Forming new associations is a fundamental process of building our knowledge system. At the brain level, how prior-knowledge influences acquisition of novel associations has not been thoroughly investigated. Based on recent cognitive neuroscience literature on multiple-component memory processing, we hypothesize that prior-knowledge triggers additional evaluative, semantic, or episodic-binding processes, mainly supported by the ventromedial prefrontal cortex (vmPFC), anterior temporal pole (aTPL), and hippocampus (HPC), to facilitate new memory encoding. To test this hypothesis, we scanned 20 human participants with functional magnetic resonance imaging (fMRI) while they associated novel houses with famous or nonfamous faces. Behaviorally, we found beneficial effects of prior-knowledge on associative memory. At the brain level, we found that the vmPFC and HPC, as well as the parahippocampal place area (PPA) and fusiform face area, showed stronger activation when famous faces were involved. The vmPFC, aTPL, HPC, and PPA also exhibited stronger activation when famous faces elicited stronger emotions and memories, and when associations were later recollected. Connectivity analyses also suggested that HPC connectivity with the vmPFC plays a more important role in the famous than nonfamous condition. Taken together, our results suggest that prior-knowledge facilitates new associative encoding by recruiting additional perceptual, evaluative, or associative binding processes.

Scene construction is a key component of memory recall, navigation, and future imagining, and relies on the medial temporal lobes (MTL). A parallel body of work suggests that eye movements may enable the imagination and construction of scenes, even in the absence of external visual input. There are vast structural and functional connections between regions of the MTL and those of the oculomotor system. However, the directionality of connections between the MTL and oculomotor control regions, and how it relates to scene construction, has not been studied directly in human neuroimaging. In the current study, we used dynamic causal modeling (DCM) to interrogate effective connectivity between the MTL and oculomotor regions using a scene construction task in which participants' eye movements were either restricted (fixed-viewing) or unrestricted (free-viewing). By omitting external visual input, and by contrasting free- versus fixed- viewing, the directionality of neural connectivity during scene construction could be determined. As opposed to when eye movements were restricted, allowing free-viewing during construction of scenes strengthened top-down connections from the MTL to the frontal eye fields, and to lower-level cortical visual processing regions, suppressed bottom-up connections along the visual stream, and enhanced vividness of the constructed scenes. Taken together, these findings provide novel, non-invasive evidence for the underlying, directional, connectivity between the MTL memory system and oculomotor system associated with constructing vivid mental representations of scenes.