Cools · Biological psychiatry 2011 · narrative review · n=?

Inverted-U-shaped dopamine actions on human working memory and cognitive control.

Cited 1737 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing theoretical models, animal data, and clinical observations without systematic review methods.

PubMed 21531388 · doi:10.1016/j.biopsych.2011.03.028 · record verified 2026-08-26

What was done

The authors reviewed literature across experimental animal studies, healthy human cohorts, and patients with Parkinson's disease to analyze the sources of variability in behavioral responses to dopaminergic manipulations during working memory and cognitive control tasks.

What was found

The abstract reports no quantitative metrics or numerical effect sizes. Conceptually, it identifies two primary drivers of response variability: baseline-dependent inverted-U-shaped dose-response curves, and differing regional neural demands where cognitive stability engages prefrontal dopamine while cognitive flexibility engages striatal dopamine.

Why it matters

This framework helps explain paradoxical or inconsistent behavioral responses to dopamine-targeting drugs by accounting for an individual's baseline neurotransmitter tone and the specific sub-components of executive function being tested.

Limits

The abstract describes a narrative review without systematic search protocols, quality assessments, or meta-analytic pooling. Specific drug classes, dosages, and sample sizes are not reported in the abstract.

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