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.

中文翻译：

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帕金森病伴冲动控制障碍的多巴胺和奖赏超敏反应。


帕金森病的冲动控制障碍是与多巴胺替代疗法相关的常见神经精神并发症。一些接受多巴胺激动剂治疗的患者会出现病理行为，例如赌博、强迫性饮食、购物或不受抑制的性行为，这可能对他们及其家人的生活产生严重影响。在这项研究中，我们研究了对奖励的过敏是否可能导致这些病理行为，以及多巴胺能药物如何影响这种行为。我们要求参与者尽快将目光转移到视觉目标上，以获得奖励。至关重要的是，所提供的奖励激励在不同的试验中有所不同。动机效应通过瞳孔测量和扫视速度来索引，并且对患者进行开启和关闭多巴胺能药物测试，使我们能够测量多巴胺能药物变化对奖励敏感性的影响。研究人员将 23 名有冲动控制障碍病史的帕金森病患者与 26 名没有这种行为的患者以及 31 名老年健康对照者进行了比较。有趣的是，据报道，大多数患有冲动控制障碍的患者除了冲动之外还存在行为冷漠。患有冲动控制障碍的个体还表现出对外源性金钱奖励提示的高度敏感性，无论是开启还是关闭（过夜戒断）多巴胺药物，这都以预期奖励时瞳孔扩张为指标。隔夜关闭多巴胺能药物并不能调节冲动控制障碍患者的瞳孔奖赏敏感性，而在对照患者中，当关闭多巴胺时，奖赏敏感性显着降低。这些影响与认知障碍或左旋多巴总当量剂量无关。 尽管多巴胺激动剂剂量确实调节瞳孔对奖赏的反应，但即使将多巴胺激动剂导致冲动控制障碍的患者排除在分析之外，结果模式也会重复。研究结果表明，对奖励的过度敏感可能是帕金森病中冲动控制障碍的一个促成因素。然而，当使用多巴胺药物时，患者组之间的奖励敏感性没有差异，这表明冲动控制障碍可能不会仅仅因为多巴胺能药物水平对奖励敏感性的直接影响而出现。这里描述的瞳孔奖赏敏感性测量提供了一种使用生理测量来区分患有冲动控制障碍的帕金森病患者与没有经历此类症状的患者的方法。此外，对对照患者的随访表明，通过奖励增加瞳孔调节可以预测未来出现冲动控制障碍的风险，从而可以为早期识别更有可能出现这些症状的患者提供潜力。