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

de Frias, Cindy M.Stockholms universitet,Psykologiska institutionen,Stockholm University (author)

authorCount :9
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.

Marklund, PetterStockholm University, Stockholm Brain Institute (author)
Eriksson, Elias,1956Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xereli (author)
Larsson, AnneUmeå universitet,Radiofysik(Swepub:umu)anelan97 (author)
Öman, LenaUmeå universitet (author)
Annerbrink, Kristina,1974Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xannkr (author)
Bäckman, LarsKarolinska Institutet (author)
Nilsson, Lars-GöranStockholms universitet,Psykologiska institutionen,Stockholm University(Swepub:su)lgn (author)
Nyberg, LarsUmeå universitet,Diagnostisk radiologi,Fysiologi(Swepub:umu)lany0001 (author)
Stockholms universitetPsykologiska institutionen (creator_code:org_t)

In:Journal of cognitive neuroscienceCambridge, Mass. : MIT Press22:7, s. 1614-16220898-929X1530-8898

By the author/editor: de Frias, Cindy ...; Marklund, Petter; Eriksson, Elias, ...; Larsson, Anne; Öman, Lena; Annerbrink, Kris ...; show more...; Bäckman, Lars; Nilsson, Lars-Gö ...; Nyberg, Lars; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

By the university: Stockholm University; Umeå University; University of Gothenburg; Karolinska Institutet

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