Working memory and anticipatory set modulate midbrain and putamen activity.

To behave adaptively, an organism must balance the accurate maintenance of information stored in working memory with the ability to update that information when the context changes. This trade-off between fidelity and flexibility may depend upon the anticipated likelihood that updating will be necessary. To address the neurobiological basis of anticipatory optimization, we acquired functional magnetic resonance imaging data, while healthy human subjects performed a modified delayed-response task. This task used cues that predicted memory updating, with high or low probability, followed by a contingent updating or maintenance event. This enabled us to compare behavior and neuronal activity during conditions in which updating was anticipated with high and low probability, and measure responses to expected and unexpected memory updating. Based on the known role of dopamine in cognitive flexibility and working memory updating, we hypothesized that differences in anticipatory set would be manifest in the dopaminergic midbrain and striatum. Consistent with our predictions, we identified sustained activation in the dopaminergic midbrain and the striatum, associated with anticipations of high versus low updating probability. We also found that this anticipatory factor affected neural responses to subsequent updating processes, which suppressed, rather than elevated, midbrain and striatal activity. Our study addresses for the first time an important and hitherto understudied aspect of working memory.