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. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Authors: Judy L Thompson; Daniel R Rosell; Mark Slifstein; Ragy R Girgis; Xiaoyan Xu; Yosefa Ehrlich; Lawrence S Kegeles; Erin A Hazlett; Anissa Abi-Dargham; Larry J Siever Journal: Psychopharmacology (Berl) Date: 2014-04-30 Impact factor: 4.530
Authors: Jamie E Podell; Fabio Sambataro; Vishnu P Murty; Matthew R Emery; Yunxia Tong; Saumitra Das; Terry E Goldberg; Daniel R Weinberger; Venkata S Mattay Journal: Neuroimage Date: 2012-06-01 Impact factor: 6.556