{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:31:17Z","timestamp":1788877877163,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"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. Neurol."],"abstract":"<jats:p>Cognitive fatigue is among the most pervasive and disabling symptoms experienced by individuals with multiple sclerosis (MS), yet it remains underrecognized and undertreated in both research and clinical settings. Despite its prevalence, cognitive fatigue is often confused with general fatigue or overlooked in standard neuropsychological assessments that rely on brief, decontextualized performance measures. This perspective argues for a paradigmatic shift in how cognitive fatigue is conceptualized and managed. This perspective define it as a core, dynamic dysfunction affecting the cognitive system\u2019s capacity to sustain effort over time, distinct from both general and subjective fatigue. A growing body of evidence, highlighted in this article, shows a frequent dissociation between perceived fatigue and objective fatigability, underscoring a fundamental flaw in current assessment tools. The authors call for the integration of prolonged, dynamic, and ecologically valid measures, such as extended neuropsychological tasks and digital phenotyping, into clinical protocols. We propose repositioning cognitive fatigue as a distinct clinical target, requiring its own specific strategies for identification, monitoring, and intervention. Reframing cognitive fatigue in this way offers a critical step toward more accurate diagnostics and truly individualized care, bridging the gap between clinical findings and the patient\u2019s lived experience.<\/jats:p>","DOI":"10.3389\/fneur.2025.1664734","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:17:28Z","timestamp":1759897048000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Tired minds, normal scores: rethinking cognitive fatigue in multiple sclerosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Davide","family":"Spinetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignazio Roberto","family":"Zarbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/S1474-4422(14)70250-9","article-title":"Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis","volume":"14","author":"Rocca","year":"2015","journal-title":"Lancet Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/S1474-4422(08)70259-X","article-title":"Cognitive impairment in multiple sclerosis","volume":"7","author":"Chiaravalloti","year":"2008","journal-title":"Lancet Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1177\/135245850000600308","article-title":"Fatigue in multiple sclerosis and its relationship to depression and neurologic disability","volume":"6","author":"Bakshi","year":"2000","journal-title":"Mult Scler"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1586\/ern.10.99","article-title":"Multiple sclerosis-associated fatigue","volume":"10","author":"Krupp","year":"2010","journal-title":"Expert Rev Neurother"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3390\/brainsci9050100","article-title":"Cognitive fatigue in multiple sclerosis: an objective approach to diagnosis and treatment by transcranial electrical stimulation","volume":"9","author":"Linnhoff","year":"2019","journal-title":"Brain Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/S0140-6736(04)15794-2","article-title":"Fatigue in neurological disorders","volume":"363","author":"Chaudhuri","year":"2004","journal-title":"Lancet"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jns.2008.01.018","article-title":"Neural correlates of cognitive fatigue in multiple sclerosis using functional MRI","volume":"270","author":"DeLuca","year":"2008","journal-title":"J Neurol Sci"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1212\/WNL.0b013e31827f07be","article-title":"Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy","volume":"80","author":"Kluger","year":"2013","journal-title":"Neurology"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"460","DOI":"10.3389\/fncel.2015.00460","article-title":"Fatigue in multiple sclerosis: neural correlates and the role of non-invasive brain stimulation","volume":"9","author":"Chalah","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1212\/wnl.55.7.934","article-title":"Fatigue and declines in cognitive functioning in multiple sclerosis","volume":"55","author":"Krupp","year":"2000","journal-title":"Neurology"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"103316","DOI":"10.1016\/j.msard.2021.103316","article-title":"Predictors of cognitive fatigue and fatigability in multiple sclerosis","volume":"56","author":"Mackay","year":"2021","journal-title":"Mult Scler Relat Disord"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1076\/jcen.26.2.200.28081","article-title":"Self-reported everyday memory and depression in patients with multiple sclerosis","volume":"26","author":"Bruce","year":"2004","journal-title":"J Clin Exp Neuropsychol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/WNN.0000000000000097","article-title":"Cognitive impairment in multiple sclerosis: a review of neuropsychological assessments","volume":"29","author":"Korakas","year":"2016","journal-title":"Cogn Behav Neurol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e78811","DOI":"10.1371\/journal.pone.0078811","article-title":"Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging","volume":"8","author":"Genova","year":"2013","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/arclin\/acy014","article-title":"Predictive models of cognitive fatigue in multiple sclerosis","volume":"34","author":"Berard","year":"2019","journal-title":"Arch Clin Neuropsychol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1231321","DOI":"10.3389\/fnins.2023.1231321","article-title":"Management of multiple sclerosis fatigue in the digital age: from assessment to treatment","volume":"17","author":"Pinarello","year":"2023","journal-title":"Front Neurosci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1111\/j.1468-1331.2009.02776.x","article-title":"Fatigue and processing speed are related in multiple sclerosis","volume":"17","author":"Andreasen","year":"2010","journal-title":"Eur J Neurol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"104229","DOI":"10.1016\/j.msard.2022.104229","article-title":"The symbol digit modalities test and the paced auditory serial addition test involve more than processing speed","volume":"68","author":"Berrigan","year":"2022","journal-title":"Mult Scler Relat Disord"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3389\/fneur.2014.00214","article-title":"Subjective cognitive fatigue in multiple sclerosis depends on task length","volume":"5","author":"Sandry","year":"2014","journal-title":"Front Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1177\/1545968314552529","article-title":"Reduced dual-task performance in MS patients is further decreased by muscle fatigue","volume":"29","author":"Wolkorte","year":"2015","journal-title":"Neurorehabil Neural Repair"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3390\/bioengineering11030277","article-title":"Evaluating cognitive-motor interference in multiple sclerosis: a technology-based approach","volume":"11","author":"Podda","year":"2024","journal-title":"Bioengineering (Basel)"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1001\/archneur.61.2.201","article-title":"The relationship between diffuse axonal damage and fatigue in multiple sclerosis","volume":"61","author":"Tartaglia","year":"2004","journal-title":"Arch Neurol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1177\/1352458514555784","article-title":"Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue","volume":"21","author":"Finke","year":"2015","journal-title":"Mult Scler"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.1212\/WNL.0b013e318296e98b","article-title":"Brain reserve and cognitive reserve in multiple sclerosis: what you've got and how you use it","volume":"80","author":"Sumowski","year":"2013","journal-title":"Neurology"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/s0022-510x(00)00411-1","article-title":"Fatigue and basal ganglia","volume":"179","author":"Chaudhuri","year":"2000","journal-title":"J Neurol Sci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1194859","DOI":"10.3389\/fnins.2023.1194859","article-title":"Dysfunction of basal ganglia functional connectivity associated with subjective and cognitive fatigue in multiple sclerosis","volume":"17","author":"Langley","year":"2023","journal-title":"Front Neurosci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1049686","DOI":"10.3389\/fmed.2022.1049686","article-title":"Real-time associations among MS symptoms and cognitive dysfunction using ecological momentary assessment","volume":"9","author":"Chen","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev.clinpsy.3.022806.091415","article-title":"Ecological momentary assessment","volume":"4","author":"Shiffman","year":"2008","journal-title":"Annu Rev Clin Psychol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1514813","DOI":"10.3389\/fimmu.2025.1514813","article-title":"Digital remote monitoring of people with multiple sclerosis","volume":"16","author":"Dini","year":"2025","journal-title":"Front Immunol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e5","DOI":"10.2196\/rehab.7805","article-title":"The use of digital and remote communication technologies as a tool for multiple sclerosis management: narrative review","volume":"5","author":"Marziniak","year":"2018","journal-title":"JMIR Rehabil Assist Technol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.jns.2012.01.021","article-title":"Detecting cognitive fatigue in multiple sclerosis: method matters","volume":"316","author":"Walker","year":"2012","journal-title":"J Neurol Sci"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1017\/S1355617709090535","article-title":"Examination of processing speed deficits in multiple sclerosis using functional magnetic resonance imaging","volume":"15","author":"Genova","year":"2009","journal-title":"J Int Neuropsychol Soc"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1177\/1352458509348519","article-title":"The fatigue scale for motor and cognitive functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue","volume":"15","author":"Penner","year":"2009","journal-title":"Mult Scler"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1097\/NPT.0000000000000452","article-title":"Self-report measures of fatigue for people with multiple sclerosis: a systematic review","volume":"48","author":"Cohen","year":"2024","journal-title":"J Neurol Phys Ther"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1177\/1352458517751049","article-title":"ECTRIMS\/EAN guideline on the pharmacological treatment of people with multiple sclerosis","volume":"24","author":"Montalban","year":"2018","journal-title":"Mult Scler"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"S8","DOI":"10.1212\/WNL.0b013e3181dbb571","article-title":"The multiple sclerosis functional composite: a clinically meaningful measure of disability","author":"Polman","year":"2010","journal-title":"Neurology"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1191\/1352458502ms845oa","article-title":"The multiple sclerosis functional composite: a new clinical outcome measure for multiple sderosis trials","volume":"8","author":"Rudick","year":"2002","journal-title":"Mult Scler"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jns.2012.08.007","article-title":"Fatigue in multiple sclerosis - a brief review","volume":"323","author":"Induruwa","year":"2012","journal-title":"J Neurol Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"225","DOI":"10.2165\/00023210-200317040-00002","article-title":"Fatigue in multiple sclerosis: definition, pathophysiology and treatment","volume":"17","author":"Krupp","year":"2003","journal-title":"CNS Drugs"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1080\/10790268.2016.1168587","article-title":"Central fatigue in multiple sclerosis: a review of the literature","volume":"39","author":"Newland","year":"2016","journal-title":"J Spinal Cord Med"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1177\/1352458509106213","article-title":"Subjective fatigue is not associated with cognitive impairment in multiple sclerosis: cross-sectional and longitudinal analysis","volume":"15","author":"Morrow","year":"2009","journal-title":"Mult Scler"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1177\/1352458519860318","article-title":"Beyond cognitive dysfunction: Relevance of ecological validity of neuropsychological tests in multiple sclerosis","volume":"25","author":"Weber","year":"2019","journal-title":"Mult Scler"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"CD009131","DOI":"10.1002\/14651858.CD009131.pub3","article-title":"Neuropsychological rehabilitation for multiple sclerosis","author":"Rosti\u2010Otaj\u00e4rvi","year":"2014","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"ref44","article-title":"Treatment of fatigue in multiple sclerosis: a systematic review of the literature","author":"Lee","year":"2008","journal-title":"Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1664734\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T04:17:28Z","timestamp":1759897048000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1664734\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":44,"alternative-id":["10.3389\/fneur.2025.1664734"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1664734","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]},"article-number":"1664734"}}