Prediction, inference, and generalization in orbitofrontal cortex

Our understanding of the orbitofrontal cortex (OFC) has significantly evolved over the past few decades. This prefrontal region has been associated with a wide range of cognitive functions, including a popular view that it primarily signals the expected value of each possible option, allowing downstream areas to use these value signals for decision-making. However, the discovery of rich, task-related information within the OFC and its essential role in inference-based behaviors has shifted our perspective and led to the proposal that the OFC holds a cognitive map used by both humans and animals for making predictions and inferences. Recent studies have further shown that these cognitive maps can be abstracted and generalized, serving both immediate and future needs. In this review, we trace the research journey leading to these evolving insights, discuss the potential neural mechanisms supporting the OFC's roles in prediction, inference, and generalization, and compare the OFC with the hippocampus, another critical region for cognitive mapping, while also exploring the interactions between these two areas.