Pattern separation in the human hippocampal CA3 and dentate gyrus

Abstract

Pattern separation, the process of transforming similar representations or memories into highly dissimilar, nonoverlapping representations, is a key component of many functions ascribed to the hippocampus. Computational models have stressed the role of the hippocampus and, in particular, the dentate gyrus and its projections into the CA3 subregion in pattern separation. We used high-resolution (1.5-millimeter isotropic voxels) functional magnetic resonance imaging to measure brain activity during incidental memory encoding. Although activity consistent with a bias toward pattern completion was observed in CA1, the subiculum, and the entorhinal and parahippocampal cortices, activity consistent with a strong bias toward pattern separation was observed in, and limited to, the CA3/dentate gyrus. These results provide compelling evidence of a key role of the human CA3/dentate gyrus in pattern separation.

Figures

Fig. 1

Sample stimuli sets showing version A and B of the same object

Fig. 2

Anatomical location and mean activity in the three task conditions for each of the eight MTL regions of interest. A model segmentation of hippocampal subfields is overlaid on each brain slice to indicate the location of the subiculum (green), CA1 (blue) and CA3/DG (red). Regions of activity within the MTL are shown in white and labeled within each slice (PHC=parahippocampal cortex, EC=entorhinal cortex. Regions of activity outside the MTL (not part of the analysis) are shown in black. 3D rendering (lateral, superior view) shows the location of each slice (white lines). The distance of each slice from the anterior commissure (y=0 in Talairach coordinates) is indicated for each slice as well (y=13–36 mm). The thicker white lines represent two adjoining slices. Bar graphs show mean activity (summed beta-coefficients) in each ROI for each trial condition.

Fig. 3

Bias scores in the MTL. A single bias score for each of the six different areas in the MTL was calculated by collapsing the bias scores for multiple ROI’s in the same area. Bias scores closer to zero connote separation while scores closer to one connote completion.