"I have often walked down this street before": fMRI studies on the hippocampus and other structures during mental navigation of an old environment.

The role of the hippocampus in recent spatial memory has been well documented in patients with damage to this structure, but there is now evidence that the hippocampus may not be needed for the storage and recovery of a spatial layout that was experienced long before injury. Such preservation may rely, instead, on a network of dissociable, extra-hippocampal regions implicated in topographical orientation. Using functional magnetic resonance imaging (fMRI), we investigated this hypothesis in healthy individuals with extensive experience navigating in a large-scale urban environment (downtown Toronto). Participants were scanned as they performed mental navigation tasks that emphasized different types of spatial representations. Tasks included proximity judgments, distance judgments, landmark sequencing, and blocked-route problem-solving. The following regions were engaged to varying degrees depending on the processing demands of each task: retrosplenial cortex, believed to be involved in assigning directional significance to locales within a relatively allocentric framework; medial and posterior parietal cortex, concerned with processing space within egocentric coordinates during imagined movement; and regions of prefrontal cortex, present in tasks heavily dependent on working memory. In a second, event-related experiment, a distinct area of inferotemporal cortex was revealed during identification of familiar landmarks relative to unknown buildings in addition to activation of many of those regions identified in the navigation tasks. This result suggests that familiar landmarks are strongly integrated with the spatial context in which they were experienced. Importantly, right medial temporal lobe activity was observed, its magnitude equivalent across all tasks, though the core of the activated region was in the parahippocampal gyrus, barely touching the hippocampus proper. Copyright 2004 Wiley-Liss, Inc.