Multimodal imaging analysis in Charles Bonnet Syndrome: a case report

Charles Bonnet syndrome (CBS) is a rare condition characterized by visual impairment associated with complex visual hallucinations in psychologically normal elderly people. Previous studies have suggested that visual hallucinations may be caused by brain damage in the visual system. However, in the case of CBS, specific brain regions in the occipital cortex have not been clearly determined and functional neuroimaging remains relatively unexplored. To our knowledge, functional connectivity by means of resting-state magnetic resonance imaging (MRI) has never been investigated in patients with CBS. We here aimed to investigate structural imaging, brain metabolism and functional connectivity in a patient with CBS. Resting-state functional and structural MRI were acquired in an 85-year-old patient with CBS and 12 age- and gender-matched normally sighted controls. Cognitive functioning was measured by behavioral assessment. A seed-based resting state fMRI was performed to investigate the default mode network (DMN), the executive control network and the visual networks connectivity. A voxel-based morphometry (VBM) analysis was employed to investigate the grey matter volume. Cortical and subcortical grey matter thickness were further investigated. Finally, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was also acquired to observe regional glucose uptake by comparing standard uptake values (SUVs). Increased functional connectivity was found between the DMN and the temporo-occipital fusiform cortex, as well as between the secondary visual cortex and the left frontal cortex, in the CBS patient compared to controls. The patient also demonstrated increased functional connectivity between the primary visual cortex and the left supramarginal gyrus and between the associative visual cortex and the superior temporal gyrus/angular gyrus, as compared to controls. Decreased grey matter volume was observed in the lateral occipital cortex/angular gyrus in our patient as compared to controls. Diminished grey matter thickness values were observed in the lateral geniculate nucleus compared to healthy controls. FDG-PET results confirmed previous work and showed bilateral hypometabolism in the occipital cortex (mean SUV reduction of 5.36%, p<0.001). Our results suggest that structural alterations in visual system in CBS are associated with compensatory/adaptive changes in functional connectivity that involve regions known to support hallucinations of faces in CBS patients. We suggest that this functional connectivity reorganization following visual structural damage may contribute to visual hallucinations. These findings might shed light on the pathophysiology underlining this rare condition.