Grant: Project Grant

Funding is requested for cognitive neurophysiology experiments to elucidate the functional architecture of prefrontal cortex enabling attention and decision making. Macaque monkeys are trained with positive reinforcement to perform visual search tasks with separate manipulations of attention allocation and of response decision. Eventual clinical relevance is enhanced because these tasks assess impairments of attention and decision making in patients with psychiatric and neurological disorders. New observations will advance well beyond any previous work by combining more sophisticated psychological testing with high-resolution neurophysiological and neuroimaging methods to sample neural signals across all layers of the cerebral cortex. The frontal eye field will be targeted based on its fundamental role in guiding attention and making decisions. Samples will also be obtained in surrounding areas of prefrontal cortex. Two major hypotheses will be tested: (1) Directing attention and deciding responses are accomplished by distinct neurons. (2) The incidence, timing, and magnitude of these signals vary across cortical layers and between cortical areas. Confirmation of these hypotheses will challenge the popular dynamical system state space framework and align with extensive evidence demonstrating variation of gene expression and structure-function relations across cortical neurons. This information is needed to construct an accurate wiring diagram of prefrontal cortex, which is essential to understand the origin of noninvasive biomarkers for discriminating diagnostic groups and predicting treatment outcomes and also to develop targeted therapies with fewer side effects.