Neuroscience of Charles Bonnet Syndrome

Charles Bonnet Syndrome (CBS) has been reported in people with visual impairment, and is surprisingly common with an estimated prevalence of 10-34% of low vision patients from local audits. It consists of complex visual hallucinations such as seeing snakes rising from people's heads or elephants inside a room (see review, Carpenter, Jolly et al. 2019). Patients experience CBS hallucinations over many years, and although they retain knowledge it is not real, the hallucinations can be frightening and cause considerable distress. Patients with CBS have a lower quality of life compared to patients with vision loss without CBS. Moreover, CBS is under reported due to the fear of being labelled with mental health disease, adding to the negative consequences.

There is currently no established treatment for CBS, with the mainstay of management in low vision clinics revolving around reassurance. Many patients receive inappropriate care from other healthcare practitioners as reported by Judith Potts, founder of Esme's Umbrella, a patient support charity dedicated to Charles Bonnet Syndrome. A clearer understanding of the mechanisms underlying CBS would help to ensure the medical community takes the condition seriously and therefore adequately counsel presenting patients. In addition, understanding the neural mechanisms of CBS can provide a model for investigating how the brain reorganizes in response to sensory impairment and may eventually lead to improvement in the management and treatment of the neurological consequences of eye disease.

Visual processing becomes more complex throughout the pathway from the retina, primary visual cortex to the more specialised processing in higher visual areas. Thus, the complex nature of the hallucinations in CBS (faces, objects, animals), in spite of blurred vision, appears to implicate the higher visual areas in the visual ventral stream that are known to be process objects.

Neurotransmitters are the chemicals that allow communication across the brain. Some neurotransmitters increase the activity in the brain (excitatory) and others reduce activity (inhibitory). A candidate mechanism for CBS from computational modelling is the imbalance of excitation:inhibition: loss of feedforward visual input may give greater prominence to feedback in higher visual areas, causing hallucinations. A recent EEG study has provided experimental support, showing that hyperexcitability of the visual cortex was a key difference between people who have hallucinations versus those who do not. A critical proof of this theory would require measurement of excitatory and inhibitory neurochemicals, glutamate and GABA respectively, in visual areas. This is still outstanding and will be tackled by this study. MRS-imaging is a cutting-edge method to quantify the concentration of neurochemicals in the brain. Rather than providing a single measurement from a large volume of tissue (30x30x30mm), this technique provides high spatial resolution (5x5x20mm) measurements that permits comparison across the visual cortex. MRSI is the only technique that can non-invasively quantify neurochemicals in the living human brain, and MRS-imaging can provide concentrations of the neurotransmitters in multiple locations, which can then be compared across groups.

In summary, based on previous work and the nature of the hallucinations, the investigators predict that patients with CBS likely show 1) changes in the neurotransmitter balance across the visual cortex; 2) increased influence of feedback mechanisms from higher visual areas and 3) abnormal activity in the ventral visual stream to visual stimulation. Our goal is to characterise the visual cortex of CBS patients by using rigorous non-invasive multi-modal MR imaging techniques. Using state-of-the-art methods, the team will measure concentrations of excitatory and inhibitory neurotransmitters, identify changes in connectivity, and measure evoked visual activity in patients with CBS and visually impaired participants without CBS. In addition, the team will obtain clinical evaluation and qualitative assessments of hallucinations.