Abstract
Animal studies indicate that hippocampal representations of environmental context modulate reward-related processing in the substantia nigra and ventral tegmental area (SN/VTA), a major origin of dopamine in the brain. Using functional magnetic resonance imaging (fMRI) in humans, we investigated the neural specificity of context-reward associations under conditions where the presence of perceptually similar neutral contexts imposed high demands on a putative hippocampal function, pattern separation. The design also allowed us to investigate how contextual reward enhances long-term memory for embedded neutral objects. SN/VTA activity underpinned specific context-reward associations in the face of perceptual similarity. A reward-related enhancement of long-term memory was restricted to the condition where the rewarding and the neutral contexts were perceptually similar, and in turn was linked to co-activation of the hippocampus (subfield DG/CA3) and SN/VTA. Thus, an ability of contextual reward to enhance memory for focal objects is closely linked to context-related engagement of hippocampal-SN/VTA circuitry.