Visual mismatch negativity in Parkinson's psychosis and potential for testing treatment mechanisms
Open accessAbstract
Psychosis and visual hallucinations are a prevalent non-motor symptom of Parkinson's disease, negatively affecting patients’ quality of life and constituting a greater risk for dementia. Understanding neural mechanisms associated to these symptoms is instrumental for treatment development. The mismatch negativity is an event-related potential evoked by a violation in a sequence of sensory events. It is widely considered an index of sensory change-detection. Reduced mismatch negativity response is one of the most replicated results in schizophrenia and has been suggested to be a superior psychosis marker. To understand whether this event-related potential component could be a similarly robust marker for Parkinson's psychosis, we used electroencephalography with a change-detection task to study the mismatch negativity in the visual modality in 20 participants with Parkinson's and visual hallucinations and 18 matched Parkinson's participants without hallucinations. We find that visual mismatch negativity is clearly present in participants with Parkinson’s disease without hallucinations at both parieto-occipital and frontal sites, whereas participants with Parkinson's and visual hallucinations show reduced or no differences in the two waveforms, confirming the sensitivity of mismatch negativity to psychosis, even within the same diagnostic group. We also explored the relationship between hallucination severity and visual mismatch negativity amplitude, finding a negative correlation between visual hallucinations severity scores and visual mismatch negativity amplitude at a central frontal and a parieto-occipital electrodes, whereby the more severe or complex (illusions, formed visual hallucinations) the symptoms the smaller the amplitude. We have also tested the potential role of the serotonergic 5-HT2A cascade in visual hallucinations in Parkinson's with these symptoms, following the receptor trafficking hypothesis. We did so with a pilot study in healthy controls (N = 18) providing support for the role of the Gi/o-dependent pathway in the psychedelic effect and a case series in participants with Parkinson's and visual hallucinations (N = 5) using a double-blind crossover design. Positive results on psychosis scores and mismatch amplitude add further to the potential role of serotonergic modulation of visual hallucinations in Parkinson's disease.
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The 5-HT2A receptor may be facilitating cortical disinhibition, consistent with previous proposals and studies showing 5-HT2A antagonists reducing psychosis-like symptoms.
“This finding may suggest that this receptor may be facilitating cortical disinhibition, consistent with previous proposals42,43 and studies showing 5-HT2A antagonists reducing psychosis-like symptoms20,42.”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [20]
The Introduction (page unavailable) reports that ketanserin, a 5-HT2A antagonist, can block psychedelic-induced visual experiences, including hallucinations. The Discussion (page unavailable) also links 5-HT2A signalling to hallucinations, but the paper does not propose cortical disinhibition as the mechanism. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe authors recently demonstrated reduced visual MMN responses in PD-VH, paralleling auditory MMN impairments observed in psychosis.
“We recently demonstrated reduced visual MMN responses in PD-VH20, paralleling auditory MMN impairments observed in psychosis15.”
From Deviations in effective connectivity explain different hallucination subtypes in Parkinson's disease psychosis (2026) · cites this paper as [20]
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References 73 · Cited by 6
- Authors
- Vignando, M., ffytche, D., Mazibuko, N., Palma, G., Montagnese, M., Dave, S., Nutt, D. J., Gabay, A. S., Tai, Y. F., Batzu, L., Leta, V., Williams Gray, C. H., Chaudhuri, K. R., & Mehta, M. A.
- Affiliations
- King's College London (GB)
- Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , London, SE5 8AF ,
- University of Southampton (GB)
- University of Cambridge (GB)
- University of London (GB)
- Hammersmith Hospital (GB)
- Ixico (United Kingdom) (GB)
- Charing Cross Hospital (GB)
- King's College Hospital NHS Foundation Trust (GB)
- John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge/Cambridge University Hospitals NHS Foundation Trust , Cambridge, CB2 0PY ,
- Parkinson Foundation Centre of Excellence, King's College Hospital NHS Foundation Trust , SW9 8R, London ,
- Corresponding author
- Vignando, Miriam
- ORCID
- Venue
- Brain Communications
- Publisher
- Oxford University Press (OUP)
- Published
- 2024
- Volume
- 6
- Issue
- 5
- Pages
- fcae291-fcae291
- ISSN
- 2632-1297 (ISSN-L)
- PMC
- PMC11443450
- OpenAlex
- W4403084519
- Cited by
- 6
- References
- 73
- Citations by year
- 2026: 4 · 2025: 2
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Brain Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- Medical Research Council (MR/R005931/1, MR/K015192)
- National Institute for Health and Care Research
- Maudsley Biomedical Research Centre
- Department of Health and Social Care
- Alzheimer’s Research UK (ARUK-RF2022B-002, MR/W029235/1)
- Cambridge Biomedical Research Centre (NIHR203312)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Hallucinations in medical conditions
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- Parkinson's disease psychosis, visual hallucinations, visual mismatch negativity, event-related potentials, change detection, hallucination severity, non-motor symptoms, therapeutic mechanisms
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