Dopamine D2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion. Show others and affiliations
2019 (English) In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 39, no 3, p. 537-547Article in journal (Refereed) Published
Abstract [en]
Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA (measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA–BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 low-performing) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n -back task along with DA D2/3 PET assessment using [11 C]raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D2/3 receptors to BOLD response in the thalamo–striatal–cortical circuit, which supports WM functioning. Critically, the DA–BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA–BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA–BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.
Place, publisher, year, edition, pages 2019. Vol. 39, no 3, p. 537-547
Keywords [en]
PET, aging, dopamine, fMRI, working memory
National Category
Neurology
Identifiers URN: urn:nbn:se:umu:diva-155492 DOI: 10.1523/JNEUROSCI.1493-18.2018 ISI: 000455849400013 PubMedID: 30478031 Scopus ID: 2-s2.0-85060157566 OAI: oai:DiVA.org:umu-155492 DiVA, id: diva2:1280295
Funder Swedish Research Council Knut and Alice Wallenberg Foundation Torsten Söderbergs stiftelse Ragnar Söderbergs stiftelse The Swedish Brain Foundation Västerbotten County Council 2019-01-182019-01-182023-03-24 Bibliographically approved