Right prefrontal cortex responds to item familiarity during a memory encoding task

In a previous word-pair encoding study (Dolan & Fletcher, 1997), we examined the effect of introducing novelty, either in studied words or in their mutual associations. A left medial temporal lobe (MTL) sensitivity to novel words and left prefrontal cortex (PFC) to novel associations was observed. In this further report on the data, we explored the extent to which the right PFC, more generally implicated in retrieval operations (Fletcher, Frith, & Rugg, 1997), was sensitive to these manipulations. Specifically, we characterised changes associated with increasing familiarity of study material. We demonstrate that the response in right ventrolateral PFC is preferentially sensitive to a condition in which all material was familiar (that is, in which all material had been presented prior to scanning). A more dorsal region in right PFC was found to be relatively more active in association with a condition in which one item in the pair was familiar but was paired with a novel associate. Our results suggest that sensitivity to stimulus familiarity is expressed in right PFC, even within the context of an encoding task. The data also provide further evidence for functional heterogeneity within right PFC, with a more ventral region responding to familiarity of complete word pairs and a more dorsal region responding to familiar single words occurring in the context of new associative relationships.