Microstimulation of primate neocortex targeting striosomes induces negative decision-making.

Here, we combined MRI-guided electrical microstimulation and viral tracing to examine the function of a corticostriatal circuit implicated by previous cortical microstimulation as modulating affective judgment and decision-making. Local microstimulation of a small part of the pregenual anterior cingulate cortex (pACC) was found to increase avoidance decisions in a cost-benefit decision-making task (Ap-Av task) in which differing amounts of "good" and "bad" options were given simultaneously. No effect of such stimulation was found when the monkeys performed a task in which both offers were rewarding, but given in different amounts. We asked whether we could identify the targets of such corticostriatal circuits when the cortical microstimulation sites were explicitly identified as affecting approach or avoidance in the Ap-Av task. We explored the pACC and caudal orbitofrontal cortex (cOFC) to look for such sites. For each cortical region, we found sites at which microstimulation induced increased avoidance behavior. After identifying these sites, we injected viral tracers carrying constructs allowing subsequent track-tracing post-mortem. For each site identified behaviorally as increasing avoidance choices, we found strong fiber projections to the anterior striatum with large parts of these targeting striosomes subsequently identified by serial section immunohistochemistry. With fMRI, we demonstrated that microstimulation in an anesthetized monkey at sites pre-identified as affecting Ap-Av choices induced blood oxygen level dependent activation of the anterior striatum, confirming that the microstimulation method that we applied was effective in activating the striatum. These findings outline circuits leading from pACC/cOFC to striosomes and causally modulating decision-making under emotional conflict.