Prolonged allocentric navigation deficits indicate hippocampal damage in TGA.

ABSTRACT

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.