Fatigue relief: the contribution of non-invasive neuromodulation (FAREviaNM)

Fatigue is a universal and constructive experience, yet chronic fatigue-defined as a persistent lack of energy that limits daily life as assessed by modified Fatigue Impact Scale (mFIS)-remains nowadays a symptom waiting for effective mitigation. Evidence across neurological, oncological, and psychosocial conditions shows that fatigue shares a common neurophysiological substrate: disrupted sensory-motor imbalances and network synchrony that can be targeted by established interventions-physical activity, mindfulness, yoga, and cognitive-behavioral therapy. Within this landscape, non-invasive neuromodulation stands out as an effective and safe tool to restore sensorimotor balance to integrate behavioral interventions. The Faremus protocol, based on five daily sessions of 15-min bilateral anodic transcranial Direct Current Stimulation (tDCS) over the somatosensory cortex, has shown consistent clinical benefits in multiple sclerosis: an average 26% reduction in fatigue severity, persisting for weeks or months, with excellent tolerability and home-use feasibility. Converging meta-analyses, neurophysiological central and behavioral investigations, and reviews confirm the reproducibility and mechanistic validity of this approach, positioning neuromodulation among the most promising evidence-based strategies in supporting fatigue relief. This perspective highlights neuromodulation as a transversal instrument to counter fatigue across conditions, and as a cornerstone of integrated, multidisciplinary strategies aimed at preserving brain plasticity, enhancing resilience, and restoring sustained well-being.