Claassen Daniel O, van den Wildenberg Wery P M, Harrison Madaline B, van Wouwe Nelleke C, Kanoff Kristen, Neimat Joseph S, Wylie Scott A
Department of Neurology, Vanderbilt University, Nashville, TN, United States.
Department of Psychology, University of Amsterdam, Netherlands.
Pharmacol Biochem Behav. 2015 Feb;129:19-25. doi: 10.1016/j.pbb.2014.11.017. Epub 2014 Nov 29.
Parkinson disease (PD) patients treated with dopamine agonist therapy can develop maladaptive reward-driven behaviors, known as impulse control disorder (ICD). In this study, we assessed if ICD patients have evidence of motor-impulsivity.
We used the stop-signal task in a cohort of patients with and without active symptoms of ICD to evaluate motor-impulsivity. Of those with PD, 12 were diagnosed with ICD symptoms (PD-ICD) and were assessed before clinical reduction of dopamine agonist medication; 12 were without symptoms of ICD [PD-control] and taking equivalent dosages of dopamine agonist. Levodopa, if present, was maintained in both settings. Groups were similar in age, duration, and severity of motor symptoms, levodopa co-therapy, and total levodopa daily dose. All were tested in the dopamine agonist medicated and acutely withdrawn (24 h) state, in a counterbalanced manner. Primary outcome measures were mean reaction time to correct go trials (go reaction time), and mean stop-signal reaction time (SSRT).
ICD patients produce faster SSRT than both Healthy Controls, and PD-Controls. Faster SSRT in ICD patients is apparent in both dopamine agonist medication states. Also, we show unique dopamine medication effects on Go Reaction time (GoRT). In dopamine agonist monotherapy patients, dopamine agonist administration speeds GoRT. Conversely, in those with levodopa co-therapy, dopamine agonist administration slows.
PD patients with active ICD symptoms are significantly faster at stopping initiated motor actions, and this is not altered by acute dopamine agonist withdrawal. In addition, the effect of dopamine agonist on GoRT is strongly influenced by the presence or absence of levodopa, even though levodopa co-therapy does not appear to influence SSRT. We discuss these findings as they pertain to the multifaceted definition of 'impulsivity,' the lack of evidence for motor-impulsivity in PD-ICD, and dopamine effects on motor-control in PD.
接受多巴胺激动剂治疗的帕金森病(PD)患者可能会出现适应不良的奖励驱动行为,即冲动控制障碍(ICD)。在本研究中,我们评估了ICD患者是否有运动冲动的证据。
我们在一组有或无ICD活动症状的患者中使用停止信号任务来评估运动冲动。在那些患有PD的患者中,12例被诊断为有ICD症状(PD-ICD),并在临床减少多巴胺激动剂药物治疗之前进行评估;12例无ICD症状[PD对照组],服用等量的多巴胺激动剂。如有左旋多巴,在两种情况下均维持使用。两组在年龄、病程、运动症状严重程度、左旋多巴联合治疗以及左旋多巴每日总剂量方面相似。所有患者均在多巴胺激动剂用药和急性撤药(24小时)状态下以平衡的方式进行测试。主要结局指标是正确的执行试验的平均反应时间(执行反应时间)和平均停止信号反应时间(SSRT)。
ICD患者的SSRT比健康对照组和PD对照组都要快。ICD患者更快的SSRT在两种多巴胺激动剂用药状态下均很明显。此外,我们显示了多巴胺药物对执行反应时间(GoRT)的独特影响。在多巴胺激动剂单药治疗的患者中,给予多巴胺激动剂会加快GoRT。相反,在接受左旋多巴联合治疗的患者中,给予多巴胺激动剂会使其减慢。
有活跃ICD症状的PD患者在停止已启动的运动动作方面明显更快,并且这不会因急性撤用多巴胺激动剂而改变。此外,多巴胺激动剂对GoRT的影响受到左旋多巴存在与否的强烈影响,尽管左旋多巴联合治疗似乎不影响SSRT。我们讨论这些发现,因为它们与“冲动性”的多方面定义、PD-ICD中缺乏运动冲动的证据以及多巴胺对PD运动控制的影响有关。