期刊
HUMAN BRAIN MAPPING
卷 36, 期 4, 页码 1325-1334出版社
WILEY
DOI: 10.1002/hbm.22704
关键词
functional magnetic resonance imaging (fMRI); memory; aging; dopamine; DRD2; updating; striatum
资金
- Swedish Research Council
- Swedish Brain Power
- Alexander von Humboldt Research Award
- af Jochnick Foundation
A number of genetic polymorphisms are related to individual differences in cognitive performance. Striatal dopamine (DA) functions, associated with cognitive performance, are linked to the TaqIA polymorphism of the DRD2/ANKK1 gene. In humans, presence of an A1 allele of the DRD2/ANKK1-TaqIA polymorphism is related to reduced density of striatal DA D2 receptors. The resource-modulation hypothesis assumes that aging-related losses of neurochemical and structural brain resources modulate the extent to which genetic variations affect cognitive functioning. Here, we tested this hypothesis using functional MRI during long-term memory (LTM) updating in younger and older carriers and noncarriers of the A1-allele of the TaqIa polymorphism. We demonstrate that older A1-carriers have worse memory performance, specifically during LTM updating, compared to noncarriers. Moreover, A1-carriers exhibited less blood oxygen level-dependent (BOLD) activation in left caudate nucleus, a region critical to updating. This effect was only seen in older adults, suggesting magnification of genetic effects on functional brain activity in aging. Further, a positive relationship between caudate BOLD activation and updating performance among non-A1 carriers indicated that caudate activation was behaviorally relevant. These results demonstrate a link between the DRD2/ANKK1-TaqIA polymorphism and neurocognitive deficits related to LTM updating, and provide novel evidence that this effect is magnified in aging. Hum Brain Mapp 36:1325-1334, 2015. (c) 2014 Wiley Periodicals, Inc.
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