Hippocampal transformations occur along dimensions of memory interference

The role of the hippocampus in resolving memory interference has been greatly elucidated by considering the relationship between the similarity of visual stimuli (input) and corresponding similarity of hippocampal activity patterns (output). However, these input-output functions can take surprisingly different forms. Here, we reconcile seemingly conflicting findings by considering the possibility that the hippocampus prioritizes different dimensions of visual similarity across different stages of learning. First, we generated a set of natural scene images from two visual categories and rigorously characterized visual similarity using a wide array of methods: neural networks, artificial intelligence models, and human perceptual and memory decisions. We then identified two orthogonal dimensions of visual similarity that each predicted memory interference, but that did so at distinct stages of learning. Using high-resolution fMRI, we then tested for dimension-specific input-output functions within the hippocampus. Within CA3 and dentate gyrus (CA3/DG), we show that dimensions of visual similarity were inverted (negative functions) at stages of learning when they contributed to memory interference. When the dimensions did not contribute to interference, functions were positive. These findings reveal that hippocampal representations of visually-similar stimuli are highly dynamic and critically depend on the dimensions of similarity that currently contribute to memory interference.