Dataset Information

The Pharmacology of Visual Hallucinations in Synucleinopathies.

ABSTRACT: Visual hallucinations (VH) are commonly found in the course of synucleinopathies like Parkinson's disease and dementia with Lewy bodies. The incidence of VH in these conditions is so high that the absence of VH in the course of the disease should raise questions about the diagnosis. VH may take the form of early and simple phenomena or appear with late and complex presentations that include hallucinatory production and delusions. VH are an unmet treatment need. The review analyzes the past and recent hypotheses that are related to the underlying mechanisms of VH and then discusses their pharmacological modulation. Recent models for VH have been centered on the role played by the decoupling of the default mode network (DMN) when is released from the control of the fronto-parietal and salience networks. According to the proposed model, the process results in the perception of priors that are stored in the unconscious memory and the uncontrolled emergence of intrinsic narrative produced by the DMN. This DMN activity is triggered by the altered functioning of the thalamus and involves the dysregulated activity of the brain neurotransmitters. Historically, dopamine has been indicated as a major driver for the production of VH in synucleinopathies. In that context, nigrostriatal dysfunctions have been associated with the VH onset. The efficacy of antipsychotic compounds in VH treatment has further supported the notion of major involvement of dopamine in the production of the hallucinatory phenomena. However, more recent studies and growing evidence are also pointing toward an important role played by serotonergic and cholinergic dysfunctions. In that respect, in vivo and post-mortem studies have now proved that serotonergic impairment is often an early event in synucleinopathies. The prominent cholinergic impairment in DLB is also well established. Finally, glutamatergic and gamma aminobutyric acid (GABA)ergic modulations and changes in the overall balance between excitatory and inhibitory signaling are also contributing factors. The review provides an extensive overview of the pharmacology of VH and offers an up to date analysis of treatment options.

SUBMITTER: Russo M

PROVIDER: S-EPMC6913661 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Pharmacology of Visual Hallucinations in Synucleinopathies.

Russo Mirella M Carrarini Claudia C Dono Fedele F Rispoli Marianna Gabriella MG Di Pietro Martina M Di Stefano Vincenzo V Ferri Laura L Bonanni Laura L Sensi Stefano Luca SL Onofrj Marco M

Frontiers in pharmacology 20191209

Visual hallucinations (VH) are commonly found in the course of synucleinopathies like Parkinson's disease and dementia with Lewy bodies. The incidence of VH in these conditions is so high that the absence of VH in the course of the disease should raise questions about the diagnosis. VH may take the form of early and simple phenomena or appear with late and complex presentations that include hallucinatory production and delusions. VH are an unmet treatment need. The review analyzes the past and r ...[more]

PMID: 31920635

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Project description:Prominent theories suggest that symptoms of schizophrenia stem from learning deficiencies resulting in distorted internal models of the world. To test these theories further, we used a visual statistical learning task known to induce rapid implicit learning of the stimulus statistics. In this task, participants are presented with a field of coherently moving dots and are asked to report the presented direction of the dots (estimation task), and whether they saw any dots or not (detection task). Two of the directions were more frequently presented than the others. In controls, the implicit acquisition of the stimuli statistics influences their perception in two ways: (i) motion directions are perceived as being more similar to the most frequently presented directions than they really are (estimation biases); and (ii) in the absence of stimuli, participants sometimes report perceiving the most frequently presented directions (a form of hallucinations). Such behaviour is consistent with probabilistic inference, i.e. combining learnt perceptual priors with sensory evidence. We investigated whether patients with chronic, stable, treated schizophrenia (n = 20) differ from controls (n = 23) in the acquisition of the perceptual priors and/or their influence on perception. We found that although patients were slower than controls, they showed comparable acquisition of perceptual priors, approximating the stimulus statistics. This suggests that patients have no statistical learning deficits in our task. This may reflect our patients' relative wellbeing on antipsychotic medication. Intriguingly, however, patients experienced significantly fewer (P = 0.016) hallucinations of the most frequently presented directions than controls when the stimulus was absent or when it was very weak (prior-based lapse estimations). This suggests that prior expectations had less influence on patients' perception than on controls when stimuli were absent or below perceptual threshold.

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.

Dataset Information

The Pharmacology of Visual Hallucinations in Synucleinopathies.

Publications

The Pharmacology of Visual Hallucinations in Synucleinopathies.

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