Evidence for a Gradient Within the Medial Temporal Lobes for Flexible Retrieval Under Hierarchical Task Rules

A fundamental question in memory research is how the hippocampus processes contextual cues to retrieve distinct mnemonic associations. Prior research has emphasized the importance of hippocampal-prefrontal interactions for context-dependent memory. Our fMRI study examined the human medial temporal lobes (MTL) and their prefrontal interactions when retrieving memories associated with hierarchically organized task contexts. Participants learned virtual object-location associations governed by subordinate and superordinate task rules, which could be independently cued to change. On each fMRI trial, participants retrieved the correct object for convergent rule and location contextual information. Results demonstrated that hippocampal activity and hippocampal-prefrontal functional interconnectivity distinguished retrieval under different levels of hierarchically organized task rules. In explicit contrast to the hippocampal tail, anterior (body and head) regions were recruited specifically for superordinate changes in the contextual hierarchy. The hippocampal body also differed in its functional connectivity with the prefrontal cortex for superordinate versus subordinate changes. Our findings demonstrate a gradient in MTL for associative retrieval under changing task rules, and advance understanding of hippocampal-prefrontal interactions that support flexible contextual memory.