Dissociable profiles of generalization/discrimination in the human hippocampus during associative retrieval

When encountering stimuli that vary slightly from previous experiences, neural signals within the CA₃ and dentate gyrus (CA₃ DG) hippocampal subfields are thought to facilitate mnemonic discrimination, whereas CA₁ may be less sensitive to minor stimulus changes, allowing for generalization across similar events. Studies have also posited a critical role for CA₁ in the comparison of events to memory-derived expectations, but the degree to which these processes are impacted by explicit retrieval demands is yet unclear. To evaluate extant accounts of hippocampal subfield function, we acquired high-resolution fMRI data as participants performed a task in which famous names were used to cue the retrieval of previously paired images. Although both left CA₃ DG and CA₁ showed match enhancement effects, responding more to original paired images (targets) than to never-before-seen images (novels), the sensitivity of these subfields to stimulus changes and task demands diverged. CA₃ DG showed a goal-independent, yet highly specific, preference for previously encountered stimuli, responding equally strongly to targets and mispaired associates, while showing equally weak responses to close lures and novels. In contrast, recognition signals in CA₁ were goal-dependent (i.e., not evoked by mispaired associates), yet accommodating of subtle stimulus differences, such that close lures evoked comparable activity as targets. © 2016 Wiley Periodicals, Inc.