One of the most important factors in decision-making is estimating the value of available options. Subregions of the prefrontal cortex, including the orbitofrontal cortex (OFC), have been deemed essential for this process. Value computations require a complex integration across numerous dimensions, including, reward magnitude, effort, internal state, and time. The importance of the temporal dimension is well illustrated by temporal discounting tasks, in which subjects select between smaller-sooner versus largerlater rewards. The specific role of OFC in telling time and integrating temporal information into decisionmaking remains unclear. Based on the current literature, in this review we reevaluate current theories of OFC function, accounting for the influence of time. Incorporating temporal information into value estimation and decision-making requires distinct, yet interrelated, forms of temporal information including the ability to tell time, represent time, create temporal expectations, and the ability to use this information for optimal decision-making in a wide range of tasks, including temporal discounting and wagering. We use the term "temporal cognition" to refer to the integrated use of these different aspects of temporal information. We suggest that the OFC may be a critical site for the integration of reward magnitude and delay, and thus important for temporal cognition.
One of the most important factors in decision making is estimating the value of available options. Subregions of the prefrontal cortex, including the orbitofrontal cortex (OFC), have been deemed essential for this process. Value computations require a complex integration across numerous dimensions, including, reward magnitude, effort, internal state, and time. The importance of the temporal dimension is well-illustrated by temporal discounting tasks, in which subjects select between smaller-sooner versus larger-later rewards. The specific role of OFC in telling time and integrating temporal information into decision making remains unclear. Based on the current literature, in this review we reevaluate current theories of OFC function, accounting for the influence of time. Incorporating temporal information into value estimation and decision making requires distinct, yet interrelated, forms of temporal information including the ability to tell time, represent time, create temporal expectations, and the ability to use this information for optimal decision making in a wide range of tasks, including temporal discounting and wagering. We use the term "temporal cognition" to refer to the integrated use of these different aspects of temporal information. We suggest that the OFC may be a critical site for the integration of reward magnitude and delay, and thus important for temporal cognition.
Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach and particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory DREADDs targeting these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We measured initial and pre-post reversal changes in accuracy to measure first detection and further adjustment to reversals, respectively. We found that inhibition of vlOFC, but not BLA, eliminated detection of stimulus-based reversals. Conversely, both BLA and vlOFC inhibition resulted in significantly slower action-based reversal learning in females, not males, indicating a sex-dependent role for these regions in this type of learning. Further, learning in females was more impacted in first reversal by vlOFC inhibition than inhibition of BLA, the latter more involved in probabilistic reversal learning. These findings add to mounting evidence of sex-dependent learning flexibility.
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