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Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task.

Journal article
Authors Cindy M de Frias
Petter Marklund
Elias Eriksson
Anne Larsson
Lena Oman
Kristina Annerbrink
Lars Bäckman
Lars-Göran Nilsson
Lars Nyberg
Published in Journal of cognitive neuroscience
Volume 22
Issue 7
Pages 1614-22
ISSN 0898-929X
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 1614-22
Language en
Links dx.doi.org/10.1162/jocn.2009.21318
Subject categories Pharmacology and Toxicology

Abstract

Abstract The catechol O-methyltransferase (COMT) gene-encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)-contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme-activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.

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