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  Amphetamine modulates brain signal variability and working memory in younger and older adults

Garrett, D. D., Nagel, I. E., Preuschhof, C., Burzynska, A. Z., Marchner, J., Wiegert, S., et al. (2015). Amphetamine modulates brain signal variability and working memory in younger and older adults. Proceedings of the National Academy of Sciences of the United States of America, 112(24), 7593-7598. doi:10.1073/pnas.1504090112.

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Garrett, Douglas D.1, 2, Author
Nagel, Irene E.1, 3, Author
Preuschhof, Claudia1, 3, 4, 5, Author
Burzynska, Agnieszka Z.1, 6, Author
Marchner, Janina1, Author
Wiegert, Steffen1, Author
Jungehülsing, Gerhard J.7, Author
Nyberg, Lars8, 9, 10, Author
Villringer, Arno11, Author              
Li, Shu-Chen1, 12, Author
Heekeren, Hauke1, 3, 11, Author              
Bäckmann, Lars13, Author
Lindenberger, Ulmann1, 2, Author
1Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany, ou_persistent22              
2Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Berlin, Germany, ou_persistent22              
3Department of Education and Psychology, FU Berlin, Germany, ou_persistent22              
4Department of Clinical Developmental Psychology, Otto von Guericke University Magdeburg, Germany, ou_persistent22              
5Center for Behavioral Brain Sciences , Magdeburg, Germany, ou_persistent22              
6Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, IL, USA, ou_persistent22              
7Klinik für Neurologie, Jüdisches Krankenhaus Berlin, Germany, ou_persistent22              
8Department of Radiation Sciences, Umeå University, Sweden, ou_persistent22              
9Department of Integrative Medical Biology, Umeå University, Sweden, ou_persistent22              
10Umeå Center for Functional Brain Imaging, Umeå University, Sweden, ou_persistent22              
11Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634549              
12Department of Psychology, TU Dresden, Germany, ou_persistent22              
13Aging Research Center, Karolinska Institute, Stockholm, Sweden, ou_persistent22              


Free keywords: Brain signal variability; Dopamine; Aging; Working memory; fMRI
 Abstract: Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI–based blood oxygen level-dependent (BOLD) signal variability (SDBOLD) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SDBOLD levels in the presence of AMPH. Drug session order greatly moderated change–change relations between AMPH-driven SDBOLD and reaction time means (RTmean) and SDs (RTSD). Older adults who received AMPH in the first session tended to improve in RTmean and RTSD when SDBOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SDBOLD decreased (for RTmean) or no effect at all (for RTSD). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.


Language(s): eng - English
 Dates: 2015-03-022015-04-222015-06-012015-06-16
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1073/pnas.1504090112
PMID: 26034283
PMC: PMC4475975
Other: Epub 2015
 Degree: -



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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Natl. Acad. Sci. USA
Source Genre: Journal
Publ. Info: National Academy of Sciences
Pages: - Volume / Issue: 112 (24) Sequence Number: - Start / End Page: 7593 - 7598 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230