Behavioural and Clinical Neurosciences Institute, Department of Experimental Psychology, Downing Site, University of Cambridge, Cambridge CB2 3EB, UK.
Brain. 2011 May;134(Pt 5):1438-46. doi: 10.1093/brain/awr080.
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.
冲动控制障碍在帕金森病中很常见,13.6%的患者会出现这种障碍。我们使用药理学干预和一项新颖的冒险任务,同时进行功能磁共振成像,研究了伴有和不伴有冲动控制障碍的帕金森病患者中多巴胺激动剂与冒险行为之间的关系。在功能磁共振成像期间,受试者在两种具有相同预期价值的选择之间进行选择:“确定”选择和具有适度风险的“赌博”选择。为了开始每次试验,在“增益”条件下,个体从 0 开始,而在“损失”条件下,个体从“确定”金额以下的-50 美元开始。每次赌博的最大和最小结果之间的差异(即范围)用作风险指数(“赌博风险”)。我们对 16 名健康志愿者进行了行为测试。对 14 名冲动控制障碍(赌博成瘾或强迫性购物)和 14 名匹配的帕金森病对照者进行了多巴胺激动剂治疗的 ON 和 OFF 测试。与帕金森病对照者相比,患有冲动控制障碍的患者在“增益”条件下做出了更冒险的选择,同时眶额皮层和前扣带皮层的活动减少,而在帕金森病对照者中则观察到相反的情况。在患有冲动控制障碍的患者中,多巴胺激动剂与风险敏感性增强有关,同时纹状体活动减少,而帕金森病对照组则相反。患有冲动控制障碍的患者似乎存在冒险选择的偏见,而不受损失厌恶的影响。多巴胺激动剂可能通过损害纹状体中的风险评估,增强冲动控制障碍患者对风险的敏感性。我们的结果提供了一个潜在的解释,说明为什么多巴胺激动剂可能会导致易感个体无意识地偏向风险。