Amphetamine modulates brain signal variability and working memory in younger and older adults
Open accessAbstract
Significance: Younger, better performing adults typically show greater brain signal variability than older, poorer performers, but the mechanisms underlying this observation remain elusive. We attempt to restore deficient functional-MRI–based blood oxygen level-dependent (BOLD) signal variability (SD BOLD ) levels in older adults by boosting dopamine via d -amphetamine (AMPH). Notably, older adults met or exceeded young adult SD BOLD levels under AMPH. AMPH-driven changes in SD BOLD also predicted AMPH-driven changes in reaction time speed and variability on a working memory task, but depended greatly on age and drug administration order. These findings ( i ) suggest that dopamine may account for adult age differences in brain signal variability and ( ii ) highlight the importance of considering practice effects and state dependencies when evaluating the neurochemical basis of age- and cognition-related brain dynamics.
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In healthy adults, amphetamine increases BOLD signal variability and exerts an equalizing effect on ventral striatum activity during incentive processing.
“In fMRI studies in healthy adults, AMP increased BOLD signal variability (137) and exerted an “equalizing” effect on ventral striatum activity during incentive processing (141).”
From The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities (2018) · cites this paper as [137]
The citation to this paper is attached to the BOLD-variability claim, not the separate ventral-striatum claim. The Discussion (page unavailable) reports that amphetamine increased BOLD signal variability in older adults, but says younger adults showed a mix of increases and decreases, with no net group change. The unqualified claim about healthy adults therefore overgeneralizes the finding. (LLM, conf=0.86)
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“Another fMRI study has shown that dexamphetamine‐induced dopamine release in older healthy individuals increased brain signal variability during the WM task, comparable to or exceeding the brain signal variability young adults had in the placebo condition (Garrett et al., 2015).”
- Authors
- Garrett, D. D., Nagel, I. E., Preuschhof, C., Burzynska, A. Z., Marchner, J., Wiegert, S., Jungehülsing, G. J., Nyberg, L., Villringer, A., Li, S.-C., Heekeren, H. R., Bäckman, L., & Lindenberger, U.
- Affiliations
- Max Planck Institute for Human Development (DE)
- University of Illinois Urbana-Champaign (US)
- Klinik für Neurologie, Jüdisches Krankenhaus, 13347 Berlin, Germany;
- Umeå University (SE)
- Max Planck Institute for Human Cognitive and Brain Sciences (DE)
- Karolinska Institutet (SE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-06
- Volume
- 112
- Issue
- 24
- Pages
- 7593-7598
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4475975
- OpenAlex
- W2134174619
- Cited by
- 103
- References
- 52
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 11 · 2023: 7 · 2022: 10 · 2021: 14 · 2020: 12 · 2019: 9 · 2018: 10 · 2017: 11 · 2016: 5 · 2015: 2
- FWCI
- 4.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Max-Planck-Gesellschaft (Intramural Innovation Fund)
- Bundesministerium für Bildung und Forschung (N/A)
- Deutsche Forschungsgemeinschaft (Leibniz Award)
- Vetenskapsrådet (N/A)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- amphetamine, brain signal variability, BOLD signal variability, working memory, cognitive aging, practice effects, reaction time variability, older adults
- MeSH terms
- Adult, Aged, Aging, Brain, Dextroamphetamine, Dopamine, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Middle Aged, Models, Neurological, Models, Psychological, Multivariate Analysis, Least-Squares Analysis, Young Adult, Functional Neuroimaging
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