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We analyzed functional connectivity and variability (measured as the standard deviation of BOLD signal amplitude) in resting state networks (RSNs) associated with cognitive deficits in different frequency bands in 25 PP-MS patients (12\u2009M, mean age 50.9\u2009\u00b1\u200910.5 years) and 20 healthy subjects (9\u2009M, mean age 51.0\u2009\u00b1\u20099.8 years). We confirmed the presence of a widespread cognitive deterioration in PP-MS patients, with main involvement of visuo-spatial and executive domains. Cognitively impaired patients showed increased variability, reduced synchronicity between networks involved in the control of cognitive macro-domains and hyper-synchronicity limited to the connections between networks functionally more segregated. CL volume was higher in patients with cognitive impairment and was correlated with functional connectivity and variability. We demonstrate, for the first time, that a functional reorganization characterized by hypo-synchronicity of functionally-related\/hyper-synchronicity of functionally-segregated large scale networks and an abnormal pattern of neural activity underlie cognitive dysfunction in PP-MS, and that CLs possibly play a role in variability and functional connectivity abnormalities.<\/jats:p>","DOI":"10.1038\/srep46411","type":"journal-article","created":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T09:48:05Z","timestamp":1492768085000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Synchronization and variability imbalance underlie cognitive impairment in primary-progressive multiple sclerosis"],"prefix":"10.1038","volume":"7","author":[{"given":"Maria","family":"Petracca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Saiote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi A.","family":"Bender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franchesca","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Farrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Magioncalda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Martino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Northoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Lublin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Inglese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,21]]},"reference":[{"key":"BFsrep46411_CR1","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1212\/WNL.0b013e31828cf82f","volume":"80","author":"A Ruet","year":"2013","unstructured":"Ruet, A., Deloire, M., Charr\u00e9-Morin, J., Hamel, D. & Brochet, B. 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Dr. Catarina Saiote has nothing to disclose. Dr. Bender has nothing to disclose. Ms. Arias has nothing to disclose. Ms. Colleen Farrell has nothing to disclose. Dr. Magioncalda has nothing to disclose. Dr. Martino has nothing to disclose. Dr. Aaron Miller has served as a consultant and\/or participant in advisory board meetings for Genzyme\/sanofi-aventis, Biogen Idec, Glaxo Smith Kline, EMD Serono (Merck Serono), Novartis, ONO, Acorda, Nuron Biotech, Teva, Questcor and Accordant Health Services. He has received research support from Acorda, Novartis, Genentech, Genzyme\/sanofi-aventis, Biogen Idec, Roche, and Questcor. He has served as Editor of Continuum, a continuing medical education publication of the AAN and currently serves as Editor of Continuum Audio. He is a member of the editorial board of Multiple Sclerosis and Related Disorders. He occasionally performs expert reviews of medical records or serves as an expert witness in medical malpractice cases. Dr. Northoff has nothing to disclose. Dr. Fred Lublin Sources of Funding for Research: Acorda Therapeutics, Inc.; Biogen Idec; Novartis Pharmaceuticals Corp; Teva Neuroscience, Inc.; Genzyme; Sanofi; Celgene; NIH; NMSS; Consulting Agreements\/Advisory Boards\/DSMB: Bayer HealthCare Pharmaceuticals; Biogen Idec; EMD Serono, Inc.; Novartis; Teva Neuroscience; Actelion; Sanofi-Aventis; Acorda; Questcor; Roche, Genentech; Celgene; Johnson & Johnson; Revalesio; Coronado Bioscience, Genzyme, MedImmune; Bristol-Myers Squibb, Xenoport, Receptos; Forward Pharma; Co-Chief Editor: Multiple Sclerosis and Related Diseases; Stock Ownership: Cognition Pharmaceuticals, Inc. Dr. Matilde Inglese has received research grants from NIH, NMSS, Novartis Pharmaceuticals Corp., Teva Neuroscience. None of the competing financial interests have influenced the presented work in any stage from conception to analysis and publication.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"46411"}}