High-Density EEG in a Charles Bonnet Syndrome Patient during and without Visual Hallucinations: A Case-Report Study.

Charles Bonnet syndrome (CBS) is a rare clinical condition characterized by complex visual hallucinations in people with loss of vision. So far, the neurobiological mechanisms underlying the hallucinations remain elusive. This case-report study aims at investigating electrical activity changes in a CBS patient during visual hallucinations, as compared to a resting-state period (without hallucinations). Prior to the EEG, the patient underwent neuropsychological, ophthalmologic, and neurological examinations. Spectral and connectivity, graph analyses and signal diversity were applied to high-density EEG data. Visual hallucinations (as compared to resting-state) were characterized by a significant reduction of power in the frontal areas, paralleled by an increase in the midline posterior regions in delta and theta bands and by an increase of alpha power in the occipital and midline posterior regions. We next observed a reduction of theta connectivity in the frontal and right posterior areas, which at a network level was complemented by a disruption of small-worldness (lower local and global efficiency) and by an increase of network modularity. Finally, we found a higher signal complexity especially when considering the frontal areas in the alpha band. The emergence of hallucinations may stem from these changes in the visual cortex and in core cortical regions encompassing both the default mode and the fronto-parietal attentional networks.

Three cases of Charles Bonnet Syndrome in patients with advanced glaucomatous visual field loss but preserved visual acuity.

PURPOSE: To describe three cases of Charles Bonnet syndrome (CBS) in glaucoma patients with preserved visual acuity. METHODS: Three glaucoma patients who had taken part in a recent CBS study were interviewed about their hallucinations. The patients underwent macular optical coherence tomography (OCT) of both eyes. The visual function was evaluated with visual field measurement (Humphrey visual field analyser) and visual acuity testing (Snellen scale). RESULTS: All three patients had preserved visual acuity (≥0.5 in both eyes) and at least one eye with advanced visual field defect (Mean Deviation worse than -12.00 decibel). They all reported vivid visual hallucinations with insight into the unreal nature of the hallucinations. CONCLUSION: Charles Bonnet syndrome can occur in glaucoma despite preserved visual acuity. Awareness of this relation is desirable among clinicians, as it will improve communication with patients.

Power spectral density and coherence analysis of eye disease with and without visual hallucination.

OBJECTIVES: Charles Bonnet Syndrome (CBS) is a rare clinical condition which has been defined as complex visual hallucinations (CVH) due to visual loss. This study investigated differences in the EEG power spectral density (PSD) and magnitude-squared coherences between patients with eye disease and hallucinations (VH+), and the control subjects with eye disease without hallucinations (VH-). METHODS: 19 scalp channels EEG was recorded in four VH+ (CBS) and four VH- subjects during an eyes-closed resting condition. Artefact-free epochs were analyzed to obtain PSD values in the delta, theta, alpha1, alpha2, beta1, beta2 and gamma frequency bands. Coherence values were calculated through inter-hemispheric and intra-hemispheric electrodes pairs of interest. All subjects were performed with neuropsychological and behavioral assessments to evaluate cognitive functions. RESULTS: The VH + group had increase PSD in theta, beta2 and gamma bands in central, parietal and occipital (O2) areas. The synchronicity was altered particularly in parietal and frontal-parietal regions especially at theta and alpha1 respectively. CONCLUSIONS: The aberrant activity in occipital and parietal regions suggest the mechanism of CBS. This is a major electrophysiological study of understanding CBS and visual hallucinations.

How do the blind 'see'? The role of spontaneous brain activity in self-generated perception.

Spontaneous activity of the human brain has been well documented, but little is known about the functional role of this ubiquitous neural phenomenon. It has previously been hypothesized that spontaneous brain activity underlies unprompted (internally generated) behaviour. We tested whether spontaneous brain activity might underlie internally-generated vision by studying the cortical visual system of five blind/visually-impaired individuals who experience vivid visual hallucinations (Charles Bonnet syndrome). Neural populations in the visual system of these individuals are deprived of external input, which may lead to their hyper-sensitization to spontaneous activity fluctuations. To test whether these spontaneous fluctuations can subserve visual hallucinations, the functional MRI brain activity of participants with Charles Bonnet syndrome obtained while they reported their hallucinations (spontaneous internally-generated vision) was compared to the: (i) brain activity evoked by veridical vision (externally-triggered vision) in sighted controls who were presented with a visual simulation of the hallucinatory streams; and (ii) brain activity of non-hallucinating blind controls during visual imagery (cued internally-generated vision). All conditions showed activity spanning large portions of the visual system. However, only the hallucination condition in the Charles Bonnet syndrome participants demonstrated unique temporal dynamics, characterized by a slow build-up of neural activity prior to the reported onset of hallucinations. This build-up was most pronounced in early visual cortex and then decayed along the visual hierarchy. These results suggest that, in the absence of external visual input, a build-up of spontaneous fluctuations in early visual cortex may activate the visual hierarchy, thereby triggering the experience of vision.

Case Report: Effect of a Retinal Prosthesis System on Charles Bonnet Visual Hallucinations.

SIGNIFICANCE: Charles Bonnet syndrome is commonly encountered and diagnosed in low-vision patients. It can be distressing for some of them, as there is no known effective treatment of this condition. Although there is a growing interest in retinal implants for blind patients with severe retinal diseases, the effect of these devices on Charles Bonnet syndrome visual hallucinations remains undocumented. PURPOSE: The aim of this study was to report changes in the Charles Bonnet syndrome of a patient with retinitis pigmentosa after implantation of the Argus II retinal prosthesis. CASE REPORT: A 65-year-old patient with retinitis pigmentosa and no light perception was frequently experiencing Charles Bonnet syndrome. In the hope of improving his vision, he received an Argus II retinal prosthesis in 2018 and participated in a 10-week rehabilitation program at the Institut Nazareth et Louis-Braille. The nature and the frequency of his Charles Bonnet syndrome were documented with the Questionnaire de repérage du syndrome de Charles Bonnet (a French questionnaire used to screen for Charles Bonnet syndrome) before the surgery and for 70 weeks after it. The patient's visual acuity and visual fields were monitored during the same period. Additional tests were administered to document the visual, psychological, and cognitive states of the patient throughout the study. CONCLUSIONS: Although this case report confirmed that Argus II retinal prosthesis improves the performance of blind patients in visual tests, the improvement was not associated with a decrease in the symptoms of Charles Bonnet syndrome.

Reversible Charles Bonnet syndrome secondary to upper lid ptosis.

Complex visual hallucinations can occur in visually impaired individuals with no underlying psychiatric disorder. This phenomenon is known as Charles Bonnet syndrome (CBS). It is more common in elderly patients who are suffering from impaired vision due to ocular or neurological disease processes, resulting in sensory deprivation. We report a case of CBS in an elderly female with marked ptosis, which was exacerbated following a knee replacement surgery under general anaesthesia. Her CBS symptoms persisted until surgical correction of the ptosis, with a rapid and dramatic resolution of her hallucinations. Although CBS is typically a chronic condition, unusually in this case it was acute and reversible.

The elephant in the room: understanding the pathogenesis of Charles Bonnet syndrome.

PURPOSE: Charles Bonnet syndrome (CBS) is a syndrome characterised by complex visual hallucinations in individuals who are cognitively normal, though often elderly and visually impaired. Although first described over 250 years ago, the condition remains poorly understood and difficult to treat. RECENT FINDINGS: Our understanding of CBS pathogenesis has advanced little since it was first described, and much of the recent literature consists of case studies strikingly similar to the first published account of CBS. However, imaging studies have provided some indication as to the cortical areas implicated in the genesis of complex visual hallucinations, and the existence of similar hallucinatory syndromes in other sensory modalities suggests a common underlying mechanism. SUMMARY: This review begins by describing what is currently known about CBS, focusing on epidemiology, clinical presentation and diagnosis. It then explores potential starting points for better understanding the pathogenesis of CBS, namely the existence of similar conditions in other sensory modalities and the reproduction of complex visual hallucinations in sensory deprivation scenarios. Finally, it discusses how CBS should be approached in clinical practice.

Resting-state functional connectivity and cortical thickness characterization of a patient with Charles Bonnet syndrome.

Charles Bonnet syndrome (CBS) is a rare condition characterized by visual impairment associated with complex visual hallucinations in elderly people. Although studies suggested that visual hallucinations may be caused by brain damage in the visual system in CBS patients, alterations in specific brain regions in the occipital cortex have not been studied. Functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI; without hallucinations) in CBS patients, has never been explored. We aimed to investigate brain structural and functional changes in a patient with CBS, as compared with late blind (LB) and normally sighted subjects. We employed voxel-based morphometry and cortical thickness analyses to investigate alterations in grey matter characteristics, and rs-fMRI to study changes in functional brain connectivity. Decreased grey matter volume was observed in the middle occipital gyrus and in the cuneus in the CBS patient, and in the middle occipital gyrus and in the lingual gyrus within LB subjects, compared to their respective control groups. Reductions in cortical thickness in associative and multimodal cortices were observed in the CBS patient when comparing with LB subjects. The precuneus exhibited increased functional connectivity with the secondary visual cortex in the CBS patient compared to the controls. In contrast, LB patients showed decreased functional connectivity compared to sighted controls between the DMN and the temporo-occipital fusiform gyrus, a region known to support hallucinations. Our findings suggest a reorganization of the functional connectivity between regions involved in self-awareness and in visual and salience processing in CBS that may contribute to the appearance of visual hallucinations.

Charles Bonnet syndrome and periodic alternating nystagmus: Moving visual hallucinations.

OBJECTIVE: To describe and discuss potential mechanisms for modulation of visual hallucinations by nystagmus. METHODS: We present 2 patients with coexistent Charles Bonnet syndrome and periodic alternating nystagmus in the context of acquired visual loss. RESULTS: The combination has given rise to a rare phenomenon: visual hallucinations that move in a manner governed by the nystagmus, specifically by the direction and velocity of the slow phase. The perceived modulation of movement is selective for a surface in one case and a landscape in the other but not present for hallucinated individual objects and people separate from the hallucinated background visual scene. CONCLUSIONS: The collision of Charles Bonnet syndrome and periodic alternating nystagmus in these 2 patients has demonstrated that some visual hallucinations can be modulated by, or collaterally with, ocular movements. We propose 2 potential mechanisms based on ocular proprioceptive input from extraocular muscles projecting to either extrastriate processing of visual scene, or to higher-order visual cortical areas involved in analysis of motion signals across the whole visual field.

Functional MRI study in a case of Charles Bonnet syndrome related to LHON.

INTRODUCTION: Charles Bonnet syndrome is characterized by simple or complex visual hallucinations (VH) due to damage along the visual pathways. We report a functional MRI study of brain correlates of VH in the context of a severe optic atrophy in a patient with Leber's Hereditary Optic Neuropathy (LHON). CASE REPORT: A 62-year-old man was diagnosed with LHON (11778/ND4 mtDNA mutation) after subacute visual loss in left eye (right eye was amblyopic). One month later, he experienced VH of a few seconds consisting in "moving red and blue miniature cartoons". One year later VH content changed in colored mosaic (10-15 s duration), usually stress-related, and blue and white flashes (2-5 s), triggered by unexpected auditory stimuli. Audiometry revealed mild sensorineural hearing loss. Three block design functional MRI paradigms were administrated: 1) random "clap", 2) "checkerboard" and 3) non-random "beep". After random "claps" simple flashes were evoked with bilateral activation of primary and secondary visual cortex, cuneus, precuneus and insula. Neither hallucinations nor cortex activation were registered after "checkerboard" stimulation, due to the severe visual impairment. Primary and secondary auditory cortices were "beep"-activated, without eliciting VH by non-random "beep". CONCLUSIONS: The peculiarity of our case is that VH were triggered by random auditory stimuli, possibly due to a cross-modal plasticity between visual and auditory networks, likely influenced by the sensorineural deafness. Functional alterations of both networks in resting conditions have been demonstrated in LHON patients, even without an auditory deficit. Finally, the absence of VH triggered by expected stimuli is consistent with the "expectation suppression theory", based on increased neural activations after unexpected but not by predicted events.

Stimulus-Driven Cortical Hyperexcitability in Individuals with Charles Bonnet Hallucinations.

Throughout the lifespan, the cerebral cortex adapts its structure and function in response to changing sensory input [1, 2]. Whilst such changes are typically adaptive, they can be maladaptive when they follow damage to the peripheral nervous system, including phantom limb pain and tinnitus [3, 4]. An intriguing example occurs in individuals with acquired ocular pathologies-most commonly age-related macular degeneration (MD) [5]-who lose their foveal vision but retain intact acuity in the peripheral visual field. Up to 40% of ocular pathology patients develop long-term hallucinations involving flashes of light, shapes, or geometric patterns and/or complex hallucinations, including faces, animals, or entire scenes, a condition known as Charles Bonnet Syndrome (CBS) [6, 7, 8]. Though CBS was first described over 250 years ago [9, 10], the neural basis for the hallucinations remains unclear, with no satisfactory explanation as to why some individuals develop hallucinations, while many do not. An influential but untested hypothesis for the visual hallucinations in CBS is that retinal deafferentation causes hyperexcitability in early visual cortex. To assess this, we investigated electrophysiological responses to peripheral visual field stimulation in MD patients with and without hallucinations and in matched controls without ocular pathology. Participants performed a concurrent attention task within intact portions of their peripheral visual field, while ignoring flickering checkerboards that drove periodic electrophysiological responses. CBS individuals showed strikingly elevated visual cortical responses to peripheral field stimulation compared with patients without hallucinations and controls, providing direct support for the hypothesis of visual cortical hyperexcitability in CBS.

Charles Bonnet syndrome.

Introduction: Charles Bonnet syndrome (CBS) is a condition that causes visual hallucinations in patients without any mental illnesses. CBS is characterized by the presence of vivid, complex and recurrent visual hallucinations, and do not occur in the setting or as part of delirium or other psychological illnesses. The condition is present in patients who have visual loss due to age-related macular degeneration (AMD), cataracts and/or other ocular diseases that influence vision. Case report: A 81-year-od woman reported to ophthalmologist complaining of visual hallucinations that consisted of white pigeons. Hallucinations were present for two years and she was well aware that hallucinations were unreal. Mental illnesses were excluded by the psychiatrist. Complete ophthalmologic examination was performed, and finding revealed visual acuity of 0.3 (right eye) and 0.5 (left eye), in both eyes cataracts and AMD (wet form). Optical coherence tomography confirmed the fundoscopic finding of AMD. The patient rejected treatment of cataracts and AMD due to old age, and hallucinations persisted. Conclusion: CBS should be considered in patients with visual hallucinations and ocular diseases that influence vision. It is essential to distinguish CBS from mental illnesses, since patients with CBS are fully aware that hallucinations are not real. Awareness of CBS could help physicians upon referring patients to ophthalmologists instead of psychiatrists, and therefore avoid patients being misdiagnosed.