Grant: Project Grant

Funding is requested for cognitive neurophysiology experiments to elucidate the functional architecture of medial frontal cortical areas enabling executive control of response inhibition. Macaque monkeys are trained with positive reinforcement of different values to perform tasks that require interruption of a rapid action with or without replacement by another action. Because such tasks are used with humans to probe response inhibition and executive control in patients with psychiatric and neurological disorders, the findings have potential for eventual clinical relevance. Innovative neurophysiological and neuroimaging methods will be used to sample neural signals (impulses and field potentials) across all layers of the cerebral cortex. Three particular areas in the midline of the frontal lobe will be targeted based on previous evidence in humans and monkeys showing their diverse contributions to monitoring consequences and adjusting subsequent actions. Published and preliminary results frame two general hypotheses: (1) Neural processes (impulses and field potentials) signaling response errors, reward prediction errors, and response conflict will be distinguished across neurons and sampling sites. (2) The incidence, timing, and magnitude of these signals will vary between cortical areas and across cortical layers. These data will provide the first comprehensive description and contrast of the distinct functions and functional architecture of these three crucial areas. This information is needed to construct an accurate wiring diagram of this part of the brain, which is essential ultimately to rationalize noninvasive biomarkers for earlier diagnosis and to develop targeted therapies with fewer side effects.