Neural Substrates of Reward Processing and Emotion

National Institute Of Mental Health

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Abstract

Altered arousal is characteristic of many mental health disorders, including major depressive disorder (MDD). Several studies link neural activity in orbitofrontal cortex (OFC) with anticipation of reward, including anticipatory sympathetic arousal, which is blunted in MDD. We therefore studied the role of OFC in acquisition and consolidation of appetitive Pavlovian memories. Four animals with selective OFC lesions and four unoperated controls were tested for acquisition of conditioned sympathetic arousal as indexed by differential pupil dilation. The key comparison was pupil dilation in response to a visual cue that predicted the delivery of a large fluid reward (CS+) vs. a cue that predicted no reward (CS–). All animals acquired a conditioned increase in pupil size in response to the CS+. However, the group with OFC lesions failed to consolidate the memory underlying this response. Control procedures ruled out global effects of the lesion on pupil dilation. In contrast to this impairment, animals with OFC lesions acquired and consolidated an operant visual discrimination for the same reward and did so at the same rate as controls. These findings point to a specialized role for OFC in consolidating memories underlying positive affective responses, which further implicates OFC dysfunction in the blunted positive affect characteristic of MDD and suggests therapeutic approaches involving enhanced consolidation and/or reconsolidation of associative memories.