The Pharmacology of Visual Hallucinations in Synucleinopathies.
Mirella Russo, Claudia Carrarini, Fedele Dono, Marianna Gabriella Rispoli, Martina Di Pietro, Vincenzo Di Stefano, Laura Ferri, Laura Bonanni, Stefano Luca Sensi, Marco Onofrj
Frontiers in Pharmacology December 9, 2019 DOI: 10.3389/fphar.2019.01379 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Default mode network |
| Keywords | Parkinson's disease Synucleinopathy Visual hallucination |
| Key findings | Argues that visual hallucinations in synucleinopathies arise when the default mode network decouples from fronto-parietal and salience network control, triggered by altered thalamic function and dysregulated neurotransmission. While dopamine has historically been considered the major driver, the authors contend that serotonergic and cholinergic dysfunction, along with glutamatergic and GABAergic imbalance, also contribute. |
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.
Comparable studies
Other narrative reviews on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Brain's Default Mode Network | 2015 | Review | |
| Default Mode Network Activity and Connectivity in Psychopathology | 2012 | Review | |
| 20 years of the default mode network: A review and synthesis | 2023 | Review | |
| On the relationship between the “default mode network” and the “social brain” | 2012 | Review | |
| The default mode network and social understanding of others: what do brain connectivity studies tell us Healthy subjects, with some studies on patients with autism and psychopathy | 2014 | Review |
Citations in the library
Cited by 9
- Understanding visual hallucinations: A new synthesis. Neuroscience & Biobehavioral Reviews July 1, 2023
- The central role of the Thalamus in psychosis, lessons from neurodegenerative diseases and psychedelics. Translational Psychiatry December 13, 2023
- Minds and Brains, Sleep and Psychiatry Psychiatric Research and Clinical Practice November 10, 2020
- Classics in Chemical Neuroscience: Muscimol. ACS Chemical Neuroscience September 18, 2024
- Visual Hallucinations in Serotonergic Psychedelics and Lewy Body Diseases Schizophrenia Bulletin April 17, 2025
and 4 more in the library
Cites 49
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- The Predictive Coding Account of Psychosis. Biological Psychiatry May 25, 2018
and 44 more in the library