Cortical Responses to Cochlear Implant Stimulation

描述（由申请人提供）：本项目的长期目标是了解人工耳蜗（CI）修复听力的神经机制。我们提出了一种新的非人类灵长类动物模型，即普通狨猴（Callithrix jacchus）。狨猴具有丰富的声乐曲目，具有高度的交流能力，可以用于研究CI受试者中与语音处理相关的声音产生和听觉反馈机制。它的听力范围与人类相似，它的听觉皮层与人类共享相似的组织，使其成为解决与人类用户相关的CI研究问题的有价值的模型。作为实现我们长期目标的第一步，我们将使用急性和慢性记录技术检查绒猴AC神经元对耳蜗电刺激的基本反应特性。目的1是绘制由声波和电流脉冲刺激引起的交流的激活区域。首先，在声学刺激下，神经活动将被记录在主要交流神经的张力轴上的许多部位。然后将动物的耳聋和植入多通道CI电极，并对电刺激进行类似的映射。将比较声学和电刺激下交流的活动模式，并评估刺激的特异性和耳蜗频率区域。为了在短时间内完成绘制，这项研究将在麻醉的狨猴中进行。由于没有人在狨猴身上尝试过CI，所以我们需要Aim 1中提出的实验来建立这个新的CI模型。临床CI处理器使用调制脉冲序列来传输语音中重要的时间特征，因此如何在大脑中表示这些信号是非常有趣的。由于麻醉会影响皮层神经元的时间加工，目的2是研究长期植入的清醒狨猴的时间调制电脉冲序列的神经表征。这些目标的结果将有助于阐明参与电听力的大脑过程，并将狨猴建立为未来CI研究的可行模型。这项资助的研究和培训目标为申请人定义了一个逐年的计划，帮助他成为一个独立和成功的学术研究人员。他将学习的方法和程序将使他能够(a)执行和批判性地分析听觉研究，(b)通过书面出版物传播知识，(c)口头交流研究成果，(d)通过拨款写作组织研究目标，以及(e)通过持续的道德培训进行适当的研究实践。为了完成这些目标，博士预科生将由生物医学工程系和耳鼻喉头颈外科的两位赞助者密切指导。提出了详细的培训和指导计划。

DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the neural mechanisms underlying restored hearing by cochlear implants (CI). We propose a new non-human primate model for CI research, the common marmoset (Callithrix jacchus). Marmosets have a rich vocal repertoire, are highly communicative, and can potentially be used to study vocal production and auditory feedback mechanisms related to speech processing in CI subjects. Its hearing range is similar to that of humans and its auditory cortex shares similar organizations as humans, making it a valuable model to address issues in CI research pertaining to human users. As a first step towards our long term goal, we will examine the basic response properties of neurons in marmoset AC to electrical stimulation of the cochlea using both acute and chronic recording techniques. Aim 1 is to map activation areas in AC elicited by acoustic tone and electric current pulse stimuli. First, neural activity will be recorded from many sites across the tonotopic axis of primary AC in response to acoustic stimuli. The animal will then be deafened and implanted with a multi-channel CI electrode, and similar mapping will be conducted in response to electric stimulation. Activity patterns across AC in response to acoustic and electric stimuli will be compared, and the specificity and cochlear frequency-place areas of stimulation will be assessed. To allow for complete mapping in a short amount of time, this study will be done acutely in anesthetized marmosets. Because no one has ever attempted CI in marmosets, the experiments proposed in Aim 1 are necessary for us to establish this new CI model. Clinical CI processors use modulated pulse trains to transmit temporal features important in speech, so it is of great interest how such signals are represented in the brain. Since anesthesia influences temporal processing of cortical neurons, Aim 2 is to study the neural representation of temporally modulated electric pulse trains in awake, chronically implanted marmosets. The results of these aims will help elucidate brain processes involved in electric hearing, and establish the marmoset as a viable model for future CI research. The research and training goals in this grant define a year-by-year plan for the applicant that help prepare him to become an independent and successful academic researcher. The methods and procedures he will learn will allow him to (a) perform and critically analyze auditory research, (b) disseminate knowledge through written publications, (c) orally communicate research findings, (d) organize research goals through grant writing, and (e) conduct proper research practices through continued ethics training. To complete these objectives, the pre-doctoral student will be closely mentored by two sponsors in the Dept of Biomedical Engineering and Otolaryngology - Head & Neck Surgery. A detailed plan for training and mentorship is presented. PUBLIC HEALTH RELEVANCE: The purpose of this research is to develop a new animal model for studying the brain functions responsible for restored hearing by cochlear implants (CI). Results from investigations into how the brain processes acoustic and electric signals may be instrumental in guiding new CI technology improvements.