Localized Microstimulation of Primate Pregenual Cingulate Cortex Induces Negative Decision-Making

The pregenual anterior cingulate cortex (pACC) has been implicated in human anxiety disorders and depression, but the circuit-level mechanisms underlying these disorders are unclear. We took as a clue evidence that in healthy individuals, the pACC is involved in cost-benefit evaluation. We developed a macaque version of an approach-avoidance decision task used to evaluate anxiety and depression in humans and, with multi-electrode recording and cortical microstimulation, we probed pACC function as monkeys performed this task. We found that the macaque pACC has an opponent-process like organization of neurons representing motivationally positive and negative subjective value. These two neuronal populations overlapped spatially, except in one pACC subzone, where neurons with negative coding were more numerous. Strikingly, microstimulation in this subzone, but not elsewhere in the pACC, increased negative decision-making, and this negative biasing was blocked by anti-anxiety drug treatment. This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.