Ventrolateral prefrontal cortex in macaques guides decisions in different learning conditions.

Flexibly adjusting our behavioral strategies based on the environmental context is critical to maximize rewards. Ventrolateral prefrontal cortex (vlPFC) has been implicated in both learning and decision-making for probabilistic rewards, but how learning new associations versus deciding between probabilistic options engages vlPFC remains unclear. We collected functional neuroimaging data while rhesus macaques performed a probabilistic task with two conditions: one that engaged learning (novel condition) and another that did not (familiar condition). We found that activity in vlPFC encoded rewards irrespective of whether learning was required, but encoded behavioral strategies that depend on reward outcome (win-stay/lose-shift) preferentially in the novel condition. Functional connectivity between vlPFC and anterior cingulate cortex varied with behavioral strategy in the novel condition, which engaged learning. By contrast, connectivity between vlPFC and mediodorsal thalamus was highest when subjects repeated prior choices. Furthermore, pharmacological D2-receptor blockade altered behavioral strategies during learning and resting-state vlPFC activity. Taken together, our study reveals a specialized role of vlPFC-linked circuits in novel association learning, highlighting its cortical and subcortical interactions as well as the involvement of dopamine D2 receptors in guiding the use of decision strategies during learning.