Conclusions
This study shows that D2 receptor activation could modulate the fronto-subthalamic pathway during sequential working memory. The D2/3 receptor agonist pramipexole downregulated the maintenance-related STN and dlPFC activity, increasing reaction times for maintaining sequences. In contrast, pramipexole upregulated the manipulation-related STN and dlPFC activity, increasing reaction time costs for manipulating sequences. In addition, pramipexole altered the dlPFC activity pattern similarity and fronto-subthalamic functional connectivity. It also reduced maintenance-related striatal activity, which did not affect the behavior. This study confirmed the role of the fronto-subthalamic pathway in sequential working memory. Furthermore, it shows that both insufficient and excessive STN activity can impair sequential working memory. Our finding does not fit neatly with existing dopaminergic models of working memory and therefore suggests the need for more work in this area.