Previous work on this project has demonstrated that reward-based decision making requires the OFC to be intact. The OFC is comprised of several anatomically distinct areas, however, and these areas have been grouped into two major networks based on their patterns of connectivity: a sensory network and a visceromotor network. The lateral OFC areas, called areas 11 and 13, correspond to the sensory network, and the medial OFC, called area 14, belongs to the medial network. Although it has been suggested that these subregions play dissociable roles in reward-guided behavior, direct evidence for this hypothesis is limited. To explore the independent contributions of OFCs subregions to behavior, we studied the effects of excitotoxic lesions targeting either areas 11/13 or area 14 in guiding object choices in the reinforcer devaluation task. In this task, the value of rewards is varied by prior consumption of the food item that serves as a reward. Eating a certain kind of food leads to a selective satiation that decreases the value of that food. Lesions of areas 11/13, but not area 14, disrupted the rapid updating of object value during selective satiation. In contrast, lesions targeting area 14, but not areas 11/13, impaired the ability to learn to stop responding to a previously rewarded object. Neither lesion disrupted performance on a serial object reversal learning task, although complete lesions of the OFC produce severe deficits on this task. We also developed a new task to examine the transitivity of value judgments, which has been proposed as a key OFC function. To test this idea, subjects were allowed to choose between objects that had been associated with different familiar foods, among which the subjects had an ordered preference. After the food associations had been learned, along with the differences between objects associated with them, subjects made choices between pairs of objects. If the OFC is important for value-based transitivity, then subjects with OFC lesions should have difficulty in choosing objects based on their food preferences. We found that subjects with lesions of area 14, relative to controls, made more choices that were inconsistent with their overall preferences. Subjects with lesions of areas 11/13 did not have this deficit. This research indicates that areas the medial and lateral aspects of OFC contribute to guiding flexible, reward-based decision making in different ways. Lateral OFC areas (areas 11/13) seem to be important for learning, representing and updating specific object-reward associations. In contrast, the medial OFC (area 14) seems to be important for value comparison after learning has occurred. As explained above, the OFC and the amygdala play a crucial role in stimulus valuation, especially when based on current (instantaneous) biological needs. It is also of interest to consider how subjects value actions. To investigate the role of the amygdala in goal-directed actions, we designed a new task. Subjects were trained to perform two different actions (tap and hold) on a touch-sensitive screen. Repetitive tapping of the screen produced one food;constant holding of the screen produced a different food. Subjects were fed one of the foods to satiety, which lowered its value. This is the same selective satiation procedure explained above for the reinforcer devaluation task. As expected, controls showed a reduction in the action associated with a devalued food. In contrast, subjects with amygdala lesions failed to show this effect. This finding needs to be replicated, but if confirmed it provides strong support for the idea that the amygdala is as important for the valuation of actions as it is for the valuation of stimuli (and objects). They also confirm our previous results showing that the amygdala plays an equally important role in positive and negative emotions. Anatomical studies have suggested a hierarchical organization in the anterior-posterior dimension of the OFC. Specifically, by analogy with sensory corticocortical connections, the posteriorly directed projections within the OFC follow the feedforward projection pattern, one characterized by projections that arise in supragranular layers (layers 2 and 3) of the cortex. For example, the preponderance of cells giving rise to the posteriorly directed projections from area 11 to area 13 and, likewise, from area 13 to the agranular insula, arise from layers 2 and 3. To date, there is little evidence for functional distinctions along this dimension. Accordingly, we examined the functional roles of the OFC using a technique involving temporary inactivation of selective subregions of the OFC. This technique provides greater spatial and temporal resolution than is possible with other methods. Following from the finding that areas 11/13, considered together, are essential for linking objects with current biological value, we aimed to assess the separate contributions of posterior OFC (area 13) and anterior OFC (area 11) to this function. We first trained subjects on the reinforcer devaluation task. On separate days, we assessed the effects on behavior of bilateral infusions of a neural inhibitor or saline. Infusions were made into one of the two OFC subregions either preceding or following the selective satiation procedure. Our preliminary findings show that inactivation of area 13 neurons before (but not after) selective satiation interferes with reinforcer devaluation effects. Inactivation of area 11 neurons produces the opposite results: when inhibitors are applied before the selective satiation procedure, they have no effect, but area 11 inactivation after selective satiation disrupts reinforcer devaluation effects. These preliminary findings indicate that area 13 is essential for encoding the change in reward value that occurs during selective satiation but not for retrieval of that information once the change has been registered. Area 11, by contrast, appears to be essential for retrieval of updated object valuations.

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Murray, Elisabeth A; Rudebeck, Peter H (2018) Specializations for reward-guided decision-making in the primate ventral prefrontal cortex. Nat Rev Neurosci 19:404-417
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Vicario-Feliciano, Raquel; Murray, Elisabeth A; Averbeck, Bruno B (2017) Ventral striatum lesions do not affect reinforcement learning with deterministic outcomes on slow time scales. Behav Neurosci 131:385-91
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Murray, Elisabeth A; Moylan, Emily J; Saleem, Kadharbatcha S et al. (2015) Specialized areas for value updating and goal selection in the primate orbitofrontal cortex. Elife 4:

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