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. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

中文翻译：

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量化倒 U：前额叶多巴胺、D1 受体和工作记忆的荟萃分析。

前额叶皮层中的多巴胺会在影响认知功能的人类疾病中被破坏，例如帕金森病 (PD)、注意力缺陷多动障碍 (ADHD) 和精神分裂症。多巴胺通过 D1 型多巴胺受体 (D1DR) 对前额叶回路产生强大的影响。有人提出前额叶多巴胺具有“倒 U 形”动态，具有最佳认知功能所需的多巴胺和 D1DR 信号传导。然而，前额叶多巴胺与认知功能之间的定量关系尚不清楚。在这里，我们对已发表的前额叶多巴胺操作及其对工作记忆的影响进行了荟萃分析，工作记忆是人类、灵长类动物和啮齿动物的一种高级执行功能，涉及在几秒钟到几分钟内维持和操纵信息。我们审查了 646 篇文章，发现 75 项研究符合纳入标准。我们对多巴胺、D1DR 和行为的影响大小的量化显示出负二次斜率。这与前额叶多巴胺和 D1DR 的倒 U 形和工作记忆性能一致，解释了 10% 的方差。值得注意的是，与单独的前额多巴胺相比，单独的前额 D1DR 的反向二次拟合要强得多，解释了 26% 的方差，解释了 10% 的方差。总之，这些来自各种操作和系统的数据表明，最佳的前额叶多巴胺信号传导与更高的认知功能有关。我们的结果提供了对前额叶多巴胺的基本动态的洞察，这可能有助于针对前额叶多巴胺能回路的药物干预，以及人类大脑疾病的病理生理学。（PsycInfo 数据库记录 (c) 2022 APA，保留所有权利）。