Modulating subjective & objective cognitive state fatigue in long COVID with repetitive anodal tDCS...double-blinded RCT, 2026, Mischke

[Dolphin]

Modulating subjective and objective cognitive state fatigue in long COVID with repetitive anodal tDCS: results from a double-blinded randomized controlled trial - BMC Neuroscience

Background Cognitive fatigue is a frequently reported and debilitating symptom of long COVID, yet effective therapeutic interventions remain limited. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) has been proposed as a promising approach to...

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Modulating subjective and objective cognitive state fatigue in long COVID with repetitive anodal tDCS: results from a double-blinded randomized controlled trial​

• Research
• Open access
• Published: 24 January 2026
• Volume 27, article number 6, (2026)
• Cite this article

You have full access to this open access article

• Magdalena Mischke &
• Tino Zaehle

Abstract​

Background​

Cognitive fatigue is a frequently reported and debilitating symptom of long COVID, yet effective therapeutic interventions remain limited. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) has been proposed as a promising approach to modulate fatigue-related neural networks. To comprehensively assess cognitive fatigue, the integration of subjective and objective behavioral and electrophysiological measures of induced state fatigue is essential.

Methods​

This double-blind, randomized, sham-controlled study investigated the effects of four consecutive daily sessions of 30-minute anodal tDCS over the left dlPFC on subjective and objective markers of cognitive state fatigue in individuals with long COVID. The present paper focuses on secondary outcomes, including subjective state fatigue ratings via visual analogue scales, behavioral performance indices, and electrophysiological markers such as temporal alterations of frontal theta and occipital alpha activity as well as p50 sensory gating.

Results​

Forty participants received either verum or sham tDCS while completing a gamified adaptive Go/No-Go task. Before and after the stimulation period, cognitive state fatigue was reliably induced using the AX-Continuous Performance Task (AX-CPT). Although tDCS did not significantly affect subjective state-fatigue ratings or behavioral performance, our findings indicate that verum stimulation may stabilize fatigue-related changes in occipital alpha power. No immediate stimulation-related improvements were found in the Go/No-Go task.

Conclusions​

These findings indicate that while tDCS may modulate neurophysiological correlates of cognitive state fatigue, its impact on subjective experience and behavioral performance remain limited under the current protocol. These results, however, underscore the importance of including neurophysiological endpoints in intervention research and highlight the need for developing more robust and individualized stimulation protocols. Future studies should consider extended stimulation regimens, alternative task paradigms, and more sensitive behavioral measures to further elucidate the neuromodulatory potential of tDCS in long COVID-related cognitive fatigue.

Trial registration​

drks.de Identifier: DRKS00031294, date of registration: 17.02.2023

 

[Sean]

These results, however, underscore the importance of including neurophysiological endpoints in intervention research and highlight the need for developing more robust and individualized stimulation protocols. Future studies should consider extended stimulation regimens, alternative task paradigms, and more sensitive behavioral measures to further elucidate the neuromodulatory potential of tDCS in long COVID-related cognitive fatigue.​

Or, it failed to show any meaningful benefit nor hence promise. Any further research in this area needs to be reconsidered.

 

[Turtle]

4 consecutive daily sessions. Going to a testing facility 4 days in a row.
For me that would have been a reason not to take part in this study.

 

[Eleanor]

They say:

the modest sample size, between-subjects design, and exclusion of severely affected individuals - due to the risk of post-exertional malaise (PEM) - reduced statistical power and generalizability. PEM remains a central challenge in long COVID research

(does that mean they think only severe patients get PEM?)

 

[Eleanor]

behavioral performance remained stable across time and showed no sensitivity to fatigue induction. No differential effects between stimulation groups were observed. Despite increasing subjective state fatigue, performance remained stable. This dissociation between subjective and behavioral indices may reflect compensatory engagement of cognitive control resources, enabling participants to maintain performance despite rising state fatigue [18].

Ref 18 is Linnhoff S, Fiene M, Heinze H-J, Zaehle T. Cognitive fatigue in multiple sclerosis: an objective approach to diagnosis and treatment by transcranial electrical stimulation. Brain Sci. 2019 May;9(5):100. https://doi.org/10.3390/brainsci9050100.