Global similarity and pattern separation in the human medial temporal lobe predict subsequent memory.

Intense debate surrounds the role of medial temporal lobe (MTL) structures in recognition memory. Using high-resolution fMRI and analyses of pattern similarity in humans, we examined the encoding computations subserved by MTL subregions. Specifically, we tested the theory that MTL cortex supports memory by encoding overlapping representations, whereas hippocampus supports memory by encoding pattern-separated representations. Consistent with this view, the relationship between encoding pattern similarity and subsequent memory dissociated MTL cortex and hippocampus: later memory was predicted by greater across-item pattern similarity in perirhinal cortex and in parahippocampal cortex, but greater pattern distinctiveness in hippocampus. Additionally, by comparing neural patterns elicited by individual stimuli regardless of subsequent memory, we found that perirhinal cortex and parahippocampal cortex exhibited differential content sensitivity for multiple stimulus categories, whereas hippocampus failed to demonstrate content sensitivity. These data provide novel evidence that complementary MTL encoding computations subserve declarative memory.