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Dopamine D-2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion
Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Wallenberg Centre for Molecular Medicine, Sweden; Umeå Center for Functional Brain Imaging, Sweden; Department of Radiation Sciences, Sweden; Umeå University, Sweden .
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Number of Authors: 152019 (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 D-2/3 PET assessment using [C-11] raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D-2/3 receptors to BOLD response in the thalamo-striatalcortical 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]
aging, dopamine, fMRI, PET, working memory
National Category
Neurosciences Geriatrics
Identifiers
URN: urn:nbn:se:su:diva-165655DOI: 10.1523/JNEUROSCI.1493-18.2018ISI: 000455849400013PubMedID: 30478031OAI: oai:DiVA.org:su-165655DiVA, id: diva2:1287050
Available from: 2019-02-08 Created: 2019-02-08 Last updated: 2019-02-08Bibliographically approved

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Jonasson, LarsAxelsson, JjanNyberg, Lars
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