ReviewFrontiers in neurology2015
The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders.
Review in Frontiers in neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 3 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
118 citing papers in PubMed, 3 syntheses or guidelines pooled it, 236 citations in OpenAlex.
- Internet-based digital interventions on rehabilitation for patients after anterior cruciate ligament reconstruction surgery: a systematic review and meta-analysis.BMC musculoskeletal disorders · 2026Pooled it
- Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: A systematic review.PloS one · 2024Pooled it
- Neurostructural and Neurophysiological Correlates of Multiple Sclerosis Physical Fatigue: Systematic Review and Meta-Analysis of Cross-Sectional Studies.Neuropsychology review · 2022Pooled it
- The effect of white noise on sleep quality and fatigue in community-dwelling older adults: a randomized controlled trial.BMC geriatrics · 2026Trial
- ESTREL-Fatigue-association of levodopa with post-stroke fatigue.European stroke journal · 2026Trial
- Using functional connectivity changes associated with cognitive fatigue to delineate a fatigue network.Scientific reports · 2020Trial
- Modafinil treatment modulates functional connectivity in stroke survivors with severe fatigue.Scientific reports · 2019Trial
- Neural correlates of perceived physical and mental fatigability in older adults: A pilot study.Experimental gerontology · 2019Trial
- Trial
- Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial.Medicine · 2016Trial
- Towards a domain-general mechanistic model of fatigue: application to Functional Neurological Disorder.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Article
- Associations Between Neuromuscular Fatigue, Anxiety, and Peripheral Biomarkers of Neuronal Injury, Inflammation, and Mitochondrial Dysfunction in Treatment-Naïve Relapsing-Remitting Multiple Sclerosis.Brain and behavior · 2026Article
- Vertical saccadic slowing is associated with fatigue in multiple sclerosis.Fatigue : biomedicine, health & behavior · 2026Article
- Brain fatigue in Graves' disease: symptoms and presentation of a possible mechanism at the cellular level.European thyroid journal · 2026Review
- Associations of Plasma Homocysteine Reflecting Vitamin BNutrients · 2026Article
- The critical role of the basal ganglia in post-stroke fatigue: A pilot study.Neuroimage. Reports · 2026Article
- Article
- Electrochemical measurements at human iPSC-derived FOXA2 dopaminergic neurons suggest a role for partial release in presynaptic plasticity.QRB discovery · 2026Article
- Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fatigue is one of the most pervasive symptoms of multiple sclerosis (MS), and has engendered hundreds of investigations on the topic. While there is a growing literature using various methods to study fatigue, a unified theory of fatigue in MS is yet to emerge. In the current review, we synthesize findings from neuroimaging, pharmacological, neuropsychological, and immunological studies of fatigue in MS, which point to a specific hypothesis of fatigue in MS: the dopamine imbalance hypothesis. The communication between the striatum and prefrontal cortex is reliant on dopamine, a modulatory neurotransmitter. Neuroimaging findings suggest that fatigue results from the disruption of communication between these regions. Supporting the dopamine imbalance hypothesis, structural and functional neuroimaging studies show abnormalities in the frontal and striatal regions that are heavily innervated by dopamine neurons. Further, dopaminergic psychostimulant medication has been shown to alleviate fatigue in individuals with traumatic brain injury, chronic fatigue syndrome, and in cancer patients, also indicating that dopamine might play an important role in fatigue perception. This paper reviews the structural and functional neuroimaging evidence as well as pharmacological studies that suggest that dopamine plays a critical role in the phenomenon of fatigue. We conclude with how specific aspects of the dopamine imbalance hypothesis can be tested in future research.
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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.