期刊
BIOLOGICAL PSYCHIATRY
卷 67, 期 6, 页码 575-580出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2009.12.013
关键词
Aging; antagonist; D1 receptors; dopamine; fMRI; pharmacology; spatial working memory
资金
- Swedish Research Council
- Swedish Brain Power
- Alexander von Humboldt Research Award
- Joint Committee for Nordic Research Councils for the Humanities and the Social Sciences
- Michael Smith Foundation for Health Research
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 dopa mine, 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.
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