Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

doi:10.1523/JNEUROSCI.0626-16.2016

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 withmore »« less

Authors:

^[1];

^[2];

^[3];

^[2];

^[3];

^[1]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States)

Publication Date:: 2016-12-14

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.

Copy to clipboard


                    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.  doi:10.1523/JNEUROSCI.0626-16.2016.

Copy to clipboard


                    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.  doi:10.1523/JNEUROSCI.0626-16.2016.  https://www.osti.gov/servlets/purl/1379613.

Copy to clipboard


                    
@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}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Accepted Manuscript (DOE)

Publisher's Version of Record

DOI: 10.1523/JNEUROSCI.0626-16.2016

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 21 works

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Works referencing / citing this record:

The Influence of Dopamine on Cognitive Flexibility Is Mediated by Functional Connectivity in Young but Not Older Adults
journal, September 2018

Berry, Anne S.; Shah, Vyoma D.; Jagust, William J.
Journal of Cognitive Neuroscience, Vol. 30, Issue 9
DOI: 10.1162/jocn_a_01286

A ge‐related changes in the ease of dynamical transitions in human brain activity
journal, February 2018

Ezaki, Takahiro; Sakaki, Michiko; Watanabe, Takamitsu
Human Brain Mapping, Vol. 39, Issue 6
DOI: 10.1002/hbm.24033

Age-related variability in decision-making: Insights from neurochemistry
journal, December 2018

Berry, Anne S.; Jagust, William J.; Hsu, Ming
Cognitive, Affective, & Behavioral Neuroscience, Vol. 19, Issue 3
DOI: 10.3758/s13415-018-00678-9

Age-Related Differences in Motivational Integration and Cognitive Control
journal, April 2019

Yee, Debbie M.; Adams, Sarah; Beck, Asad
Cognitive, Affective, & Behavioral Neuroscience, Vol. 19, Issue 3
DOI: 10.3758/s13415-019-00713-3

Similar records in OSTI.GOV collections:

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

Journal Article Marks, Shawn M. ; Lockhart, Samuel N. ; Baker, Suzanne L. ; ... - Journal of Neuroscience

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turnmore »« less
DOI: 10.1523/JNEUROSCI.3769-16.2017
Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

Journal Article Leal, Stephanie L. ; Landau, Susan M. ; Bell, Rachel K. ; ... - eLife

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore »« less
Cited by 14
DOI: 10.7554/eLife.22978

Full Text Available
Overlapping patterns of brain activation to food and cocaine cues in cocaine abusers: Association to striatal D2/D3 receptors

Journal Article Tomasi, Dardo ; Wang, Gene -Jack ; Wang, Ruiliang ; ... - Human Brain Mapping

Cocaine, through its activation of dopamine (DA) signaling, usurps pathways that process natural rewards. However, the extent to which there is overlap between the networks that process natural and drug rewards and whether DA signaling associated with cocaine abuse influences these networks have not been investigated in humans. We measured brain activation responses to food and cocaine cues with fMRI, and D2/D3 receptors in the striatum with [ ¹¹C]raclopride and PET in 20 active cocaine abusers. Compared to neutral cues, food and cocaine cues increasingly engaged cerebellum, orbitofrontal, inferior frontal and premotor cortices and insula and disengaged cuneus and defaultmore »« less
Cited by 29
DOI: 10.1002/hbm.22617

Full Text Available
Characterization of D/sub 1/ dopamine receptors in the central nervous system

Thesis/Dissertation Hess, E.J.

Several lines of evidence suggest an association of central nervous system dopaminergic systems in the etiology of the schizophrenia. Interest in the role of D/sub 1/ dopamine receptors has revived with the advent of selective drugs for this dopamine receptor, particularly the D/sub 1/ dopamine receptor antagonists, SCH23390. (/sup 3/H)SCH23390 represents a superior radioligand for labeling the two-state striatal D/sub 1/ dopamine receptor in that its high percent specific binding makes it especially suitable for detailed mechanistic studies of this receptor. Striatal D/sub 1/ dopamine receptors have been shown to mediate the stimulation of adenylate cyclase activity via a guaninemore »« less
Radiofluorinated 3-(2{prime}-fluoroethyl)-2-thienylspiperone (FETS): Synthesis, pharmacologic characterization, tissue distribution and primate imaging of a selective radioligand for mapping D2 receptor sites by PET

Journal Article Goodman, M.M. ; Shi, B. ; Hoffman, J. - Journal of Nuclear Medicine

Abnormally high dopaminergic neurotransmission has been implicated in schizophrenia. A number of radiolabeled analogs of spiperone, a potent antipyschotic with a high (nanomolar) affinity for dopamine D2 receptors, have been synthesized for quantifying D2 receptors in humans. An undesired property accompanying high striatal uptake of radiolabeled spiperone (SPIP) analogs is high affinity for serotonin 5-IIT2 receptors. A potent spiperone analog which selectively binds to D2 receptors would be valuable in studying regional dopaminergic aberrations in schizophrenia. We have synthesized new potent radioligands [F-18] labeled 3-(2{prime}-fluoroethyl)-2-thienylspiperone (FETS) and 3-(3{prime}-fluoropropyl)-2-thienylspiperone (FPTS) for quantifying D2 receptors by PET. In vitro binding studies formore »« less

Similar Records

Title: Aging Affects Dopaminergic Neural Mechanisms of Cognitive Flexibility

Abstract

Citation Formats

The Influence of Dopamine on Cognitive Flexibility Is Mediated by Functional Connectivity in Young but Not Older Adults journal, September 2018

A ge‐related changes in the ease of dynamical transitions in human brain activity journal, February 2018

Age-related variability in decision-making: Insights from neurochemistry journal, December 2018

Age-Related Differences in Motivational Integration and Cognitive Control journal, April 2019

The Influence of Dopamine on Cognitive Flexibility Is Mediated by Functional Connectivity in Young but Not Older Adults
journal, September 2018

A ge‐related changes in the ease of dynamical transitions in human brain activity
journal, February 2018

Age-related variability in decision-making: Insights from neurochemistry
journal, December 2018

Age-Related Differences in Motivational Integration and Cognitive Control
journal, April 2019