Functional Brain Connectivity Patterns Associated with Visual Hallucinations in Dementia with Lewy Bodies.
Ontology highlight
ABSTRACT: Background
The 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.Objective
The aim of the present pilot study was to investigate whether there were any alterations in functional connectivity associated with VH in DLB.Methods
Seed-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.Results
Seed-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).Conclusion
Functional 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.
SUBMITTER: Pezzoli S
PROVIDER: S-EPMC8150258 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
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:Introductionpresence hallucinations (PH) are frequent in dementia with Lewy bodies (DLB), but their cortico-subcortical origin is unknown. Recent studies have defined key frontal and temporal areas contributing to the occurrence of PH (PH-network) and tested their relevance in subjects with Parkinson's disease (PD). With the present study, we aimed at disentangling the metabolic and dopaminergic correlates of pH as well as their relation to a recently defined PH brain network in DLB.Methodsfor the present study, we included 34 DLB subjects (10 with PH (PH + ); 24 without PH (PH-)), who underwent 18F-FDG PET and 123I-FP-CIT SPECT imaging. We performed 18F-FDG PET group comparisons, as well as interregional correlation analyses using 18F-FDG PH-network regions as a seed.ResultsPH + versus PH- had reduced 18F-FDG uptake in precentral, superior frontal and parietal gyri, involving ventral premotor cortex (vPMC) of the PH-network that showed strongly reduced functional connectivity with bilateral cortical regions. 18F-FDG vPMC uptake was negatively correlated with caudate 123I-FP-CIT uptake in PH+ (p = 0.028) and interregional correlation analysis seeding from the vPMC showed widespread fronto-parietal 18F-FDG decreases in PH + .Discussionthese findings uncover the pivotal role of vPMC (involved in a PH-network) and its cortico-striatal connections in association with PH in DLB, improving our understanding of psychosis in neurodegeneration.
| S-EPMC8403753 | biostudies-literature
Project description:We studied the dynamic functional connectivity profile of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) compared to controls, how it differs between the two dementia subtypes, and a possible relation between dynamic connectivity alterations and temporally transient clinical symptoms in DLB. Resting state fMRI data from 31 DLB, 29 AD, and 31 healthy control participants were analyzed using dual regression to determine between-network functional connectivity. Subsequently, we used a sliding window approach followed by k-means clustering and dynamic network analyses to study dynamic functional connectivity. Dynamic connectivity measures that showed significant group differences were tested for correlations with clinical symptom severity. Our results show that AD and DLB patients spent more time than controls in sparse connectivity configurations with absence of strong positive and negative connections and a relative isolation of motor networks from other networks. Additionally, DLB patients spent less time in a more strongly connected state and the variability of global brain network efficiency was reduced in DLB compared to controls. There were no significant correlations between dynamic connectivity measures and clinical symptom severity. An inability to switch out of states of low inter-network connectivity into more highly and specifically connected network configurations might be related to the presence of dementia in general as it was observed in both AD and DLB. In contrast, the loss of global efficiency variability in DLB might indicate the presence of an abnormally rigid brain network and the lack of economical dynamics, factors which could contribute to cognitive slowing and an inability to respond appropriately to situational demands.
| S-EPMC6462776 | biostudies-literature
Project description:Dementia with Lewy bodies (DLB) is neuropathologically defined by the presence of α-synuclein aggregates, but many DLB cases show concurrent Alzheimer's disease pathology in the form of amyloid-β plaques and tau neurofibrillary tangles. The first objective of this study was to investigate the effect of Alzheimer's disease co-pathology on functional network changes within the default mode network (DMN) in DLB. Second, we studied how the distribution of tau pathology measured with PET relates to functional connectivity in DLB. Twenty-seven DLB, 26 Alzheimer's disease and 99 cognitively unimpaired participants (balanced on age and sex to the DLB group) underwent tau-PET with AV-1451 (flortaucipir), amyloid-β-PET with Pittsburgh compound-B (PiB) and resting-state functional MRI scans. The resing-state functional MRI data were used to assess functional connectivity within the posterior DMN. This was then correlated with overall cortical flortaucipir PET and PiB PET standardized uptake value ratio (SUVr). The strength of interregional functional connectivity was assessed using the Schaefer atlas. Tau-PET covariance was measured as the correlation in flortaucipir SUVr between any two regions across participants. The association between region-to-region functional connectivity and tau-PET covariance was assessed using linear regression. Additionally, we identified the region with highest and the region with lowest tau SUVrs (tau hot- and cold spots) and tested whether tau SUVr in all other brain regions was associated with the strength of functional connectivity to these tau hot and cold spots. A reduction in posterior DMN connectivity correlated with overall higher cortical tau- (r = -0.39, P = 0.04) and amyloid-PET uptake (r = -0.41, P = 0.03) in the DLB group, i.e. patients with DLB who have more concurrent Alzheimer's disease pathology showed a more severe loss of DMN connectivity. Higher functional connectivity between regions was associated with higher tau covariance in cognitively unimpaired, Alzheimer's disease and DLB. Furthermore, higher functional connectivity of a target region to the tau hotspot (i.e. inferior/medial temporal cortex) was related to higher flortaucipir SUVrs in the target region, whereas higher functional connectivity to the tau cold spot (i.e. sensory-motor cortex) was related to lower flortaucipir SUVr in the target region. Our findings suggest that a higher burden of Alzheimer's disease co-pathology in patients with DLB is associated with more Alzheimer's disease-like changes in functional connectivity. Furthermore, we found an association between the brain's functional network architecture and the distribution of tau pathology that has recently been described in Alzheimer's disease. We show that this relationship also exists in patients with DLB, indicating that similar mechanisms of connectivity-dependent occurrence of tau pathology might be at work in both diseases.
| S-EPMC8634124 | biostudies-literature
Project description:Using resting-state functional magnetic resonance imaging, spontaneous low-frequency fluctuations in the blood oxygenation level-dependent signal were measured to investigate connectivity between key brain regions hypothesized to be differentially affected in dementia with Lewy bodies compared with Alzheimer's disease and healthy controls. These included connections of the hippocampus, because of its role in learning, and parietal and occipital areas involved in memory, attention and visual processing. Connectivity was investigated in 47 subjects aged 60 years and over: 15 subjects with dementia with Lewy bodies, 16 subjects with Alzheimer's disease and 16 control subjects. Subjects were scanned using a 3 Tesla magnetic resonance imaging system. The mean blood oxygenation level-dependent signal time series was extracted from seed regions in the hippocampus, posterior cingulate cortex, precuneus and primary visual cortex and correlated with all other brain voxels to determine functional connectivity. Both subjects with dementia with Lewy bodies and Alzheimer's disease showed greater connectivity than control subjects. Compared with controls, the dementia with Lewy bodies group had greater connectivity between the right posterior cingulate cortex and other brain areas. In dementia with Lewy bodies, there were no significant differences in hippocampal connectivity compared with controls, but in Alzheimer's disease left hippocampal connectivity was greater compared with controls. There were no significant differences between groups for precuneus or primary visual cortex connectivity. No seed regions showed significantly less connectivity in subjects with dementia with Lewy bodies or Alzheimer's disease compared with controls. We found greater connectivity with the posterior cingulate in dementia with Lewy bodies and with the hippocampus in Alzheimer's disease. Consistent with the known relative preservation of memory in dementia with Lewy bodies compared with Alzheimer's disease, hippocampal connectivity was not found to be greater in dementia with Lewy bodies. Importantly, while metabolic imaging shows functional change in primary visual cortex in dementia with Lewy bodies, which is hypothesized to account for visual hallucinations, we found connectivity with this region to be unaffected. This implicates areas beyond visual sensory input level in the visual symptoms and visual-perceptual dysfunction seen in dementia with Lewy bodies.
| S-EPMC3708629 | biostudies-literature
Project description:Dementia with Lewy bodies (DLB) is a common form of dementia and is characterized by cognitive fluctuations, visual hallucinations, and Parkinsonism. The phenotypic expression of the disease may, in part, relate to alterations in functional connectivity within and between brain networks. This resting-state study sought to clarify this in DLB, how networks differed from Alzheimer's disease (AD), and whether they were related to clinical symptoms in DLB. Resting-state networks were estimated using independent component analysis. We investigated functional connectivity changes in 31 DLB patients compared to 31 healthy controls and a disease comparator group of 29 AD patients using dual regression and FSLNets. Within-network connectivity was generally decreased in DLB compared to controls, mainly in motor, temporal, and frontal networks. Between-network connectivity was mainly intact; only the connection between a frontal and a temporal network showed increased connectivity in DLB. Differences between AD and DLB were subtle and we did not find any significant correlations with the severity of clinical symptoms in DLB. This study emphasizes the importance of reduced connectivity within motor, frontal, and temporal networks in DLB with relative sparing of the default mode network. The lack of significant correlations between connectivity measures and clinical scores indicates that the observed reduced connectivity within these networks might be related to the presence, but not to the severity of motor and cognitive impairment in DLB patients. Furthermore, our results suggest that AD and DLB may show more similarities than differences in patients with mild disease.
| S-EPMC5900719 | biostudies-literature
Project description:Patients rarely experience visual hallucinations while being observed by clinicians. Therefore, instruments to detect visual hallucinations directly from patients are needed. Pareidolias, which are complex visual illusions involving ambiguous forms that are perceived as meaningful objects, are analogous to visual hallucinations and have the potential to be a surrogate indicator of visual hallucinations. In this study, we explored the clinical utility of a newly developed instrument for evoking pareidolic illusions, the Pareidolia test, in patients with dementia with Lewy bodies-one of the most common causes of visual hallucinations in the elderly. Thirty-four patients with dementia with Lewy bodies, 34 patients with Alzheimer's disease and 26 healthy controls were given the Pareidolia test. Patients with dementia with Lewy bodies produced a much greater number of pareidolic illusions compared with those with Alzheimer's disease or controls. A receiver operating characteristic analysis demonstrated that the number of pareidolias differentiated dementia with Lewy bodies from Alzheimer's disease with a sensitivity of 100% and a specificity of 88%. Full-length figures and faces of people and animals accounted for >80% of the contents of pareidolias. Pareidolias were observed in patients with dementia with Lewy bodies who had visual hallucinations as well as those who did not have visual hallucinations, suggesting that pareidolias do not reflect visual hallucinations themselves but may reflect susceptibility to visual hallucinations. A sub-analysis of patients with dementia with Lewy bodies who were or were not treated with donepzil demonstrated that the numbers of pareidolias were correlated with visuoperceptual abilities in the former and with indices of hallucinations and delusional misidentifications in the latter. Arousal and attentional deficits mediated by abnormal cholinergic mechanisms and visuoperceptual dysfunctions are likely to contribute to the development of visual hallucinations and pareidolias in dementia with Lewy bodies.
| S-EPMC3407420 | biostudies-literature
Project description:BackgroundVisual hallucinations (VH) are associated with visual prediction error in patients with dementia with Lewy bodies (DLB). Given this relationship, environmental adjustments have been suggested, but detailed contents for implementing such environmental adjustments and assessments are poorly documented. This case report preliminarily demonstrates methods for improving VH through our experience with two patients with DLB. We conducted familial interviews to assess the phenomenological features of VH and reviewed photographs of patients' homes to identify the environmental triggers of VH, known as photo assessment of the living environment (PA-LE).Case descriptionPatient 1 was a 78-year-old woman with a Mini-Mental State Examination (MMSE) score of 11/30. She experienced seeing a stranger, children, and cats at home, which frightened her. VH frequently occurred in the living room and bedroom. The PA-LE showed that several environmental features, such as cushions on a sofa, the pattern on a carpet under a table, and clothing on hangers, were suggestive triggers of VH. Patient 2 was an 88-year-old woman with a MMSE score of 5/30. She had seen strangers, children, and animals at home, some of which were linked to a theft delusion. VH frequently occurred in the living room and bedroom. The PA-LE found that several environmental features, such as clothing on hangers and dolls, were suggestive of VH triggers. Non-pharmacological approaches were tailored to the patients' environmental and psychological states using interviews and PA-LE. This included removing environmental triggers, reducing negative mood, and providing coping strategies for VH. This improved their VH and their caregivers' knowledge of VH.ConclusionPhenomenological assessments using photographs of the patient's home could identify the environmental triggers associated with VH in patients with DLB and assist in environmental adjustments.
| S-EPMC10978580 | 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:The clinical phenotype of dementia with Lewy bodies (DLB) is different from Alzheimer's disease (AD), suggesting a divergence between these diseases in terms of brain network organization. To fully understand this, we studied functional networks from resting-state functional magnetic resonance imaging in cognitively matched DLB and AD patients. The DLB group demonstrated a generalized lower synchronization compared with the AD and healthy controls, and this was more severe for edges connecting distant brain regions. Global network measures were significantly different between DLB and AD. For instance, AD showed lower small-worldness than healthy controls, while DLB showed higher small-worldness (AD < controls < DLB), and this was also the case for global efficiency (DLB > controls > AD) and clustering coefficient (DLB < controls < AD). Differences were also found for nodal measures at brain regions associated with each disease. Finally, we found significant associations between network performance measures and global cognitive impairment and severity of cognitive fluctuations in DLB. These results show network divergences between DLB and AD which appear to reflect their neuropathological differences.
| S-EPMC4706129 | biostudies-literature