Mensen Armand, Poryazova Rositsa, Huegli Gordana, Baumann Christian R, Schwartz Sophie, Khatami Ramin
Department of Sleep Medicine, Clinic Barmelweid, 5017 Aargau, Switzerland.
Department of Neurology, University Hospital Zurich, 8006 Zurich, Switzerland.
PLoS One. 2015 Nov 23;10(11):e0142432. doi: 10.1371/journal.pone.0142432. eCollection 2015.
The proper functioning of the mesolimbic reward system is largely dependent on the neurotransmitter dopamine. Recent evidence suggests that the hypocretin system has significant projections to this reward system. We examined the distinct effects of reduced dopamine or reduced hypocretin levels on reward activity in patients with Parkinson's disease, dopamine deficient, as well as patients with narcolepsy-cataplexy, hypocretin depleted, and healthy controls. Participants performed a simple game-like task while high-density electroencephalography was recorded. Topography and timing of event-related potentials for both reward cue, and reward feedback was examined across the entire dataset. While response to reward cue was similar in all groups, two distinct time points were found to distinguish patients and controls for reward feedback. Around 160 ms both patient groups had reduced ERP amplitude compared to controls. Later at 250 ms, both patient groups also showed a clear event-related potential (ERP), which was absent in controls. The initial differences show that both patient groups show a similar, blunted response to reward delivery. The second potential corresponds to the classic feedback-related negativity (FRN) potential which relies on dopamine activity and reflects reward prediction-error signaling. In particular the mismatch between predicted reward and reward subsequently received was significantly higher in PD compared to NC, independent of reward magnitude and valence. The intermediate FRN response in NC highlights the contribution of hypocretin in reward processing, yet also shows that this is not as detrimental to the reward system as in Parkinson's. Furthermore, the inability to generate accurate predictions in NC may explain why hypocretin deficiency mediates cataplexy triggered by both positive and negative emotions.
中脑边缘奖赏系统的正常运作很大程度上依赖于神经递质多巴胺。最近的证据表明，下丘脑分泌素系统对该奖赏系统有重要投射。我们研究了多巴胺减少或下丘脑分泌素水平降低对帕金森病患者（多巴胺缺乏）、发作性睡病-猝倒症患者（下丘脑分泌素缺乏）以及健康对照者奖赏活动的不同影响。参与者在进行一项简单的类似游戏的任务时，记录高密度脑电图。在整个数据集中检查了奖赏线索和奖赏反馈的事件相关电位的地形图和时间。虽然所有组对奖赏线索的反应相似，但发现有两个不同的时间点可区分患者和对照者的奖赏反馈。在约160毫秒时，与对照组相比，两个患者组的事件相关电位振幅均降低。在稍后的250毫秒时，两个患者组也显示出明显的事件相关电位（ERP），而对照组中没有。最初的差异表明，两个患者组对奖赏发放都表现出相似的、减弱的反应。第二个电位对应于经典的反馈相关负波（FRN）电位，它依赖于多巴胺活动并反映奖赏预测误差信号。特别是，与发作性睡病患者相比，帕金森病患者中预测奖赏与随后获得的奖赏之间的不匹配显著更高，与奖赏大小和效价无关。发作性睡病患者的中间FRN反应突出了下丘脑分泌素在奖赏处理中的作用，但也表明这对奖赏系统的损害不像在帕金森病中那样严重。此外，发作性睡病患者无法做出准确预测可能解释了为什么下丘脑分泌素缺乏会介导由积极和消极情绪引发的猝倒。
