{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:20:45Z","timestamp":1789906845542,"version":"4.0.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Integr. Neurosci."],"abstract":"<jats:p>Chronic fatigue is widely discussed across clinical and non-clinical contexts, yet its definition and measurement remain heterogeneous and debated. In this fragmented landscape, adopting an efficacy-informed perspective grounded in mitigating interventions offers a reliable pathway to delineate the core features and regulatory mechanisms of chronic fatigue. This Mini Review aims to identify and synthesize interventions shown to be effective in mitigating chronic fatigue. A preliminary screening was conducted using the terms \u201cfatigue\u201d AND (\u201crelief\u201d OR \u201cmitigation\u201d OR \u201ctreatment\u201d), thereby inherently focusing on persistent and functionally impairing forms of fatigue. The analysis was then restricted to the most cited evidence to highlight the most consolidated findings. Four classes of behavioral interventions consistently emerged as effective across heterogeneous conditions (stroke, cancer, multiple sclerosis, traumatic brain injury, and non-clinical contexts): cognitive behavioral therapy, mindfulness-based approaches, yoga, and physical activity. Their convergence suggests that chronic fatigue reflects, rather than condition-specific processes, the alteration of shared regulatory mechanisms, likely involving neurophysiological dynamics and associated biological markers, which can be further elucidated by integrating evidence from effective interventions with their neurophysiological and biomarker correlates. The evidence from this Mini Review on the transversal effectiveness of the same interventions supports leveraging their efficacy and the associated neurophysiological and biochemical changes to identify sensitive markers that track treatment response and inform the underlying mechanisms of fatigue. Future research should therefore prioritize standardized measures, shared markers, and personalized interventions, potentially supported by biochemical and neuromodulatory approaches.<\/jats:p>","DOI":"10.3389\/fnint.2026.1822424","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:27:10Z","timestamp":1780291630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Fatigue relief is possible"],"prefix":"10.3389","volume":"20","author":[{"given":"M.","family":"De Ventura","sequence":"first","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]},{"name":"Department of Psychology, \u201cSapienza\u201d University of Rome","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Mattioni","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]},{"name":"Department of Psychology, \u201cSapienza\u201d University of Rome","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"L\u2019Abbate","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]},{"name":"Italian Association of Multiple Sclerosis (AISM)","place":["Pescara, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Bertoli","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]},{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara","place":["Chieti, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Grifoni","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Persichilli","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Canelli","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]},{"name":"Faculty of Psychology, Uninettuno University","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"D\u2019Onofrio","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]},{"name":"Faculty of Psychology, Uninettuno University","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Paulon","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]},{"name":"Independent Researcher","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Tecchio","sequence":"additional","affiliation":[{"name":"Laboratory of Electrophysiology for Translational Neuroscience (LET\u2019S)\u2014ISTC, CNR","place":["Rome, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3825","DOI":"10.1002\/cncr.30815","article-title":"The efficacy of internet-based cognitive behavioral therapy for severely fatigued survivors of breast cancer compared with care as usual: a randomized controlled trial","volume":"123","author":"Abrahams","year":"2017","journal-title":"Cancer"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"449","DOI":"10.5812\/ircmj.3597","article-title":"Comparison of the effect of 8 weeks aerobic and yoga training on ambulatory function, fatigue and mood status in MS patients","volume":"15","author":"Ahmadi","year":"2013","journal-title":"Iran Red Crescent Med J"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"813965","DOI":"10.3389\/fneur.2022.813965","article-title":"Fatigue in multiple sclerosis: a review of the exploratory and therapeutic potential of non-invasive brain stimulation","volume":"13","author":"Ayache","year":"2022","journal-title":"Front. Neurol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"124703","DOI":"10.1155\/2012\/124703","article-title":"Effects of yoga interventions on fatigue: a meta-analysis","volume":"2012","author":"Boehm","year":"2012","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1037\/0022-3514.84.4.822","article-title":"The benefits of being present: mindfulness and its role in psychological well-being","volume":"84","author":"Brown","year":"2003","journal-title":"J. Pers. Soc. Psychol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1136\/bjsports-2020-102955","article-title":"World Health Organization 2020 guidelines on physical activity and sedentary behaviour","volume":"54","author":"Bull","year":"2020","journal-title":"Br. J. Sports Med."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"165410","DOI":"10.1155\/2012\/165410","article-title":"Effects of yoga on mental and physical health: a short summary of reviews","volume":"2012","author":"B\u00fcssing","year":"2012","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1177\/1352458517720528","article-title":"Personalized, bilateral whole-body somatosensory cortex stimulation to relieve fatigue in multiple sclerosis","volume":"24","author":"Cancelli","year":"2018","journal-title":"Mult. Scler. J."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1207\/s15327558ijbm1204_9","article-title":"Impact of Mindfulness-Based Stress Reduction (MBSR) on Sleep, Mood, Stress and Fatigue Symptoms in Cancer Outpatients","volume":"12","author":"Carlson","year":"2005","journal-title":"Int J Behav Med."},{"key":"ref10","first-page":"126","article-title":"Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research","volume":"100","author":"Caspersen","year":"1985","journal-title":"Public Health Rep"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1176\/ajp.154.3.408","article-title":"Cognitive behavior therapy for chronic fatigue syndrome: a randomized controlled trial","volume":"154","author":"Deale","year":"1997","journal-title":"Am J Psychiatry"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1093\/ije\/dyp147","article-title":"A systematic review of chronic fatigue, its syndromes and ethnicity: prevalence, severity, co-morbidity and coping. In","volume":"38","author":"Dinos","year":"2009","journal-title":"Int. J. Epidemiol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s10549-019-05278-w","article-title":"Yoga has a solid effect on cancer-related fatigue in patients with breast cancer: a meta-analysis","volume":"177","author":"Dong","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1186\/s12889-017-4623-y","article-title":"Fatigue in the general population associations to age, sex, socioeconomic status, physical activity, sitting time and self-rated health: the northern Sweden MONICA study 2014","volume":"17","author":"Engberg","year":"2017","journal-title":"BMC Public Health"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"S79","DOI":"10.1093\/clinids\/18.Supplement_1.S79","article-title":"Measuring the functional impact of fatigue: initial validation of the fatigue impact scale","volume":"18","author":"Fisk","year":"1994","journal-title":"Clin. Infect. Dis."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12904-020-00542-z","article-title":"Fatigue, barriers to physical activity and predictors for motivation to exercise in advanced Cancer patients","volume":"19","author":"Frikkel","year":"2020","journal-title":"BMC Palliat. Care"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"16311","DOI":"10.1038\/s41598-021-95084-6","article-title":"tDCS randomized controlled trials in no-structural diseases: a quantitative review","volume":"11","author":"Gianni","year":"2021","journal-title":"Sci. Rep."},{"key":"ref3001","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1634\/theoncologist.2010-0092","article-title":"Is increasing physical activity necessary to diminish fatigue during cancer treatment? Comparing cognitive behavior therapy and a brief nursing intervention with usual care in a multicenter randomized controlled trial","volume":"15","author":"Goedendorp","year":"2010","journal-title":"Oncologist"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cpr.2015.01.006","article-title":"How do mindfulness-based cognitive therapy and mindfulness-based stress reduction improve mental health and wellbeing? A systematic review and meta-analysis of mediation studies","volume":"37","author":"Gu","year":"2015","journal-title":"Clin. Psychol. Rev."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s10608-012-9476-1","article-title":"The efficacy of cognitive behavioral therapy: a review of Meta-analyses","volume":"36","author":"Hofmann","year":"2012","journal-title":"Cogn. Ther. Res."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"479","DOI":"10.2147\/NDT.S150464","article-title":"The effect of exercise on cancer-related fatigue in cancer survivors: a systematic review and meta-analysis","volume":"14","author":"Kessels","year":"2018","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1093\/brain\/awx153","article-title":"The fatigue conundrum","volume":"140","author":"Kuppuswamy","year":"2017","journal-title":"Brain"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1177\/1073858420985447","article-title":"The neurobiology of pathological fatigue: new models new questions","volume":"28","author":"Kuppuswamy","year":"2022","journal-title":"Neuroscientist"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.cpr.2007.10.004","article-title":"Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis","volume":"28","author":"Malouff","year":"2008","journal-title":"Clin. Psychol. Rev."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1152\/physrev.00041.2006","article-title":"Physiology and neurobiology of stress and adaptation: central role of the brain","volume":"87","author":"McEwen","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.critrevonc.2017.12.011","article-title":"Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: a systematic review and meta-analysis of randomized trials","volume":"122","author":"Oberoi","year":"2018","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.jpainsymman.2020.02.017","article-title":"Mindfulness-based cognitive therapy for psychological distress, fear of Cancer recurrence, fatigue, spiritual well-being, and quality of life in patients with breast Cancer\u2014a randomized controlled trial","volume":"60","author":"Park","year":"2020","journal-title":"J. Pain Symptom Manag."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/nrneurol.2017.117","article-title":"Fatigue as a symptom or comorbidity of neurological diseases","volume":"13","author":"Penner","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref3002","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.annonc.2019.09.002","article-title":"Cognitive behavioral therapy or graded exercise therapy compared with usual care for severe fatigue in patients with advanced cancer during treatment: a randomized controlled trial","volume":"31","author":"Poort","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/S0140-6736(00)04198-2","article-title":"Cognitive behaviour therapy for chronic fatigue syndrome","volume":"357","author":"Prins","year":"2001","journal-title":"Lancet"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"767","DOI":"10.2165\/00007256-200636090-00004","article-title":"Physical activity and feelings of energy and fatigue epidemiological evidence","volume":"36","author":"Puetz","year":"2006","journal-title":"Sports Med."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1080\/1359432X.2015.1015516","article-title":"Assessing the effect of a cognitive behaviour therapy (CBT)-based workshop on work-related rumination, fatigue, and sleep","volume":"25","author":"Querstret","year":"2016","journal-title":"Eur. J. Work Organ. Psychol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1093\/sleep\/zsad069","article-title":"Beyond the symptom: the biology of fatigue","volume":"46","author":"Raizen","year":"2023","journal-title":"Sleep"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s12883-020-01654-y","article-title":"The impact of physical exercise on the fatigue symptoms in patients with multiple sclerosis: a systematic review and meta-analysis","volume":"20","author":"Razazian","year":"2020","journal-title":"BMC Neurol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1002\/cpp.793","article-title":"Mindfulness-based cognitive therapy for people with chronic fatigue syndrome still experiencing excessive fatigue after cognitive behaviour therapy: a pilot randomized study","volume":"20","author":"Rimes","year":"2013","journal-title":"Clin. Psychol. Psychother."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.explore.2013.04.005","article-title":"Effects of yoga interventions on fatigue in cancer patients and survivors: a systematic review of randomized controlled trials","volume":"9","author":"Sadja","year":"2013","journal-title":"Explore"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.neubiorev.2009.10.005","article-title":"Motor control and aging: links to age-related brain structural, functional, and biochemical effects","volume":"34","author":"Seidler","year":"2010","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s11571-010-9111-3","article-title":"Electrophysiological correlates of listening effort: neurodynamical modeling and measurement","volume":"4","author":"Strauss","year":"2010","journal-title":"Cogn. Neurodyn."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"102576","DOI":"10.1016\/j.msard.2020.102576","article-title":"Tired of not knowing what that fatigue score means? Normative data of the modified fatigue impact scale (MFIS)","volume":"46","author":"Strober","year":"2020","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1136\/bmj.38301.587106.63","article-title":"Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial","volume":"330","author":"Stulemeijer","year":"2005","journal-title":"Br. Med. J."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"106276","DOI":"10.1016\/j.msard.2025.106276","article-title":"Fatigue relief in multiple sclerosis by personalized neuromodulation: a multicenter pilot study [FaremusGE]","volume":"94","author":"Tecchio","year":"2025","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1007\/s00415-014-7377-9","article-title":"Multiple sclerosis fatigue relief by bilateral somatosensory cortex neuromodulation","volume":"261","author":"Tecchio","year":"2014","journal-title":"J. Neurol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"103813","DOI":"10.1016\/j.msard.2022.103813","article-title":"Home treatment against fatigue in multiple sclerosis by a personalized, bilateral whole-body somatosensory cortex stimulation","volume":"63","author":"Tecchio","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/S42466-023-00273-5","article-title":"Resting state EEG as biomarker of cognitive training and physical activity\u2019s joint effect in Parkinson\u2019s patients with mild cognitive impairment","volume":"5","author":"Trenado","year":"2023","journal-title":"Neurol. Res. Pract."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"912","DOI":"10.3389\/fpsyg.2016.00912","article-title":"Clinical utility of mindfulness training in the treatment of fatigue after stroke, traumatic brain injury and multiple sclerosis: a systematic literature review and meta-analysis","volume":"7","author":"Ulrichsen","year":"2016","journal-title":"Front. Psychol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"104927","DOI":"10.1016\/j.msard.2023.104927","article-title":"Non-invasive brain stimulation on clinical symptoms in multiple sclerosis patients: a systematic review and meta-analysis","volume":"78","author":"Uygur-Kucukseymen","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.jpsychores.2016.09.002","article-title":"Effectiveness of cognitive behavioral therapy for the treatment of fatigue in patients with multiple sclerosis: a systematic review and meta-analysis","volume":"90","author":"van den Akker","year":"2016","journal-title":"J. Psychosom. Res."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1136\/jnnp-2022-330463","article-title":"Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis","volume":"94","author":"White","year":"2023","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.3389\/fphys.2018.01865","article-title":"The promise of stochastic resonance in falls prevention","volume":"9","author":"White","year":"2019","journal-title":"Front. Physiol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"109916","DOI":"10.1016\/j.jpsychores.2019.109916","article-title":"Mindfulness-based stress reduction can alleviate cancer related fatigue: a meta-analysis","volume":"130","author":"Xie","year":"2020","journal-title":"J. Psychosom. Res."},{"key":"ref49","first-page":"125","article-title":"Do yoga and aerobic exercise training have impact on functional capacity, fatigue, peripheral muscle strength, and quality of life in breast cancer survivors?","volume-title":"Integr. Cancer Ther.","author":"Ya\u0287li","year":"2015"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1192121","DOI":"10.3389\/fpubh.2023.1192121","article-title":"The demographic features of fatigue in the general population worldwide: a systematic review and meta-analysis","volume":"11","author":"Yoon","year":"2023","journal-title":"Front. Public Health"}],"container-title":["Frontiers in Integrative Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnint.2026.1822424\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:27:11Z","timestamp":1780291631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnint.2026.1822424\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":52,"alternative-id":["10.3389\/fnint.2026.1822424"],"URL":"https:\/\/doi.org\/10.3389\/fnint.2026.1822424","relation":{},"ISSN":["1662-5145"],"issn-type":[{"value":"1662-5145","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]},"article-number":"1822424"}}