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

Research output: Contribution to journalArticleScientificpeer-review

54 Citations (Scopus)


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

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.

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.

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
Issue number6
Publication statusPublished - 2010
Externally publishedYes


Dive into the research topics of 'Simulating neurocognitive aging: Effects of a dopaminergic antagonist on brain activity during working memory'. Together they form a unique fingerprint.

Cite this