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

Background: Current research does not provide a clear explanation for why some patients with Parkinson9s Disease (PD) develop psychotic symptoms. In the field of schizophrenia research the 9aberrant salience hypothesis9 of psychosis has been influential. According to the theory, dopaminergic dysregulation leads to the inappropriate attribution of salience to otherwise irrelevant or non-informative stimuli, allowing for the formation of hallucinations and delusions. This theory has not yet been extensively investigated in the context of psychosis in PD. Methods: We investigated salience processing in 14 PD patients with a history of psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients received dopaminergic medication. We examined emotional salience using a visual oddball fMRI paradigm (Bunzeck and Duezel, 2006) that previously has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI. Results: We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms revealed senhanced brain responses in the striatum, the hippocampus and the amygdala compared to PD patients without psychotic symptoms. PD patients with psychotic symptoms also showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. Furthermore, our data provide a first indication for dysfunctional top-down processes, measured in a 9jumping to conclusions9 bias. Conclusion: Our study suggests that enhanced signalling in the striatum, hippocampus and amygdala together with deficient top-down cognitive regulations is associated with the development of psychotic symptoms in PD which is similar to that proposed in the 9aberrant salience hypothesis9 of psychosis in schizophrenia.