Task-induced functional brain connectivity mediates the relationship between striatal D2/3 receptors and working memory

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.