Orbitofrontal dysfunction is implicated in a host of human neuropsychiatric disease, including depression, mania, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, and addiction. In most of these disease states, the role of orbitofrontal cortex is only beginning to be understood. Existing theories rely on animal research showing that orbitofrontal cortex is critical to decision-making because of the role it plays in promoting associative learning and the inhibition of inappropriate responses. However recent work in animals now suggests that the conceptualization of orbitofrontal contributions to associative learning is incorrect. Instead orbitofrontal cortex may contribute to associative learning and decision-making due to its role in generating dynamic, prospective predictions regarding the likelihood of future outcomes. Such ?outcome-expectancies? would both guide appropriate decisions and also facilitate associative learning in other brain regions in the face of unexpected outcomes. Such a conceptualization would be fundamentally different from current theories that view orbitofrontal cortex as a static, retrospective ?associative look-up table?. The experiments in this proposal will provide a critical test of this hypothesis, manipulating rats'expectations for rewarding outcomes in two different settings, in order to demonstrate orbitofrontal cortex signals these expectations. Further we will show that these signals facilitate flexible behavior in the face of unexpected outcomes due to their ability to their ability to alter associative representations stored in downstream brain regions. These results will advance our understanding of the fundamental function of orbitofrontal cortex, beyond the current common conceptualization of this area. As such, they will clarify the role this area plays in the neuropsychiatric diseases described above and how manipulation of that role may facilitate treatment of these diseases.
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