Antonelli Francesca, Ko Ji Hyun, Miyasaki Janis, Lang Anthony E, Houle Sylvain, Valzania Franco, Ray Nicola J, Strafella Antonio P
Morton and Gloria Shulman Movement Disorder Unit, E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada.
Hum Brain Mapp. 2014 Jun;35(6):2499-506. doi: 10.1002/hbm.22344. Epub 2013 Sep 3.
The control of impulse behavior is a multidimensional concept subdivided into separate subcomponents, which are thought to represent different underlying mechanisms due to either disinhibitory processes or poor decision-making. In patients with Parkinson's disease (PD), dopamine-agonist (DA) therapy has been associated with increased impulsive behavior. However, the relationship among these different components in the disease and the role of DA is not well understood. In this imaging study, we investigated in PD patients the effects of DA medication on patterns of brain activation during tasks testing impulsive choices and actions. Following overnight withdrawal of antiparkinsonian medication, PD patients were studied with a H2 ((15)) O PET before and after administration of DA (1 mg of pramipexole), while they were performing the delay discounting task (DDT) and the GoNoGo Task (GNG). We observed that pramipexole augmented impulsivity during DDT, depending on reward magnitude and activated the medial prefrontal cortex and posterior cingulate cortex and deactivated ventral striatum. In contrast, the effect of pramipexole during the GNG task was not significant on behavioral performance and involved different areas (i.e., lateral prefrontal cortex). A voxel-based correlation analysis revealed a significant negative correlation between the discounting value (k) and the activation of medial prefrontal cortex and posterior cingulate suggesting that more impulsive patients had less activation in those cortical areas. Here we report how these different subcomponents of inhibition/impulsivity are differentially sensitive to DA treatment with pramipexole influencing mainly the neural network underlying impulsive choices but not impulsive action.
冲动行为的控制是一个多维度概念,可细分为不同的子成分,由于去抑制过程或决策能力差,这些子成分被认为代表了不同的潜在机制。在帕金森病(PD)患者中,多巴胺激动剂(DA)治疗与冲动行为增加有关。然而,在该疾病中这些不同成分之间的关系以及DA的作用尚未得到充分理解。在这项影像学研究中,我们在PD患者中研究了DA药物对测试冲动选择和行动任务期间大脑激活模式的影响。在隔夜停用抗帕金森病药物后,对PD患者在服用DA(1毫克普拉克索)之前和之后进行H2((15))O PET研究,同时他们执行延迟折扣任务(DDT)和停止信号任务(GNG)。我们观察到,普拉克索在DDT期间增强了冲动性,这取决于奖励大小,并激活了内侧前额叶皮质和后扣带回皮质,同时使腹侧纹状体失活。相比之下,普拉克索在GNG任务期间对行为表现的影响不显著,且涉及不同区域(即外侧前额叶皮质)。基于体素的相关性分析显示,折扣值(k)与内侧前额叶皮质和后扣带回的激活之间存在显著负相关,这表明冲动性更强的患者在这些皮质区域的激活较少。在此我们报告了抑制/冲动性的这些不同子成分如何对普拉克索的DA治疗有不同的敏感性,普拉克索主要影响冲动选择而非冲动行动背后的神经网络。