Simulating neurocognitive aging: Effects of a dopaminergic antagonist on brain activity during working memory

Håkan Fischer, Lars Nyberg, Sari Karlsson, Per Karlsson, Yvonne Brehmer, Anna Rieckmann, Stuart W.s. Macdonald, Lars Farde, Lars Bäckman

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Abstract

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 [11C]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.
Original languageEnglish
Pages (from-to)575-580
JournalBiological Psychiatry
Volume67
Issue number6
DOIs
Publication statusPublished - 2010
Externally publishedYes

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    Fischer, H., Nyberg, L., Karlsson, S., Karlsson, P., Brehmer, Y., Rieckmann, A., Macdonald, S. W. S., Farde, L., & Bäckman, L. (2010). Simulating neurocognitive aging: Effects of a dopaminergic antagonist on brain activity during working memory. Biological Psychiatry, 67(6), 575-580. https://doi.org/10.1016/j.biopsych.2009.12.013