Levodopa boosts hippocampal activity and strengthens generalizable rule representations in prefrontal cortex during the inference of meaning

Dopamine has long been implicated in a variety of higher-order cognitive functions, including language processing. However, the neural processes and representations by which dopamine influences language processing remain unclear. Here we show that administration of levodopa to young healthy volunteers (n = 70, 47 females) boosts hippocampal processing and neural representations of generalizable abstract rules for successful inference of novel word meaning. We used a novel experimental paradigm that required participants to build new artificial word meanings by inferring and applying abstract affixation rules. A repetition suppression procedure was combined with multivariate representational similarity analyses to isolate the neural locus of both the abstract rules required for the compositional inference process, as well as the novel word meaning representations that were composed based on these abstract rules. Levodopa modulated not only inference-related signals in the hippocampal formation, but also abstract rule representations in the medial frontal cortex. These results support the hypothesis that dopamine boosts hippocampal activity and strengthens prefrontal representations of abstract rules when building novel meaning. Significance statement Dopamine has long been implicated in a variety of higher-order cognitive functions, including language processing. However, the neural processes by which dopamine boosts language processing have remained unclear. Here we show that administration of levodopa to young healthy volunteers enhances hippocampal activity and strengthens prefrontal representations of generalizable abstract rules when building novel word meanings.