SynthesisBehavioral neuroscience2022
Quantifying the inverted U: A meta-analysis of prefrontal dopamine, D1 receptors, and working memory.
Synthesis in Behavioral neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Dopaminergic Treatment and Episodic Memory in Parkinson's Disease: A Meta-analysis of the Literature.Neuropsychology review · 2025Pooled it
- Differential and state-dependent effects of the GluN2A-selective positive allosteric modulator GNE-5729 on executive functions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Ropinirole adjunct to methylphenidate versus placebo adjunct to methylphenidate for attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled trial.European child & adolescent psychiatry · 2026Article
- The therapeutic potential of COMT inhibition: cognition and beyond.Molecular psychiatry · 2026Review
- A comprehensive overview of the biological foundations of ADHD.Bioscience reports · 2026Review
- Artificial intelligence analysis of facial movements and satisfaction in online medical lectures: a cross-sectional study.BMC medical education · 2026Article
- The dynamics of explore-exploit decisions suggest a threshold mechanism for reduced random exploration in older adults.PLoS computational biology · 2025Article
- Dual roles ofiScience · 2025Article
- Sensory integration deficits in Parkinson's disease with freezing of gait: cortical network dynamics and paradoxical dopaminergic modulation.Journal of neurology · 2025Article
- Perfluorooctanoic acid, perfluorobutanoic acid, and undecafluoro-2-methyl-3-oxahexanoic acid disrupt neurotransmitter release and cholinesterase activity.Chemosphere · 2025Article
- Review
- Amphetamine increases timing variability by degrading prefrontal temporal encoding.Neuropharmacology · 2025Article
- Burnout and the Brain-A Mechanistic Review of Magnetic Resonance Imaging (MRI) Studies.International journal of molecular sciences · 2025Review
- Dopaminergic modulation and dosage effects on brain state dynamics and working memory component processes in Parkinson's disease.Nature communications · 2025Article
- Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and cognition impairment in patients with schizophrenia.Psychopharmacology · 2024Article
- Adolescent oral oxycodone self-administration disrupts neurobehavioral and neurocognitive development.Neuropharmacology · 2024Article
- The polymorphisms of candidate pharmacokinetic and pharmacodynamic genes and their pharmacogenetic impacts on the effectiveness of risperidone maintenance therapy among Saudi children with autism.European journal of clinical pharmacology · 2024Article
- Cannabinoids and monoaminergic system: implications for learning and memory.Frontiers in neuroscience · 2024Review
- A Homogeneous Colorimetric Strategy Based on Rose-like CuS@Prussian Blue/Pt for Detection of Dopamine.Sensors (Basel, Switzerland) · 2023Article
- Indirect evidence for altered dopaminergic neurotransmission in very premature-born adults.Human brain mapping · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
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).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.