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Simulating neurocognitive aging: effects of a dopaminergic antagonist on brain activity during working memory
Karolinska Institute.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Karolinska Institute.
Karolinska Hospital.
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2010 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 67, no 6, 575-580 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity.

METHODS: We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [(11)C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults.

RESULTS: An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response.

CONCLUSIONS: These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.

Place, publisher, year, edition, pages
Elsevier, 2010. Vol. 67, no 6, 575-580 p.
Keyword [en]
Aging, antagonist, D1 receptors, dopamine, fMRI, pharmacology, spatial working memory
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:umu:diva-31985DOI: 10.1016/j.biopsych.2009.12.013ISI: 000275390900011PubMedID: 20138255OAI: oai:DiVA.org:umu-31985DiVA: diva2:301935
Available from: 2010-03-03 Created: 2010-02-26 Last updated: 2017-12-12Bibliographically approved

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