The hippocampus is sensitive to the mismatch in novelty between items and their contexts.

In previous functional magnetic resonance imaging (fMRI) studies of continuous recognition memory it was reported that new items elicit greater hippocampal activity than old (repeated) items (hippocampal 'novelty' effects). Rather than reflecting recency differences between new and old items, hippocampal novelty effects may instead reflect the novelty of the association between test items and the experimental context, or a mismatch in the novelty of the test item and the context. The present continuous recognition study assessed these possibilities by manipulating item-context associations on a trial-by-trial basis. Each trial comprised the presentation of an object-word (context-item) pair. Repeated items were paired either with the same context as on their first presentation, a different but previously presented context, or a new context. The task was to judge whether each item was old or new, regardless of the study status of the associated context. We found no evidence that hippocampal novelty effects reflected either item and context recency, or the novelty of the item-context association. Rather, enhanced hippocampal activity was elicited when the novelty of the item and its context mismatched. These findings support the possibility that hippocampal novelty effects reflect, at least in part, the disjunction in novelty between test items and their contexts.