title: Amphetamine modulates brain signal variability and working memory in younger and older adults.
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 (SD(BOLD)) 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 SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). 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.
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, 14195 Berlin, Germany; garrett@mpib-berlin.mpg.de.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Garrett
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany; Department of Education and Psychology, Freie Universität Berlin, 14195 Berlin, Germany;
authors.forename: Irene E
authors.initials: IE
authors.lastname: Nagel
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany; Department of Education and Psychology, Freie Universität Berlin, 14195 Berlin, Germany; Department of Clinical Developmental Psychology, Center for Behavioral and Brain Sciences, Otto von Guericke University Magdeburg, 39106 Magdeburg, Germany;
authors.forename: Claudia
authors.initials: C
authors.lastname: Preuschhof
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany; Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, IL 61820;
authors.forename: Agnieszka Z
authors.initials: AZ
authors.lastname: Burzynska
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany;
authors.forename: Janina
authors.initials: J
authors.lastname: Marchner
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany;
authors.forename: Steffen
authors.initials: S
authors.lastname: Wiegert
authors.affiliation: Klinik für Neurologie, Jüdisches Krankenhaus, 13347 Berlin, Germany;
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Jungehülsing
authors.affiliation: Departments of Radiation Sciences and Integrative Medical Biology, and Umeå Center for Functional Brain Imaging, Umeå University, SE-901 87 Umeå, Sweden;
authors.forename: Lars
authors.initials: L
authors.lastname: Nyberg
authors.affiliation: Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany;
authors.forename: Arno
authors.initials: A
authors.lastname: Villringer
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany; Department of Psychology, TU Dresden, 01062 Dresden, Germany;
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Li
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany; Department of Education and Psychology, Freie Universität Berlin, 14195 Berlin, Germany; Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany;
authors.forename: Hauke R
authors.initials: HR
authors.lastname: Heekeren
authors.affiliation: Aging Research Center, Karolinska Institute, SE-113 30 Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
authors.affiliation: Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, 14195 Berlin, Germany;
authors.forename: Ulman
authors.initials: U
authors.lastname: Lindenberger
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology* / Q000523:psychology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D008959:Models, Neurological; D008960:Models, Psychological; D015999:Multivariate Analysis; D055815:Young Adult
chemical_list: D003913:Dextroamphetamine; D004298:Dopamine
keywords: aging; brain signal variability; dopamine; fMRI; working memory