Mapping delusions of space onto a structural disconnectome that decouples familiarity and place networks.

Interpretation of space is an important determinant of human behaviour. Delusions of space, or reduplicative paramnesias, are a particularly disturbing form of spatial disorientation characterized by the patients' strong belief of place reduplication, transformation or mislocation. Their occurrence following focal brain damage provides a unique opportunity to unveil the structural-functional basis of space misinterpretations. First, we identified reports of lesion-associated reduplicative paramnesias with brain images available through a systematic review of the literature (n = 24). Each lesion was matched with 4 stroke controls and the sample was randomly split in an exploratory (n = 60) and in a validation (n = 60) dataset. Second, we used 178 7T tractographies to compute structural disconnectome maps and analysed lesion topography and disconnection patterns. Delusions of space were significantly associated with structural disconnection of right ventrolateral prefrontal and right temporal regions, and this finding was replicated in the validation sample. Third, we performed a functional meta-analysis of syndrome-related terms. We demonstrated that the structural disconnectomes of delusions of space were spatially correlated with the functional meta-analytic maps of familiarity and place, and replicated the previous evidence that the lesion topography maps are spatially correlated with belief-related functional networks. No association was found with control terms. These results reveal that structural disconnection putatively mediates functional changes associated with reduplicative paramnesias and provide a possible neural basis for the content specificity for places that characterizes these delusional beliefs.