Cross-species studies on orbitofrontal control of inference-based behavior.

Many decisions are guided by expectations about their outcomes. These expectations can arise from two fundamentally different sources: from direct experience with outcomes and the events and actions that precede them or from mental simulations and inferences when direct experience is missing. Here we discuss four elegant tasks from animal learning theory (devaluation, sensory preconditioning, Pavlovian-to-instrumental transfer, and Pavlovian overexpectation) and how they can be used to isolate behavior that is based on such mental simulations from behavior that can be based solely on experience. We then review findings from studies in rodents, nonhuman primates, and humans that use these tasks in combination with neural recording and loss-of-function experiments to understand the role of the orbitofrontal cortex (OFC) in outcome inference. The results of these studies show that activity in the OFC is correlated with inferred outcome expectations and that an intact OFC is necessary for inference-based behavior and learning. In summary, these findings provide converging cross-species support for the idea that the OFC is critical for behavior that is based on inferred outcomes, whereas it is not required when expectations can be based on direct experience alone. This conclusion may have important implications for our understanding of the role of OFC in psychiatric disorders and how we may be able to treat them. (PsycInfo Database Record (c) 2021 APA, all rights reserved).