Dopamine Modulates Striatal Activity When Controlling the Output of Working Memory

Cognitive control depends on capacity-limited mechanisms that require selection. Working memory (WM) therefore relies on an input-gate to filter information into WM and an output-gate to transform current WM representations into a prioritized state to guide behavior. According to current theory, such WM gating processes are modulated by dopamine in the striatum, yet empirical evidence for this hypothesis remains sparse. We fill this gap by directly testing the role of dopamine for both WM input- and output-gating in a double-blind, placebo-controlled within-subject functional magnetic resonance imaging study (N = 34; 23 female, 11 male human subjects), using a 400 mg oral dose of the dopamine D2 receptor antagonist sulpiride. In our cued delayed-response task, which separated input- from output-gating, sulpiride altered neural activity in the striatum during output-gating. This effect was accompanied by a sulpiride-induced decrease in the neural stimulus-selectivity of gated sensory representations in visual association cortex, with greater decreases in stimulus-selectivity correlating with reduced behavioral accuracy in the task. Together, the results establish a role for striatal dopamine during the control of cortical outflow of WM.