Rule learning is associated with lasting changes in prefrontal activity. However, experiments typically focus on learning a single set of rules or task, and there remains a significant gap regarding how related mechanisms may reflect behavioral improvements in different contexts, especially when examining across different tasks and modalities. We therefore recorded single units from chronic electrode arrays implanted in the prefrontal cortex of four monkeys as they were trained to perform spatial and object working memory tasks with the goal of assessing the resulting activity changes that would be induced by rule learning. Progression of training allowed behavioral improvements to be correlated with a variety of neural effects that could be observed across different task contexts, including increases or decreases of both firing rate and decoding, increases in the proportion of firing rate variance that was unexplained by sensory stimuli and motor actions, and the increased separation of population response trajectories in state space. Our results thus reveal how rule learning induces plasticity of prefrontal cortical activity, and the aspects of neural activity changes that were unique to individual tasks and modalities or common across them. Our results ultimately reveal new patterns of training effects, identifying the generalized prefrontal mechanisms that are responsible for rule learning.

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