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Impulsive-compulsive behaviours in Parkinson’s disease: a behavioural, neuroimaging and neurophysiological investigation

Martini, Alice

Impulsive-compulsive behaviours in Parkinson’s disease: a behavioural, neuroimaging and neurophysiological investigation Thumbnail


Authors

Alice Martini



Contributors

Nicola Edelstyn
Supervisor

Abstract

Background: Persons with Parkinson’s (PwP) may develop Impulsivecompulsive behaviours (ICBs) as side-effect of dopamine replacement therapy (DRT). The unresolved question addressed by this thesis is why only some PwP develop ICBs. This is an important clinical question that impacts on other populations, and has implications for incentive-driven decision-making theories. The thesis objectives are to integrate and extend the body of knowledge using systematic reviews, meta-analyses and original studies. The guiding framework is the use of multiple levels of analyses that include behavioural correlates (cognition, mood and motivation), brain circuits and neurophysiology. The underlying premise is that for any feature to be a reliable marker, it should be evident across multiple levels of analyses.

Method: Study 1 is a behavioural small-scale study of ICBs correlates that informs Study 3; Study 2 is a meta-analysis of behavioural correlates of ICBs; Study 3 is a behavioural multicentre replication study; Study 4 is a pilot neurophysiological study; Study 5 is a systematic review of structural and functional neural correlates of ICBs; Study 6 is a meta-analysis of striatal dopaminergic neurotransmission in ICBs.

Results: First, ICBs showed reduced negative feedback processing in the behavioural small-scale study, but not in the multicentre and in the neurophysiological studies. Second, ICBs showed increased functional activity and dopaminergic neurotransmission in reward processing brain areas in the systematic review and in the meta-analysis. Third, ICBs showed poorer cognitive control in the behavioural meta-analysis and in the multicentre study. The systematic review evidenced reduced frontostriatal connectivity, important for cognitive control. Forth, ICBs showed increased depression in all behavioural studies. Fifth, ICBs showed reduced dopamine transporter binding in the meta-analysis.

Conclusions: This thesis partially addressed the objective of understanding why only some PwP develop ICBs. A longitudinal study is required for understating whether correlates reflect pre-existing traits, DRT-related changes or both.

Thesis Type Thesis
Publicly Available Date Mar 28, 2024
Award Date 2022-06

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