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Simulating neurocognitive aging: effects of a dopaminergic antagonist on brain activity during working memory
Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
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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
New York: Plenum Publishing, 2010. Vol. 67, no 6, 575-580 p.
National Category
Social Sciences
URN: urn:nbn:se:su:diva-84983DOI: 10.1016/j.biopsych.2009.12.013PubMedID: 20138255OAI: diva2:585503
Available from: 2013-01-10 Created: 2013-01-04 Last updated: 2013-09-17Bibliographically approved

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