Vignando Miriam, Ffytche Dominic, Mazibuko Ndabezinhle, Palma Giulio, Montagnese Marcella, Dave Sonali, Nutt David J, Gabay Anthony S, Tai Yen F, Batzu Lucia, Leta Valentina, Williams Gray Caroline H, Chaudhuri K Ray, Mehta Mitul A
Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.
Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.
Brain Commun. 2024 Sep 3;6(5):fcae291. doi: 10.1093/braincomms/fcae291. eCollection 2024.
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-HT 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 ( = 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 ( = 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.
精神病和视幻觉是帕金森病常见的非运动症状，会对患者的生活质量产生负面影响，且增加患痴呆症的风险。了解与这些症状相关的神经机制对治疗的发展至关重要。失配负波是由感觉事件序列中的违反情况诱发的一种事件相关电位。它被广泛认为是感觉变化检测的指标。失配负波反应降低是精神分裂症中最反复出现的结果之一，并且被认为是一种更优的精神病标志物。为了了解这种事件相关电位成分是否可能是帕金森病精神病同样可靠的标志物，我们对20名患有帕金森病且有视幻觉的参与者和18名匹配的无幻觉帕金森病参与者进行了脑电图检查，并采用变化检测任务来研究视觉模态下的失配负波。我们发现，在顶枕部和额部位置，无幻觉的帕金森病参与者中明显存在视觉失配负波，而患有帕金森病且有视幻觉的参与者在这两种波形上显示出降低或无差异，这证实了失配负波对精神病的敏感性，即使在同一诊断组内也是如此。我们还探讨了幻觉严重程度与视觉失配负波幅度之间的关系，发现在中央额部和顶枕部电极处，视幻觉严重程度评分与视觉失配负波幅度呈负相关，即症状越严重或越复杂（错觉、成形视幻觉），幅度越小。我们还根据受体转运假说，测试了血清素能5 - HT级联在患有这些症状的帕金森病视幻觉中的潜在作用。我们在健康对照者（n = 18）中进行了一项初步研究，为Gi/o依赖性途径在致幻效应中的作用提供了支持，并在患有帕金森病且有视幻觉的参与者（n = 5）中采用双盲交叉设计进行了病例系列研究。精神病评分和失配幅度的阳性结果进一步证明了血清素能调节在帕金森病视幻觉中的潜在作用。
