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Title: Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

Abstract

Aging is accompanied by profound changes in the brain’s dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases. Using the PET tracer 6-[18F]fluoro-L-m-tyrosine, we found strong support for upregulated striatal dopamine synthesis capacity in healthy older adult humans free of amyloid pathology, relative to young people. We next used fMRI to define the functional impact of elevated synthesis capacity on cognitive flexibility, a core component of executive function. We found clear evidence in young adults that low levels of synthesis capacity were suboptimal, associated with diminished cognitive flexibility and altered frontoparietal activation relative to young adults with highest synthesis values. Critically, these relationships between dopamine, performance, and activation were transformed in older adults with higher synthesis capacity. Variability in synthesis capacity was related to intrinsic frontoparietal functional connectivity across groups, suggesting that striatal dopamine synthesis influences the tuning of networks underlying cognitive flexibility. Altogether, these findings define striatal dopamine’s association with cognitive flexibilitymore » and its neural underpinnings in young adults, and reveal the alteration in dopamine-related neural processes in aging.« less

Authors:
ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [2]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [3]; ORCiD logo [1]
+ Show Author Affiliations
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  3. Univ. of California, Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE
OSTI Identifier:
1379613
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Neuroscience
Additional Journal Information:
Journal Volume: 36; Journal Issue: 50; Journal ID: ISSN 0270-6474
Publisher:
Society for Neuroscience
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; aging; cognitive flexibility; dopamine; fMRI; PET; task switching

Citation Formats

Berry, Anne S., Shah, Vyoma D., Baker, Suzanne L., Vogel, Jacob W., O'Neil, James P., Janabi, Mustafa, Schwimmer, Henry D., Marks, Shawn M., and Jagust, William J. Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility. United States: N. p., 2016. Web. doi:10.1523/JNEUROSCI.0626-16.2016.
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Berry, Anne S., Shah, Vyoma D., Baker, Suzanne L., Vogel, Jacob W., O'Neil, James P., Janabi, Mustafa, Schwimmer, Henry D., Marks, Shawn M., & Jagust, William J. Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility. United States. https://doi.org/10.1523/JNEUROSCI.0626-16.2016
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Berry, Anne S., Shah, Vyoma D., Baker, Suzanne L., Vogel, Jacob W., O'Neil, James P., Janabi, Mustafa, Schwimmer, Henry D., Marks, Shawn M., and Jagust, William J. Wed . "Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility". United States. https://doi.org/10.1523/JNEUROSCI.0626-16.2016. https://www.osti.gov/servlets/purl/1379613.
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@article{osti_1379613,
title = {Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility},
author = {Berry, Anne S. and Shah, Vyoma D. and Baker, Suzanne L. and Vogel, Jacob W. and O'Neil, James P. and Janabi, Mustafa and Schwimmer, Henry D. and Marks, Shawn M. and Jagust, William J.},
abstractNote = {Aging is accompanied by profound changes in the brain’s dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases. Using the PET tracer 6-[18F]fluoro-L-m-tyrosine, we found strong support for upregulated striatal dopamine synthesis capacity in healthy older adult humans free of amyloid pathology, relative to young people. We next used fMRI to define the functional impact of elevated synthesis capacity on cognitive flexibility, a core component of executive function. We found clear evidence in young adults that low levels of synthesis capacity were suboptimal, associated with diminished cognitive flexibility and altered frontoparietal activation relative to young adults with highest synthesis values. Critically, these relationships between dopamine, performance, and activation were transformed in older adults with higher synthesis capacity. Variability in synthesis capacity was related to intrinsic frontoparietal functional connectivity across groups, suggesting that striatal dopamine synthesis influences the tuning of networks underlying cognitive flexibility. Altogether, these findings define striatal dopamine’s association with cognitive flexibility and its neural underpinnings in young adults, and reveal the alteration in dopamine-related neural processes in aging.},
doi = {10.1523/JNEUROSCI.0626-16.2016},
journal = {Journal of Neuroscience},
number = 50,
volume = 36,
place = {United States},
year = {2016},
month = {12}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1523/JNEUROSCI.0626-16.2016
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