The Human Retrosplenial Cortex and Thalamus Code Head Direction in a Global Reference Frame

Abstract

Spatial navigation is a multisensory process involving integration of visual and body-based cues. In rodents, head direction (HD) cells, which are most abundant in the thalamus, integrate these cues to code facing direction. Human fMRI studies examining HD coding in virtual environments (VE) have reported effects in retrosplenial complex and (pre-)subiculum, but not the thalamus. Furthermore, HD coding appeared insensitive to global landmarks. These tasks, however, provided only visual cues for orientation, and attending to global landmarks did not benefit task performance. In the present study, participants explored a VE comprising four separate locales, surrounded by four global landmarks. To provide body-based cues, participants wore a head-mounted display so that physical rotations changed facing direction in the VE. During subsequent MRI scanning, subjects saw stationary views of the environment and judged whether their orientation was the same as in the preceding trial. Parameter estimates extracted from retrosplenial cortex and the thalamus revealed significantly reduced BOLD responses when HD was repeated. Moreover, consistent with rodent findings, the signal did not continue to adapt over repetitions of the same HD. These results were supported by a whole-brain analysis showing additional repetition suppression in the precuneus. Together, our findings suggest that: (1) consistent with the rodent literature, the human thalamus may integrate visual and body-based, orientation cues; (2) global reference frame cues can be used to integrate HD across separate individual locales; and (3) immersive training procedures providing full body-based cues may help to elucidate the neural mechanisms supporting spatial navigation.

Significance statement: In rodents, head direction (HD) cells signal facing direction in the environment via increased firing when the animal assumes a certain orientation. Distinct brain regions, the retrosplenial cortex (RSC) and thalamus, code for visual and vestibular cues of orientation, respectively. Putative HD signals have been observed in human RSC but not the thalamus, potentially because body-based cues were not provided. Here, participants encoded HD in a novel virtual environment while wearing a head-mounted display to provide body-based cues for orientation. In subsequent fMRI scanning, we found evidence of an HD signal in RSC, thalamus, and precuneus. These findings harmonize rodent and human data, and suggest that immersive training procedures provide a viable way to examine the neural basis of navigation.

Keywords: fMRI; head direction; human; navigation; retrosplenial cortex; thalamus.

Figure 1.

The VE environment in which participants learned individual images associated with different HDs, and an example subject-specific RSC region-of-interest (ROI). a, The environment comprised four separate enclosed galleries connected by a handrail; (b) participants were required to monitor their orientation relative to global landmarks (eg, a cityscape) located at cardinal HDs; landmarks were visible only when outside of the galleries; (c) each gallery contained four paintings from a particular category of stimuli (eg, animals), and individual paintings occupied positions concordant with directions to the global landmarks; (d) individual images cueing specific HDs were presented during a subsequently scanned one-back task. Participants were required to judge whether the HD associated with the current image was the “same” or “different” to the preceding image; (e) Freesurfer was used to identify the RSC bilaterally in each participant (left RSC, red; right RSC, blue), (f) and these ROIs warped to standard space and used to extract average percentage signal change values for the different repetition conditions.

Figure 2.

Behavioral performance (mean accuracy and RT ± SEM) on the one-back task, separated according to orientation and repetition. a, The fMRI sample (n = 9) showed very accurate performance on this task, with mean accuracy and RT matched across different orientations; (b) the excellent behavioral performance was replicated in a larger sample (n = 24), where these participants showed a small benefit in RT for stimuli cueing the 270° orientation.

Figure 3.

Group average percentage signal change values (mean ± SEM) extracted from anatomical ROIs. a, In bilateral RSC, significant repetition suppression was associated with repeat HD relative to non-repeat HD trials. The percentage signal adaptation between these two conditions for each participant is also provided; positive values demonstrate that repetition of HD led to a reduction of the BOLD signal; (b) the same adaptation effect was evident also in bilateral thalamus; (c) in RSC attenuation did not continue over multiple repetitions of stimuli cueing the same HD; (d) and this plateau was apparent also in the thalamus. To test more directly for evidence of a plateau in the BOLD response after the first repetition of HD, the difference in activity between non-repeat HD and one-back repeat HD was compared with the difference in activity between one-back repeat HD and two-back repeat HD conditions. In both (e) RSC, and (f) the thalamus, significantly greater adaptation was found after the first repeat of HD compared with when HD was repeated over multiple trials. Individual-subject data are displayed here, with dashed lines connecting each subject's data points (*p < 0.05).

Figure 4.

Whole-brain contrast image (non-repeat HD > repeat HD) with corresponding plots of mean percentage signal change values ± SEM extracted from the peak voxel in each cluster. Supporting the ROI analyses, significant repetition suppression was evident in the whole-brain contrast image in a number of regions including: (a) left RSC, (b) left thalamus, (c) right thalamus, and (d) precuneus. TFCE results are displayed on the MNI template brain, using a threshold of p < 0.01, FWE-corrected.

Figure 5.

Significant repetition suppression effect in bilateral thalamus overlaid with the Morel (2007) thalamic atlas. According to this atlas, the peak coordinate of left thalamus cluster (−10, −16, 8; displayed center in the top row of the figure, accompanied by adjacent sagittal slices) was located in the ventral division of the ventral lateral posterior nucleus [VLpv; the second row of the figure comprises enlarged views of the left thalamus with color-coded overlay of the Morel (2007) atlas]. This cluster extended to the dorsal division of the ventral lateral posterior nucleus (VLpd), the central lateral nucleus (CL), the lateral dorsal nucleus (LD), lateral posterior nucleus (LP), the parvocellular division of the mediodorsal nucleus (MDpc), and the posterior division of the ventral posterior lateral nucleus (VPLp). The right thalamus cluster (12, −12, 18; third row center, again displayed center alongside two adjacent sagittal slices) spanned the same thalamic subregions. The peak, however, was located on the border of the dorsal division of the ventral lateral posterior nucleus (4th row of figure). Results are displayed on the MNI template brain, with TFCE statistical map thresholded, p < 0.01 FWE-corrected.

Figure 6.

Consistency of repetition suppression in the RSC and thalamus in individual participants. a, Significant clusters of activity in the RSC were evident in seven of the nine participants. Clusters are significant at the whole-brain level (Z > 2.3, p < 0.05), overlaid (cyan) with the individual participant's RSC anatomical ROI. b, Peak voxel in the thalamus associated with the repetition suppression contrast at the single-subject level. Eight participants showed repetition suppression when HD was repeated over consecutive trials. This effect was significant in six participants using a small volume correction comprising the participant-specific bilateral thalamus mask (Z > 2.3, p < 0.05, corrected for multiple comparisons); this effect did not survive correction for multiple comparisons in participants (P)2 and P8 (images for these participants displayed at p = 0.01, uncorrected).