Dopaminergic fronto-striatal connectivity underlies schema-dependent learning

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.

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.

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).

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.