Fatigue relief through neuroimaging-informed neuromodulation: A perspective from the Italian Society of Neuromodulation and Neurotechnologies

Physiological fatigue is a universal adaptive experience reflecting the need to recover resources after sustained effort and typically resolves with adequate rest. When this restorative process fails and the lack of energy persists, fatigue may become chronic and interfere with daily functioning. Chronic fatigue is a multidimensional construct encompassing central and peripheral, cognitive and physical components, whose relative contribution varies across individuals and clinical conditions. Here, we use the term "fatigue" to refer to a persistent lack of physical and mental energy that substantially interferes with daily functioning and quality of life. At present, its severity is primarily assessed using validated patient-reported outcome measures, such as the modified Fatigue Impact Scale (mFIS), while objective biomarkers suitable for routine clinical use are still lacking. As such, fatigue is one of the most prevalent and disabling symptoms across clinical and non-clinical conditions. Recent international initiatives have emphasized the need to clarify the biological mechanisms underlying fatigue and its relationship with brain–body regulation (Raizen et al., 2023). Accumulating evidence suggests that fatigue is not necessarily irreversible and may be mitigated through targeted interventions. While no pharmacological treatment is currently established for chronic fatigue across conditions, and available medications may be associated with relevant adverse effects, behavioral interventions —including cognitive-behavioral therapy, physical activity, mindfulness, and yoga— have consistently shown beneficial effects (De Ventura et al., 2026). Accordingly, behavioral interventions remain the first-line approach. When these prove insufficient to restore functional balance, neuromodulation may help restore altered brain network dynamics.