Anterior Hippocampal Engagement during Memory Formation Predicts Subsequent False Recognition of Similar Experiences.

People better remember experiences when they orient to meaning over surface-level perceptual features. Such an orientation-related memory boost has been associated with engagement of both hippocampus (HPC) and neocortex during encoding. However, less is known about the neural mechanisms by which a cognitive orientation toward meaning might also promote memory errors, with one open question being whether the HPC-a region traditionally implicated in precise memory formation-also contributes to behavioral imprecision. We used fMRI to characterize encoding-phase signatures as people oriented toward the meaning (story) versus perceptual style (artist) of storybook-style illustrations and then linked them to subsequent true and false memories. We found that story and artist orientation tasks were each associated with both unique univariate profiles and consistent neural states defined using multivoxel patterns. Linking these neural signatures to behavior, we found that greater medial pFC activation and alignment of neural patterns to the story (but not artist) state was related to subsequent memory success on a trial-by-trial basis. Moreover, among successfully remembered experiences, greater anterior HPC engagement at encoding was associated with a higher likelihood of related false recognitions, consistent with the encoding of broad traces in this region. Interestingly, these effects did not reliably vary by cued orientation. These results suggest that, irrespective of the cued encoding orientation, neocortical and hippocampal mechanisms associated with orienting to meaning (story) over perceptual (artist) features may support memory, with the formation of generalizable memories being a specialty of anterior HPC.