Chemogenetic suppression of the macaque dorsolateral prefrontal cortex during oculomotor tasks reveals its role in...

Goal-directed behavior relies on the ability to suppress inappropriate or premature actions, an executive function termed inhibitory control. The dorsolateral prefrontal cortex (dlPFC) is known to play a crucial role in this process; however, how its neural activity supports inhibition, and whether this role is distinct from working memory, remains unclear. To address this question, we combined chemogenetic suppression of the dlPFC with oculomotor paradigms in macaque monkeys. Two monkeys performed memory-guided (MGS), visually guided (VGS), and memory-guided with distractor (MGSD) saccade tasks while neuronal activity was recorded. Systemic administration of deschloroclozapine (DCZ) to activate inhibitory hM4Di receptors markedly increased fixation breaks during delay periods across all tasks, including the VGS task with minimal memory demands. In contrast, errors in saccade direction-indicative of memory failure-remained unaffected, even under high cognitive load (MGSD). Local field potential recordings revealed consistent reductions in gamma-band power following DCZ administration. These results indicate that the dlPFC supports inhibitory control in a manner dissociable from working memory processes. Our findings offer translational insights into the neural mechanisms underlying impulsivity and inhibitory deficits in psychiatric disorders.