Prolonged allocentric navigation deficits indicate hippocampal damage in TGA.

OBJECTIVE: To investigate long-term recovery of allocentric and egocentric spatial orientation as a sensitive marker for hippocampal and extrahippocampal network function in transient global amnesia (TGA). METHODS: A group of 18 patients with TGA performed an established real-space navigation paradigm, requiring allo- and egocentric spatial orientation abilities, 3 days (postacute stage) and 3 months (follow-up) after symptom onset. Visual exploration behavior and navigation strategy were documented by a gaze-controlled, head-fixed camera. Allo- and egocentric spatial orientation performance was compared to that of 12 age-matched healthy controls. Navigation-induced brain activations were measured using [18F]-fluorodeoxyglucose-PET in a subgroup of 8 patients in the postacute stage and compared to those of the controls. RESULTS: In the postacute stage, the patients navigated worse and had higher error rates than controls in allocentric (p = 0.002), but not in egocentric, route planning (p = 0.30), despite complete recovery of verbal (p = 0.58) and figural memory (p = 0.11). Until follow-up, allocentric navigation deficits improved, but higher error rates and reduced use of shortcuts persisted (p < 0.0001). Patients still exhibited relatively more fixations of unique landmarks during follow-up (p = 0.05). PET measurements during the postacute stage showed increased navigation-induced brain activations in the right hippocampus, bilateral retrosplenial, parietal, and mesiofrontal cortices, and cerebellar dentate nucleus in patients compared to controls (p < 0.005). CONCLUSIONS: Patients with TGA show selective and prolonged deficits of allocentric spatial orientation. Activations in right hippocampal and extrahippocampal hubs of the cerebral navigation network functionally substitute for the deficit in creating and updating the internal cognitive map in TGA.

Anisotropy of Human Horizontal and Vertical Navigation in Real Space: Behavioral and PET Correlates.

Spatial orientation was tested during a horizontal and vertical real navigation task in humans. Video tracking of eye movements was used to analyse the behavioral strategy and combined with simultaneous measurements of brain activation and metabolism ([18F]-FDG-PET). Spatial navigation performance was significantly better during horizontal navigation. Horizontal navigation was predominantly visually and landmark-guided. PET measurements indicated that glucose metabolism increased in the right hippocampus, bilateral retrosplenial cortex, and pontine tegmentum during horizontal navigation. In contrast, vertical navigation was less reliant on visual and landmark information. In PET, vertical navigation activated the bilateral hippocampus and insula. Direct comparison revealed a relative activation in the pontine tegmentum and visual cortical areas during horizontal navigation and in the flocculus, insula, and anterior cingulate cortex during vertical navigation. In conclusion, these data indicate a functional anisotropy of human 3D-navigation in favor of the horizontal plane. There are common brain areas for both forms of navigation (hippocampus) as well as unique areas such as the retrosplenial cortex, visual cortex (horizontal navigation), flocculus, and vestibular multisensory cortex (vertical navigation). Visually guided landmark recognition seems to be more important for horizontal navigation, while distance estimation based on vestibular input might be more relevant for vertical navigation.