Contributions of the hippocampal subfields and entorhinal cortex to disambiguation during working memory

The hippocampus and medial temporal lobes (MTL) support the successful formation of new memories without succumbing to interference from related, older memories. Computational models and animal findings have implicated the dentate gyrus (DG), CA3, CA1, and entorhinal cortex (EC) in the disambiguation and encoding of well-established, episodic events that share common elements. However, it is unknown if these hippocampal subfields and MTL (entorhinal, perirhinal, parahippocampal) cortices also contribute during working memory when overlapping stimuli that share related features are rapidly encoded and subsequently maintained over a brief temporal delay. We hypothesized that activity in CA3/DG hippocampal subfields would be greater for the rapid encoding of stimuli with overlapping features than for the rapid encoding of stimuli with distinct features. In addition, we predicted that CA1 and EC, regions that are associated with creating long-term episodic representations, would show greater sustained activity across both encoding and delay periods for representations of stimuli with overlapping features than for those with distinct features. We used high-resolution fMRI during a delayed matching-to-sample (DMS) task using face pairs that either shared (overlapping condition, OL) or did not share (non-overlapping condition, NOL) common elements. We contrasted the OL condition with the NOL condition separately at sample (encoding) and during a brief delay (maintenance). At sample, we observed activity localized to CA3/DG, the subiculum, and CA1. At delay, we observed activity localized to the subiculum and CA1 and activity within the entorhinal, perirhinal, and parahippocampal cortices. Our findings are consistent with our hypotheses and suggest that CA3/DG, CA1 and the subiculum support the disambiguation and encoding of overlapping representations while CA1, subiculum and entorhinal cortex maintain these overlapping representations during working memory. © 2013 Wiley Periodicals, Inc