[Functional Roles of Prefrontal-Subcortical Circuits in Primate Adaptive Behavior: Neural Basis of Experience and...

Adaptive behavior in primates relies on the prefrontal cortex (PFC) and its extensive interactions with subcortical structures. This review summarizes recent findings on the functionally distinct roles of prefronto-subcortical pathways, as revealed by an imaging-guided, pathway-selective chemogenetic manipulation in macaque monkeys. Specifically, we focus on the parallel output pathways from the PFC to the striatum and the mediodorsal thalamus (MD). While the prefronto-striatal pathways are primarily involved in direct value updating based on "experience" and action biasing, the prefronto-thalamic pathways are crucial for working memory and updating values through "inference" based on internal models. These results challenge the classical view of the thalamus as a simple relay, highlighting the neural pathways connecting the PFC and MD as an active "cognitive switch" that maintains and manipulates neural representations according to the current context. Understanding these pathway-specific functions provides essential insights into potential circuit-based therapeutic interventions for psychiatric disorders.