Alterations in resting-state functional connectivity in Charles Bonnet Syndrome

Charles Bonnet Syndrome (CBS) is a debilitating phenomenon where individuals experience complex visual hallucinations secondary to vision loss, e.g., age-related macular degeneration, and glaucoma. Altered resting-state networks may contribute to the visual hallucinatory manifestations of CBS. Additionally, CBS symptoms may arise from increased glutamatergic and decreased 𝛾-aminobutyric acid (GABA) receptor activity in areas surrounding deafferented cells in visual cortex. The current study examined functional connectivity between resting-state networks and visual cortex GABA+ and glutamate (Glx) concentrations in CBS. A CBS participant was compared to healthy age-matched controls. A multi-band multi-echo resting-state fMRI sequence and seed-to-target analysis of network connectivity was performed. A MEscher-GArwood Point RESolved Spectroscopy (MEGA-PRESS) sequence was performed with a 25 mm3 voxel placed medially in the visual cortex to quantify GABA+ and Glx concentrations. The CBS participant showed changes in connectivity (both increases and decreases) within the salience network (SN), default mode network (DMN) and visual network (VN). For example, there were decreases in connectivity of the VN with the medial pre-frontal cortex in the DMN; decreases in connectivity with the precuneus in the VN; and decreases in connectivity with the superior temporal gyrus and an increase with the fusiform gyrus within the SN. There was no change in GABA+ or Glx concentrations in V1 between the participant with CBS and controls. Our findings of functional cortical changes but no neurometabolite changes in the CBS participant suggest network level alterations in CBS which could account for the experience of their visual hallucinations.