Recent hypotheses have posited that orbital frontal cortex (OFC) is important for using inferred consequences to guide behavior. Less clear is OFC’s contribution to goal-directed or model-based behavior, where the decision to act is controlled by previous experience with the consequence or outcome. Investigating OFC’s role in learning about changed outcomes separate from decision-making is not trivial and often the two are confounded. Here we adapted an incentive learning task to mice, where we investigated processes controlling experience-based outcome updating independent from inferred action control. We found chemogenetic OFC attenuation did not alter the ability to perceive motivational state-induced changes in outcome value but did prevent the experience-based updating of this change. Optogenetic inhibition of OFC excitatory neuron activity selectively when experiencing an outcome change disrupted the ability to update, leaving mice unable to infer the appropriate behavior. Our findings support a role for OFC in learning that controls decision-making.

Psychiatric disease often produces symptoms that have divergent effects on neural activity. For example, in drug dependence, dysfunctional value-based decision-making and compulsive-like actions have been linked to hypo- and hyper-activity of orbital frontal cortex (OFC)-basal ganglia circuits, respectively, however, the underlying mechanisms are unknown. Here we show that alcohol exposed mice have enhanced activity in OFC terminals in dorsal striatum (OFC-DS) associated with actions, but reduced activity of the same terminals during periods of outcome retrieval, corresponding with a loss of outcome control over decision-making. Disrupted OFC-DS terminal activity was due to a dysfunction of dopamine-type 1 receptors on spiny projection neurons (D1R SPNs) that resulted in increased retrograde endocannabinoid (eCB) signaling at OFC-D1R SPN synapses reducing OFC-DS transmission. Blocking CB1 receptors restored OFC-DS activity in vivo and rescued outcome-based control over decision-making. These findings demonstrate a circuit-, synapse-, and computation specific mechanism gating OFC activity in alcohol exposed mice.

Although hearing often declines with age, prior research has shown that older adults may benefit from multisensory input to a greater extent when compared to younger adults, a concept known as inverse effectiveness. While there is behavioral evidence in support of this phenomenon, less is known about its neural basis. The present functional MRI (fMRI) study examined how older and younger adults processed multimodal auditory-visual (AV) phonemic stimuli which were either congruent or incongruent across modalities. Incongruent AV pairs were designed to elicit the McGurk effect. Behaviorally, reaction times were significantly faster during congruent trials compared to incongruent trials for both age-groups, and overall older adults responded more slowly. The interaction was not significant, suggesting that older adults processed the AV stimuli similarly to younger adults. Although there were minimal behavioral differences, age-related differences in functional activation were identified: Younger adults elicited greater activation than older adults in primary sensory regions including superior temporal gyrus, the calcarine fissure, and left postcentral gyrus. In contrast, older adults elicited greater activation than younger adults in dorsal frontal regions including middle and superior frontal gyri, as well as dorsal parietal regions. These data suggest that while there is age-related stability in behavioral sensitivity to multimodal stimuli, the neural bases for this effect differed between older and younger adults. Our results demonstrated that older adults underrecruited primary sensory cortices and had increased recruitment of regions involved in executive function, attention, and monitoring processes, which may reflect an attempt to compensate.

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Recent hypotheses have posited that orbital frontal cortex (OFC) is important for using inferred consequences to guide behavior. Less clear is OFC's contribution to goal-directed or model-based behavior, where the decision to act is controlled by previous experience with the consequence or outcome. Investigating OFC's role in learning about changed outcomes separate from decision-making is not trivial and often the two are confounded. Here we adapted an incentive learning task to mice, where we investigated processes controlling experience-based outcome updating independent from inferred action control. We found chemogenetic OFC attenuation did not alter the ability to perceive motivational state-induced changes in outcome value but did prevent the experience-based updating of this change. Optogenetic inhibition of OFC excitatory neuron activity selectively when experiencing an outcome change disrupted the ability to update, leaving mice unable to infer the appropriate behavior. Our findings support a role for OFC in learning that controls decision-making.