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

**Authors:** Magdalena Mischke, Tino Zaehle

PMC · DOI: 10.1186/s12868-025-00989-x · BMC Neuroscience · 2026-01-24

## TL;DR

A study tested tDCS to reduce cognitive fatigue in long COVID patients but found limited effects on subjective and behavioral measures, though some neurophysiological changes were observed.

## Contribution

The study introduces a novel application of tDCS over the dlPFC to modulate cognitive fatigue in long COVID using combined subjective and objective measures.

## Key findings

- tDCS did not significantly affect subjective fatigue ratings or behavioral performance.
- Verum tDCS may stabilize fatigue-related changes in occipital alpha power.
- No immediate improvements were observed in the Go/No-Go task.

## Abstract

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.

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.

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.

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.

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

## Full-text entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** fatigability (MESH:D009759), cognitive exhaustion (MESH:D006359), deficits in executive functioning (MESH:D001289), hypoxic (MESH:D002534), seizure (MESH:D012640), Cognitive fatigue (MESH:D005221), neuroinflammation (MESH:D000090862), neurodegenerative disorders (MESH:D019636), psychiatric (MESH:D001523), infection (MESH:D007239), Long COVID (MESH:D000094024), Parkinson's disease (MESH:D010300), chronic inflammation (MESH:D007249), cardiac arrhythmias (MESH:D001145), structural abnormalities (MESH:C566527), MS (MESH:D009103), ischemic injury (MESH:D017202), cognitive fatigability (MESH:D003072), function (MESH:D003291), PEM (MESH:D000092202), impaired inhibitory control (MESH:D007174), Chronic Fatigue Syndrome (MESH:D015673), Frontal hypoactivity (MESH:D020018), Depression (MESH:D003866), COVID-19 (MESH:D000086382)
- **Chemicals:** AX-CPT (-), AX (MESH:D000658), CPT (MESH:C000708228)
- **Species:** Malus domestica (apple, species) [taxon 3750], Homo sapiens (human, species) [taxon 9606], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12849268/full.md

## References

15 references — full list in the complete paper: https://tomesphere.com/paper/PMC12849268/full.md

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Source: https://tomesphere.com/paper/PMC12849268