PT - JOURNAL ARTICLE AU - Shine, Jonathan P. AU - Valdés-Herrera, José P. AU - Hegarty, Mary AU - Wolbers, Thomas TI - The Human Retrosplenial Cortex and Thalamus Code Head Direction in a Global Reference Frame AID - 10.1523/JNEUROSCI.1268-15.2016 DP - 2016 Jun 15 TA - The Journal of Neuroscience PG - 6371--6381 VI - 36 IP - 24 4099 - http://www.jneurosci.org/content/36/24/6371.short 4100 - http://www.jneurosci.org/content/36/24/6371.full SO - J. Neurosci.2016 Jun 15; 36 AB - 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.