Defining the Neuromuscular Mechanisms of Vocal Error Correction

描述（由申请人提供）：神经信号到肌肉活动到行为输出的转换定义了大脑如何控制行为，对大脑功能的全面描述要求我们理解这种转换。发声运动控制对我们的交流能力至关重要，但我们仍然不明白大脑是如何控制发声肌肉活动和声音输出的。这种理解上的差距阻碍了我们理解发声行为的一般原理，也阻碍了我们为影响数百万美国人的各种语言障碍开发有效的治疗方法。鸣禽大脑的特征和相对简单的组织使其成为理解正常和紊乱的声音控制的理想模型系统。此外，我们的实验室还开发了创新的行为范式，利用听觉反馈操作诱导成年鸣禽的声音错误纠正，为听觉反馈操作用于治疗人类声音障碍提供了一个模型。在我的提案中描述的研究将包括在人类受试者中不可能的实验方法，以了解改变的感觉反馈如何在声音错误纠正过程中改变声带肌肉激活的模式，并揭示这种适应性修改是如何由大脑实施的。因此，该研究将显著推进鸣禽作为动物模型的研究机制和优化设计的行为范式的声乐康复。本研究的目的是量化发声肌肉活动模式如何转化为声音输出，在发声错误纠正过程中重塑，并由单个运动前神经元（即直接激活运动神经元的神经元，运动神经元反过来激活发声肌肉）控制。这项工作将利用电生理学记录运动前神经元和肌电图（EMG）记录声带肌肉。假设每个前运动神经元控制多个肌肉，每个肌肉反过来控制多个声学参数，因此，在声乐学习过程中，发声肌肉的子集必须改变它们的活动，以改变单个歌曲的声学参数。目的1将揭示发声肌肉活动向声学参数转化的机制。歌曲的声学特征将与肌内电极记录的肌电图活动相关联，并使用单个声带肌肉的定向电刺激来驱动这些声学特征的变化。目的2将量化发声学习过程中发声肌肉活动的变化，以展示鸣禽系统如何利用发声器官的可用力学实现学习。目的3将描述从单个运动前神经元到声带肌肉的功能投影，同时使用神经和肌肉记录。定量分析（峰值触发肌电图）将用于确定单个运动前神经元是控制单个还是多个肌肉来驱动歌曲。这项工作将为进一步研究语音学习和运动控制的神经肌肉机制奠定基础，并为今后语音控制和感觉运动学习的研究奠定基础。

DESCRIPTION (provided by applicant): The transformation of neural signals to muscle activity to behavioral output defines how the brain controls behavior, and a full account of brain function demands that we understand this transformation. Vocal motor control is critical to our ability to communicate, and yet we still do not understand how the brain controls vocal muscle activity and acoustic output. This gap in understanding hinders our ability to understand the general principles of vocal behavior and develop effective treatments for the various speech disorders affecting millions of Americans. The well-characterized and relatively simple organization of the songbird brain makes it an ideal model system for understanding normal and disordered vocal control. Furthermore, our lab has developed innovative behavioral paradigms that use auditory feedback manipulations to induce vocal error correction in adult songbirds, providing a model for the auditory feedback manipulations used to treat vocal disorders in humans. The research described in my proposal will include experimental approaches not possible in human subjects to learn how altered sensory feedback can modify patterns of vocal muscle activation during vocal error correction and reveal how such adaptive modifications are implemented by the brain. The proposed research will therefore significantly advance the songbird as an animal model for investigating the mechanisms and optimizing the design of behavioral paradigms for vocal rehabilitation. The objective of this proposal is to quantify how patterns of vocal muscle activity are transformed into acoustic output, reshaped during vocal error correction, and controlled by individual premotor neurons (i.e. those that directly activate motor neurons, which in turn activate the vocal muscles). This work will utilize electrophysiology to record premotor neurons and electromyography (EMG) to record vocal muscles. It is hypothesized that each premotor neuron controls multiple muscles, each of which, in turn, controls multiple acoustic parameters and, thus, subsets of vocal muscles must change their activity in concert to shift individual acoustic parameters of song during vocal learning. Aim 1 wil reveal the mechanics of the transformation from vocal muscle activity to acoustic parameters. Acoustic features of song will be correlated with EMG activity recorded using intramuscular electrodes, and targeted electrical stimulation of single vocal muscles will be used to drive changes in those acoustic features. Aim 2 will quantify changes in vocal muscle activity during vocal learning to demonstrate how the songbird system implements learning using the available mechanics of the vocal organ. Aim 3 will characterize the functional projections from single premotor neurons to the vocal muscles using simultaneous neural and muscular recording. Quantitative analysis (spike-triggered EMG) will then be used to determine whether individual premotor neurons control single or multiple muscles to drive song. This work will provide insight into the neuromuscular mechanisms underlying vocal learning and motor control while laying a foundation for future studies in speech control and sensorimotor learning.