Understanding Charles Bonnet syndrome: mechanisms and intervention

Abstract

Background: Charles Bonnet Syndrome (CBS) is defined by the occurrence of vivid, recurring visual hallucinations (VH) secondary to visual impairment in the absence of psychiatric illness or cognitive impairment. Previous research has proposed that deafferentation, due to loss of sensory input from the eyes, leads to spontaneous hyperexcitability in the visual cortex resulting in VH. Approximately one-third of people with CBS report distress and disruption to daily functioning as a consequence of VH, however there are currently no effective treatments and a lack of research into the aetiology of VH has hindered their development. Aims: 1) To investigate the role of visual cortical activity in the production of VH in CBS, compared to non-hallucinating controls, to better understand why VH occur in some patients but not others. 2) To investigate whether inhibitory non-invasive transcranial direct current stimulation (tDCS) could be used to remediate VH by reducing cortical excitability in CBS. Methods: Study 1: A comparison study consisting of people with CBS (n=19) and nonhallucinating sight-matched controls (n=18) was performed utilising transcranial magnetic stimulation, functional magnetic resonance imaging, and magnetic resonance spectroscopy to compare differences in visual cortical activity between groups. Study 2: Informed by a pilot study in continuous CBS hallucinators, sixteen members of the CBS group received 4- consecutive days of active and sham inhibitory tDCS over the primary visual cortex, comparing visual cortical activity and VH ratings before and after stimulation between active and sham weeks. Results: Study 1: Comparable visual cortical excitability was observed in both groups, although greater excitability was associated with more severe VH in the CBS group. Functional activation of the visual cortex was observed to be lower in the CBS group than controls during an eye movement task, with greater functional activation associated with lower visual cortical excitability. Study 2: Active cathodal tDCS of the primary visual cortex resulted in a significant decrease to VH frequency and intrusiveness compared to sham stimulation. No significant changes to cortical activity were observed following stimulation. Conclusions: This thesis constitutes the largest neurophysiological comparison and treatment study performed in CBS to date. These data support the role of changes to visual cortical activity in the production of VH following sight loss, providing a basis for further study.

Furthermore, tDCS was observed to present a potential effective new treatment option for CBS, however further study is needed to understand underlying mechanisms.