{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:07:23Z","timestamp":1784700443786,"version":"3.55.0"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Cognitive reserve (CR) is associated with better cognitive outcomes in people with multiple sclerosis (PwMS), yet the neurophysiological factors mediating this relationship remain poorly understood. In this context, alpha (\n                      <jats:italic>\u03b1<\/jats:italic>\n                      ) oscillatory activity has been linked to both CR and semantic processing, making it a plausible neural mediator of reserve-related resilience. We investigated whether resting-state \u03b1 activity statistically mediates the relationship between CR and semantic verbal fluency (SVF) in PwMS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty-four PwMS and 46 age- and sex-matched healthy controls underwent resting-state electroencephalography to compute cortical global spectral power. CR was assessed using the Cognitive Reserve Index questionnaire, and verbal fluency was evaluated with the semantic and phonemic verbal fluency tests. Regression and mediation analyses examined associations among CR, spectral power, and verbal fluency, adjusted for demographic, clinical, and patient-reported factors. Exploratory moderated mediation analyses assessed potential variation across levels of disability and perceived disease impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PwMS exhibited reduced upper \u03b1 power (\u03b12; 10\u201313\u202fHz) compared with healthy controls. \u03b12 power statistically mediated the relationship between CR and SVF, such that individuals with higher CR showed \u03b12 activity closer to healthy norms, which in turn was associated with better SVF performance. No such associations were observed for phonemic verbal fluency, and this mediation was not replicated in healthy controls. Regional analyses indicated that these indirect effects were most evident in bilateral frontal, left central, and right parietal regions. The mediation was not formally moderated by disease burden, although conditional indirect effects suggested the CR\u202f\u2192\u202f\u03b12\u202f\u2192\u202fSVF path was present at moderate and moderate-to-high levels of physical disability and perceived disease impact, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that preserved \u03b12 oscillatory activity is a candidate neurophysiological mechanism linking CR and semantic-language functioning in PwMS. To the best of our knowledge, this is the first study in MS to jointly examine CR, oscillatory preservation, and SVF within a single analytical framework, advancing current understanding of the neural basis of reserve-related resilience in PwMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      , identifier NCT04806568.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1869738","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:56:21Z","timestamp":1784699781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preserved \u03b12 oscillations underpin reserve-related resilience of semantic verbal fluency in multiple sclerosis"],"prefix":"10.3389","volume":"20","author":[{"given":"Alexandra","family":"Anagnostopoulou","sequence":"first","affiliation":[{"name":"Medical Physics and Digital Innovation Laboratory, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]},{"name":"Department of Electrical and Computer Engineering, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis E.","family":"Kartsidis","sequence":"additional","affiliation":[{"name":"Medical Physics and Digital Innovation Laboratory, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nefeli","family":"Tsoukaki","sequence":"additional","affiliation":[{"name":"Medical Physics and Digital Innovation Laboratory, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Karagianni","sequence":"additional","affiliation":[{"name":"Medical Physics and Digital Innovation Laboratory, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Melanitis","sequence":"additional","affiliation":[{"name":"AINIGMA Technologies, Innovation and Incubation Center KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasia","family":"Liozidou","sequence":"additional","affiliation":[{"name":"Laboratory of Cognitive Neuroscience and Clinical Neuropsychology, Scientific College of Greece","place":["Athens, Greece"]},{"name":"1st Neurology Department, Athens Medical School, National and Kapodistrian University of Athens","place":["Athens, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Nikolaidis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hippokration General Hospital of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Chatzichristos","sequence":"additional","affiliation":[{"name":"AINIGMA Technologies, Innovation and Incubation Center KU Leuven","place":["Leuven, Belgium"]},{"name":"Department of Electrical Engineering, STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahe","family":"Poghosyan","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology, National Neuroscience Institute, King Fahad Medical City","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Grigoriadis","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, 2nd Department of Neurology, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leontios J.","family":"Hadjileontiadis","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]},{"name":"Department of Biomedical Engineering and Biotechnology, Khalifa University of Science and Technology","place":["Abu Dhabi, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis D.","family":"Bamidis","sequence":"additional","affiliation":[{"name":"Medical Physics and Digital Innovation Laboratory, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charis","family":"Styliadis","sequence":"additional","affiliation":[{"name":"Medical Physics and Digital Innovation Laboratory, Aristotle University of Thessaloniki","place":["Thessaloniki, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e0222929","DOI":"10.1371\/journal.pone.0222929","article-title":"Cognitive impairment in multiple sclerosis: an exploratory analysis of environmental and lifestyle risk factors","volume":"14","author":"Amato","year":"2019","journal-title":"PLoS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1037\/1040-3590.10.2.176","article-title":"Psychometric properties of the 42-item and 21-item versions of the depression anxiety stress scales in clinical groups and a community 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