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Cited by 11Transcranial Magnetic Stimulation StudiesMultiple Sclerosis Research StudiesTraumatic Brain Injury Research

Effects of repetitive twice-weekly transcranial direct current stimulations on fatigue and fatigability in people with multiple sclerosis

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Linnhoff, Stefanie, Haghikia, Aiden, Zaehle, Tino·2023·Scientific Reports
DOI 10.1038/s41598-023-32779-yPMC PMC10090173

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Abstract

Fatigue is associated with a dramatically decreased quality of life in people with multiple sclerosis (pwMS). It refers to a constant subjective feeling of exhaustion and performance decline, known as fatigability. However, inconsistency and heterogeneity in defining and assessing fatigue have led to limited advances in understanding and treating MS-associated fatigue. Transcranial direct current stimulation (tDCS) has emerged as a promising, non-pharmaceutical treatment strategy for subjective fatigue. However, whether repetitive tDCS also have long-term effects on time-on-task performance has not yet been investigated. This pseudorandomized, single-blinded, and sham-controlled study investigated tDCS effects on behavioral and electrophysiological parameters. 18 pwMS received eight twice-weekly 30 min stimulations over the left dorsolateral prefrontal cortex. Fatigability was operationalized as time-on-task-related changes in reaction time variability and P300 amplitude. Additionally, subjective trait and state fatigue ratings were assessed. The results revealed an overall decrease in subjective trait fatigue ratings that lasted at least four weeks after the stimulations. However, the ratings declined after both anodal and sham tDCS. No effects were found on subjective state fatigue and objective fatigability parameters. Linear Mixed Models and Bayesian Regression models likewise favored the absence of a tDCS effect on fatigability parameters. The results confirm the complex relationship between MS-associated fatigue and fatigability. Reliable and clinically relevant parameters need to be established to extend the potential of tDCS for treating fatigability. Furthermore, our results indicate that consecutive stimulations rather than twice-weekly stimulations should be the preferred stimulation scheme in future studies.

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  • Our findings align with prior studies on neuromodulation.

    “Yet, our findings align with prior studies on neuromodulation, which highlight placebo effects driven by interpersonal dynamics and participant expectations, that could overshadow tDCS-specific effects [10].”

    From Evaluating the efficacy of repetitive anodal transcranial direct current stimulation on cognitive fatigue in long COVID: A randomized controlled trial (2025) · cites this paper as [10]

    The Discussion’s “Placebo effect” section says that positive experimenter–participant interactions likely promoted a stimulation-independent placebo effect. It also reports that placebo effects in a prior tDCS study may have partially masked anodal effects. The paper does not identify participant expectations as a driver, so that part of the attributed claim is unsupported. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Placebo effects driven by interpersonal dynamics and participant expectations could overshadow tDCS-specific effects.

    “which highlight placebo effects driven by interpersonal dynamics and participant expectations, that could overshadow tDCS-specific effects [10].”

    From Evaluating the efficacy of repetitive anodal transcranial direct current stimulation on cognitive fatigue in long COVID: A randomized controlled trial (2025) · cites this paper as [10]

    The Discussion’s “Placebo effect” section links the observed placebo effect to positive experimenter–participant interactions and reports that placebo effects may partially mask anodal tDCS effects. It does not identify participant expectations as a driver of those effects. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Linnhoff, S., Haghikia, A., & Zaehle, T.
Affiliations
  • Otto-von-Guericke-Universität Magdeburg (DE)
  • German Center for Neurodegenerative Diseases (DE)
  • Center for Behavioral Brain Sciences (DE)
Corresponding author
Zaehle, Tino
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-04-11
Volume
13
Issue
1
Pages
5878-5878
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-32779-y
PMC
PMC10090173
OpenAlex
W4364378129
Cited by
11
References
1
Citations by year
2026: 4 · 2025: 5 · 2024: 2
FWCI
1.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DZNE Pub (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Gemeinnützige Hertie-Stiftung (P1180018)
  • Otto-von-Guericke-Universität Magdeburg
Topics
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
multiple sclerosis, fatigue, fatigability, transcranial direct current stimulation, dorsolateral prefrontal cortex, reaction time variability, P300 amplitude, stimulation frequency
MeSH terms
Dorsolateral Prefrontal Cortex, Bayes Theorem, Fatigue, Humans, Multiple Sclerosis, Quality of Life, Reaction Time, Task Performance and Analysis, Single-Blind Method, Transcranial Direct Current Stimulation

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