The neural mechanisms of Charles Bonnet syndrome

Abstract Charles Bonnet Syndrome (CBS) describes the experience of visual hallucinations that cannot be explained by any other cause in individuals with visual impairment. CBS remains underrecognized and is poorly understood, with limited knowledge of its underlying mechanisms. This review examines the neurobiological basis of CBS, discussing neuroimaging, neurophysiological, structural, and biochemical perspectives. The review identifies evidence on the roles of neural compensation and cortical hyperexcitability in the emergence of visual hallucinations following visual deprivation. Despite methodological heterogeneity, local changes are observed alongside brain-wide alterations in cortico-cortical connectivity within and beyond visual cortical areas, particularly in attentional networks. Evidence of CBS-specific structural changes remains limited, with observed differences largely attributable to visual deprivation. The review also examines neuroimaging, case studies, and computational work highlighting potential links to biochemical changes, particularly those associated with the GABAergic system and acetylcholine. Finally, the review proposes future avenues leveraging advances in neuroimaging and deep neural network modelling to address gaps in the understanding of mechanisms and dynamics underlying hallucinatory and non-hallucinatory states in CBS patients.