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.

Multi-facetted impulsivity following nigral degeneration and dopamine replacement therapy

“…Importantly, our results showing that PPX differentially alters impulsive actions and waiting impulsivity are in agreement with a recent study demonstrating that dimensions of impulsivity are not equally affected by PPX in PD patients (Antonelli et al., 2014). This effect of PPX is also in line with clinical and neurocomputational results demonstrating that enhanced D2 stimulation favors a “Go” bias and decreases the ability to suppress inappropriate responses (“NoGo”) (Frank et al., 2004).…”

Adolescent methylphenidate treatment differentially alters adult impulsivity and hyperactivity in the Spontaneously Hypertensive Rat model of ADHD

“…Impulsivity, including response inhibition deficits under DRL, is associated with decreased DA function in prefrontal cortex of adult outbred rats (Sokolowski and Salamone 1994, Peterson, Wolf et al 2003, Antonelli, Ko et al 2013, Pardey, Kumar et al 2013, Simon, Beas et al 2013). Both DAT and NET clear extracellular DA in prefrontal cortex (Moron, Brockington et al 2002, Berridge, Devilbiss et al 2006).…”

Dementia, Decision Making, and Capacity

“…Patients with ICD given dopamine agonists performed worse on a delayed discounting task, which involves value-based decision-making, but normal on a tests of executive function, compared to Parkinson’s patients without ICD’s 66,67 . In fact, patients with ICD in general perform better on tests of executive function compared with patients without ICD’s 68 .…”