Lateral orbitofrontal cortex integrates predictive information across multiple cues to guide behavior.

Individuals are often faced with multiple cues that concurrently predict the same outcome, and combining these predictions may benefit behavior. Previous work has studied the neural basis of decision-making, predominantly using isolated sensory stimuli, and so the mechanisms that allow us to leverage multiple cues remain unclear. In two experiments, we used neuroimaging and network-targeted brain stimulation to probe how the brain integrates outcome predictions to guide adaptive behavior. We identified neural signatures of outcome integration in the lateral orbitofrontal cortex (OFC), where concurrently presented cues evoke stronger pattern-based representations of expected outcomes. Moreover, perturbing lateral OFC network activity impairs subjects' ability to leverage predictions from multiple cues to facilitate responding. Intriguingly, we found similar behavioral and brain mechanisms for reward-predicting cues and for cues predicting the absence of reward. These findings highlight a causal role for the lateral OFC in utilizing outcome predictions from multiple cues to guide behavior.