Motivational control is implemented by a cingulo-prefrontal network

Adaptive cognitive functions are associated with interactions between the midcingulate cortex (MCC) and dorsolateral prefrontal cortex (dlPFC), two regions of the primate brain thought to implement executive functions at different timescales.^1,2,3 The MCC-dlPFC interaction is proposed to play a role in short-term adaptation such as post-error adaptation, which can be revealed trial to trial by (for example) post-error slowing.⁴ Analyses of correlative neural dynamics in MCC and LPFC support such interactions^5,6,7; however, it is unclear whether this is through direct MCC-dlPFC connections or via indirect subcortical pathways.⁸ The MCC-dlPFC interaction could also contribute to long-term adaptation. MCC neurons integrate outcome information over many trials,⁹ which could provide dlPFC with information to drive choices about when and how to engage in a task or to make exploit-explore shifts during foraging.¹⁰ Beyond theoretical conjectures, it remains unclear how networks of prefrontal cortical regions implement these functions. Here we used pathway-specific DREADDs in primates to reveal the unique contribution of the direct neuronal connections between the MCC and the dlPFC to voluntary behavior. Combining behavioral, neuroimaging, and immunohistological tools, we show that DREADD-mediated activation of feedback projections from MCC to dlPFC in macaques specifically leads to increased engagement in a foraging task, but it does not alter animals' trial-to-trial adaptive strategy. We conclude that a critical role for the MCC-dlPFC pathway is in the temporally extended motivational control of behavior rather than in rapid adaptation.