Lesions causing Alice in Wonderland Syndrome map to a common brain network linking body and size perception

Background In Lewis Carroll’s 1865 novel “Alice’s Adventures in Wonderland”, the protagonist experiences distortions in the size of her body and those of others. This fiction becomes reality in neurological patients with Alice in Wonderland Syndrome (AIWS). Brain lesions causing AIWS may offer unique insights into the syndrome’s elusive neuroanatomy. Methods A systematic literature search identified 37 cases of lesion-induced AIWS. Lesion locations were mapped onto a brain atlas and functional connectivity between each lesion location and other brain regions was estimated using resting-state fMRI data from 1000 healthy subjects. Connections common to AIWS lesions were identified and compared to connections from 1073 lesions associated with 25 other neuropsychiatric disorders. Alignment between this lesion-derived AIWS network and neuroimaging findings from patients with AIWS due to other etiologies was assessed. Results Although AIWS lesions occurred in many different brain locations, these lesions fell within a specific, functionally connected brain network. This network was defined by connectivity to the right extrastriate body area, a brain region selectively activated by viewing body parts, and the inferior parietal cortex, a brain region involved in processing of size and scale. This connectivity pattern was specific to AIWS when compared to lesions causing other neuropsychiatric disorders and aligned with neuroimaging findings in patients with AIWS from other etiologies. Conclusion Lesions causing AIWS fall within a specific brain network defined by connectivity to two distinct brain regions, one region involved in body perception and another in processing of size and scale.