Cracking and packing information about the features of expected rewards in the orbitofrontal cortex.

The orbitofrontal cortex (OFC) is crucial for tracking various aspects of expected outcomes, thereby helping to guide choices and support learning. Our previous study showed that the effects of reward timing and size on the activity of single units in OFC were dissociable when these attributes were manipulated independently (Roesch et al., 2006). However, in real-life decision-making scenarios, outcome features often change simultaneously, so here we investigated how OFC neurons in male rats integrate information about the timing and identity (flavor) of reward and respond to changes in these features, according to whether they were changed simultaneously or separately. We found that a substantial number of OFC neurons fired differentially to immediate versus delayed reward and to the different reward flavors. However, contrary to the previous study, selectivity for timing was strongly correlated with selectivity for identity. Taken together with the previous research, these results suggest that when reward features are correlated, OFC tends to "pack" them into unitary constructs, whereas when they are independent, OFC tends to "crack" them into separate constructs. Furthermore, we found that when both reward timing and flavor were changed, reward-responsive OFC neurons showed unique activity patterns preceding and during the omission of an expected reward. Interestingly, this OFC activity is similar and slightly preceded the ventral tegmental area dopamine (VTA DA) activity that observed in a previous study (Takahashi et al., 2023), consistent with a role for OFC in providing predictive information to VTA DA neurons.Significant Statement Although multiple features of outcomes can change simultaneously in real-life decision-making scenarios, how OFC neurons integrate information about the reward timing and identity and respond to changes in these features remains unexplored. Here we found that OFC neurons integrate information about reward timing and identity when the two features changed simultaneously. Combining with prior research (Roesch et al., 2006), these findings suggest that OFC tends to integrate correlated features into unitary constructs, while segregating independent features into separate constructs. Additionally, we observed distinct activities in general reward-responsive neurons preceding the omission of an expected reward when both identity and timing changed. This implies OFC might convey predictions to VTA that track reward timing separately based on reward identity.

Chronic Ethanol Exposure Produces Persistent Impairment in Cognitive Flexibility and Decision Signals in the Striatum.

Lack of cognitive flexibility is a hallmark of substance use disorders and has been associated with drug-induced synaptic plasticity in the dorsomedial striatum (DMS). Yet the possible impact of altered plasticity on real-time striatal neural dynamics during decision-making is unclear. Here, we identified persistent impairments induced by chronic ethanol (EtOH) exposure on cognitive flexibility and striatal decision signals. After a substantial withdrawal period from prior EtOH vapor exposure, male, but not female, rats exhibited reduced adaptability and exploratory behavior during a dynamic decision-making task. Reinforcement learning models showed that prior EtOH exposure enhanced learning from rewards over omissions. Notably, neural signals in the DMS related to the decision outcome were enhanced, while those related to choice and choice-outcome conjunction were reduced, in EtOH-treated rats compared to the controls. These findings highlight the profound impact of chronic EtOH exposure on adaptive decision-making, pinpointing specific changes in striatal representations of actions and outcomes as underlying mechanisms for cognitive deficits.