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bioRxiv · 10.64898/2026.02.01.703151

Dopamine modulates striatal activity when controlling the output of working memory

Nielsen, N. M.·Calcott, R. D.·van den Bosch, R.·Olraun, H. S.·Spronkers, F. S.·den Ouden, H. E. M.·Cools, R.
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Abstract

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 prioritised state to guide behaviour. 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 fMRI 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 de-crease in the neural stimulus selectivity of gated sensory representations in visual association cortex, with greater decreases in stimulus selectivity correlating with reduced behavioural accuracy in the task. Together, the results establish a role for striatal dopamine during the control of cortical outflow of WM. Significance StatementTo act on a goal, the brain holds information in mind and brings the important parts into focus to guide what we do next. Scientists believe that this "selection" process involves dopamine, a chemical messenger, in a brain area called the striatum. We tested this by giving people a drug that alters dopamine activity in the brain. The drug changed how the striatum reacted when people selected information from memory. It also made the brains visual areas represent this information less clearly, and this change affected peoples behaviour. Therefore, we conclude that dopamine in the striatum plays a role when our brain controls which information in working memory is sent to other parts of the brain to guide actions.

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Nielsen, N. M., Calcott, R. D., van den Bosch, R., Olraun, H. S., Spronkers, F. S., den Ouden, H. E. M., Cools, R.. 2026-02-02. Dopamine modulates striatal activity when controlling the output of working memory. https://doi.org/10.64898/2026.02.01.703151

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