Abstract
Using multimodal neuroimaging in humans, we demonstrate specific interactions between prefrontal activity and midbrain dopaminergic synthesis. A common V(108/158)M substitution in the gene for catecholamine-O-methyltransferase (COMT), an important enzyme regulating prefrontal dopamine turnover, predicted reduced dopamine synthesis in midbrain and qualitatively affected the interaction with prefrontal cortex. These data implicate a dopaminergic tuning mechanism in prefrontal cortex and suggest a systems-level mechanism for cognitive and neuropsychiatric associations with COMT.
MeSH terms
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Adult
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Amino Acid Substitution / genetics
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Brain Mapping
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Catechol O-Methyltransferase / genetics*
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Cognition / physiology*
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Dopamine / metabolism*
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Feedback / physiology
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Female
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Genotype
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Humans
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Male
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Memory, Short-Term / physiology
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Mesencephalon / diagnostic imaging
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Mesencephalon / enzymology*
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Metabolic Clearance Rate / physiology
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Neural Pathways / diagnostic imaging
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Neural Pathways / enzymology*
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Neuropsychological Tests
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Positron-Emission Tomography
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Prefrontal Cortex / diagnostic imaging
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Prefrontal Cortex / enzymology*
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Reaction Time / genetics
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Synaptic Transmission / physiology
Substances
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Catechol O-Methyltransferase
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Dopamine