Ordered thought and behavior rests on the brain's capacity to absorb the structure of experience associated with favorable outcomes, i.e., rules. This allows us to imagine possible goals and provides mental navigation to reach them. These mechanisms are dysfunctional or lost following frontal lobe stroke and in schizophrenia and Parkinson's disease. They are also co-opted by drugs of addiction. During the last funding period, we used multiple electrodes (up to 50) to compare and contrast brain areas in the frontal lobe and temporal lobe of monkeys, areas critical for goal-directed behavior and implicated in neuropsychiatric disorders and drug addiction, while monkeys performed disparate rule-guided behaviors. We now aim to use our lab's expertise in multiple electrode recording and complex behaviors to test major hypotheses of their role in goal-directed rule learning. Our results so far are in line with models suggesting that the basal ganglia is specialized for fast acquisition of simple associations and that it helps train slower acquisition of more elaborate rules in the executive prefrontal cortex: Thus, is critical to know how ubiquitous or rare these effects are. Finding the same pattern for different types of learning would strongly support these hypotheses, while determining its limitations would provide insight into functional specializations. We will record simultaneously from the prefrontal cortex and striatum during different types of stimulus-response (SR) learning, compare SR and stimulus-stimulus learning, and determine the influence of reversal learning, which is known to be prefrontal cortex-dependent. We will also test the hypothesis that the prefrontal cortex and striatum are specialized for elaborate versus simple rules, respectively. Our monkeys will switch between applying three different rules, the basic logical operations, AND, OR, and XOR, while we record from the prefrontal and striatum. These rules bridge a critical distinction (linear versus non-linear) yet share a logical relation (one can be built from the other two). This allows head-to-head comparison between rules that have different complexities but have the same formal requirements. Because rule-learning is a fundamental cognitive function, data from this project has the potential to impact on a wide range of human behaviors and disorders and by doing so open a path to drug and behavioral therapies that will alleviate them. ? ? ?
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