Cortical Responses to Cochlear Implant Stimulation

该项目的长期目标是了解人工耳蜗(CI)恢复听力的神经机制。我们提出了一种新的用于CI研究的非人类灵长类动物模型--普通绒猴(Callithrix Jacchus)。绒猴拥有丰富的发声曲目，具有很强的交际性，可用于研究脑梗塞受试者的发声和与语音处理相关的听觉反馈机制。它的听力范围与人类相似，其听觉皮质与人类共享相似的组织，使其成为解决与人类用户有关的CI研究问题的有价值的模型。 作为迈向我们长期目标的第一步，我们将使用急性和慢性记录技术来检测绒猴AC中神经元对耳蜗电刺激的基本反应特性。目的1是绘制声调和电流脉冲刺激引起的交流电的激活区。首先，神经活动将被记录跨越初级AC的正直轴线的多个部位，以响应声刺激。然后，动物将被致聋并植入多通道CI电极，并将对电刺激进行类似的标测。将比较AC对声和电刺激的反应的活动模式，并评估刺激的特异性和耳蜗区的频率。为了在短时间内完成测绘，这项研究将在麻醉的绒猴身上进行。由于还没有人尝试在绒猴体内进行CI实验，因此目标1中提出的实验对于我们建立这种新的CI模型是必要的。 临床CI处理器使用调制的脉冲序列来传输语音中重要的时间特征，因此这些信号在大脑中如何表示引起了极大的兴趣。由于麻醉影响皮质神经元的时间处理，目标2是研究清醒的、长期植入的绒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，并为未来的CI研究建立一个可行的模型。 这项资助中的研究和培训目标为申请者制定了一个逐年计划，帮助他为成为一名独立和成功的学术研究人员做好准备。他将学习的方法和程序将使他能够(A)进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)口头交流研究结果，(D)通过撰写拨款来组织研究目标，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，博士前学生将得到生物医学工程系和耳鼻喉科-头颈外科两个赞助商的密切指导。提出了详细的培训和指导计划。

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.