Developmental topographical disorientation and decreased hippocampal functional connectivity.

Developmental topographical disorientation (DTD) is a newly discovered cognitive disorder in which individuals experience a lifelong history of getting lost in both novel and familiar surroundings. Recent studies have shown that such a selective orientation defect relies primarily on the inability of the individuals to form cognitive maps, i.e., mental representations of the surrounding that allow individuals to get anywhere from any location in the environment, although other orientation skills are additionally affected. To date, the neural correlates of this developmental condition are unknown. Here, we tested the hypothesis that DTD may be related to ineffective functional connectivity between the hippocampus (HC; known to be critical for cognitive maps) and other brain regions critical for spatial orientation. A group of individuals with DTD and a group of control subjects underwent a resting-state functional magnetic resonance imaging (rsfMRI) scan. In addition, we performed voxel-based morphometry to investigate potential structural differences between individuals with DTD and controls. The results of the rsfMRI study revealed a decreased functional connectivity between the right HC and the prefrontal cortex (PFC) in individuals with DTD. No structural differences were detected between groups. These findings provide evidence that ineffective functional connectivity between HC and PFC may affect the monitoring and processing of spatial information while moving within an environment, resulting in the lifelong selective inability of individuals with DTD to form cognitive maps that are critical for orienting in both familiar and unfamiliar surroundings.