Human hippocampal CA1 involvement during allocentric encoding of spatial information

Abstract

A central component of our ability to navigate an environment is the formation of a memory representation that is allocentric and thus independent of our starting point within that environment. Computational models and rodent electrophysiological recordings suggest a critical role for the CA1 subregion of the hippocampus in this type of coding; however, the hippocampal neural basis of spatial learning in humans remains unclear. We studied subjects learning virtual environments using high-resolution functional magnetic resonance imaging (1.6 mm x 1.6 mm in-plane) and computational unfolding to better visualize substructural changes in neural activity in the hippocampus. We show that the right posterior CA1 subregion is active and positively correlated with performance when subjects learn a spatial environment independent of starting point and direction. Altogether, our results demonstrate that the CA1 subregion is involved in our ability to learn a map-like representation of an environment.

Figure 1.

Virtual city snapshots. A, Snapshot of virtual city from a sample starting point. B, Sample store stimulus used. C, Subjects' learned store locations within 4 × 3 grid cities from a varying initial starting point within a city for the MSP encoding condition (blue arrows) and from a single initial starting point within the city for the SSP encoding condition (red arrows). D, Layout of city without stores used in the direction-pressing control baseline condition. Both tasks used this control condition. E, Both the SSP and MSP tasks consisted of alternating blocks of encoding (Learn) and retrieval (Recall) interspersed with blocks of control (Ctl).

Figure 2.

Unfolding method. A, B, Each subject's gray matter (green) is created by segmenting white matter and CSF. The gray matter is then computationally unfolded (A) and boundaries between regions are projected onto the unfolded flat map (B). C, Voxels in 2-D space are projected into 3-D space to create anatomical regions of interest showing posterior regions (left): CA23DG (red), CA1 (orange), subiculum (yellow), PHC (green), and fusiform gyrus (blue). D, An averaged group flat map (shown is the left) is created showing regions CA2, 3, and dentate gyrus, CA1, subiculum (Sub), ERC, PRC, PHC, and fusiform gyrus.

Figure 3.

A, Group voxel-based mixed-effects unfolded t test maps (n = 18, statistical maps of significantly activated and deactivated regions; −2.4 ≥ t ≥ 2.4; p < 0.05 corrected) for the left and right MTL regions during the MSP and SSP tasks separately compared with baseline. B, Group voxel-based mixed-effects unfolded t test maps (n = 18, statistical maps of significantly difference in activity between MSP and SSP conditions; −2.4 ≥ t ≥ 2.4; p < 0.05 corrected) for the left and right MTL regions. Regions shown include CA2, 3, and dentate gyrus, CA1, subiculum (Sub), ERC, PRC, PHC, and fusiform gyrus.

Figure 4.

Results from hippocampal anatomical regions of interest. Average percentage signal change (n = 18, error bars correspond to the SE across subjects) for the SSP and MSP tasks separately compared with baseline within left and right hippocampal subregions CA23DG (A) and subiculum (C) show no significant differences between MSP and SSP conditions or between right and left hemispheric regions. B, Average percentage signal change from baseline within left and right posterior CA1 for MSP and SSP encoding indicate a significant difference between hemisphere (right > left, t₍₁₇₎ = 3.29; p < 0.05) and conditions (MSP > SSP, t₍₁₇₎ = 2.26; p < 0.05).

Figure 5.

Behavioral performance (percentage correct) versus percentage signal change. A, Subjects' performance on the MSP task significantly correlated with percentage signal change in the right CA1 subregion during encoding (n = 18, Spearman's ρ = 0.53; p < 0.05). B, Subjects' performance on the SSP task did not significantly correlate with percentage signal change in the right CA1 subregion during encoding (n = 18, Spearman's ρ = −0.488; n.s.).