Functional distinctions between orbitofrontal cortex and anterior cingulate cortex subregions in decision-making and autonomic regulation

Mood disorders are associated with complex disruptions in brain networks, including those associated with the orbitofrontal cortex (OFC) and pregenual anterior cingulate cortex (pACC). Differential functions of these regions, especially the functions of the far-caudal OFC, are incompletely understood. We trained macaques to perform an approach-avoidance task and recorded cOFC and pACC neuronal activity and autonomic/somatic responses during performance, including during electrical microstimulation (EMS) of the cOFC. The cOFC was sensitive to both positive and negative stimuli, whereas the pACC was significantly more active during aversive outcomes. cOFC EMS increased avoidance, suggesting a causal cOFC function in cost-benefit decision-making. The cOFC activity led pACC activity during the decision period, supporting cOFC network prominence. Autonomic and somatic responses were positively correlated with behavioral patterns, consistent with a coordinated body-brain involvement during emotionally significant decision-making. We suggest that dysfunction of this network could potentially contribute to the etiology of mood disorders. The roles of orbitofrontal and cingulate cortex in emotional decisions remain unclear. Here the authors show distinct timing between caudal orbitofrontal and cingulate signals, that orbitofrontal stimulation increases avoidance, and that physiological responses mirror behavior.