Institute of Psychiatry, Psychology and Neuroscience (IOPPN), King's College London, London, United Kingdom.
MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, London, United Kingdom.
Elife. 2019 Jul 10;8:e45045. doi: 10.7554/eLife.45045.
Working memory performance is thought to depend on both striatal dopamine 2/3 receptors (D2/3Rs) and task-induced functional organisation in key cortical brain networks. Here, we combine functional magnetic resonance imaging and D2/3R positron emission tomography in 51 healthy volunteers, to investigate the relationship between working memory performance, task-induced default mode network (DMN) functional connectivity changes, and striatal D2/3R availability. Increasing working memory load was associated with reduced DMN functional connectivity, which was itself associated with poorer task performance. Crucially, the magnitude of the DMN connectivity reduction correlated with striatal D2/3R availability, particularly in the caudate, and this relationship mediated the relationship between striatal D2/3R availability and task performance. These results inform our understanding of natural variation in working memory performance, and have implications for understanding age-related cognitive decline and cognitive impairments in neuropsychiatric disorders where dopamine signalling is altered.
工作记忆表现被认为依赖于纹状体多巴胺 2/3 受体（D2/3R）和关键皮质脑网络中任务诱导的功能组织。在这里，我们结合功能磁共振成像和 D2/3R 正电子发射断层扫描，在 51 名健康志愿者中进行研究，以调查工作记忆表现、任务诱导的默认模式网络（DMN）功能连接变化与纹状体 D2/3R 可用性之间的关系。增加工作记忆负荷与 DMN 功能连接的减少有关，而 DMN 功能连接的减少与较差的任务表现有关。至关重要的是，DMN 连接减少的幅度与纹状体 D2/3R 的可用性相关，特别是在尾状核，并且这种关系介导了纹状体 D2/3R 的可用性与任务表现之间的关系。这些结果为我们理解工作记忆表现的自然变化提供了信息，并为理解与多巴胺信号改变有关的神经精神障碍中的年龄相关认知衰退和认知障碍提供了启示。
