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1.  Impulsive choice and response in dopamine agonist-related impulse control behaviors 
Psychopharmacology  2009;207(4):645-659.
Rationale
Dopaminergic medication-related Impulse Control Disorders (ICDs) such as pathological gambling and compulsive shopping have been reported in Parkinson disease (PD).
Hypothesis
We hypothesized that dopamine agonists (DAs) would be associated with greater impulsive choice, or greater discounting of delayed rewards, in PD patients with ICDs (PDI).
Methods
Fourteen PDI patients, 14 PD controls without ICDs and 16 medication-free matched normal controls were tested on (i) the Experiential Discounting Task (EDT), a feedback-based intertemporal choice task, (ii) spatial working memory and (iii) attentional set shifting. The EDT was used to assess impulsivity choice (hyperbolic K-value), reaction time (RT) and decision conflict RT (the RT difference between high conflict and low conflict choices). PDI patients and PD controls were tested on and off DA.
Results
On the EDT, there was a group by medication interaction effect [F(1,26)=5.62; p=0.03] with pairwise analyses demonstrating that DA status was associated with increased impulsive choice in PDI patients (p=0.02) but not in PD controls (p=0.37). PDI patients also had faster RT compared to PD controls F(1,26)=7.51 p=0.01]. DA status was associated with shorter RT [F(3,24)=8.39, p=0.001] and decision conflict RT [F(1,26)=6.16, p=0.02] in PDI patients but not in PD controls. There were no correlations between different measures of impulsivity. PDI patients on DA had greater spatial working memory impairments compared to PD controls on DA (t=2.13, df=26, p=0.04).
Conclusion
Greater impulsive choice, faster RT, faster decision conflict RT and executive dysfunction may contribute to ICDs in PD.
doi:10.1007/s00213-009-1697-y
PMCID: PMC3676926  PMID: 19838863
dopamine agonist; gambling; impulse control; Parkinson disease; delay discounting
2.  Non-substance Addictive Behaviors in Youth: Pathological Gambling and Problematic Internet Use 
doi:10.1016/j.chc.2010.03.012
PMCID: PMC3673531  PMID: 20682225
Adolescence; Gambling; Internet; Computer Use; Treatment; Prevention
3.  Dopamine agonists and risk: impulse control disorders in Parkinson's; disease 
Brain  2011;134(5):1438-1446.
Impulse control disorders are common in Parkinson's; disease, occurring in 13.6% of patients. Using a pharmacological manipulation and a novel risk taking task while performing functional magnetic resonance imaging, we investigated the relationship between dopamine agonists and risk taking in patients with Parkinson's; disease with and without impulse control disorders. During functional magnetic resonance imaging, subjects chose between two choices of equal expected value: a ‘Sure’ choice and a ‘Gamble’ choice of moderate risk. To commence each trial, in the ‘Gain’ condition, individuals started at $0 and in the ‘Loss’ condition individuals started at −$50 below the ‘Sure’ amount. The difference between the maximum and minimum outcomes from each gamble (i.e. range) was used as an index of risk (‘Gamble Risk’). Sixteen healthy volunteers were behaviourally tested. Fourteen impulse control disorder (problem gambling or compulsive shopping) and 14 matched Parkinson's; disease controls were tested ON and OFF dopamine agonists. Patients with impulse control disorder made more risky choices in the ‘Gain’ relative to the ‘Loss’ condition along with decreased orbitofrontal cortex and anterior cingulate activity, with the opposite observed in Parkinson's; disease controls. In patients with impulse control disorder, dopamine agonists were associated with enhanced sensitivity to risk along with decreased ventral striatal activity again with the opposite in Parkinson's; disease controls. Patients with impulse control disorder appear to have a bias towards risky choices independent of the effect of loss aversion. Dopamine agonists enhance sensitivity to risk in patients with impulse control disorder possibly by impairing risk evaluation in the striatum. Our results provide a potential explanation of why dopamine agonists may lead to an unconscious bias towards risk in susceptible individuals.
doi:10.1093/brain/awr080
PMCID: PMC3097893  PMID: 21596771
Parkinson's; disease; dopamine; gambling; decision making; risk
4.  Emotional stimuli and motor conversion disorder 
Brain  2010;133(5):1526-1536.
Conversion disorder is characterized by neurological signs and symptoms related to an underlying psychological issue. Amygdala activity to affective stimuli is well characterized in healthy volunteers with greater amygdala activity to both negative and positive stimuli relative to neutral stimuli, and greater activity to negative relative to positive stimuli. We investigated the relationship between conversion disorder and affect by assessing amygdala activity to affective stimuli. We conducted a functional magnetic resonance imaging study using a block design incidental affective task with fearful, happy and neutral face stimuli and compared valence contrasts between 16 patients with conversion disorder and 16 age- and gender-matched healthy volunteers. The patients with conversion disorder had positive movements such as tremor, dystonia or gait abnormalities. We also assessed functional connectivity between the amygdala and regions associated with motor preparation. A group by affect valence interaction was observed. Post hoc analyses revealed that whereas healthy volunteers had greater right amygdala activity to fearful versus neutral compared with happy versus neutral as expected, there were no valence differences in patients with conversion disorder. There were no group differences observed. The time course analysis also revealed greater right amygdala activity in patients with conversion disorder for happy stimuli (t = 2.96, P = 0.006) (with a trend for fearful stimuli, t = 1.81, P = 0.08) compared with healthy volunteers, with a pattern suggestive of impaired amygdala habituation even when controlling for depressive and anxiety symptoms. Using psychophysiological interaction analysis, patients with conversion disorder had greater functional connectivity between the right amygdala and the right supplementary motor area during both fearful versus neutral, and happy versus neutral ‘stimuli’ compared with healthy volunteers. These results were confirmed with Granger Causality Modelling analysis indicating a directional influence from the right amygdala to the right supplementary motor area to happy stimuli (P < 0.05) with a similar trend observed to fearful stimuli (P = 0.07). Our data provide a potential neural mechanism that may explain why psychological or physiological stressors can trigger or exacerbate conversion disorder symptoms in some patients. Greater functional connectivity of limbic regions influencing motor preparatory regions during states of arousal may underlie the pathophysiology of motor conversion symptoms.
doi:10.1093/brain/awq054
PMCID: PMC2859149  PMID: 20371508
conversion disorder; arousal; amydala; affect; psychogenic movement disorder
5.  Mechanisms underlying dopamine-mediated reward bias in compulsive behaviors 
Neuron  2010;65(1):135.
Summary
Pathological behaviors such as problem gambling or shopping are characterized by compulsive choice despite alternative options and negative costs. Reinforcement learning algorithms allow a computation of prediction error, a comparison of actual and expected outcomes, which updates our predictions and influence our subsequent choices. Using a reinforcement learning model, we show data consistent with the idea that dopamine agonists in susceptible individuals with Parkinson's disease increase the rate of learning from gain outcomes. Dopamine agonists also increase striatal prediction error activity thus signifying a “better than expected” outcome. Thus, our findings are consistent with a model whereby a distorted estimation of the gain cue underpins a choice bias towards gains.
doi:10.1016/j.neuron.2009.12.027
PMCID: PMC2822730  PMID: 20152119

Results 1-5 (5)