Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behavior, Kapittelweg 29, 6525 EN Nijmegen, The Netherlands.
Neuroimage. 2012 Feb 15;59(4):3339-46. doi: 10.1016/j.neuroimage.2011.11.073. Epub 2011 Dec 6.
Dopamine has been implicated in reward-related impulsivity, but the exact relationship between dopamine, reward and impulsivity in humans remains unknown. We address this question in Parkinson's disease (PD), which is characterized by severe dopamine depletion. PD is associated primarily with motor and cognitive inflexibility, but can also be accompanied by reward-related impulsivity. This paradoxical symptom of PD has often been attributed to dopaminergic overstimulation by antiparkinson medication, which is necessary to relieve the motor and cognitive inflexibility. However, factors other than medication may also contribute to aberrant impact of reward. Here we assess whether cognitive inflexibility and aberrant reward impact in PD are two sides of the same coin, namely dopamine cell loss. To measure dopamine cell loss, we employed (123)I-FP-CIT Single Photon Emission Computed Tomography (SPECT) in 32 PD patients (10 never-medicated patients and 22 patients after withdrawal of all medication for >12h) and related the values to behavior on a rewarded task-switching paradigm. Dopamine cell loss was associated not only with cognitive inflexibility (under low reward), but also with aberrant impact of reward. These effects could not be attributed to medication use. Relative to controls (n=26), aberrant reward processing in PD was particularly expressed as reduced capacity to maintain (i.e., repeat) the current task-set under high reward. Our findings demonstrate that factors intrinsically related to PD may underlie the paradoxical symptoms of inflexibility and reward-related impulsivity in PD. The present results concur with observations that low baseline dopamine states predispose to drug and other addictions.
多巴胺与奖赏相关的冲动性有关，但人类多巴胺、奖赏和冲动性之间的确切关系仍不清楚。我们在帕金森病（PD）中解决了这个问题，PD 的特征是多巴胺严重耗竭。PD 主要与运动和认知灵活性差有关，但也可能伴有与奖赏相关的冲动性。PD 的这种矛盾症状通常归因于抗帕金森病药物的多巴胺过度刺激，这种药物对于缓解运动和认知灵活性差是必要的。然而，除了药物之外，其他因素也可能导致奖赏的异常影响。在这里，我们评估 PD 中的认知灵活性和异常奖赏影响是否是同一枚硬币的两面，即多巴胺细胞丢失。为了测量多巴胺细胞丢失，我们在 32 名 PD 患者（10 名从未接受过药物治疗的患者和 22 名停药> 12 小时的患者）中使用（123）I-FP-CIT 单光子发射计算机断层扫描（SPECT），并将这些值与奖赏任务转换范式中的行为相关联。多巴胺细胞丢失不仅与认知灵活性差（在低奖赏下）有关，还与奖赏的异常影响有关。这些影响不能归因于药物的使用。与对照组（n=26）相比，PD 中异常的奖赏处理表现为在高奖赏下维持（即重复）当前任务集的能力降低。我们的研究结果表明，与 PD 固有相关的因素可能是 PD 中灵活性和与奖赏相关的冲动性的矛盾症状的基础。目前的结果与观察结果一致，即低基线多巴胺状态易导致药物和其他成瘾。
