Dopaminergic fronto-striatal connectivity underlies schema-dependent learning.

BACKGROUND: Long-term memory for novel information can be supported by presenting it within a known semantic context. This so-called congruency effect has long been described as an example of schema-dependent learning, but the underlying neural mechanisms still remain unclear. Therefore, we tested the hypothesis that dopamine modulates it through the regulation of prefrontal and mesolimbic brain regions. METHODS: In a double-blind mixed-design, 90 healthy humans (70 female, 20 male) received either a dopamine agonist (1.25 mg bromocriptine), a dopamine antagonist (400 mg sulpiride), or a placebo before the encoding of semantically congruent and incongruent words, while their brain activity was scanned using functional magnetic resonance imaging. RESULTS: Behaviorally, semantic congruency enhanced recognition memory on the next day in all three groups, and this effect was modulated by drug following an inverted U-shaped function. Specifically, the congruency effect was highest under placebo and significantly reduced by both the agonist and antagonist. On the neural level, this was paralleled by robust non-linear modulations of striatal activity and its functional connectivity with the prefrontal cortex (superior frontal gyrus). CONCLUSION: Our findings give novel insights by showing that schema-dependent learning is modulated by dopamine, and they suggest that this relates to fronto-striatal connectivity.