Schedule of Events | Symposia

Dopamine modulates prefrontal connectivity to promote schema-dependent learning

Poster Session B - Sunday, March 30, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Mushfa Yousuf¹ (mus.yousuf@uni-luebeck.de), Jannik Prasuhn^2,3,4, Norbert Brüggemann^2,3,4, Lluís Fuentemilla^5,6,7, Nico Bunzeck^1,4; ¹Universität zu Lübeck, ²Department of Neurology, University Medical Center Schleswig-Holstein, Lübeck, Germany 3 Institute of Neurogenetics, University of Lübeck, Germany, ³Institute of Neurogenetics, University of Lübeck, Germany, ⁴Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany, ⁵Cognition and Brain Plasticity Group, Bellvitge Institute for Biomedical Research, Hospitalet de Llobregat 08907, Spain, ⁶Department of Cognition, Development and Educational Psychology, University of Barcelona, Barcelona 08035, Spain, ⁷Institute of Neurosciences, University of Barcelona, Barcelona 08035, Spain

The integration of novel information into long-term memory can be supported by presenting it within a known semantic context. This so-called congruency effect has long been described in the psychological literature as an example for schema-dependent learning, but the underlying neural mechanisms still remain unclear. Therefore, and on the basis of theoretical frameworks, we tested the hypothesis that dopamine plays a critical role through the regulation of prefrontal connectivity. In a double-blind between-subjects design, healthy humans 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 (fMRI). Behaviorally, semantic congruency was associated with 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, semantic congruency was associated with activity in the prefrontal cortex and medial temporal lobe regions, including the hippocampus. Importantly, subsequent memory effects for congruent items in the left inferior frontal gyrus and its connectivity with the left substantia nigra and right nucleus accumbens, respectively, was also modulated by drug in a quadratic fashion resembling the behavioral pattern. Taken together, our findings give novel insights by showing that schema-dependent learning is modulated by prefrontal dopamine and interconnected mesolimbic regions.

Topic Area: EXECUTIVE PROCESSES: Working memory