Trial reportProceedings of the National Academy of Sciences of the United States of America2015
Amphetamine modulates brain signal variability and working memory in younger and older adults.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04191811 (Moment-to-moment Neural Variability as a Predictor of Treatment Outcome in Patients With Common Psychiatric Disorders), which is not on this map. Cited by 57 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Moment-to-moment Neural Variability as a Predictor of Treatment Outcome in Patients With Common Psychiatric Disorders: Major Depressive Disorder, Insomnia and Social Anxiety Disorder
Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 117 citations in OpenAlex.
- Within-Individual BOLD Signal Variability and its Implications for Task-Based Cognition: A Systematic Review.Neuropsychology review · 2024Pooled it
- Systematic reviews of the acute effects of amphetamine on working memory and other cognitive performances in healthy individuals, with a focus on the potential influence of personality traits.Human psychopharmacology · 2023Pooled it
- Methamphetamine-induced adaptation of learning rate dynamics depend on baseline performance.eLife · 2025Trial
- Trial
- Dynamic Recovery: GABA Agonism Restores Neural Variability in Older, Poorer Performing Adults.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Trial
- Fronto-striatal dopamine D2 receptor availability is associated with cognitive variability in older individuals with low dopamine integrity.Scientific reports · 2021Trial
- Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD.NeuroImage. Clinical · 2017Trial
- Dopaminergic mechanisms supporting hippocampal postencoding dynamics in humans.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The biological role of local and global fMRI BOLD signal variability in multiscale human brain organization.Nature communications · 2026Article
- BOLD complexity characterizes glioblastoma survival via voxel-wise and localized sample entropy.Journal of neuro-oncology · 2026Article
- 10-year longitudinal dopamine D2-receptor losses are associated with cognitive decline in healthy aging.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Neural variability in the default mode network compresses with increasing belief precision during Bayesian inference.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Modulation of brain signal variability in visual cortex reflects aging, GABA, and behavior.eLife · 2025Article
- Age-related changes in brain signal variability in autism spectrum disorder.Molecular autism · 2025Article
- Review
- Broadscale dampening of uncertainty adjustment in the aging brain.Nature communications · 2024Article
- Electroencephalography Spectral-power Volatility Predicts Problem-solving Outcomes.Journal of cognitive neuroscience · 2024Article
- Local signal variability and functional connectivity: Sensitive measures of the excitation-inhibition ratio?Cognitive neurodynamics · 2024Article
- Hyper-brain hyper-frequency network topology dynamics when playing guitar in quartet.Frontiers in human neuroscience · 2024Article
- Chemogenetic inhibition of dopaminergic neurons reduces stimulus-induced dopamine release, thereby altering the hemodynamic response function in the prefrontal cortex.Imaging neuroscience (Cambridge, Mass.) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.