Dopamine‐agonists and impulsivity in Parkinson's disease: Impulsive choices vs. impulsive actions

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. Hum Brain Mapp 35:2499–2506, 2014. © 2013 Wiley Periodicals, Inc.

[1]  W. Bickel,et al.  The neuroeconomics of nicotine dependence: A preliminary functional magnetic resonance imaging study of delay discounting of monetary and cigarette rewards in smokers , 2012, Psychiatry Research: Neuroimaging.

[2]  K. Sasaki,et al.  Suppression of visually initiated hand movement by stimulation of the prefrontal cortex in the monkey , 1989, Brain Research.

[3]  The Unified Parkinson's Disease Rating Scale (UPDRS): Status and recommendations , 2003, Movement disorders : official journal of the Movement Disorder Society.

[4]  Y. Miyashita,et al.  Common inhibitory mechanism in human inferior prefrontal cortex revealed by event-related functional MRI. , 1999, Brain : a journal of neurology.

[5]  George Ainslie,et al.  Frontoparietal cortical activity of methamphetamine‐dependent and comparison subjects performing a delay discounting task , 2007, Human brain mapping.

[6]  J. Cummings,et al.  The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment , 2005, Journal of the American Geriatrics Society.

[7]  S. Houle,et al.  Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD , 2010, Neurology.

[8]  B. Sahakian,et al.  The neuropsychiatry of impulsivity , 2007, Current opinion in psychiatry.

[9]  Karl J. Friston,et al.  A unified statistical approach for determining significant signals in images of cerebral activation , 1996, Human brain mapping.

[10]  S. Houle,et al.  Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study. , 2009, Brain : a journal of neurology.

[11]  T. Robbins,et al.  Impulsive Choice Induced in Rats by Lesions of the Nucleus Accumbens Core , 2001, Science.

[12]  J. C. Crowley,et al.  Saccade Reward Signals in Posterior Cingulate Cortex , 2003, Neuron.

[13]  Martin P. Paulus,et al.  Time and decision making: differential contribution of the posterior insular cortex and the striatum during a delay discounting task , 2007, Experimental Brain Research.

[14]  K. K. Harnishfeger,et al.  The development of cognitive inhibition: Theories, definitions, and research evidence , 1995 .

[15]  W. Bickel,et al.  Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. , 1999, Journal of experimental psychology. General.

[16]  J. Missimer,et al.  Reward mechanisms in the brain and their role in dependence: evidence from neurophysiological and neuroimaging studies , 2001, Brain Research Reviews.

[17]  E. Barratt,et al.  The biological basis of impulsiveness: the significance of timing and rhythm disorders , 1983 .

[18]  Karl J. Friston,et al.  A multivariate analysis of PET activation studies , 1996, Human brain mapping.

[19]  Antonio P. Strafella,et al.  Impulsivity and Parkinson's disease: More than just disinhibition , 2011, Journal of the Neurological Sciences.

[20]  Samuel M. McClure,et al.  Separate Neural Systems Value Immediate and Delayed Monetary Rewards , 2004, Science.

[21]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[22]  S. Houle,et al.  Stimulation of the subthalamic nucleus and impulsivity: Release your horses , 2009, Annals of neurology.

[23]  K. Kirby,et al.  Concave utility, transaction costs, and risk in measuring discounting of delayed rewards. , 2003, Journal of experimental psychology. Learning, memory, and cognition.

[24]  A. Aron The Neural Basis of Inhibition in Cognitive Control , 2007, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[25]  J. Richards,et al.  Acute Administration of d-Amphetamine Decreases Impulsivity in Healthy Volunteers , 2002, Neuropsychopharmacology.

[26]  Mark Hallett,et al.  Impulse control disorders in Parkinson's disease: recent advances. , 2011, Current opinion in neurology.

[27]  Ji Hyun Ko,et al.  Extrastriatal dopaminergic abnormalities of DA homeostasis in Parkinson's patients with medication-induced pathological gambling: A [11C] FLB-457 and PET study , 2012, Neurobiology of Disease.

[28]  H. de Wit,et al.  Delay or probability discounting in a model of impulsive behavior: effect of alcohol. , 1999, Journal of the experimental analysis of behavior.

[29]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[30]  L. Wasserman,et al.  Operating characteristics and extensions of the false discovery rate procedure , 2002 .

[31]  A. Nambu,et al.  No-go activity in the frontal association cortex of human subjects , 1993, Neuroscience Research.

[32]  M. Paulus,et al.  Decision making, impulsivity and time perception , 2008, Trends in Cognitive Sciences.

[33]  Michael J. Frank,et al.  Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism , 2007, Science.

[34]  S. Mitchell,et al.  Measures of impulsivity in cigarette smokers and non-smokers , 1999, Psychopharmacology.

[35]  A. Strafella,et al.  Continuous theta burst stimulation of right dorsolateral prefrontal cortex induces changes in impulsivity level , 2010, Brain Stimulation.

[36]  A. Damasio,et al.  Emotion, decision making and the orbitofrontal cortex. , 2000, Cerebral cortex.