Dopaminergic Neuromodulation of Congruence Dependent Memory Formation

Declarative long-term memory can be improved by presenting the tobe- learned information within a known context. In humans, this has often been demonstrated with a priori semantic information followed by congruent (vs. incongruent) material, and has, therefore, been labelled semantic congruence effect. After previous work has pinpointed the neural oscillatory bands (i.e. theta, 4-8 Hz, and alpha, 9-13 Hz), and corresponding brain regions (i.e. medial temporal lobe,MTL, and prefrontal cortex, PFC) involved, here I consider recent frameworks suggesting that dopamine (DA) plays a critical role in regulating the connectivity between the PFC and MTL as well as prefrontal theta/alpha oscillations. Indeed, DA has long been implicated in various memory processes, including long-term potentiation (LTP), novelty encoding, consolidation and retrieval. However, the precise function of DA in congruence dependent memory formation remains unclear. I plan to use our established semantic congruence paradigm in combination withpsychopharmacology in two experiments. These will follow previous research strategies of a double-blind, placebo controlled, withinsubjects design including a DA agonist (sulpiride) and a DA Antagonist (bromocriptine) in combination with fMRI (experiment 1) and EEG recordings (experiment 2). I expect that, in contrast to placebo, the DA agonist will further enhance the congruence effect, while the DA antagonist is expected to diminish it (experiment 1 and 2). Moreover, I expect that effective connectivity between the PFC and MTL, whichunderlies the congruence effect, is enhanced by the DA agonist and reduced by the DA antagonist (experiment 1, fMRI). Further, prefrontal theta (and possibly alpha) oscillations, which could be linked to the congruence effect, are expected to be enhanced by the DA agonistand reduced by the DA antagonist. Taken together, the project aims to close an apparent gap in our understanding of the role of DA in congruence dependent memory formation. As such, it has animportant bearing on the nature of human memory, and the proposed studies will help to further pinpoint the interplay between DA, neural oscillations, the PFC and MTL.