The article discusses the inverted-U shaped dopamine (DA) effects on human working memory and cognitive control. It highlights that dopamine's role in cognition is complex and depends on baseline levels of DA in different brain regions. The prefrontal cortex (PFC) and striatum are key areas involved in cognitive control, with the PFC associated with cognitive stability and the striatum with cognitive flexibility. Manipulating dopamine can have paradoxical effects on these processes depending on baseline levels. Evidence from animal and human studies shows that DA levels in the PFC and striatum vary, influencing cognitive performance. For example, low DA levels in the PFC impair working memory, while high levels can lead to perseveration. Similarly, in the striatum, high DA levels may enhance flexible updating but impair stability. These findings are supported by genetic studies, such as the COMT gene polymorphism, which influences DA levels and cognitive performance. Human studies using PET scans have shown that individuals with higher working memory capacity have higher striatal DA synthesis. Dopaminergic drugs like bromocriptine can improve cognitive performance in individuals with low DA levels but worsen it in those with high levels, illustrating the inverted-U relationship. Parkinson's disease (PD) patients exhibit cognitive deficits, particularly in flexible updating, due to striatal DA depletion. However, they also show enhanced cognitive stabilization when off medication, suggesting a paradoxical effect of DA on cognitive control. These findings support the idea that DA's role in cognition is regionally and baseline-dependent, with the PFC and striatum playing distinct roles in cognitive stability and flexibility, respectively. The study underscores the importance of understanding DA's complex interactions in the brain to develop effective treatments for cognitive disorders.The article discusses the inverted-U shaped dopamine (DA) effects on human working memory and cognitive control. It highlights that dopamine's role in cognition is complex and depends on baseline levels of DA in different brain regions. The prefrontal cortex (PFC) and striatum are key areas involved in cognitive control, with the PFC associated with cognitive stability and the striatum with cognitive flexibility. Manipulating dopamine can have paradoxical effects on these processes depending on baseline levels. Evidence from animal and human studies shows that DA levels in the PFC and striatum vary, influencing cognitive performance. For example, low DA levels in the PFC impair working memory, while high levels can lead to perseveration. Similarly, in the striatum, high DA levels may enhance flexible updating but impair stability. These findings are supported by genetic studies, such as the COMT gene polymorphism, which influences DA levels and cognitive performance. Human studies using PET scans have shown that individuals with higher working memory capacity have higher striatal DA synthesis. Dopaminergic drugs like bromocriptine can improve cognitive performance in individuals with low DA levels but worsen it in those with high levels, illustrating the inverted-U relationship. Parkinson's disease (PD) patients exhibit cognitive deficits, particularly in flexible updating, due to striatal DA depletion. However, they also show enhanced cognitive stabilization when off medication, suggesting a paradoxical effect of DA on cognitive control. These findings support the idea that DA's role in cognition is regionally and baseline-dependent, with the PFC and striatum playing distinct roles in cognitive stability and flexibility, respectively. The study underscores the importance of understanding DA's complex interactions in the brain to develop effective treatments for cognitive disorders.