Neural Substrates of Reward Processing and Emotion

National Institute Of Mental Health

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Abstract

Lesion studies suggest dissociable functions of medial prefrontal cortex (MFC) and orbitofrontal cortex (OFC), with MFC being essential for social cognition and OFC being essential for value-based decision making. Although bilateral amygdala damage also results in impairments in these domains, it is not known whether the dissociable functional roles of MFC and OFC critically depend on interactions with the amygdala. To test this possibility, we compared the performance of animals with crossed surgical disconnection of the prelimbic cortex, a subregion of MFC, and amygdala (MFC x AMY) and animals with surgical disconnection of the OFC and amygdala (OFC x AMY), to a group of controls (CON). All animals were assessed for food-retrieval latency while viewing videos of social stimuli (a test of social interest) and object choices based on current food value (devaluation task, a test of value-based decision making). Compared to the CON group, group MFC x AMY, but not group OFC x AMY, showed significantly reduced latencies to reach for a reward in the presence of videos of conspecifics, indicating reduced social valuation and/or reduced social interest. In a test of value-based decision making, however, the opposite pattern was observed; group OFC x AMY, but not group MFC x AMY, displayed severe deficits on object choice following selective satiation. These data indicate that MFC and OFC interact with the amygdala to subserve distinct behavioral contributions in the domains of social valuation and object valuation, respectively. That these prefrontal-amygdala circuits are functionally dissociable lends support to the idea that MFC and OFC make independent contributions to cognitive appraisals of the environment. The MFC has been identified as encoding not only reward value but also features of conspecifics and of oneself. Physiological studies in animals and fMRI studies in humans have identified MFC as supporting social cognition. Relatedly, a growing body of evidence suggests that some species find the sight of another individual receiving a reward reinforcing, called vicarious reinforcement, and that this capacity is supported by a network of brain areas including the MFC. Indeed, single neurons in MFC selectively code reward delivery to the self, a partner, both animals, or neither animal. We used a vicarious reinforcement task to measure prosocial tendencies in animals. Two animals participated in each test session: an actor and a recipient. Actors learned that three different visual cues mapped onto three distinct reward outcomes: to Self, the Other animal, or Neither animal. On each trial, actors saw a cue that predicted one of the three juice offers and could accept the offer by making a saccade to a peripheral target or reject the offer by breaking fixation. All six actors displayed prosocial preferences, indicated by their greater tendency to give reward to Other relative to Neither. Analyses of autonomic arousal have been increasingly used to contextualize and guide neural research, especially for studies of reward processing. We therefore collected pupil diameter while animals performed the vicarious reinforcement task. Contrary to our expectations, we found that pupils were widest in anticipation of juice to the self, moderately-sized in anticipation of juice to nobody, and narrowest in anticipation of juice to a social partner. The seemingly paradoxical pupil effect can be explained by a model in which pupil size tracks outcome salience, prosocial tendencies track outcome valence, and the relation between salience and valence is U-shaped. Although ACC lesions disrupted animals social decision making, as evidenced by altered acquisition of prosocial tendencies, there was no effect on autonomic arousal in anticipation of those same outcomes. Thus, our results indicate that the ACC is not part of the neural circuitry responsible for producing the socially modulated pupil response seen during vicarious reinforcement.