Compensatory shifts in visual perception are associated with hallucinations in Lewy body disorders.
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ABSTRACT:
SUBMITTER: Bowman AR
PROVIDER: S-EPMC5442189 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hallucinations are a common and distressing feature of many psychiatric and neurodegenerative conditions. In Lewy body disease, visual hallucinations are a defining feature, associated with worse outcomes; yet their mechanisms remain unclear and treatment options are limited. Here, we show that hallucinations in Lewy body disease are associated with altered integration of top-down predictions with incoming sensory evidence, specifically with an increased relative weighting of prior knowledge. We tested 37 individuals with Lewy body disease, 17 habitual hallucinators and 20 without hallucinations, and 20 age-matched healthy individuals. We employed an image-based learning paradigm to test whether people with Lewy body disease and visual hallucinations show higher dependence on prior knowledge. We used two-tone images that are difficult to disambiguate without any prior information but generate a strong percept when information is provided. We measured discrimination sensitivity before and after this information was provided. We observed that in people with Lewy body disease who experience hallucinations, there was greater improvement in discrimination sensitivity after information was provided, compared to non-hallucinators and controls. This suggests that people with Lewy body disease and hallucinations place higher relative weighting on prior knowledge than those who do not hallucinate. Importantly, increased severity of visual hallucinations was associated with an increased effect of prior knowledge. Together these findings suggest that visual hallucinations in Lewy body disease are linked to a shift towards top-down influences on perception and away from sensory evidence, perhaps due to an increase in sensory noise. This provides important mechanistic insights to how hallucinations develop in Lewy body disease, with potential for revealing new therapeutic targets.
| S-EPMC6924538 | biostudies-literature
Project description:Visual hallucinations (VH) in Lewy body disease (LBD) have a heterogenous phenomenology classified into minor phenomena (MVH) and complex hallucinations (CVH). Mechanisms underpinning VH and their temporal aspects are largely unknown. According to the hodotopic model, we investigated whether changes in distinct cognitive domains and neural networks in the hallucination trait underpin temporal aspects of MVH and CVH in the hallucination state. 35 LBD patients with VH underwent a complete neuropsychological evaluation and resting-state fMRI. North-East-Visual-Hallucinations-Interview was used to assess their typical VH content, duration, and frequency. We found that MVH was not associated with cognitive impairment, while CVH was associated with impairments in visuoperceptual processes, attention and visual abstract reasoning. In seed-to-seed functional connectivity (FC) analysis we identified functional couplings associated with MVH and CVH temporal severity (duration x frequency), duration and frequency. MVH severity was negatively associated with FC between early visual areas (EVA) and ventral-visual-stream regions, and negatively associated with FC between brainstem and EVA, which may be linked to LBD brainstem neuropathology. CVH duration was positively associated with FC between ventral-visual stream and salience network (SN). CVH frequency was negatively associated with FC between DMN and SN. Functional alterations in distinct visual and attentional networks and their dynamic interaction in trait LBD hallucinators are linked to both the phenomenology of state content and its temporal characteristics. Within a network, VH frequency and duration may be linked to different types of functional alterations: increased connectivity leading to sustained activity prolonging VH (duration) and decreased connectivity increasing dysregulated, spontaneous activity (frequency). These findings support the hodotopic hypothesis of VH and may reflect a link between VH phenomenology, LBD neuropathological progression and the involvement of specific neurotransmitter systems.
| S-EPMC9217885 | biostudies-literature
Project description: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.
| S-EPMC9246710 | biostudies-literature
Project description:Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural correlates of VH in LBD, namely Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Following a systematic literature search, 56 neuroimaging studies of VH in PD and DLB were critically reviewed and evaluated for quality assessment. The main structural neuroimaging results on VH in LBD revealed grey matter loss in frontal areas in patients with dementia, and parietal and occipito-temporal regions in PD without dementia. Parietal and temporal hypometabolism was also reported in hallucinating PD patients. Disrupted functional connectivity was detected especially in the default mode network and fronto-parietal regions. However, evidence on structural and functional connectivity is still limited and requires further investigation. The current literature is in line with integrative models of VH suggesting a role of attention and perception deficits in the development of VH. However, despite the close relationship between VH and cognitive impairment, its associations with brain structure and function have been explored only by a limited number of studies.
| S-EPMC5532597 | biostudies-literature
Project description:BackgroundThe presence of recurrent, complex visual hallucinations (VH) is among the core clinical features of dementia with Lewy bodies (DLB). It has been proposed that VH arise from a disrupted organization of functional brain networks. However, studies are still limited, especially investigating the resting-state functional brain features underpinning VH in patients with dementia.ObjectiveThe aim of the present pilot study was to investigate whether there were any alterations in functional connectivity associated with VH in DLB.MethodsSeed-based analyses and independent component analysis (ICA) of resting-state fMRI scans were carried out to explore differences in functional connectivity between DLB patients with and without VH.ResultsSeed-based analyses reported decreased connectivity of the lateral geniculate nucleus, the superior parietal lobule and the putamen with the medial frontal gyrus in DLB patients with VH. Visual areas showed a pattern of both decreased and increased functional connectivity. ICA revealed between-group differences in the default mode network (DMN).ConclusionFunctional connectivity analyses suggest dysfunctional top-down and bottom-up processes and DMN-related alterations in DLB patients with VH. This impairment might foster the generation of false visual images that are misinterpreted, ultimately resulting in VH.
| S-EPMC8150258 | biostudies-literature
Project description:Mathematical and computational approaches were used to investigate dementia with Lewy bodies (DLB), in which recurrent complex visual hallucinations (RCVH) is a very characteristic symptom. Beginning with interpretative analyses of pathological symptoms of patients with RCVH-DLB in comparison with the veridical perceptions of normal subjects, we constructed a three-module scenario concerning function giving rise to perception. The three modules were the visual input module, the memory module, and the perceiving module. Each module interacts with the others, and veridical perceptions were regarded as a certain convergence to one of the perceiving attractors sustained by self-consistent collective fields among the modules. Once a rather large but inhomogeneously distributed area of necrotic neurons and dysfunctional synaptic connections developed due to network disease, causing irreversible damage, then bottom-up information from the input module to both the memory and perceiving modules were severely impaired. These changes made the collective fields unstable and caused transient emergence of mismatched perceiving attractors. This may account for the reason why DLB patients see things that are not there. With the use of our computational model and experiments, the scenario was recreated with complex bifurcation phenomena associated with the destabilization of collective field dynamics in very high-dimensional state space.
| S-EPMC9391481 | biostudies-literature
Project description:Lewy body disorders (LBD), characterized by the deposition of misfolded α-synuclein (α-Syn), are clinically heterogeneous. We hypothesized that this heterogeneity might reflect α-Syn molecular diversity, between both patients and different brain regions. Using an ultra-sensitive assay, we evaluated α-Syn seeding from 30 LBD patients with different clinical phenotypes and disease durations. Interestingly, α-Syn from patients with rapid disease progression (<3 years) had a higher nigral seeding capacity than the rest of the patients included. We performed a proteomic-wide profiling of the substantia nigra from 5 high and 5 low seeder patients. The proteomic data suggests a significant disruption in mitochondrial function and lipid metabolism in high seeder cases compared to the low seeders.
2022-07-20 | PXD034441 | Pride
Project description:BackgroundComplex visual hallucinations are common in Lewy body dementia (LBD) and can cause significant patient and caregiver distress. Current treatments are primarily pharmacological in nature and have limited efficacy and associated side effects. The objective of this study was to assess the effects of consecutive sessions of transcranial direct current stimulation (tDCS) on visual hallucination frequency and severity in LBD, at short-term and long-term follow-up stages.MethodsThe study was a randomised, double-blind, placebo-controlled trial involving 40 participants with LBD (Mage = 75.52 years, SDage = 8.69 years) which was conducted at a single site between November 2013 and December 2017. Participants received two consecutive 20-min sessions of active (0.048 mA/cm2) or placebo tDCS, separated by a 30-min break, over 5 consecutive days. The anodal electrode was applied to the right parietal cortex (P4) and the cathodal electrode was applied to the occipital cortex (Oz). The primary outcome measure was the Neuropsychiatric Inventory (NPI) hallucinations subscale, as completed by a caregiver/informant at baseline and day 5 (short-term) follow-up, and month 1 and month 3 (long-term) follow-up. Secondary outcome measures included visual cortical excitability, as measured using transcranial magnetic stimulation, computerised attentional and visuoperceptual tasks, and measures of global cognition and cognitive fluctuations.ResultsComplete study data were obtained from 36 participants. There was an overall improvement in visual hallucinations (NPI) for both groups at day 5 relative to baseline, with a medium-to-large effect size; however, compared to placebo, active tDCS did not result in any improvements in visual hallucinations (NPI) at day 5 relative to baseline, or at month 1 or month 3 follow-up time points. Additionally, comparisons of secondary outcome measures showed that active tDCS did not result in any improvements on any measure (visual cortical excitability, attentional and visuoperceptual tasks or cognitive measures) at any time point.ConclusionsRepeated consecutive sessions of parietal anodal tDCS, and occipital cathodal tDCS, do not improve visual hallucinations or visuoperceptual function, or alter visual cortical excitability in LBD.Trial registrationISRCTN, ISRCTN40214749 . Registered on 25 October 2013.
| S-EPMC6339360 | biostudies-literature
Project description:BackgroundDeficits in basic vision are associated with visual hallucinations in Parkinson's disease. Of particular interest is contrast sensitivity loss in this disorder and its effect on object identification.ObjectivesEvaluate whether increased contrast improves object perception in persons with Parkinson's disease and visual hallucinations, without dementia.MethodsWe assessed 26 individuals with mild to moderate idiopathic Parkinson's disease, half of whom reported one or more episodes of hallucinations/unusual perceptual experiences in the past month, with a letter-identification task that determined the contrast level required to achieve 80% accuracy. Contrast sensitivity was further assessed with a chart that presented stimuli at multiple spatial frequencies. The groups were closely matched for demographic and clinical characteristics except for experience of hallucinations.ResultsRelative to participants without visual hallucinations, those with hallucinations had poorer spatial frequency contrast sensitivity and required significantly greater contrast to correctly identify the letters on the identification task. Specifically, participants with hallucinations required a mean contrast of 52.8%, whereas participants without hallucinations required 35.0%. When given sufficient contrast, the groups with and without hallucinations were equally accurate in letter identification.ConclusionsCompared to those without hallucinations, individuals with Parkinson's disease and hallucinations without dementia showed poorer contrast sensitivity. Once contrast was individually enhanced, the groups were equally accurate at object identification. These findings suggest the potential of visual perception tests to predict, and perception-based interventions to reduce, hallucinations in Parkinson's disease.
| S-EPMC7780942 | biostudies-literature
Project description:It has been proposed that there is an increased frequency of glucosidase-beta mutations in Lewy body disorders. Our comprehensive DNA sequencing approach found a small number of glucosidase-beta mutations in 101 neuropathologically defined Lewy body disease cases (3%) compared to 99 healthy post-mortem controls (1%); odds ratio 3.0 (95% CI: 0.3-29, p=0.3). All three affected carriers were classified as diffuse Lewy body disease (n=3/50; 6%). Our study suggests glucosidase-beta variants have a limited role in susceptibility to Lewy body disease in North America.
| S-EPMC2970615 | biostudies-literature