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Vanderbilt Addiction Center

Fast Optical Imaging of Cortical Signals in the Behaving Primate

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.

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