Transcranial Direct Current Stimulation in the Treatment of Visual Hallucinations in Charles Bonnet Syndrome: A Randomized Placebo-Controlled Crossover Trial.

OBJECTIVE: To investigate the potential therapeutic benefits and tolerability of inhibitory transcranial direct current stimulation (tDCS) on the remediation of visual hallucinations in Charles Bonnet syndrome (CBS). DESIGN: Randomized, double-masked, placebo-controlled crossover trial. PARTICIPANTS: Sixteen individuals diagnosed with CBS secondary to visual impairment caused by eye disease experiencing recurrent visual hallucinations. INTERVENTION: All participants received 4 consecutive days of active and placebo cathodal stimulation (current density: 0.29 mA/cm2) to the visual cortex (Oz) over 2 defined treatment weeks, separated by a 4-week washout period. MAIN OUTCOME MEASURES: Ratings of visual hallucination frequency and duration following active and placebo stimulation, accounting for treatment order, using a 2 × 2 repeated-measures model. Secondary outcomes included impact ratings of visual hallucinations and electrophysiological measures. RESULTS: When compared with placebo treatment, active inhibitory stimulation of visual cortex resulted in a significant reduction in the frequency of visual hallucinations measured by the North East Visual Hallucinations Interview, with a moderate-to-large effect size. Impact measures of visual hallucinations improved in both placebo and active conditions, suggesting support and education for CBS may have therapeutic benefits. Participants who demonstrated greater occipital excitability on electroencephalography assessment at the start of treatment were more likely to report a positive treatment response. Stimulation was found to be tolerable in all participants, with no significant adverse effects reported, including no deterioration in preexisting visual impairment. CONCLUSIONS: Findings indicate that inhibitory tDCS of visual cortex may reduce the frequency of visual hallucinations in people with CBS, particularly individuals who demonstrate greater occipital excitability prior to stimulation. tDCS may offer a feasible intervention option for CBS with no significant side effects, warranting larger-scale clinical trials to further characterize its efficacy.

Investigation of structural brain changes in Charles Bonnet Syndrome.

BACKGROUND AND OBJECTIVES: In Charles Bonnet Syndrome (CBS), visual hallucinations (VH) are experienced by people with sight loss due to eye disease or lesional damage to early visual pathways. The aim of this cross-sectional study was to investigate structural brain changes using magnetic resonance imaging (MRI) in CBS. METHODS: Sixteen CBS patients, 17 with eye disease but no VH, and 19 normally sighted people took part. Participants were imaged on a 3T scanner, with 1 mm resolution T1 weighted structural imaging, and diffusion tensor imaging with 64 diffusion directions. RESULTS: The three groups were well matched for age, sex and cognitive scores (MMSE). The two eye disease groups were matched on visual acuity. Compared to the sighted controls, we found reduced grey matter in the occipital cortex in both eye disease groups. We also found reductions of fractional anisotropy and increased diffusivity in widespread areas, including occipital tracts, the corpus callosum, and the anterior thalamic radiation. We did not find any significant differences between the eye disease participants with VH versus without VH, but did observe a negative association between hippocampal volume and VH severity in the CBS group. DISCUSSION: Our findings suggest that although there are cortical and subcortical effects associated with sight loss, structural changes do not explain the occurrence of VHs. CBS may relate instead to connectivity or excitability changes in brain networks linked to vision.

Cognition, hallucination severity and hallucination-specific insight in neurodegenerative disorders and eye disease.

Introduction: Hallucinations occur across neurodegenerative disorders, with increasing severity, poorer cognition and impaired hallucination-specific insight associated with worse outcomes and faster disease progression. It remains unclear how changes in cognition, temporal aspects of hallucinations, hallucination-specific insight and distress relate to each other.Methods: Extant samples of patients experiencing visual hallucinations were included in the analyses: Parkinson's Disease (n = 103), Parkinson's Disease Dementia (n = 41), Dementia with Lewy Bodies (n = 27) and Eye Disease (n = 113). We explored the relationship between factors of interest with Spearman's correlations and random-effect linear models.Results: Spearman's correlation analyses at the whole-group level showed that higher hallucination-specific insight was related to higher MMSE score (rs = 0.39, p < 0.001) and less severe hallucinations (rs = -0.28, p < .01). Linear mixed-models controlling for diagnostic group showed that insight was related to higher MMSE (p < .001), to hallucination severity (p = 0.003), and to VH duration (p = 0.04). Interestingly, insight was linked to the distress component but not the frequency component of severity. No significant relationship was found between MMSE and hallucination severity in these analyses.Conclusion: Our findings highlight the importance of hallucination-specific insight, distress and duration across groups. A better understanding of the role these factors play in VH may help with the development of future therapeutic interventions trans-diagnostically.

The utility and application of electrophysiological methods in the study of visual hallucinations.

Visual hallucinations (VH) are a common symptom in multiple clinical and non-clinical populations. Although structural and functional neuroimaging has informed the understanding of VH, temporal resolution is limited. Electrophysiological techniques provide a complementary perspective on dynamic and temporal aspects of neural functioning, offering greater insight into the mechanisms underlying their formation. In this review we examine and critically evaluate the emerging evidence base utilising electrophysiological approaches in the study of VH. Overall, increased visual system excitability, dysfunctional visual processing and network connectivity, and cholinergic dysfunction have been consistently observed in VH-prone pathologies. However, a major limitation is in the lack of robust experimental studies and the reliance on single case reports. We conclude that electrophysiology provides tentative evidence for the contribution of bottom-up, top-down, and network dysfunction in the aetiology of VH, supporting several existing VH models. Furthermore, we discuss how electrophysiology has been directly utilised in specific clinical interventions for VH. Further exploration utilising electrophysiology in combination with, for example, neuroimaging will help better understand VH aetiology while aiding in the development of novel therapeutic interventions for this difficult to treat symptom.