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

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  • dc.contributor.author Knolle, Franziska
  • dc.contributor.author Garofalo, S.
  • dc.contributor.author Viviani, R.
  • dc.contributor.author Justicia Díaz, Azucena
  • dc.contributor.author Ermakova, Anna O.
  • dc.contributor.author Blank, H.
  • dc.contributor.author Williams, G.B.
  • dc.contributor.author Arrondo, G.
  • dc.contributor.author Ramachandra, P.
  • dc.contributor.author Tudor-Sfetea, C.
  • dc.contributor.author Tudor-Sfetea, C.
  • dc.contributor.author Bunzeck, Nico
  • dc.contributor.author Düzel, Emrah
  • dc.contributor.author Robbins, T.W.
  • dc.contributor.author Barker, R.A.
  • dc.contributor.author Murray, Graham K.
  • dc.date.accessioned 2020-10-23T07:01:15Z
  • dc.date.available 2020-10-23T07:01:15Z
  • dc.date.issued 2020
  • dc.description.abstract Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
  • dc.description.sponsorship This study was supported by a MRC Clinician Scientist [G0701911] and an Isaac Newton Trust award to G.K.M., and by the Cambridge NIHR Biomedical Research Centre; and by the European Union’s Horizon 2020 to F.K. [754462]. T.W.R. discloses consultancy with Cambridge Cognition, Unilever and Greenfield Bioventures; he receives royalties from Cambridge Cognition, research grants from Shionogi & Co and GlaxoSmithKline, and editorial honoraria from Springer Nature and Elsevier. None of these conflict with the findings reported in this manuscript. None of the other authors report any conflicts of interest. R.A.B. discloses consultancy with Living Cell Technologies; Novo Nordisk; BlueRock Therapeutics; Fujifilm Cellular Dynamics Inc; Aspen Neuroscience and UCB pharma and editorial honoraria from Springer Nature. None of these conflict with the findings reported in this manuscript.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Knolle F, Garofalo S, Viviani R, Justicia A, Ermakova AO, Blank H. Altered subcortical emotional salience processing differentiates parkinson's patients with and without psychotic symptoms. Neuroimage Clin. 2020; 27:102277. DOI: 10.1016/j.nicl.2020.102277
  • dc.identifier.doi http://dx.doi.org/10.1016/j.nicl.2020.102277
  • dc.identifier.issn 2213-1582
  • dc.identifier.uri http://hdl.handle.net/10230/45564
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754462
  • dc.rights Copyright © 2020 Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Parkinson, Malaltia de
  • dc.subject.other Subcortical emotional salience
  • dc.subject.other Ssychotic symptoms
  • dc.title Altered subcortical emotional salience processing differentiates parkinson's patients with and without psychotic symptoms
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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