- Different strategies may be spontaneously adopted to solve most navigation tasks. These strategies are associated with dissociable brain systems. Here, we use brain-imaging and cognitive tasks to test the hypothesis that individuals living with Schizophrenia Spectrum Disorders (SSD) have selective impairment using a hippocampal-dependent spatial navigation strategy. Brain activation and memory performance were examined using functional magnetic resonance imaging (fMRI) during the 4-on-8 virtual maze (4/8VM) task, a human analog of the rodent radial-arm maze that is amenable to both response-based (egocentric or landmark-based) and spatial (allocentric, cognitive mapping) strategies to remember and navigate to target objects. SSD (schizophrenia and schizoaffective disorder) participants who adopted a spatial strategy performed more poorly on the 4/8VM task and had less hippocampal activation than healthy comparison participants using either strategy as well as SSD participants using a response strategy. This study highlights the importance of strategy use in relation to spatial cognitive functioning in SSD. Consistent with a selective-hippocampal dependent deficit in SSD, these results support the further development of protocols to train impaired hippocampal-dependent abilities or harness non-hippocampal dependent intact abilities.