Functional connectivity in Lewy body disease with visual hallucinations.

BACKGROUND AND PURPOSE: Visual hallucinations are a common, potentially distressing experience of people with Lewy body disease (LBD). The underlying brain changes giving rise to visual hallucinations are not fully understood, although previous models have posited that alterations in the connectivity between brain regions involved in attention and visual processing are critical. METHODS: Data from 41 people with LBD and visual hallucinations, 48 with LBD without visual hallucinations and 60 similarly aged healthy comparator participants were used. Connections were investigated between regions in the visual cortex and ventral attention, dorsal attention and default mode networks. RESULTS: Participants with visual hallucinations had worse cognition and motor function than those without visual hallucinations. In those with visual hallucinations, reduced functional connectivity within the ventral attention network and from the visual to default mode network was found. Connectivity strength between the visual and default mode network correlated with the number of correct responses on a pareidolia task, and connectivity within the ventral attention network with visuospatial performance. CONCLUSIONS: Our results add to evidence of dysfunctional connectivity in the visual and attentional networks in those with LBD and visual hallucinations.

Non-clinical hallucinations and mental imagery across sensory modalities.

INTRODUCTION: Vivid mental imagery has been proposed to increase the likelihood of experiencing hallucinations. Typically, studies have employed a modality general approach to mental imagery which compares imagery across multiple domains (e.g., visual, auditory and tactile) to hallucinations in multiple senses. However, modality specific imagery may be a better predictor of hallucinations in the same domain. The study examined the contribution of imagery to hallucinations in a non-clinical sample and specifically whether imagery best predicted hallucinations at a modality general or modality specific level. METHODS: In study one, modality general and modality specific accounts of the imagery-hallucination relationship were contrasted through application of self-report measures in a sample of 434 students. Study two used a subsample (n = 103) to extend exploration of the imagery-hallucinations relationship using a performance-based imagery task. RESULTS: A small to moderate modality general relationship was observed between self-report imagery and hallucination proneness. There was only evidence of a modality specific relationship in the tactile domain. Performance-based imagery measures were unrelated to hallucinations and self-report imagery. CONCLUSIONS: Mental imagery may act as a modality general process increasing hallucination proneness. The observed distinction between self-report and performance-based imagery highlights the difficulty of accurately measuring internal processes.

Functional and structural brain network correlates of visual hallucinations in Lewy body dementia.

Visual hallucinations are a common feature of Lewy body dementia. Previous studies have shown that visual hallucinations are highly specific in differentiating Lewy body dementia from Alzheimer's disease dementia and Alzheimer-Lewy body mixed pathology cases. Computational models propose that impairment of visual and attentional networks is aetiologically key to the manifestation of visual hallucinations symptomatology. However, there is still a lack of experimental evidence on functional and structural brain network abnormalities associated with visual hallucinations in Lewy body dementia. We used EEG source localization and network based statistics to assess differential topographical patterns in Lewy body dementia between 25 participants with visual hallucinations and 17 participants without hallucinations. Diffusion tensor imaging was used to assess structural connectivity between thalamus, basal forebrain and cortical regions belonging to the functionally affected network component in the hallucinating group, as assessed with network based statistics. The number of white matter streamlines within the cortex and between subcortical and cortical regions was compared between hallucinating and not hallucinating groups and correlated with average EEG source connectivity of the affected subnetwork. Moreover, modular organization of the EEG source network was obtained, compared between groups and tested for correlation with structural connectivity. Network analysis showed that compared to non-hallucinating patients, those with hallucinations feature consistent weakened connectivity within the visual ventral network, and between this network and default mode and ventral attentional networks, but not between or within attentional networks. The occipital lobe was the most functionally disconnected region. Structural analysis yielded significantly affected white matter streamlines connecting the cortical regions to the nucleus basalis of Meynert and the thalamus in hallucinating compared to not hallucinating patients. The number of streamlines in the tract between the basal forebrain and the cortex correlated with cortical functional connectivity in non-hallucinating patients, while a correlation emerged for the white matter streamlines connecting the functionally affected cortical regions in the hallucinating group. This study proposes, for the first time, differential functional networks between hallucinating and not hallucinating Lewy body dementia patients, and provides empirical evidence for existing models of visual hallucinations. Specifically, the outcome of the present study shows that the hallucinating condition is associated with functional network segregation in Lewy body dementia and supports the involvement of the cholinergic system as proposed in the current literature.

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.

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.

Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management.

Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson's disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson's disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop.Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.

Seeing for ourselves: Insights into the development of moral behaviour from models of visual perception and misperception.

Parallels from visual processing support Doris's cognitive architecture underlying moral agency. Unconscious visual processes change with conscious reflection. The sparse and partial representations of vision, its illusions, and hallucinations echo biases in moral reasoning and behaviour. Traditionally, unconscious moral processes are developed by teaching and reflection. Modern neuroscience could bypass reflection and directly influence unconscious processes, creating new dangers.

Visual Hallucinations in Eye Disease and Lewy Body Disease.

OBJECTIVES: Visual hallucinations (VH) most commonly occur in eye disease (ED), Parkinson disease (PD), and Lewy body dementia (LBD). The phenomenology of VH is likely to carry important information about the brain areas within the visual system generating them. METHODS: Data from five controlled cross-sectional VH studies (164 controls, 135 ED, 156 PD, 79 [PDD 48 + DLB 31] LBD) were combined and analyzed. The prevalence, phenomenology, frequency, duration, and contents of VH were compared across diseases and sex. RESULTS: Simple VH were most common in ED patients (ED 65% versus LBD 22% versus PD 9%, χ(2) = 31.43, df = 2, p < 0.001), whereas complex VH were more common in LBD (LBD 76% versus ED 38%, versus PD 28%, χ(2) = 96.80, df = 2, p < 0.001). The phenomenology of complex VH was different across diseases and sex. ED patients reported more "flowers" (ED 21% versus LBD 6% versus PD 0%, χ(2) = 10.04, df = 2, p = 0.005) and "body parts" (ED 40% versus LBD 17% versus PD 13%, χ(2) = 11.14, df = 2, p = 0.004); in contrast, LBD patients reported "people" (LBD 85% versus ED 67% versus PD 63%, χ(2) = 6.20, df = 2, p = 0.045) and "animals/insects" (LBD 50% versus PD 42% versus ED 21%, χ(2) = 9.76, df = 2, p = 0.008). Men reported more "machines" (13% versus 2%, χ(2) = 6.94, df = 1, p = 0.008), whereas women reported more "family members/children" (48% versus 29%, χ(2) = 5.10, df = 1, p = 0.024). CONCLUSIONS: The phenomenology of VH is likely related to disease-specific dysfunctions within the visual system and to past, personal experiences.

Visual Priming and Visual Hallucinations in Parkinson's Disease. Evidence for Normal Top-Down Processes.

BACKGROUND: Visual hallucinations (VH) are common in Parkinson's disease (PD) and are associated with increased morbidity and mortality. Current explanations for VH in PD suggest combined impairments in top-down attentional and bottom-up perceptual processes, which allow the passive "release" of stored images. Alternative models in other disorders have suggested that top-down factors may actively encourage hallucinations. In order to explore the interaction between top-down and bottom-up visual processing in PDVH, we developed novel experimental priming tasks in which top-down verbal cues were used to prime the bottom-up recognition of partial or ambiguous pictures. METHOD: Two groups of PD participants with (PD + VH, n = 16), and without VH (PD - VH, n = 20) were compared to a group of healthy older adults (NC, n = 20) on 3 novel measures of visual priming. RESULTS: All tasks showed significant priming effects. The PD + VH group was more impaired at accurately identifying silhouette and fragmented images compared to the PD - VH group. There were no differences in priming between the 2 PD groups. CONCLUSIONS: The study showed that VH in PD are not associated with relatively greater top-down activation, and that the interaction between top-down and bottom-up processes is intact.

Visual Hallucinations in Older People: Appraisals but not Content or Phenomenology Influence Distress.

BACKGROUND: A previous study (Gauntlett-Gilbert and Kuipers, 2005) has suggested that distress associated with complex visual hallucinations (CVHs) in younger adults with psychosis may more strongly relate to appraisals of meaning than to the content of the hallucination. However, visual hallucinations are most commonly seen in the disorders of later life, where this relationship has not been investigated. AIM: To establish if there is a relationship between appraisals of CVHs and distress in older, non-psychotic people with CVHs. METHOD: All variables were measured using a semi-structured interview and were compared between a high distress group (n = 16) and a low distress group (n = 19). RESULTS: The high distress group rated their hallucinations as more malevolent and omnipotent, with greater negative implications for physical and mental health. There was no significant difference between groups on ratings of hallucination content (independently rated), frequency, awareness or control. CONCLUSION: Appraisals of CVHs are linked to distress.

Is Seeing Believing? The Process of Change During Cognitive-behavioural Therapy for Distressing Visual Hallucinations.

UNLABELLED: People with psychosis often report distressing visual hallucinations (VH). In contrast to auditory hallucinations, there is little empirical evidence on effective interventions. The effectiveness of a novel-focused cognitive-behavioural therapy (CBT) intervention for VH was explored using a multiple baseline single case design with four participants. Change to individual appraisals, emotional and behavioural responses to VH were measured with daily diaries kept throughout the baseline and intervention phase lasting up to 16 sessions. Maintenance of change was tracked during a follow-up period of one month. Changes in appraisals, distress and response in accordance with the theory was evident in two out of four of the cases. However, change occurred within the baseline phase that limited the conclusions that change could be attributed to CBT alone. There was some evidence of clinically significant change and reliable change for two out of four of the cases at follow-up on one of the standardized psychiatric assessments. The research reported here has theoretical and clinical implications for refinement of the model and interventions for distressing VH. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Distressing visual hallucinations (VH) are a relatively common symptom of psychosis. Visual hallucinations seem to be associated with greater impairment and disability. We have no specific treatment for VH. The appraisal of the visual experience and the behavioural response is important in maintaining the distress. Cognitive-behavioural therapy for VH at present has limited value.

Patient and Informant Views on Visual Hallucinations in Parkinson Disease.

OBJECTIVE: Visual hallucinations (VHs) are a very personal experience, and it is not clear whether information about them is best provided by informants or patients. Some patients may not share their hallucinatory experiences with caregivers to avoid distress or for fear of being labeled insane, and others do not have informants at all, which limits the use of informant-based questionnaires. The aim of this study was to compare patient and caregiver views about VHs in Parkinson disease (PD), using the North-East Visual Hallucinations Interview (NEVHI). METHODS: Fifty-nine PD patient-informant pairs were included. PD patients and informants were interviewed separately about VHs using the NEVHI. Informants were additionally interviewed using the four-item version of the Neuropsychiatric Inventory. Inter-reliability and concurrent validity of the different measures were compared. RESULTS: VHs were more commonly reported by patients than informants. The inter-rater agreement between NEVHI-patient and NEVHI-informant was moderate for complex VHs (Cohen's kappa = 0.44; 95% confidence interval [CI]: 0.13-0.75; t = 3.43, df = 58, p = 0.001) and feeling of presence (Cohen's kappa = 0.35; 95% CI: 0.00-0.70; t = 2.75, df = 58, p = 0.006), but agreement was poor for illusions (Cohen's kappa = 0.25; 95% CI: -0.07-0.57; t = 2.36, df = 58, p = 0.018) and passage hallucinations (Cohen's kappa = 0.16; 95% CI: -0.04-0.36; t = 2.26, df = 58, p = 0.024). CONCLUSION: When assessing VHs in PD patients, it is best to rely on patient information, because not all patients share the details of their hallucinations with their caregivers.

The assessment of cognition in visually impaired older adults.

BACKGROUND: visual and cognitive impairments are common in later life. Yet there are very few cognitive screening tests for the visually impaired. OBJECTIVE: to screen for cognitive impairment in the visually impaired. METHODS: case-control study including 150 elderly participants with visual impairment (n = 74) and a control group without visual impairment (n = 76) using vision-independent cognitive tests and cognitive screening tests (MMSE and clock drawing tests (CDT)) which are in part vision dependent. RESULTS: the scoring of the two groups did not differ in the vision-independent cognitive tests. Visually impaired patients performed poorer than controls in the vision-dependent items of the MMSE (T = 7.3; df: 148; P < 0.001) and in CDT (T = 3.1; df: 145; P = 0.003). No group difference was found when vision-independent items were added to MMSE and CDT. The test score gain by the use of vision-independent items correlated with the severity of visual impairment (P < 0.002). CONCLUSION: visually impaired patients benefit from cognitive tests, which do not rely on vision. The more visually impaired the greater the benefit.

What is the frequency and nature of visual hallucinations in non-clinical participants?

OBJECTIVES: There is a paucity of psychological treatments for visual hallucinations (VH). A key aspect in the psychological treatment of hallucination-related distress is normalisation to explain that these experiences are commonplace and can be non-distressing. In order to normalise VH, it is vital that more is known about VH in non-clinical populations. This study investigated the prevalence, content, context, appraisals, distress, and behavioural reactions to VH in a non-clinical sample. DESIGN: A cross-sectional study was conducted. METHODS: 466 students completed the Multi-Modality Unusual Sensory Experiences Questionnaire-VH subscale with additional contextual follow-up questions. RESULTS: Of the 466 participants, 395 (84.8%) reported anomalous visual experiences. 176 (37.77%) participants reported VH similar to the content seen in psychosis. Of the overall sample, 17.38% felt their experience met the VH definition. Participants mainly saw figures, when alone and in the evening. Participants endorsed normalising appraisals: 112 out of 176 (78.87%) believed their mind was playing tricks on them and 83 (58.45%) believed they were tired. However, many also believed the VH was a threat to their mental (66, 46.48%) or physical well-being (41, 28.87%). These negative appraisals were associated with distress. CONCLUSION: VH are seemingly common in non-clinical populations and are similar in a number of ways to those of people with psychosis. Awareness that VH occur on a continuum could normalise people's experiences and reduce their negative appraisals and related distress.

Understanding visual hallucinations: A new synthesis.

Despite decades of research, we do not definitively know how people sometimes see things that are not there. Eight models of complex visual hallucinations have been published since 2000, including Deafferentation, Reality Monitoring, Perception and Attention Deficit, Activation, Input, and Modulation, Hodological, Attentional Networks, Active Inference, and Thalamocortical Dysrhythmia Default Mode Network Decoupling. Each was derived from different understandings of brain organisation. To reduce this variability, representatives from each research group agreed an integrated Visual Hallucination Framework that is consistent with current theories of veridical and hallucinatory vision. The Framework delineates cognitive systems relevant to hallucinations. It allows a systematic, consistent, investigation of relationships between the phenomenology of visual hallucinations and changes in underpinning cognitive structures. The episodic nature of hallucinations highlights separate factors associated with the onset, persistence, and end of specific hallucinations suggesting a complex relationship between state and trait markers of hallucination risk. In addition to a harmonised interpretation of existing evidence, the Framework highlights new avenues of research, and potentially, new approaches to treating distressing hallucinations.

Identifying specific interpretations and use of safety behaviours in people with distressing visual hallucinations: an exploratory study.

BACKGROUND: Visual hallucinations (VH) are a common experience and can be distressing and disabling, particularly for people suffering from psychotic illness. However, not everyone with visual hallucinations reports the experience to be distressing. Models of VH propose that appraisals of VH as a threat to wellbeing and the use of safety seeking behaviours help maintain the distress. AIMS: This study investigated whether people with distressing VH report threat appraisals and use safety behaviours. METHOD: The study utilized a single group descriptive design, in which 15 participants with psychosis and VH were asked questions in order to assess the content, distress, appraisals, and behaviours associated with visual hallucinations. RESULTS: People who found visual hallucinations distressing (n = 13) held negative appraisals about those hallucinations and specifically saw them as a threat to their physical or psychological wellbeing. They also engaged in safety seeking behaviours that were logically related to the appraisal and served to maintain the distress. CONCLUSIONS: People with distressing VH regard them as a threat to their wellbeing and use safety seeking behaviours as a result of this perceived threat. These key processes are potential targets for treatments that will alleviate the distress associated with VH.

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.

Dreaming and hallucinations - continuity or discontinuity? Perspectives from dementia with Lewy bodies.

Comparing the phenomenology, neurochemical pathology, and psychopharmacology of hallucinations and dreaming is limited by the available data. Evidence to date reveals no simple correspondence between the two states. Differences in the phenomenology of visual hallucinations and the visual component of dreams may reflect variations in visual context acting on the same underlying mechanism - the minimal visual input during dreaming contrasts with the more substantial perceived context in hallucinations. Variations in cholinergic, dopaminergic and serotonergic neurotransmitter function during sleep and during hallucinations in Lewy body dementias, together with relevant drug effects suggest that, on the whole, different, potentially opposite, changes characterise the two states. A similar analysis of other psychotic features in Lewy body dementia and other disorders suggests that, in contrast to hallucinations, there may be more convincing parallels between dreaming and delusional states.

A Review of Multimodal Hallucinations: Categorization, Assessment, Theoretical Perspectives, and Clinical Recommendations.

Hallucinations can occur in different sensory modalities, both simultaneously and serially in time. They have typically been studied in clinical populations as phenomena occurring in a single sensory modality. Hallucinatory experiences occurring in multiple sensory systems-multimodal hallucinations (MMHs)-are more prevalent than previously thought and may have greater adverse impact than unimodal ones, but they remain relatively underresearched. Here, we review and discuss: (1) the definition and categorization of both serial and simultaneous MMHs, (2) available assessment tools and how they can be improved, and (3) the explanatory power that current hallucination theories have for MMHs. Overall, we suggest that current models need to be updated or developed to account for MMHs and to inform research into the underlying processes of such hallucinatory phenomena. We make recommendations for future research and for clinical practice, including the need for service user involvement and for better assessment tools that can reliably measure MMHs and distinguish them from other related phenomena.

Exploring Bottom-Up Visual Processing and Visual Hallucinations in Parkinson's Disease With Dementia.

Visual hallucinations (VH) are a common symptom of Parkinson's disease with dementia (PDD), affecting up to 65% of cases. Integrative models of their etiology posit that a decline in executive control of the visuo-perceptual system is a primary mechanism of VH generation. The role of bottom-up processing in the manifestation of VH in this condition is still not clear although visual evoked potential (VEP) differences have been associated with VH at an earlier stage of PD. Here we compared the amplitude and latency pattern reversal VEPs in healthy controls (n = 21) and PDD patients (n = 34) with a range of VH severities. PDD patients showed increased N2 latency relative to controls, but no significant differences in VEP measures were found for patients reporting complex VH (CVH) (n = 17) compared to those without VH. Our VEP findings support previous reports of declining visual system physiology in PDD and some evidence of visual system differences between patients with and without VH. However, we did not replicate previous findings of a major relationship s between the integrity of the visual pathway and VH.