Figure 1.
Non-invasive brain stimulation (NIBS) techniques for the treatment of individual pathomechanisms of Long-COVID-related fatigue (LCOF). Transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to have anti-inflammatory effects through its efferent projections, the so-called cholinergic anti-inflammatory pathway (1 81), and could have a stabilizing effect on the dysregulated immune-system after an acute COVID-19 infection that could lead to LCOF. First positive effects support this hypothesis and show a reduction of mental fatigue in people with LCOF after repetitive taVNS sessions (2 16). Transcranial direct current stimulation (tDCS) and alternating current stimulation (tACS) have been shown to modulate neuronal responsiveness (3 78) and to induce long-term effects via long-term potentiation (4 82). They could therefore be used to counteract the observed frontoparietal hypometabolism after an acute COVID-19 infection that has been associated with LCOF. Preliminary data to support this hypotheses show positive effects on self-reported fatigue scores after repetitive sessions in people with LCOF (5 83, 6 84). Following neuronal acitivity or via direct vascular responses, tDCS and tACS have also been shown to increase cerebral blood flow (7 85). Therefore they might also be an optimal strategy to counteract the observed blood flow reduction in people with LCOF. However, while several data exists that has shown increased cerebral blood flow after tDCS and tACS in healthy subjects and other neurological diseases, no data exists for LCOF.