Oregon fMRI study: hippocampal CA3/DG inverts visual similarity when it causes memory interference
In a high-resolution fMRI study, University of Oregon researchers found that CA3/DG representations of similar images repel each other at learning stages when that similarity drives interference.
Researchers at the University of Oregon, together with colleagues from Princeton University and the University of Southern California, report in Nature Communications that the hippocampus represents visually similar images differently depending on which dimension of similarity causes memory interference at a given stage of learning. The study, by Soroush Mirjalili, Guo Wanjia, Dominik Grätz, Eric Z. Wang, Ulrich Mayr and Brice A. Kuhl, was published on 6 November 2026. nature.com
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Conflicting input-output functions
Earlier work clarified how the hippocampus resolves memory interference by relating the similarity of visual stimuli (input) to the similarity of hippocampal activity patterns (output). However, these input-output functions can take surprisingly different forms. The authors proposed a way to reconcile the conflicting findings: the hippocampus may prioritize different dimensions of visual similarity at different stages of learning.
Two dimensions of similarity in CA3/DG
To test this, the team generated a set of natural scene images from two visual categories. They characterized visual similarity with a wide array of methods, including computational models and human perceptual and memory decisions. From this they identified two orthogonal dimensions of visual similarity. Each predicted memory interference, but at distinct stages of learning.
The researchers then used high-resolution fMRI to test for dimension-specific input-output functions within the hippocampus. In CA3 and dentate gyrus (CA3/DG), a dimension of visual similarity was inverted, a pattern the authors call repulsion, at stages of learning when that dimension contributed to memory interference. When a dimension did not contribute to interference, CA3/DG preserved similarity. nature.com
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According to the authors, these findings show that hippocampal representations of visually similar stimuli are highly dynamic and depend on the dimensions of similarity that currently contribute to memory interference.
