Catechol-O-Methyltransferase Val158Met Modulation of Prefrontal–Parietal–Striatal Brain Systems during Arithmetic and Temporal Transformations in Working Memory
Open accessAbstract
Working memory (WM) is critically mediated by dopaminergic tuning of signal-to-noise in cortical neural assemblies. However, little is known about the distributed neuronal networks impacted by dopaminergic modulation in the component processes of WM. Here, we used the genotype of the Val158Met polymorphism in catechol-O-methyltransferase (COMT) as an index of relative cortical dopamine bioavailability and tuning efficiency, to examine the spatial and subprocess specificity by which dopaminergic modulation occurs within the prefrontal-parietal-striatal network during WM, thus empirically showing that dopamine plays key roles in updating and stabilizing new information at the neural systems level. In an event-related fMRI task dissociating component numerical WM subprocesses, baseline numerical size comparison engaged ventrolateral prefrontal cortical activation that correlated with COMT Val-allele load (COMT Val>Met), while performing arithmetic transformations further engaged this genotype effect in dorsolateral prefrontal cortex (DLPFC), as well as in parietal and striatal regions. Critically, additional temporal integration of information in WM disproportionately engaged greater COMT Val>Met effects only at DLPFC.COMT Val>Met effects were also observed in DLPFC during encoding of new information into WM, but not at its subsequent retrieval. Thus, temporal updating operations, but less so the retrieval of already encoded representations, engaged relatively specific dopaminergic tuning at the DLPFC. Manipulating and rapidly updating representations were sensitive to dopaminergic modulation of neural signaling in a larger prefrontal-parietal-striatal network. These findings add to the integration of dopaminergic signaling in basic cortical assemblies with their roles in specific human brain networks during the orchestration of information processing in WM.
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Single nucleotide polymorphisms tied to glucocorticoid and catecholamine activity in prefrontal corticolimbic circuitry are associated with variation in executive function and possibly with susceptibility to early stress effects on cognition in humans.
“Increasing numbers of studies in human populations indicate that single nucleotide polymorphisms associated with glucocorticoid and catecholamine activity in PFC corticolimbic circuitry are related to variation in EF and perhaps, to some extent, susceptibility to early stress effects on cognition (Hariri, Drabant, & Weinberger, 2006; Pezawas et al., 2005; Tan et al., 2007).”
From Stress and the development of self-regulation in context (2010) · cites this paper as Tan et al., 2007
Genetic background differences play a major role in how stress relates to development.
“Individual differences in genetic background figure largely in relations between stress and development.”
From Stress and the development of self-regulation in context (2010) · cites this paper as Tan et al., 2007
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“tion in EF and perhaps, to some extent, susceptibility to early stress effects on cognition (Hariri, Drabant, & Weinberger, 2006; Pezawas et al., 2005; Tan et al., 2007).”
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- Authors
- Tan, H.-Y., Chen, Q., Goldberg, T. E., Mattay, V. S., Meyer-Lindenberg, A., Weinberger, D. R., & Callicott, J. H.
- Affiliations
- National Institutes of Health (US)
- Zucker Hillside Hospital (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-12-05
- Volume
- 27
- Issue
- 49
- Pages
- 13393-13401
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6673107
- OpenAlex
- W2057198064
- Cited by
- 144
- References
- 55
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 9 · 2014: 7 · 2013: 11 · 2012: 13
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- working memory, catechol-O-methyltransferase, COMT Val158Met polymorphism, dopamine, dopaminergic modulation, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, temporal integration
- MeSH terms
- Adolescent, Adult, Catechol O-Methyltransferase, Corpus Striatum, Dopamine, Female, Humans, Male, Mathematics, Memory, Short-Term, Methionine, Parietal Lobe, Reaction Time, Valine, Prefrontal Cortex, Amino Acid Substitution
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