Visual mismatch negativity in Parkinson’s psychosis and potential for testing treatment mechanisms

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Psychosis and visual hallucinations are a prevalent non-motor symptom of Parkinson’s disease (PD), 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 (MMN) 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 ERP component could be a similarly robust marker for PD psychosis, we used electroencephalography with a change-detection task to study the MMN in the visual modality (vMMN) in 20 patients with PD and visual hallucinations and 18 matched PD without hallucinations. We find that vMMN is clearly present in patients with PD without hallucinations at both parieto-occipital and frontal sites, whereas PD-VH show reduced or no differences in the two waveforms, confirming the sensitivity of MMN to psychosis, even within the same diagnostic group. We also explored the relationship between VH severity and vMMN amplitude, finding a negative correlation between visual hallucinations severity scores and vMMN amplitude at a central frontal (FZ) and parieto-occipital (POZ) electrodes, whereby the more severe or complex (illusions, formed VH) the symptoms the smaller the amplitude.

We have also tested the potential role of the serotonergic 5-HT2A cascade in VH in PD with hallucinations, 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 PD-VH (N=5) using a double-blind crossover design. Positive results on psychosis scores and MMN amplitude add further to the potential role of serotonergic modulation of visual hallucinations in Parkinson’s disease.
Original languageEnglish
JournalBrain Communications
Publication statusAccepted/In press - 14 May 2024


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