Fast Optical Imaging of Cortical Signals in the Behaving Primate

描述(由申请人提供)： 这项研究计划的目标是开发一种快速的时间分辨率光学成像方法，用于清醒、行为正常的猴子。如果成功，这种方法将在高空间分辨率(10‘S)和高时间分辨率(1-10毫秒)下提供脑功能的在线可视化。人们一直致力于研究麻醉和清醒猕猴感觉皮质的解剖组织和生理反应。然而，关于清醒行为动物在工作记忆任务执行过程中前额叶皮质激活的空间模式，我们知之甚少。其目的是观察行为过程中神经元激活皮质活动的簇状和分布性簇。这些数据还将提供单一单位生理学、功能成像研究和行为研究之间的关键联系。重要的是，拟议的技术开发将为研究与视觉、注意力、记忆和认知功能有关的皮质加工的空间(功能组织)和时间方面提供新的方法。从这种方法获得的数据的临床相关性将与精神分裂症等疾病的认知功能障碍相关。这项建议的具体目标是：1)开发清醒的、行为正常的猴子的快速光学成像系统。这一目标将包括开发电压敏感染料方法，用于光学检测神经元活动的降噪技术，适用于大量流数据的快速图像处理技术，以及串联电生理记录。2)将该方法应用于研究前额叶皮质的工作记忆过程。猕猴将接受眼球运动延迟反应任务的训练。前额叶皮层的延迟期活动将在高时间性(1-10毫秒)下成像，以监测取决于任务需求的时空活动模式的变化。这种方法将为检验大脑皮质组织与行为的关系提供一种新的方法，这种方法将补充其他现有技术的时空能力，如功能磁共振成像和单单位电生理学。

DESCRIPTION (provided by applicant): The goal of this research proposal is to develop a fast temporal resolution optical imaging methodology for use in awake, behaving monkeys. If successful, this methodology would provide online visualization of brain function at both high spatial (10's of ums) and high temporal (1-10 msec) resolution. Intense effort has been devoted to studying anatomical organization and physiological responses of sensory cortex in anesthetized and awake monkeys. However, little is known about the spatial patterns of activation in prefrontal cortex of awake, behaving animals during performance of working memory tasks. The goal is to observe clustered and distributed clusters of neuronal activation of cortical activity during behavior. These data would also provide a critical link between single-unit physiology, functional imaging studies, and behavioral studies. Importantly, the proposed technology development will provide new methodologies for studying spatial (functional organizational) and temporal aspects of cortical processing relating to vision, attention, memory, and cognitive function. Clinical relevance of data obtained from this approach would be relevant to cognitive dysfunctions in diseases such as schizophrenia. The specific aims of this proposal are: 1) development of fast optical imaging system for awake, behaving monkeys. This aim would include development of voltage sensitive dye methodology, noise reduction techniques for optical detection of neuronal activity, rapid image processing techniques suitable for large volumes of streamed data, and tandem electrophysiological recordings. 2) application of this method to study working memory processes in prefrontal cortex. Macaque monkeys would be trained on oculomotor delay response tasks. Delay period activity in prefrontal cortex would be imaged at high temporal (1-10 msec) to monitor changing spatiotemporal activity patterns depending on task demands. This methodology will provide a new approach for examining relationship of cortical organization with behavior, one that will complement the spatiotemporal capabilities of other existing technologies such as fMRI and single unit electrophysiology.