Abstract
Impulse control disorders in Parkinson's disease are common neuropsychiatric complications associated with dopamine replacement therapy. Some patients treated with dopamine agonists develop pathological behaviours, such as gambling, compulsive eating, shopping, or disinhibited sexual behaviours, which can have a severe impact on their lives and that of their families. In this study we investigated whether hypersensitivity to reward might contribute to these pathological behaviours and how this is influenced by dopaminergic medication. We asked participants to shift their gaze to a visual target as quickly as possible, in order to obtain reward. Critically, the reward incentive on offer varied over trials. Motivational effects were indexed by pupillometry and saccadic velocity, and patients were tested ON and OFF dopaminergic medication, allowing us to measure the effect of dopaminergic medication changes on reward sensitivity. Twenty-three Parkinson's disease patients with a history of impulse control disorders were compared to 26 patients without such behaviours, and 31 elderly healthy controls. Intriguingly, behavioural apathy was reported alongside impulsivity in the majority of patients with impulse control disorders. Individuals with impulse control disorders also exhibited heightened sensitivity to exogenous monetary rewards cues both ON and OFF (overnight withdrawal) dopamine medication, as indexed by pupillary dilation in anticipation of reward. Being OFF dopaminergic medication overnight did not modulate pupillary reward sensitivity in impulse control disorder patients, whereas in control patients reward sensitivity was significantly reduced when OFF dopamine. These effects were independent of cognitive impairment or total levodopa equivalent dose. Although dopamine agonist dose did modulate pupillary responses to reward, the pattern of results was replicated even when patients with impulse control disorders on dopamine agonists were excluded from the analysis. The findings suggest that hypersensitivity to rewards might be a contributing factor to the development of impulse control disorders in Parkinson's disease. However, there was no difference in reward sensitivity between patient groups when ON dopamine medication, suggesting that impulse control disorders may not emerge simply because of a direct effect of dopaminergic drug level on reward sensitivity. The pupillary reward sensitivity measure described here provides a means to differentiate, using a physiological measure, Parkinson's disease patients with impulse control disorder from those who do not experience such symptoms. Moreover, follow-up of control patients indicated that increased pupillary modulation by reward can be predictive of the risk of future emergence of impulse control disorders and may thereby provide the potential for early identification of patients who are more likely to develop these symptoms.
Highlights
Idiopathic Parkinson’s disease is known to be associated with a wide range of non-motor symptoms including potential impairment in cognition, mood and motivation (Chaudhuri et al, 2011, 2006)
There were no significant differences between the PD + Impulse control disorders (ICDs) and PD-no-ICD groups in age, cognitive impairment (MoCA), depression (BDI) or anhedonia (SHAPS/Temporal Experience of Pleasure Scale (TEPS)), or anxiety (Depression Anxiety Stress Scale, DASS) (Table 1)
There was no significant difference between PD + ICD and PD-no-ICD groups in dopamine agonist levodopa equivalent dose (DA-LEDD) and there were no significant correlations between impulsivity (UPPS-P) or apathy (LARS) with duration of symptoms, duration of disease, or age
Summary
Idiopathic Parkinson’s disease is known to be associated with a wide range of non-motor symptoms including potential impairment in cognition, mood and motivation (Chaudhuri et al, 2011, 2006). Impulse control disorders (ICDs) are recognized to be important neuropsychiatric complications in Parkinson’s disease (Okai et al, 2011; Averbeck et al, 2014; Goerlich-Dobre et al, 2014; Ricciardi et al, 2016; Voon et al, 2017; Weintraub and Mamikonyan, 2019), with the most common ICDs being compulsive buying, gambling, eating and disinhibited sexual behaviour (Housden et al, 2010; Weintraub et al, 2010; Piray et al, 2014; Erga et al, 2017) These can have devastating personal, financial and social consequences, contributing to the breakup of families and loss of life savings (Leroi et al, 2012b; Bartlett, 2013; Okai et al, 2013; Stenberg, 2016; Erga et al, 2017). The difference in reported prevalence most likely reflects a recent shift in focus from categorical assessments of these behaviours to a more dimensional approach, differences in definitions, assessment methodology and sociocultural characteristics of the study sample (Callesen et al, 2013; Sharma et al, 2015; Vela et al, 2016; Antonini et al, 2017; Molde et al, 2018; Baig et al, 2019; Evans et al, 2019)
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