Repetition reveals ups and downs of hippocampal, thalamic, and neocortical engagement during mnemonic decisions.

The extent to which current information is consistent with past experiences and our capacity to recognize or discriminate accordingly are key factors in flexible memory-guided behavior. Despite a wealth of evidence linking hippocampal and neocortical computations to these phenomena, many important factors remain poorly understood. One such factor is repeated encoding of learned information. In this experiment, participants completed a task in which study stimuli were incidentally encoded either once or three separate times during high-resolution fMRI scanning. We asked how repetition influenced recognition and discrimination memory judgments, and how this affects engagement of hippocampal and neocortical regions. Repetition revealed shifts in engagement in an anterior (ventral) CA1-thalamic-medial prefrontal network related to true and false recognition. Conversely, repetition revealed shifts in a posterior (dorsal) dentate/CA3-parahippocampal-restrosplenial network related to accurate discrimination. These differences in engagement were accompanied by task-related correlations in respective anterior and posterior networks. In particular, the anterior thalamic region observed during recognition judgments is functionally and anatomically consistent with nucleus reuniens in humans, and was found to mediate correlations between the anterior CA1 and medial prefrontal cortex. These findings offer new insights into how repeated experience affects memory and its neural substrates in hippocampal-neocortical networks. © 2016 Wiley Periodicals, Inc.