年龄的增长，我们使用某些类型的音高线索的能力会下降，即使是听力正常的人也是如此。因此，了解脑细胞如何计算音高，以及年龄和经验如何改变这些过程，可能有助于改善老年人的听力。虽然我们作为倾听者可以毫不费力地区分低音和高音，但要完全了解我们的大脑如何完成这一壮举，对神经科学来说是一个巨大的挑战。对人类的功能成像研究表明，大脑的某些部分可能是专门用于音高感知的，但关于大脑的“音高中心”到底在哪里仍然有很多争论。此外，这些大脑成像技术没有足够的分辨率来告诉我们大脑中的神经细胞如何代表声音的音高。因此，测量动物个体脑细胞活动的实验对于回答这个开放的研究问题至关重要。我们在牛津大学的研究将使用现代神经科学方法的创新组合来揭示音高感知的神经基础。目前还不清楚许多动物的音高感知与人类的音高感知有何关系。因此，我们将开始我们的研究，通过比较声音的物理特性，人类和我们的动物模型，雪貂，用来确定其音高。我们将训练动物在行为任务中区分低音和高音，人类志愿者将接受类似任务的训练。由于耳朵中的神经细胞比脑细胞更容易理解和简单，我们可以建立计算机模型来预测耳朵中的神经细胞如何对不同的声音做出反应。通过将这些模型预测与真实的行为表现进行比较，我们将确定动物和人类如何使用声音特征进行音高判断。为了发现大脑不同部位的神经元如何代表与音高感知相关的声音特征，我们使用微电极测量动物执行音高判断任务时神经细胞的活动。微电极将在手术麻醉下植入，这样动物就不会感到疼痛。通过记录动物的大脑活动，当它们被训练从不同的声音属性中获得音高时，我们将揭示大脑对音高的表征如何通过经验来适应。最后，我们将使用新的基于激光的显微镜技术来拍摄动物在听声音时大量脑细胞活动的视频。这些实验将使我们能够绘制出音高选择性神经细胞如何分布在大脑表面，其密度和分辨率前所未有。研究结果将表明大脑中是否存在音高中心，如果存在，它位于何处。总之，这些实验将大大推进我们对大脑过程的认识，这些过程使我们能够跟随我们最喜欢的曲调的旋律。

After a sound wave enters your ear, the activity of hundreds of thousands of neurons throughout your brain transforms this signal into a perceptual experience. The tonal quality that we ascribe to sounds, known as their "pitch", is one of the most important features of this experience. Pitch perception allows us to recognize a familiar musical melody, the low growl of a lion, or the inquisitive tone of someone's voice. Many animal species also use pitch to communicate and interpret their world. For instance, mother monkeys have been shown to raise the pitch of their voice when calling their young, just as human mothers do when speaking to their children. As we age, our ability use some types of pitch cues declines, even in individuals with normal hearing thresholds. Therefore, an understanding of how brain cells compute pitch, and how age and experience can change these processes, may help to improve hearing in elderly people.While our ability to distinguish a low note from a high note comes effortlessly to us as listeners, it has proved a great challenge for neuroscience to fully understand how our brain accomplishes this feat. Functional imaging studies in humans suggest that certain parts of the brain may be specialized for pitch perception, but there is still much debate over where exactly the brain's "pitch center" is located. Moreover, these brain imaging techniques do not have sufficient resolution to tell us how nerve cells in the brain represent the pitch of a sound. Experiments that measure the activity of individual brain cells in animals are therefore essential to answering to this open research question. Our research at the University of Oxford will use an innovative combination of modern neuroscience methods to uncover the neural basis of pitch perception. It is unclear how pitch perception in many animals relates to that that of humans. We will therefore begin our studies by comparing the physical properties of sound that humans and our animal model, the ferret, use to determine its pitch. We will train the animals to distinguish low- from high-pitched sounds on a behavioural task, and human volunteers will be trained on a similar task. Because the nerve cells in the ear are better understood and simpler than brain cells, we can build computer models that predict how nerve cells in the ear will respond to different sounds. By comparing these model predictions to real behavioural performance, we will determine how animals and humans use sound features to make pitch judgments. To discover how neurons in different parts of the brain represent sound features that are relevant to pitch perception, we use microelectrodes to measure the activity of nerve cells in the animals while they perform the pitch judgment task. The microelectrodes will be implanted under surgical anaesthesia, so that the animals do not feel pain. By recording brain activity in the animals as they are trained to derive pitch from different sound properties, we will reveal how the brain's representation of pitch can adapt through experience. Finally, we will use new, laser-based microscope technology to make videos of the activity of large numbers of brain cells while animals are listening to sounds. These experiments will allow us to map out how pitch-selective nerve cells are distributed across the surface of the brain, with a density and resolution that have never before been possible. The results will indicate whether a pitch center exists in the brain, and, if so, where it is located. Together, these experiments will significantly advance our knowledge of the brain processes that allow us to follow the melody of our favourite tune.