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.

A century of prosopometamorphopsia studies.

Prosopometamorphopsia is an extremely rare disorder of visual perception characterised by facial distortions. We here review 81 cases (eight new ones and 73 cases published over the past century) to shed light on the perception of face gestalts. Our analysis indicates that the brain systems underlying the perception of face gestalts have genuine network properties, in the sense that they are widely disseminated and built such that spatially normal perception of faces can be maintained even when large parts of the network are compromised. We found that bilateral facial distortions were primarily associated with right-sided and bilateral occipital lesions, and unilateral facial distortions with lesions ipsilateral to the distorted hemifield and with the splenium of the corpus callosum. We also found tentative evidence for the involvement of the left frontal regions in the fusing of vertical hemi-images of faces, and of right parietal regions in the fusing of horizontal hemi-images. Evidence supporting the remarkable adaptability of the network comes from the relatively high recovery rates that we found, from the ipsilateral hemifield predominance of hemi-prosopometamorphopsia, and from a phenomenon called cerebral asthenopia (heightened visual fatigability) which points to the dynamic nature of compensatory mechanisms maintaining normal face perception, even in chronic cases of prosopometamorphopsia. Finally, our analysis suggests that specialised networks for the representation of face gestalts in familiar-versus-unfamiliar faces and for own-versus-other face may be present, although this is in need of further study.

Resting-state EEG alpha/theta ratio related to neuropsychological test performance in Parkinson's Disease.

OBJECTIVE: To determine possible associations of hemispheric-regional alpha/theta ratio (α/θ) with neuropsychological test performance in Parkinson's Disease (PD) non-demented patients. METHODS: 36 PD were matched to 36 Healthy Controls (HC). The α/θ in eight hemispheric regions was computed from the relative power spectral density of the resting-state quantitative electroencephalogram (qEEG). Correlations between α/θ and performance in several neuropsychological tests were conducted, significant findings were included in a moderation analysis. RESULTS: The α/θ in all regions was lower in PD than in HC, with larger effect sizes in the posterior regions. Right parietal, and right and left occipital α/θ had significant positive correlations with performance in Judgement of Line Orientation Test (JLOT) in PD. Adjusted moderation analysis indicated that right, but not left, occipital α/θ influenced the JLOT performance related to PD. CONCLUSIONS: Reduction of the occipital α/θ, in particular on the right side, was associated with visuospatial performance impairment in PD. SIGNIFICANCE: Visuospatial impairment in PD, which is highly correlated with the subsequent development of dementia, is reflected in α/θ in the right posterior regions. The right occipital α/θ may represent a useful qEEG marker for evaluating the presence of early signs of cognitive decline in PD and the subsequent risk of dementia.

Hallucinations and other psychotic experiences across diagnoses: A comparison of phenomenological features.

Although psychotic experiences are prevalent across many psychiatric, neurological, and medical disorders, investigation of these symptoms has largely been restricted to diagnostic categories. This study aims to examine phenomenological similarities and differences across a range of diagnoses. We assessed frequency, severity and phenomenology of psychotic experiences in 350 outpatients including; participants with schizophrenia spectrum disorders, hearing impairment, Parkinson's disease, Lewy Body Dementia, Alzheimer's disease, visual impairment, posttraumatic stress disorder, borderline personality disorder, and participants with recent major surgery. Psychotic phenomena were explored between these groups using the Questionnaire for Psychotic Experiences (QPE). Participants with major psychiatric disorders reported a combination of several psychotic experiences, and more severe experiences compared to all other disorders. Participants with recent major surgery or visual impairment experienced isolated visual hallucinations. Participants with hearing impairment reported isolated auditory hallucinations, whereas the neurodegenerative disorders reported visual hallucinations, occasionally in combination with hallucinations in another modality or delusions. The phenomenology between neurodegenerative disorders, and within major psychiatric disorders showed many similarities. Our findings indicate that the phenomenology of psychotic experiences is not diagnosis specific, but may rather point to the existence of various subtypes across diagnoses. These subtypes could have a different underlying etiology requiring specific treatment.

Drug and Disease Effects in Parkinson's Psychosis: Revisiting the Role of Dopamine.

BACKGROUND: Levodopa and dopamine agonists (dopamine replacement therapy [DRT]) are implicated in Parkinson's disease psychosis (PDP), but the relationship between DRT and neurotransmitter dysfunction inherent to PD remains unclear. OBJECTIVES: To examine the relationship between baseline striatal dopamine transporter (DAT) binding in drug-naïve idiopathic PD, introduction of DRT, or dose change and incident early-onset PDP. METHODS: Baseline DAT binding was compared between patients with and without incident psychosis (defined here as hallucinations or delusions), controlling for age, sex, baseline cognition, and prospective DRT in the Parkinson's Progression Markers Initiative cohort. Incident illusions were not considered psychosis symptoms. RESULTS: Of 386 patients, 30 (8%) developed PDP (predominantly hallucinations, mean onset 42 months) and 355 (92%) had either no PDP symptoms (mean follow-up 64 months) or reported illusions only (111/355, 31%). Incident PDP was associated with reduced baseline striatal DAT binding, controlling for confounders (F 1,377 = 10.9; P = 0.001), but not with a specific DRT regime. A total of 6 patients developed PDP when DRT free. There was no suggestion that PDP onset was coincident with starting levodopa or levodopa dose increase. Incident illusions were not associated with reduced DAT binding. CONCLUSION: The findings highlight the role of disease-related dopamine mechanisms in the pathophysiology of hallucinations in Parkinson's disease alongside medication. It remains to be determined how dopamine mechanisms, medication, and other neurotransmitter systems implicated in PDP interact.

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.

Successful management of persistent distressing neuropsychiatric symptoms by clozapine in a patient suffering from dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia associated with poor prognosis and high carers' burden. Neuropsychiatric symptoms worsen this prognosis and are a high source of distress for service users and their carers. However, there is currently insufficient evidence to support the pharmacological and non-pharmacological management of these symptoms. Acetylcholinesterase inhibitors are the first-line pharmacological option, but challenging risky behaviours may persist despite their use. Antipsychotic medications are indicated in such clinical scenarios, but there is very limited evidence to support the efficacy and safety of these medications for managing neuropsychiatric symptoms in DLB. Hence, we report an individual with DLB with severe distressing persistent visual hallucinations and agitation. After multiple treatment options had failed, clozapine was successfully initiated with substantial improvement in both clinical and functional outcomes. Further studies are warranted for evaluating the efficacy of clozapine in managing neuropsychiatric symptoms in DLB.

Psychosis in Parkinson's Disease.

Although illusions, hallucinations and delusions did not play a prominent role in James Parkinson's original clinical descriptions, the longitudinal view of disease progression he advocated has important lessons for the study of such symptoms today. A focus on longitudinal progression rather than individual symptoms led to the concept of PD psychosis-a spectrum of positive symptoms in Parkinson's disease. The publication of criteria for PD psychosis in 2007 helped unify the disparate set of symptoms, raising their profile and resulting in a rapid expansion of literature focussing on clinical aspects, mechanisms, and treatment. Here we review this literature and the evolving view of PD psychosis. Adding to previous evidence of a prospective risk for dementia and the move to supervised care, key recent developments include: recognition of prevalence increase with disease duration; a broadening of symptoms included in PD psychosis; better characterization of higher visual and cognitive dysfunction risk factors; structural, functional, and neurotransmitter imaging biomarker evidence; and approval of pimavanserin in the United States for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research that promise a better understanding of the clinical management of PD psychosis and its role as a biomarker for PD stage and progression.

Cognitive decline in Parkinson disease.

Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition - or even reversal to normal cognition - is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-ß42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

Risk factors for early psychosis in PD: insights from the Parkinson's Progression Markers Initiative.

BACKGROUND: Parkinson's Disease (PD) psychosis refers to the spectrum of illusions, formed hallucinations and delusions that occur in PD. Visual hallucinations and illusions are thought to be caused by specific cognitive and higher visual function deficits and patients who develop such symptoms early in the disease course have greater rates of cognitive decline and progression to dementia. To date, no studies have investigated whether such deficits are found prior to the onset of PD psychosis. METHOD: Here we compare baseline cognitive, biomarker (structural imaging and cerebrospinal fluid) and other PD psychosis risk factor data in patients who go on to develop illusions or hallucinations within 3-4 years of follow-up in the Parkinson's Progression Markers Initiative cohort of newly diagnosed PD. RESULTS: Of n=423 patients with PD, n=115 (27%) reported predominantly illusions with the median time of onset at 19.5 months follow-up. At study entry these patients had reduced CSF amyloid Aß1-42, lower olfaction scores, higher depression scores and increased REM sleep behaviour disorder symptoms compared to patients without early onset PD psychosis but no differences in cognitive, higher visual or structural imaging measures. A subset of patients with early onset formed hallucinations (n=21) had reduced higher visual function at baseline, cortical thinning in parietal, occipital and frontal cortex and reduced hippocampal volume. CONCLUSIONS: The findings suggest early onset illusions and formed hallucinations are linked to amyloid pathology in PD and point to a difference in the underlying pathophysiological mechanism of illusions and formed hallucinations, with implications for their respective links to future cognitive decline.

The psychosis spectrum in Parkinson disease.

In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication. We discuss recent developments, including recognition of an increase in the prevalence of psychosis with disease duration, addition of new visual symptoms to the psychosis continuum, and identification of frontal executive, visual perceptual and memory dysfunction at different disease stages. In addition, we highlight novel risk factors - for example, autonomic dysfunction - that have emerged from prospective studies, structural MRI evidence of frontal, parietal, occipital and hippocampal involvement, and approval of pimavanserin for the treatment of PD psychosis. The accumulating evidence raises novel questions and directions for future research to explore the clinical management and biomarker potential of PD psychosis.

Voxel-based magnetic resonance imaging investigation of poor and preserved clinical insight in people with schizophrenia.

AIM: To define regional grey-matter abnormalities in schizophrenia patients with poor insight (Insight(-)), relative to patients with preserved clinical insight (Insight(+)), and healthy controls. METHODS: Forty stable schizophrenia outpatients (20 Insight(-) and 20 Insight(+)) and 20 healthy controls underwent whole brain magnetic resonance imaging (MRI). Insight in all patients was assessed using the Birchwood Insight Scale (BIS; a self-report measure). The two patient groups were pre-selected to match on most clinical and demographic parameters but, by design, they had markedly distinct BIS scores. Voxel-based morphometry employed in SPM8 was used to examine group differences in grey matter volumes across the whole brain. RESULTS: The three participant groups were comparable in age [F(2,57) = 0.34, P = 0.71] and the patient groups did not differ in age at illness onset [t(38) = 0.87, P = 0.39]. Insight(-) and Insight(+) patient groups also did not differ in symptoms on the Positive and Negative Syndromes scale (PANSS): Positive symptoms [t(38) = 0.58, P = 0.57], negative symptoms [t(38) = 0.61, P = 0.55], general psychopathology [t(38) = 1.30, P = 0.20] and total PANSS scores [t(38) = 0.21, P = 0.84]. The two patient groups, as expected, varied significantly in the level of BIS-assessed insight [t(38) = 12.11, P < 0.001]. MRI results revealed lower fronto-temporal, parahippocampal, occipital and cerebellar grey matter volumes in Insight(-) patients, relative to Insight(+) patients and healthy controls (for all clusters, family-wise error corrected P < 0.05). Insight(+) patient and healthy controls did not differ significantly (P > 0.20) from each other. CONCLUSION: Our findings demonstrate a clear association between poor clinical insight and smaller fronto-temporal, occipital and cerebellar grey matter volumes in stable long-term schizophrenia patients.

Are stroke survivors with delirium at higher risk of post-stroke dementia? Current evidence and future directions.

OBJECTIVES: The idea that delirium is a risk factor for dementia, broadly defined, is derived from heterogeneous patient samples. We reviewed available evidence as to whether stroke survivors who developed delirium during the acute phase of treatment are at a higher prospective risk of incident post-stroke cognitive impairment or dementia. DESIGN: We searched 8721 records in the Cochrane database for reviews or protocols dealing with the study objective, Medline, EMBASE, PsycInfo and CINAHL for observational studies in the general adult population and PubMed for in-process articles. Additional searches of the reference lists of retrieved articles were also undertaken. Qualitative syntheses and meta-analysis were conducted according to conventional guidelines. RESULTS: Twelve relevant articles were fully appraised. Four out of these studies, comprising 743 stroke survivors, including 199 with delirium, met criteria for qualitative syntheses. Overall, the studies presented low to moderate level evidence suggesting an association between post-stroke delirium and dementia. CONCLUSIONS: There is a need for further studies to investigate the association of post-stroke delirium and dementia using well-defined cohorts of patients and controlling for factors such as pre-stroke cognition, stroke severity and location and the presence of persistent delirium. Such studies will help understand the place of delirium identification and prevention in reducing the risk of dementia after stroke. © 2016 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

Mapping Depression in Schizophrenia: A Functional Magnetic Resonance Imaging Study.

Depressive symptoms are common in schizophrenia, often left untreated, and associated with a high relapse rate, suicidal ideation, increased mortality, reduced social adjustment and poor quality of life. The neural mechanisms underlying depression in psychosis are poorly understood. Given reports of altered brain response to negative facial affect in depressive disorders, we examined brain response to emotive facial expressions in relation to levels of depression in people with psychosis. Seventy outpatients (final N= 63) and 20 healthy participants underwent functional magnetic resonance imaging during an implicit affect processing task involving presentation of facial expressions of fear, anger, happiness as well as neutral expressions and a (no face) control condition. All patients completed Beck Depression Inventory (BDI-II) and had their symptoms assessed on the Positive and Negative Syndrome Scale (PANSS). In patients, depression (BDI-II) scores associated positively with activation of the left thalamus, extending to the putamen-globus pallidus, insula, inferior-middle frontal and para-post-pre-central gyri during fearful expressions. Furthermore, patients with moderate-to-severe depression had significantly higher activity in these brain regions during fearful expressions relative to patients with no, minimal, or mild depression and healthy participants. The study provides first evidence of enhanced brain response to fearful facial expressions, which signal an uncertain source of threat in the environment, in patients with psychosis and a high level of self-reported depression.

Is it me? Verbal self-monitoring neural network and clinical insight in schizophrenia.

Self-monitoring, defined as the ability to distinguish between self-generated stimuli from other-generated ones, is known to be impaired in schizophrenia. This impairment has been theorised as the basis for many of the core psychotic symptoms, in particular, poor clinical insight. This study aimed to investigate verbal self-monitoring related neural substrates of preserved and poor clinical insight in schizophrenia. It involved 40 stable schizophrenia outpatients, 20 with preserved and 20 with poor insight, and 20 healthy participants. All participants underwent functional magnetic resonance imaging with brain coverage covering key areas in the self-monitoring network during a verbal self-monitoring task. Healthy participants showed higher performance accuracy and greater thalamic activity than both preserved and poor insight patient groups. Preserved insight patients showed higher activity in the putamen extending into the caudate, insula and inferior frontal gyrus, compared to poor insight patients, and in the anterior cingulate and medial frontal gyrus, compared to healthy participants. Poor insight patients did not show greater activity in any brain area compared to preserved insight patients or healthy participants. Future studies may pursue therapeutic avenues, such as meta-cognitive therapies to promote self-monitoring or targeted stimulation of relevant brain areas, as means of enhancing insight in schizophrenia.

Common and distinct neural effects of risperidone and olanzapine during procedural learning in schizophrenia: a randomised longitudinal fMRI study.

RATIONALE: Most cognitive domains show only minimal improvement following typical or atypical antipsychotic treatments in schizophrenia, and some may even worsen. One domain that may worsen is procedural learning, an implicit memory function relying mainly on the integrity of the fronto-striatal system. OBJECTIVES: We investigated whether switching to atypical antipsychotics would improve procedural learning and task-related neural activation in patients on typical antipsychotics. Furthermore, we explored the differential effects of the atypical antipsychotics risperidone and olanzapine. METHODS: Thirty schizophrenia patients underwent functional magnetic resonance imaging during a 5-min procedural (sequence) learning task on two occasions: at baseline and 7-8 weeks later. Of 30 patients, 10 remained on typical antipsychotics, and 20 were switched randomly in equal numbers to receive either olanzapine (10-20 mg) or risperidone (4-8 mg) for 7-8 weeks. RESULTS: At baseline, patients (all on typical antipsychotics) showed no procedural learning. At follow-up, patients who remained on typical antipsychotics continued to show a lack of procedural learning, whereas those switched to atypical antipsychotics displayed significant procedural learning (p = 0.001) and increased activation in the superior-middle frontal gyrus, anterior cingulate and striatum (cluster-corrected p < 0.05). These neural effects were present as a linear increase over five successive 30-s blocks of sequenced trials. A switch to either risperidone or olanzapine resulted in comparable performance but with both overlapping and distinct task-related activations. CONCLUSIONS: Atypical antipsychotics restore procedural learning deficits and associated neural activity in schizophrenia. Furthermore, different atypical antipsychotics produce idiosyncratic task-related neural activations, and this specificity may contribute to their differential long-term clinical profiles.

On visual hallucinations and cortical networks: a trans-diagnostic review.

Our current clinical approach to visual hallucinations is largely derived from work carried out by Georges de Morsier in the 1930s. Now, almost a century after his influential papers, we have the research tools to further explore the ideas he put forward. In this review, we address de Morsier's proposal that visual hallucinations in all clinical conditions have a similar neurological mechanism by comparing structural imaging studies of susceptibility to visual hallucinations in Parkinson's disease, Alzheimer's disease, Dementia with Lewy bodies and schizophrenia. Systematic review of the literature was undertaken using PubMed searches. A total of 18 studies across conditions were identified reporting grey matter differences between patients with and without visual hallucinations. Grey matter changes were categorised into brain regions relevant to current theories of visual hallucinations. The distribution of cortical atrophy supports de Morsier's premise that visual hallucinations are invariably linked to aberrant activity within visual thalamo-cortical networks. Further work is required to determine by what mechanism these networks become predisposed to spontaneous activation, and whether the frontal lobe and hippocampal changes identified are present in all conditions. The findings have implications for the development of effective treatments for visual hallucinations.

Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease.

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications.

From tones in tinnitus to sensed social interaction in schizophrenia: how understanding cortical organization can inform the study of hallucinations and psychosis.

The content, modality, and perceptual attributes of hallucinations and other psychotic symptoms may be related to neural representation at a single cell and population level in the cerebral cortex. A brief survey of some principles and examples of cortical representation and organization will be presented together with evidence for a correspondence between the neurobiology of brain areas activated at the time of a hallucination and the content of the corresponding hallucinatory and psychotic experiences. Contrasting the hallucinations of schizophrenia with other conditions, we highlight phenomenological aspects of hallucinations that are ignored in clinical practice but carry potentially important information about the brain regions and dysfunctions underlying them. Knowledge of cortical representation and organization are being used to develop animal models of hallucination and to test treatments that are now beginning to translate to the clinical domain.

Negative outcome Charles Bonnet syndrome.

BACKGROUND: Charles Bonnet Syndrome (CBS) is widely considered a transient condition without adverse consequence, questioning the need for treatment. Yet, while this view may be true of the majority of people with CBS, it is recognised that some have negative experiences and outcomes. Here, we attempt to better understand negative outcome CBS and the factors that influence it. METHODS: 4000 members of the Macular Society were sent a structured questionnaire covering the phenomenology of CBS, its prognosis and impact, symptom reporting, patient knowledge and sources of information. RESULTS: 492 people with CBS were identified. Kaplan-Meier analysis suggested 75% had CBS for 5 years or more. Thirty-two per cent had negative outcome. Factors associated with negative outcome were: (1) frequent, fear-inducing, longer-lasting hallucination episodes, (2) one or more daily activities affected, (3) attribution of hallucinations to serious mental illness, (4) not knowing about CBS at the onset of symptoms. Duration of CBS or the type of content hallucinated were not associated with negative outcome. CONCLUSIONS: CBS is of longer duration than previously suspected with clinically relevant consequences in a third of those affected. Interventions that reduce the frequency, duration or fear of individual hallucination episodes and education prior to hallucination onset may help reduce negative outcome.