The contents of working memory must be maintained in the face of distraction, but updated when appropriate. To manage these competing demands of stability and flexibility, maintained representations in working memory are complemented by distinct gating mechanisms that selectively transmit information into and out of memory stores. The operations of such dopamine-dependent gating systems in the midbrain and striatum and their complementary dopamine-dependent memory maintenance operations in the cortex may therefore be dissociable. If true, selective increases in cortical dopamine tone should preferentially enhance maintenance over gating mechanisms. To test this hypothesis, tolcapone, a catechol-O-methyltransferase inhibitor that preferentially increases cortical dopamine tone, was administered in a randomized, double-blind, placebo-controlled, within-subject fashion to 49 participants who completed a hierarchical working memory task that varied maintenance and gating demands. Tolcapone improved performance in a condition with higher maintenance requirements and reduced gating demands, reflected in a reduction in the slope of RTs across the distribution. Resting-state fMRI data demonstrated that the degree to which tolcapone improved performance in individual participants correlated with increased connectivity between a region important for first-order stimulus response mappings (left dorsal premotor cortex) and cortical areas implicated in visual working memory, including the intraparietal sulcus and fusiform gyrus. Together, these results provide evidence that augmenting cortical dopamine tone preferentially improves working memory maintenance.

工作记忆的内容在分心时必须保持，但在适当的时候更新。为了管理这些对稳定性和灵活性的相互竞争的需求，工作记忆中保持的表示由不同的门控机制来补充，这些门控机制选择性地将信息传入和传出内存存储。因此，中脑和纹状体中这种多巴胺依赖性门控系统的操作以及它们在皮层中互补的多巴胺依赖性记忆维持操作可能是可分离的。如果属实，皮质多巴胺张力的选择性增加应该优先增强门控机制的维持。为了检验这一假设，托卡朋，一种儿茶酚-O优先增加皮质多巴胺张力的甲基转移酶抑制剂以随机、双盲、安慰剂对照、受试者内的方式给予 49 名参与者，这些参与者完成了不同维护和门控要求的分层工作记忆任务。Tolcapone 在维护要求更高和门控需求减少的条件下提高了性能，这反映在整个分布中 RT 斜率的降低。静息状态 fMRI 数据表明，tolcapone 提高个体参与者表现的程度与对一级刺激反应映射（左背前运动皮层）和涉及视觉工作记忆的皮层区域（包括顶叶）之间的连接性增加相关。沟和梭状回。一起，