Medial temporal lobe (MTL) dependent long-term memory for novel events is modulated by a circuitry that also responds to reward and includes the ventral striatum, dopaminergic midbrain, and medial orbitofrontal cortex (mOFC). This common neural network may reflect a functional link between novelty and reward whereby novelty motivates exploration in the search for rewards; a link also termed novelty "exploration bonus." We used fMRI in a scene encoding paradigm to investigate the interaction between novelty and reward with a focus on neural signals akin to an exploration bonus. As expected, reward related long-term memory for the scenes (after 24 hours) strongly correlated with activity of MTL, ventral striatum, and substantia nigra/ventral tegmental area (SN/VTA). Furthermore, the hippocampus showed a main effect of novelty, the striatum showed a main effect of reward, and the mOFC signalled both novelty and reward. An interaction between novelty and reward akin to an exploration bonus was found in the hippocampus. These data suggest that MTL novelty signals are interpreted in terms of their reward-predicting properties in the mOFC, which biases striatal reward responses. The striatum together with the SN/VTA then regulates MTL-dependent long-term memory formation and contextual exploration bonus signals in the hippocampus. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.
