Altered subcortical emotional salience processing differentiates Parkinson's patients with and without psychotic symptoms.

F Knolle,R.A Barker,A Justicia,P Ramachandra,H Blank,E Duezel,G Arrondo,G.B Williams,G.K Murray,T.W Robbins,A.O Ermakova,S Garofalo,C Tudor-Sfetea,N Bunzeck,R Viviani

doi:10.1016/j.nicl.2020.102277

Abstract

Current research does not provide a clear explanation for why some patients with Parkinson's Disease (PD) develop psychotic symptoms. The 'aberrant salience hypothesis' of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms. We investigated salience processing in 14 PD patients with psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients were on dopaminergic medication for their PD. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI. We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms had enhanced brain responses in the striatum, dopaminergic midbrain, hippocampus and amygdala compared to patients without psychotic symptoms. PD patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. Our study suggests that enhanced signalling in the striatum, dopaminergic midbrain, the hippocampus and amygdala is associated with the development of psychotic symptoms in PD, in line with that proposed in the 'aberrant salience hypothesis' of psychosis in schizophrenia.

Highlights

Parkinson’s disease (PD) patients frequently suffer from psychotic symptoms which most commonly takes the form of visual hallucinations, delusions and illusions (Aarsland et al, 1999)
In the current study we investigated negative emotional salience in Parkinson’s Disease (PD) patients with and without psychotic symptoms and compared them to healthy controls
PD patients with psychotic symptoms showed slightly stronger, but insignificantly different BOLD signals compared to controls in all regions bar the substantia nigra/VTA, suggesting maintained emotional salience processing in the patients with psychotic symptoms

Summary

Introduction

Parkinson’s disease (PD) patients frequently suffer from psychotic symptoms which most commonly takes the form of visual hallucinations, delusions and illusions (Aarsland et al, 1999). PD psychosis characterises a spectrum of such psychotic symptoms that occur throughout the course of the disease, but especially in those with longer disease duration, higher age and possibly higher doses of, or certain kinds of, dopaminergic medication, giving an overall prevalence of 26% (Forsaa et al, 2010; Gibson et al, 2013; Mack et al, 2012). There are clear differences between the primary psychiatric disorder of (schizophrenia spectrum) psychosis and PD psychosis, a disturbed dopaminergic system is a unifying element in both diseases, possibly contributing to the occurrence of psychotic symptoms in both disorders (Carter and Ffytche, 2015; Garofalo et al, 2017). PD psychosis is interesting as it is commonly found as a comorbidity in PD patients but does not affect all

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