Increased weighting on prior knowledge in Lewy body-associated visual hallucinations

Abstract 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.

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Visuo-Perceptual and Decision-Making Contributions to Visual Hallucinations in Mild Cognitive Impairment in Lewy Body Disease: Insights from a Drift Diffusion Analysis

Brain Sciences ◽

10.3390/brainsci10080540 ◽

2020 ◽

Vol 10 (8) ◽

pp. 540

Author(s):

Lauren Revie ◽

Calum A Hamilton ◽

Joanna Ciafone ◽

Paul C Donaghy ◽

Alan Thomas ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Reaction Time ◽

Diffusion Model ◽

Lewy Body ◽

Drift Rate ◽

Lewy Body Disease ◽

Visual Hallucinations ◽

Drift Diffusion Model ◽

Drift Diffusion

Background: Visual hallucinations (VH) are a common symptom in dementia with Lewy bodies (DLB); however, their cognitive underpinnings remain unclear. Hallucinations have been related to cognitive slowing in DLB and may arise due to impaired sensory input, dysregulation in top-down influences over perception, or an imbalance between the two, resulting in false visual inferences. Methods: Here we employed a drift diffusion model yielding estimates of perceptual encoding time, decision threshold, and drift rate of evidence accumulation to (i) investigate the nature of DLB-related slowing of responses and (ii) their relationship to visuospatial performance and visual hallucinations. The EZ drift diffusion model was fitted to mean reaction time (RT), accuracy and RT variance from two-choice reaction time (CRT) tasks and data were compared between groups of mild cognitive impairment (MCI-LB) LB patients (n = 49) and healthy older adults (n = 25). Results: No difference was detected in drift rate between patients and controls, but MCI-LB patients showed slower non-decision times and boundary separation values than control participants. Furthermore, non-decision time was negatively correlated with visuospatial performance in MCI-LB, and score on visual hallucinations inventory. However, only boundary separation was related to clinical incidence of visual hallucinations. Conclusions: These results suggest that a primary impairment in perceptual encoding may contribute to the visuospatial performance, however a more cautious response strategy may be related to visual hallucinations in Lewy body disease. Interestingly, MCI-LB patients showed no impairment in information processing ability, suggesting that, when perceptual encoding was successful, patients were able to normally process information, potentially explaining the variability of hallucination incidence.

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Shift toward prior knowledge confers a perceptual advantage in early psychosis and psychosis-prone healthy individuals

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1503916112 ◽

2015 ◽

Vol 112 (43) ◽

pp. 13401-13406 ◽

Cited By ~ 100

Author(s):

Christoph Teufel ◽

Naresh Subramaniam ◽

Veronika Dobler ◽

Jesus Perez ◽

Johanna Finnemann ◽

...

Keyword(s):

Information Processing ◽

Prior Knowledge ◽

Early Psychosis ◽

Psychotic Symptoms ◽

Psychotic Experiences ◽

Healthy Individuals ◽

Top Down ◽

Bottom Up ◽

Psychosis Proneness ◽

Sensory Evidence

Many neuropsychiatric illnesses are associated with psychosis, i.e., hallucinations (perceptions in the absence of causative stimuli) and delusions (irrational, often bizarre beliefs). Current models of brain function view perception as a combination of two distinct sources of information: bottom-up sensory input and top-down influences from prior knowledge. This framework may explain hallucinations and delusions. Here, we characterized the balance between visual bottom-up and top-down processing in people with early psychosis (study 1) and in psychosis-prone, healthy individuals (study 2) to elucidate the mechanisms that might contribute to the emergence of psychotic experiences. Through a specialized mental-health service, we identified unmedicated individuals who experience early psychotic symptoms but fall below the threshold for a categorical diagnosis. We observed that, in early psychosis, there was a shift in information processing favoring prior knowledge over incoming sensory evidence. In the complementary study, we capitalized on subtle variations in perception and belief in the general population that exhibit graded similarity with psychotic experiences (schizotypy). We observed that the degree of psychosis proneness in healthy individuals, and, specifically, the presence of subtle perceptual alterations, is also associated with stronger reliance on prior knowledge. Although, in the current experimental studies, this shift conferred a performance benefit, under most natural viewing situations, it may provoke anomalous perceptual experiences. Overall, we show that early psychosis and psychosis proneness both entail a basic shift in visual information processing, favoring prior knowledge over incoming sensory evidence. The studies provide complementary insights to a mechanism by which psychotic symptoms may emerge.

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Accumulation of sensory evidence is impaired in Parkinson’s disease with visual hallucinations

10.1101/111278 ◽

2017 ◽

Author(s):

Claire O’Callaghan ◽

Julie M. Hall ◽

Alessandro Tomassini ◽

Alana J. Muller ◽

Ishan C. Walpola ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sensory Processing ◽

Sensory Input ◽

Decision Time ◽

Visual Hallucinations ◽

Top Down ◽

Evidence Accumulation ◽

Sensory Evidence ◽

Response Output

AbstractModels of hallucinations across disorders emphasise an imbalance between sensory input and top-down influences over perception. However, the psychological and mechanistic correlates of this imbalance remain underspecified. Visual hallucinations in Parkinson’s disease (PD) are associated with impairments in lower level visual processes and attention, accompanied by over activity and connectivity in higher-order association brain networks. PD therefore provides an attractive framework to explore the relative contributions of bottom-up versus top-down disturbances in hallucinations. Here, we characterised sensory processing in PD patients with and without visual hallucinations, and in healthy controls, by fitting a hierarchical drift diffusion model (hDDM) to an attentional task. The hDDM uses Bayesian estimates to decompose reaction time and response output into parameters reflecting drift rates of evidence accumulation, decision thresholds and non-decision time. We observed slower drift rates in PD patients with hallucinations, which were insensitive to changes in task demand. In contrast, wider decision boundaries and shorter non-decision times relative to controls were found in PD regardless of hallucinator status. Inefficient and less flexible sensory evidence accumulation emerge as unique features of PD hallucinators. We integrate these results with current models of hallucinations, suggesting that slow and inefficient sensory input in PD is less informative, and may therefore be down-weighted leading to an over reliance on top-down influences. Our findings provide a novel computational framework to better specify the impairments in dynamic sensory processing that are a risk factor for visual hallucinations.

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110 Atrophy of the mediodorsal thalamus is associated with visual hallucinations in lewy body diseases

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-anzan.109 ◽

2018 ◽

Vol 89 (6) ◽

pp. A43.3-A44

Author(s):

Elie Matar ◽

Daniel Brooks ◽

Antony Harding ◽

Glenda Halliday

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Lewy Body ◽

Neuronal Degeneration ◽

Neuronal Loss ◽

Lewy Body Disease ◽

Visual Hallucinations ◽

Volume Loss ◽

Thalamic Nuclei ◽

Mediodorsal Thalamus

IntroductionAlthough limbic system dysfunction has been thought to underlie visual hallucinations in patients with Lewy body disorders, neuropathology within thalamic structures subserving limbic functions have not been examined. In this study, we assessed the degree of neuronal degeneration in thalamic regions involved in perceptual integration in patients with Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB).MethodsPost-mortem samples were acquired from twenty-four individuals with Lewy body disease (5 PD, 9 PDD, 10 DLB) and 10 age-matched controls. The anterior principal (AP) and mediodorsal (MD) thalamic nuclei were delineated and analysed using stereological and quantitative neuropathological techniques.ResultsVolume loss within the MD nucleus was observed in patients with DLB (31%) and PDD (18%) but not PD compared to controls (ANOVA, p<0.05). The atrophy was significantly greater in those patients with hallucinations than those without (p<0.05). Somal atrophy was seen in all patient groups and did not correlate with volume loss or visual hallucinations. Interestingly, there was no neuronal loss in this region compared to controls in the Lewy body disease groups. Analysis of the AP nucleus revealed similar patterns of volume loss but with somal atrophy only in patients with PDD and DLB. Both these measures did not correlate significantly with visual hallucinations, but was significantly different in patients with dementia compared to PD only and controls (p<0.05).ConclusionThese results suggest that afferent denervation of the mediodorsal thalamus may contribute to visual hallucinations. This appears to support models that implicate upstream components of the limbic circuitry in the generation of this phenomenon.

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Structural and Functional Neuroimaging of Visual Hallucinations in Lewy Body Disease: A Systematic Literature Review

Brain Sciences ◽

10.3390/brainsci7070084 ◽

2017 ◽

Vol 7 (12) ◽

pp. 84 ◽

Cited By ~ 9

Author(s):

Stefania Pezzoli ◽

Annachiara Cagnin ◽

Oliver Bandmann ◽

Annalena Venneri

Keyword(s):

Literature Review ◽

Systematic Literature Review ◽

Lewy Body ◽

Functional Neuroimaging ◽

Lewy Body Disease ◽

Visual Hallucinations

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Circular inference in bistable perception

10.1101/521195 ◽

2019 ◽

Author(s):

Pantelis Leptourgos ◽

Charles-Edouard Notredame ◽

Marion Eck ◽

Renaud Jardri ◽

Sophie Denève

Keyword(s):

Prior Knowledge ◽

Bayesian Approach ◽

Necker Cube ◽

Top Down ◽

Inference Model ◽

Bottom Up ◽

Bistable Perception ◽

Sensory Evidence ◽

The Brain ◽

Healthy Participants

AbstractWhen facing fully ambiguous images, the brain cannot commit to a single percept and instead switches between mutually exclusive interpretations every few seconds, a phenomenon known as bistable perception. Despite years of research, there is still no consensus on whether bistability, and perception in general, is driven primarily by bottom-up or top-down mechanisms. Here, we adopted a Bayesian approach in an effort to reconcile these two theories. Fifty-five healthy participants were exposed to an adaptation of the Necker cube paradigm, in which we manipulated sensory evidence (by shadowing the cube) and prior knowledge (e.g., by varying instructions about what participants should expect to see). We found that manipulations of both sensory evidence and priors significantly affected the way participants perceived the Necker cube. However, we observed an interaction between the effect of the cue and the effect of the instructions, a finding incompatible with Bayes-optimal integration. In contrast, the data were well predicted by a circular inference model. In this model, ambiguous sensory evidence is systematically biased in the direction of current expectations, ultimately resulting in a bistable percept.

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Does past or present depression differentiate Lewy body from Alzheimer disease?

International Psychogeriatrics ◽

10.1017/s1041610214001793 ◽

2014 ◽

Vol 27 (4) ◽

pp. 693-694 ◽

Cited By ~ 1

Author(s):

Jed Falkowski ◽

Linda S. Hynan ◽

Kyle B. Womack ◽

Kimmo J. Hatanpaa ◽

Charles L. White ◽

...

Keyword(s):

Alzheimer Disease ◽

Lewy Body ◽

Lewy Body Disease ◽

Visual Hallucinations ◽

Symptoms Of Depression

Clinical differentiation of Lewy body disease (LBD) from Alzheimer disease (AD) is still problematic. Many persons with LBD lack the cardinal features of visual hallucinations, fluctuations in cognition, and mild Parkinsonism proposed by McKeith et al. (2005). Some studies suggest that history or presence of depression may help distinguish LBD from AD, but this is confounded because many clinically diagnosed LBD patients have significant co-morbid AD pathology and vice versa (Ranginwala et al., 2008). We aimed to clarify whether history or symptoms of depression differentiate LBD from AD, in autopsy-confirmed patients, excluding patients with mixed AD and LBD pathology.

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VISUAL HALLUCINATIONS IN LEWY BODY DISEASE: NEUROPSYCHOLOGICAL AND NEUROANATOMICAL CORRELATES

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.07.527 ◽

2017 ◽

Vol 13 (7) ◽

pp. P1461

Author(s):

Stefania Pezzoli ◽

Annachiara Cagnin ◽

Annalena Venneri

Keyword(s):

Lewy Body ◽

Lewy Body Disease ◽

Visual Hallucinations

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Delirium prior to dementia as a clinical phenotype of Lewy body disease: an autopsied case report

International Psychogeriatrics ◽

10.1017/s1041610216001265 ◽

2016 ◽

Vol 29 (4) ◽

pp. 687-689 ◽

Cited By ~ 2

Author(s):

Hiroshige Fujishiro ◽

Ito Kawakami ◽

Kenichi Oshima ◽

Kazuhiro Niizato ◽

Shuji Iritani

Keyword(s):

Lewy Body ◽

Clinical Phenotype ◽

Lewy Bodies ◽

Lewy Body Disease ◽

Japanese Woman ◽

Visual Hallucinations ◽

Limited Information ◽

Lewy Body Pathology ◽

Old Japanese ◽

The Relationship

ABSTRACTAlthough delirium shares clinical characteristics with dementia with Lewy bodies (DLB), there is limited information regarding the relationship between delirium and Lewy body pathology. Here, we report an 89-year-old Japanese woman with an episode of delirium who was pathologically confirmed to have limbic-type Lewy body disease (LBD). Although she exhibited transient visual hallucinations during the delirium, she had no overt dementia. She developed no core clinical features of DLB and died of pneumonia at the age of 90 years. This autopsied case suggests that delirium may be one of the clinical phenotypes of LBD prior to the onset of dementia.

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