title: Dopamine-agonists and impulsivity in Parkinson's disease: impulsive choices vs. impulsive actions.
abstract: The control of impulse behavior is a multidimensional concept subdivided into separate subcomponents, which are thought to represent different underlying mechanisms due to either disinhibitory processes or poor decision-making. In patients with Parkinson's disease (PD), dopamine-agonist (DA) therapy has been associated with increased impulsive behavior. However, the relationship among these different components in the disease and the role of DA is not well understood. In this imaging study, we investigated in PD patients the effects of DA medication on patterns of brain activation during tasks testing impulsive choices and actions. Following overnight withdrawal of antiparkinsonian medication, PD patients were studied with a H2 ((15)) O PET before and after administration of DA (1 mg of pramipexole), while they were performing the delay discounting task (DDT) and the GoNoGo Task (GNG). We observed that pramipexole augmented impulsivity during DDT, depending on reward magnitude and activated the medial prefrontal cortex and posterior cingulate cortex and deactivated ventral striatum. In contrast, the effect of pramipexole during the GNG task was not significant on behavioral performance and involved different areas (i.e., lateral prefrontal cortex). A voxel-based correlation analysis revealed a significant negative correlation between the discounting value (k) and the activation of medial prefrontal cortex and posterior cingulate suggesting that more impulsive patients had less activation in those cortical areas. Here we report how these different subcomponents of inhibition/impulsivity are differentially sensitive to DA treatment with pramipexole influencing mainly the neural network underlying impulsive choices but not impulsive action.
authors.affiliation: Morton and Gloria Shulman Movement Disorder Unit, E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada.
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonelli
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Ko
authors.forename: Janis
authors.initials: J
authors.lastname: Miyasaki
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Lang
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Franco
authors.initials: F
authors.lastname: Valzania
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Ray
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Strafella
mesh_terms: D052160:Benzothiazoles / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D049268:Positron-Emission Tomography; D000077487:Pramipexole; D012201:Reward; D012815:Signal Processing, Computer-Assisted; D013647:Task Performance and Analysis
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D000077487:Pramipexole
keywords: Parkinson's disease; dopamine agonists; impulsivity
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