Examining hippocampal function in schizophrenia using a virtual reality spatial navigation task

Background: Structural pathology in the hippocampus is well-documented in schizophrenia, but brain functional changes have not been consistently found. We used spatial navigation in a virtual reality environment, a task that is known to produce robust hippocampal activation in healthy subjects, to examine task-related activations and de-activations in the disorder.

Methods: Twenty-seven DSM IV schizophrenia patients and 32 healthy controls underwent fMRI while they navigated to a goal through a virtual reality town. Activations and de-activations were examined at the whole brain level and also using a region-of-interest (ROI) in the hippocampus.

Results: Spatial navigation was associated with activation in the posterior hippocampus and parahippocampal gyrus plus widespread neocortical areas. The patients showed reduced activation compared to the controls in the left dorsolateral prefrontal cortex (DLPFC) and the left occipital/temporal cortex. No differences in hippocampal activation were seen either at the whole-brain level or in the ROI analysis. The patients showed failure of de-activation affecting some but not all subregions of the default mode network.

Conclusions: Schizophrenia is associated with task-related hypoactivation in the DLPFC during spatial navigation, but not with functional changes in the hippocampus. The failure of de-activation also found adds to evidence for default mode network dysfunction in the disorder.