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White-Matter Integrity and Working Memory: Links to Aging and Dopamine-Related Genes
Aging Research Center, Karolinska Institute and Stockholm University, Solna, Sweden.
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Aging Research Center, Karolinska Institute and Stockholm University, Solna, Sweden.
Aging Research Center, Karolinska Institute and Stockholm University, Solna, Sweden; Department of Psychiatry and Behavioral Sciences, School of Medicine, Stanford University, CA, Stanford, United States.
Aging Research Center, Karolinska Institute and Stockholm University, Solna, Sweden.
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2022 (English)In: eNeuro, E-ISSN 2373-2822, Vol. 9, no 2, article id ENEURO.0413-21.2022Article in journal (Refereed) Published
Abstract [en]

Working memory, a core function underlying many higher-level cognitive processes, requires cooperation of multiple brain regions. White matter refers to myelinated axons, which are critical to interregional brain communication. Past studies on the association between white-matter integrity and working memory have yielded mixed findings. Using voxelwise tract-based spatial statistics analysis, we investigated this relationship in a sample of 328 healthy adults from 25 to 80 years of age. Given the important role of dopamine (DA) in working-memory functioning and white matter, we also analyzed the effects of dopamine-related genes on them. There were associations between white-matter integrity and working memory in multiple tracts, indicating that working-memory functioning relies on global connections between different brain areas across the adult life span. Moreover, a mediation analysis suggested that white-matter integrity contributes to age-related differences in working memory. Finally, there was an effect of the COMT Val158Met polymorphism on white-matter integrity, such that Val/Val carriers had lower fractional anisotropy values than any Met carriers in the internal capsule, corona radiata, and posterior thalamic radiation. As this polymorphism has been associated with dopaminergic tone in the prefrontal cortex, this result provides evidence for a link between DA neurotransmission and white matter. Together, the results support a link between white-matter integrity and working memory, and provide evidence for its interplay with age-and DA-related genes.

Place, publisher, year, edition, pages
Society for Neuroscience , 2022. Vol. 9, no 2, article id ENEURO.0413-21.2022
Keywords [en]
aging, COMT, dopamine, DTI, white matter, working memory
National Category
Neurosciences Neurology
Identifiers
URN: urn:nbn:se:umu:diva-194337DOI: 10.1523/ENEURO.0413-21.2022ISI: 000789037300003PubMedID: 35346961Scopus ID: 2-s2.0-85128165001OAI: oai:DiVA.org:umu-194337DiVA, id: diva2:1655919
Funder
Swedish Research Council, 421-2013- 1039The Swedish Brain Foundation, F02014-0224Available from: 2022-05-04 Created: 2022-05-04 Last updated: 2023-09-05Bibliographically approved

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Salami, Alireza

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