Charles Bonnet Syndrome (CBS) has been defined as complex visual hallucinations (CVH) due to visual loss. The underlying mechanism of CBS is not clear and the underlying pathophysiology of the visual hallucinations in CBS patients and pure visually impaired patients is still not clear. In our study, we have scanned three with eye disease and CBS (VH+) and three patients with eye disease without CBS (VH-) using FDG-PET. Our results showed underactivity in the pons and overactivity in primary right left visual cortex and inferior parietal cortex in VH- patients and underactivity in left Broca, left inf frontal primary visual cortex and anterior and posterior cingulate cortex in VH+ patients relative to the normative 18F-FDG PET data that was taken from the database consisting of 50 age-matched healthy adults without neuropsychiatric disorders. From this distributed pattern of activity changes, we conclude that the generation of visual hallucination in CBS is associated with bottom-up and top-down mechanism rather than the generally accepted visual deafferentation-related hyperexcitability theory.

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IntroductionThe microstate analysis is a method to convert the electrical potentials on the multi-channel electrode array to topographical electroencephalography (EEG) data. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that can modulate brain networks. This study explores the pathophysiological changes through microstate analysis in two different neurodegenerative diseases, Alzheimer’s (AD) and Parkinson’s disease (PD), characterized by motor and cognitive symptoms and analysis the effect of rTMS on the impaired cognitive and motor functions.Materials and MethodsWe included 18 AD, 8 PD patients, and 13 age-matched controls. For both groups, we applied 5 Hz rTMS on the left pre-SMA in PD patients while 20 Hz rTMS on the left lateral parietal region in AD patients. Each patient was re-evaluated 1 week after the end of the sessions, which included a detailed clinical evaluation and measurement of EEG microstates.ResultsAt the baseline, the common findings between our AD and PD patients were altered microstate (MS) B, MS D durations and transition frequencies between MS A–MS B, MS C–MS D while global explained variance (GEV) ratio and the extent and frequency of occurrence of MS A, MS B, and MS D were separately altered in AD patients. Although no specific microstate parameter adequately differentiated between AD and PD patients, we observed significant changes in MS B and MS D parameters in PD patients. Further, we observed that Mini-Mental State Examination (MMSE) performances were associated with the transition frequencies between MS A–MS B and MS C–MS D and GEV ratio. After left parietal rTMS application, we have observed significantly increased visual memory recognition and clock drawing scores after left parietal rTMS application associated with improved microstate conditions prominent, especially in the mean duration of MS C in AD patients. Also, pre-SMA rTMS resulted in significant improvement in motor scores and frequency of transitions from MS D to MS C in PD patients.ConclusionThis study shows that PD and AD can cause different and similar microstate changes that can be modulated through rTMS, suggesting the role of MS parameters and rTMS as a possible combination in monitoring the treatment effect in neurodegenerative diseases.

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Background: Charles Bonnet syndrome (CBS) is a prototype phenomenon for investigating complex visual hallucination. Our research focuses on resting state neural networks features of CBS patients with a comparison of patients with equally matched visual loss and healthy subjects in order to investigate the mechanism behind complex visual hallucinations. Material and Methods: Four CBS patients CBS(+), three patients with visual loss but no visual hallucinations CBS(-) and 15 healthy individuals (HS) undergo resting state fMRI recordings and their resting state data is analyzed for Default Mode Network (DMN) changes through dual regression analysis. Cognitive functions of the participants were also evaluated through Mini Mental State Examination and University of Miami - Parkinson's Disease Hallucination Questionnaire (um-PDHQ). Results: Although we found no difference in Default Mode Networks between CBS(-) and CBS(+), and between the CBS(-) and HC groups, we detected decreased connectivity in CBS(+) compared to the HC group especially in visual heteromodal association centers (bilateral lateral occipital gyrus, bilateral lingual gyrus, occipital pole, right medial temporal cortex, right temporo-occipital cortex) when left angular gyrus was selected as ROI. Similarly, we detected decreased connectivity in CBS(+) compared to HC in right medial frontal gyrus, right posterior cingulate gyrus, left inferior temporal gyrus, right supramarginal gyrus, and right angular gyrus when selected right superior frontal gyrus as ROI. In contrast, increased connectivity was detected in CBS +compared to HC, in bilateral occipital poles, bilateral occipital fusiform gyrus, bilateral intracalcarine cortex, right lingual gyrus and precuneus regions when left medial temporal gyrus was selected as ROI. Conclusion: Our findings suggest a combined mechanism in CBS related to increased internal created images caused by decreased visual external input causing visual hallucinations as well as impaired frontotemporal resource tracking system that together impair cognitive processing.