Integrative functions of primate prefrontal cortex

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"Divide and conquer" seems to dominate many neural analyses: There are specialized systems for analyzing different types of information. Cognition requires synthesizing their results. To plan and execute complex, goal-directed behaviors we must learn "the rules of the game": predictive relationships between disparate sensory events, environmental context, the possible actions and consequences. This depends on brain systems specialized for learning and memory: the prefrontal cortex (PFC), basal ganglia (BG) and hippocampal systems (HS). Damage to any of these systems, or their disconnection, impairs rule learning. Previous studies have shown that neural correlates of acquisition and/or representation of concrete (specific) rules and higher-level abstract rules (general principles) are prevalent in the PFC, a brain region central to rule-based behaviors. But our understanding is limited by our lack of knowledge about the respective contributions of, and PFC interactions with, the other critical systems: the BG and HS. The main goal of this project is to provide that knowledge. We plan to simultaneously study neural activity from up to 28 electrodes implanted these systems while monkeys larn and follow concrete rules )conditional visuomoter associations between an object and a saccade direction) and follow abstract rules (matching and non-matching rules applied to new stimuli). This will afford a precise assessment of the respective contributions of the PFC, BG, and GS to complex goal-directed behaviors and insight into the underlying neural circuitry. Our specific aims are: 1. To compare and contrast the neural representation of concrete rules in the PFC with anatomically and functionally-related systems (BG and HS). 2. To assess the relative contributions of PFC, BG and HS to rule acquisition by comparing neural correlates of their learning. 3. To compare and contrast the neural representation of abstract rules in the PFC with the BG, and HS. As rule learning is fundamental to all higher-order behavior, data from this project has the potential to impact on our understanding of a wide range of behaviors and human and human disorders. The ability to glean rules and principles from experience is disrupted in a variety of neuropsychiatric disorders such as autism and schizophrenia. By identifying brain structures important for these abilities, discerning their relative roles, and uncovering their neural mechanisms, we can open a path to drug therapies designed to alleviate their dysfunction.