Cooperative interactions between hippocampal and striatal systems support flexible navigation

Abstract

Research in animals and humans has demonstrated that the hippocampus is critical for retrieving distinct representations of overlapping sequences of information. There is recent evidence that the caudate nucleus and orbitofrontal cortex are also involved in disambiguation of overlapping spatial representations. The hippocampus and caudate are functionally distinct regions, but both have anatomical links with the orbitofrontal cortex. The present study used an fMRI-based functional connectivity analysis in humans to examine the functional relationship between the hippocampus, caudate, and orbitofrontal cortex when participants use contextual information to navigate well-learned spatial routes which share common elements. Participants were trained outside the scanner to navigate virtual mazes from a first-person perspective. Overlapping condition mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping condition mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required contextual information identifying the current navigational route to guide the appropriate response for a given trial. Results revealed greater functional connectivity between the hippocampus, caudate, and orbitofrontal cortex for overlapping mazes compared to non-overlapping mazes. The current findings suggest that the hippocampus and caudate interact with prefrontal structures cooperatively for successful contextually dependent navigation.

Figure 1

Virtual maze design.(a) Overhead layout of the 12 mazes used in the task. The overlapping mazes (OL) are depicted on the left and the non-overlapping mazes (NOL) are depicted on the right. Mazes began at the “^” and end at the “X.” The colored, elongated, segments represent the hallways of the paths. One color represents one path. The gray segments represent the incorrect “foil” hallways. The black squares represent intersections between hallways. The yellow segments in the overlapping mazes represent overlapping hallways. The final hallway of an overlapping segment before the paths split apart (indicated with “*”) was labeled the “critical hall.” (b) Perspective of NOL5 during the turn into the fourth hall. This image is representative of how participants viewed the mazes. (c) Connectivity seed regions. The hippocampal head, body, and tail are indicated by red, green, and purple dots, respectively. Depictions of hippocampal seed locations are approximate, due to curvature of the structure. The seed regions in the medial caudate nucleus are shown in light blue.

Figure 2

Scanning day behavioral performance. Error bars reflect the standard error (s.e.m.). The overlapping (OL) condition is represented in dark gray, the non-overlapping (NOL) condition is represented in light gray. (a) Proportion of correct trials for the 1st hall and Critical hall periods. (b) Reaction times (RT) in milliseconds for the 1st hall and Critical hall periods.

Figure 3

Changes in connectivity between hippocampal subregions and the striatum during 1st hall and Critical hall periods for the overlapping compared to the non-overlapping condition (OL > NOL). The images are thresholded to p < 0.01, corrected for multiple comparisons with a voxel extent of 140. The specific seed region is labeled above each connectivity map. The 1st hall period (a) had greater functional connectivity between the hippocampus and the caudate head and body (blue arrows), and the hippocampus and the putamen (green arrows). The Critical hall period (b) had greater functional connectivity between the hippocampus and the caudate head and body (blue arrows).

Figure 4

Changes in connectivity for the hippocampus and caudate with the orbitofrontal cortex during the Critical hall period for the overlapping compared to the non-overlapping condition (OL > NOL). The images are thresholded to p < 0.01, corrected for multiple comparisons with a voxel extent of 140. The specific seed region is labeled above each connectivity map. The left hippocampus (a) and right caudate (b) had significantly greater connectivity with the orbitofrontal cortex.

Figure 5

Changes in connectivity for hippocampus and caudate with the lateral prefrontal cortex during the Critical hall period for the overlapping compared to the non-overlapping condition (OL > NOL). The images are thresholded to p < 0.01, corrected for multiple comparisons with a voxel extent of 140. The specific seed region is labeled above each connectivity map. The hippocampus (a) and caudate (b) had significantly greater connectivity with the middle frontal gyrus (blue arrows) and the inferior frontal gyrus (green arrows).