Complementary yet Dissociable Influences of Medial and Lateral Orbitofrontal Cortex over Cue-Guided Decisions Involving Reward Magnitude and Uncertainty

Converging evidence suggests that orbitofrontal cortex (OFC) subregions subserve distinct roles in decision-making across a variety of tasks. Cost/benefit decisions can require an organism to choose between options based on information available in the environment (externally guided) and knowledge from experience (internally guided). Studies in humans have implicated both medial and lateral subdivisions of OFC (mOFC, lOFC) in externally and internally guided choice, yet rodent studies have primarily focused on OFC regulation of internally guided decisions. To address this gap, we examined how inactivation of these OFC subregions alters cue-guided, probabilistic decision-making using a "Blackjack" task. Male rats were required to choose between a certain, 1-pellet small reward and larger, 4-pellet reward delivered with varying probability, signaled trail-to-trial with explicit auditory stimuli indicating whether the odds of receiving the larger reward was good (50%) or poor (12.5%). Inactivation of the mOFC or lOFC induced generalized decreases or increases in large/risky choice, respectively, that were associated with opposite effects on loss (but not win) sensitivity and on rats' likelihood of making consecutive choices of the small/certain option. Inactivation of the adjacent anterior agranular insular cortex had no effect. Inactivation of either OFC subregion also disrupted cue-guided reward magnitude discrimination, where tones signal which action delivered a deterministic larger reward, but did not affect a simpler conditional discrimination involving choice between rewarded and unrewarded actions. Together these data highlight complementary yet heterogeneous roles for different OFC regions in using discriminative stimuli to guide action toward higher-value targets.