• Kim A Meijer, Anand J C Eijlers, Geurts Jeroen J G JJG Department of Anatomy and Neurosciences, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands., and Menno M Schoonheim.
• Department of Anatomy and Neurosciences, VUmc MS Center Amsterdam, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
• J. Neurol. Neurosurg. Psychiatr. 2018 Feb 1; 89 (2): 205-210.

ObjectiveFunctional connectivity is known to increase as well as decrease throughout the brain in multiple sclerosis (MS), which could represent different stages of the disease. In addition, functional connectivity changes could follow the atrophy pattern observed with disease progression, that is, moving from the deep grey matter towards the cortex. This study investigated when and where connectivity changes develop and explored their clinical and cognitive relevance across different MS stages.MethodsA cohort of 121 patients with early relapsing-remitting MS (RRMS), 122 with late RRMS and 53 with secondary progressive MS (SPMS) as well as 96 healthy controls underwent MRI and neuropsychological testing. Functional connectivity changes were investigated for (1) within deep grey matter connectivity, (2) connectivity between the deep grey matter and cortex and (3) within-cortex connectivity. A post hoc regional analysis was performed to identify which regions were driving the connectivity changes.ResultsPatients with late RRMS and SPMS showed increased connectivity of the deep grey matter, especially of the putamen and palladium, with other deep grey matter structures and with the cortex. Within-cortex connectivity was decreased, especially for temporal, occipital and frontal regions, but only in SPMS relative to early RRMS. Deep grey matter connectivity alterations were related to cognition and disability, whereas within-cortex connectivity was only related to disability.ConclusionIncreased connectivity of the deep grey matter became apparent in late RRMS and further increased in SPMS. The additive effect of cortical network degeneration, which was only seen in SPMS, may explain the sudden clinical deterioration characteristic to this phase of the disease.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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