Repulsion refers to the phenomenon of highly similar events generating patterns of hippocampal activity that are (counterintuitively) less similar to each other than are those generated by unrelated events. Although observable in human neuroimaging data, repulsion is not explained by standard rodent or human models of hippocampal function, and the factors that lead to its occurrence remain unclear. Wanjia et al. now show in humans that repulsion effects occur specifically in the CA3 subfield and dentate gyrus (CA3/DG) of the hippocampus and are associated with the presence of distinct internal beliefs about highly similar visual inputs.

The researchers conducted a spatial route-learning experiment inspired by rodent T-maze studies, in which 40 healthy adults each viewed a series of 100 images that depicted one of four possible routes, organized as two partially overlapping pairs. The overlapping part of each route pair comprised an identical segment (25 pictures) followed by a highly similar segment (50 pictures of the same route obtained on different occasions). The two routes of each pair then diverged and finished at a unique destination (25 pictures). Participants repeatedly viewed each series of images before, during and after high-resolution functional MRI (fMRI). During the pre-fMRI phase, participants were asked to predict the route destination once during each route segment and to indicate whether they felt sure or unsure of their choice. During fMRI, the researchers manipulated participants’ beliefs about the route destination by preceding the image series with a text cue that suggested the likely route destination. Valid cues (75%) indicated the correct destination, whereas invalid cues (25%) always indicated the overlapping destination. During post-fMRI rounds, the researchers investigated the effect of beliefs about ambiguous inputs by asking participants to press a button when they were “at least 90% sure” of the route destination and to identify their choice by selecting one of the four possible destinations. The correct destination was selected in ~95% of such trials.