Adaptive goal-directed actions require the ability to quickly relearn behaviors in a changing environment, yet how the brain supports this ability is barely understood. Using functional magnetic resonance imaging and a novel reversal learning paradigm, the present study examined the neural mechanisms associated with reversal learning for outcomes versus motor responses. Participants were extensively trained to classify novel visual symbols (Japanese Hiraganas) into two arbitrary classes ("male" or "female"), in which subjects could acquire both stimulus-outcome associations and stimulus-response associations. They were then required to relearn either the outcome or the motor response associated with the symbols, or both. The results revealed that during reversal learning, a network including anterior cingulate, posterior inferior frontal, and parietal regions showed extended activation for all types of reversal trials, whereas their activation decreased quickly for trials not involving reversal, suggesting their role in domain-general interference resolution. The later increase of right ventral lateral prefrontal cortex and caudate for reversal of stimulus-outcome associations suggests their importance in outcome reversal learning in the face of interference.
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