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

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