The Orbitofrontal Cortex Underlies Consolidation of Pavlovian Anticipatory Arousal Responses in Macaque Monkeys

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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 the orbitofrontal cortex (OFC) with anticipation of reward, including anticipatory sympathetic arousal, which is blunted in MDD. We therefore studied acquisition and consolidation of appetitive pavlovian memories in two groups of adult male rhesus monkeys: unoperated controls ( N = 4) and those with selective neurotoxic lesions of OFC ( N = 4). The dependent measure was conditioned sympathetic arousal as indexed by differential pupil dilation, and the key comparison was dilation in response to a visual cue that predicted the delivery of a large fluid reward (CS+) versus a cue that predicted no reward (CS−). Control procedures ruled out global effects of the lesion on pupil dilation. All four unoperated controls and all four monkeys with OFC lesions acquired a conditioned increase in the pupil size in response to the CS+. However, three of the four monkeys in the lesion group failed to consolidate the memory underlying this response. In contrast to this impairment, monkeys 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 of 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.
Funding Information
  • HHS | NIH | National Institute of Mental Health (ZIAMH002887)

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