Department of Psychology, University of Lübeck, 23562 Lübeck, Germany; Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
Department of Psychology, University of Lübeck, 23562 Lübeck, Germany; Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.
Neuroimage. 2018 May 15;172:341-356. doi: 10.1016/j.neuroimage.2018.01.048. Epub 2018 Feb 2.
Dopamine underlies important aspects of cognition, and has been suggested to boost cognitive performance. However, how dopamine modulates the large-scale cortical dynamics during cognitive performance has remained elusive. Using functional MRI during a working memory task in healthy young human listeners, we investigated the effect of levodopa (l-dopa) on two aspects of cortical dynamics, blood oxygen-level-dependent (BOLD) signal variability and the functional connectome of large-scale cortical networks. We here show that enhanced dopaminergic signaling modulates the two potentially interrelated aspects of large-scale cortical dynamics during cognitive performance, and the degree of these modulations is able to explain inter-individual differences in l-dopa-induced behavioral benefits. Relative to placebo, l-dopa increased BOLD signal variability in task-relevant temporal, inferior frontal, parietal and cingulate regions. On the connectome level, however, l-dopa diminished functional integration across temporal and cingulo-opercular regions. This hypo-integration was expressed as a reduction in network efficiency and modularity in more than two thirds of the participants and to different degrees. Hypo-integration co-occurred with relative hyper-connectivity in paracentral lobule and precuneus, as well as posterior putamen. Both, l-dopa-induced BOLD signal variability modulation and functional connectome modulations proved predictive of an individual's l-dopa-induced benefits in behavioral performance, namely response speed and perceptual sensitivity. Lastly, l-dopa-induced modulations of BOLD signal variability were correlated with l-dopa-induced modulation of nodal connectivity and network efficiency. Our findings underline the role of dopamine in maintaining the dynamic range of, and communication between, cortical systems, and their explanatory power for inter-individual differences in benefits from dopamine during cognitive performance.
多巴胺是认知的重要基础，并且被认为可以提高认知表现。然而，多巴胺如何调节认知表现期间的皮质大范围动力学仍然难以捉摸。在健康的年轻人类听众进行工作记忆任务期间使用功能磁共振成像，我们研究了左旋多巴（l-dopa）对皮质大范围动力学的两个方面的影响，即血氧水平依赖性（BOLD）信号变异性和大尺度皮质网络的功能连接组。我们在这里表明，增强的多巴胺能信号调节认知表现期间大尺度皮质动力学的两个潜在相关方面，并且这些调节的程度能够解释 l-dopa 诱导的行为益处的个体间差异。与安慰剂相比，l-dopa 增加了与任务相关的颞叶、下额叶、顶叶和扣带回区域的 BOLD 信号变异性。然而，在连接组水平上，l-dopa 降低了颞叶和扣带前回区域之间的功能整合。这种低整合表现为超过三分之二的参与者的网络效率和模块性降低，并且程度不同。低整合与中后顶叶和旁中央小叶以及后壳核的相对超连接同时发生。BOLD 信号变异性诱导的 l-dopa 调制和功能连接组调制都证明可以预测个体的 l-dopa 诱导的行为表现，即反应速度和感知敏感性的益处。最后，BOLD 信号变异性诱导的 l-dopa 调制与节点连接和网络效率诱导的 l-dopa 调制相关。我们的研究结果强调了多巴胺在维持皮质系统之间的动态范围和通讯中的作用，以及它们在认知表现期间多巴胺对个体间差异的解释力。
