Linking working memory maintenance and readout in monkey sensory and prefrontal cortex

Abstract Despite extensive research, the neural implementation of working memory, from information maintenance to readout that guides behavior, remains elusive. We provide direct evidence that neurons in auditory and prefrontal cortices of monkeys maintain tone-specific information via persistent changes in spiking during the memory delay. Crucially, during the subsequent readout phase, these same memory neurons transition to reflect the monkeys’ behavioral decisions, demonstrating a direct role in translating maintained information into action. The functional necessity of this neuronal implementation is confirmed by causal perturbations that impaired working memory performance. Notably, memory neurons could only be identified by comparing delay periods between tasks with different memory demands, rather than the typical approach of contrasting delay and baseline periods within a single task. These findings challenge previous efforts to localize working memory neurons and necessitate a fundamental reassessment of working memory mechanisms, reshaping both conceptual and methodological frameworks for future research.