4.2 Article

Quantifying the Inverted U: A Meta-Analysis of Prefrontal Dopamine, D1 Receptors, and Working Memory

期刊

BEHAVIORAL NEUROSCIENCE
卷 136, 期 3, 页码 207-218

出版社

AMER PSYCHOLOGICAL ASSOC
DOI: 10.1037/bne0000512

关键词

prefrontal cortex; dopamine; D1 receptors; working memory

资金

  1. NIH [UL1TR002537, R01 MH116043, R01 NS120987]

向作者/读者索取更多资源

Dopamine in the prefrontal cortex has an inverted U-shaped relationship with cognitive function, with optimal dopamine and D1DR signaling being required for peak cognitive function. The relationship explains 10% of the variance in working memory performance. Prefrontal D1DR signaling has a stronger effect, explaining 26% of the variance. These findings provide insights into the dynamics of prefrontal dopamine and have implications for pharmacological interventions and the pathophysiology of brain diseases.
Dopamine in the prefrontal cortex can be disrupted in human disorders that affect cognitive function such as Parkinson's disease (PD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia. Dopamine has a powerful effect on prefrontal circuits via the D1-type dopamine receptor (D1DR). It has been proposed that prefrontal dopamine has inverted U-shaped dynamics, with optimal dopamine and D1DR signaling required for peak cognitive function. However, the quantitative relationship between prefrontal dopamine and cognitive function is not clear. Here, we conducted a meta-analysis of published manipulations of prefrontal dopamine and the effects on working memory, a high-level executive function in humans, primates, and rodents that involves maintaining and manipulating information over seconds to minutes. We reviewed 646 articles and found that 75 studies met criteria for inclusion. Our quantification of effect sizes for dopamine, D1DRs, and behavior revealed a negative quadratic slope. This is consistent with the proposed inverted U-shape of prefrontal dopamine and D1DRs and working memory performance, explaining 10% of the variance. Of note, the inverted quadratic fit was much stronger for prefrontal D1DRs alone, explaining 26% of the variance, compared to prefrontal dopamine alone, explaining 10% of the variance. Taken together, these data, derived from a variety of manipulations and systems, demonstrate that optimal prefrontal dopamine signaling is linked with higher cognitive function. Our results provide insight into the fundamental dynamics of prefrontal dopamine, which could be useful for pharmacological interventions targeting prefrontal dopaminergic circuits, and into the pathophysiology of human brain disease.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.2
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据