Functional connectivity alterations reveal complex mechanisms based on clinical and radiological status in mild relapsing remitting multiple sclerosis

Simple item page
dc.contributor.authorCasellazzi G
dc.contributor.authorDebernard L
dc.contributor.authorMelzer TR
dc.contributor.authorDalrymple-Alford JC
dc.contributor.authorD'Angelo E
dc.contributor.authorMiller DH
dc.contributor.authorWheeler-Kingshott CAM
dc.contributor.authorMason DF
dc.date.accessioned2018-09-27T02:22:51Z
dc.date.available2018-09-27T02:22:51Z
dc.date.issued2018en
dc.date.updated2018-08-02T12:01:32Z
dc.description.abstractResting state functional MRI (rs-fMRI) has provided important insights into functional reorganization in subjects with Multiple Sclerosis (MS) at different stage of disease. In this cross-sectional study we first assessed, by means of rs-fMRI, the impact of overall T2 lesion load (T2LL) and MS severity score (MSSS) on resting state networks (RSNs) in 62 relapsing remitting MS (RRMS) patients with mild disability (MSSS < 3). Independent Component Analysis (ICA) followed by dual regression analysis confirmed functional connectivity (FC) alterations of many RSNs in RRMS subjects compared to healthy controls. The anterior default mode network (DMNa) and the superior precuneus network (PNsup) showed the largest areas of decreased FC, while the sensory motor networks area M1 (SMNm1) and the medial visual network (MVN) showed the largest areas of increased FC. In order to better understand the nature of these alterations as well as the mechanisms of functional alterations in MS we proposed a method, based on linear regression, that takes into account FC changes and their correlation with T2LL and MSSS. Depending on the sign of the correlation between FC and T2LL, and furthermore the sign of the correlation with MSSS, we suggested the following possible underlying mechanisms to interpret altered FC: (1) FC reduction driven by MS lesions, (2) “true” functional compensatory mechanism, (3a) functional compensation attempt, (3b) “false” functional compensation, (4a) neurodegeneration, (4b) pre-symptomatic condition (damage precedes MS clinical manifestation). Our data shows areas satisfying 4 of these 6 conditions (i.e., 1,2,3b,4b), supporting the suggestion that increased FC has a complex nature that may exceed the simplistic assumption of an underlying compensatory mechanism attempting to limit the brain damage caused by MS progression. Exploring differences between RRMS subjects with short disease duration (MSshort) and RRMS with similar disability but longer disease duration (MSlong), we found that MSshort and MSlong were characterized by clearly distinct pattern of FC, involving predominantly sensory and cognitive networks respectively. Overall, these results suggest that the analysis of FC alterations in multiple large-scale networks in relation to radiological (T2LL) and clinical (MSSS, disease duration) status may provide new insights into the pathophysiology of relapse onset MS evolution.en
dc.identifier.citationA Castellazzi, G., Debernard, L., Melzer, T. R., Dalrymple-Alford, J. C., D’Angelo, E., Miller, D. H., … Mason, D. F. (2018). Functional Connectivity Alterations Reveal Complex Mechanisms Based on Clinical and Radiological Status in Mild Relapsing Remitting Multiple Sclerosis. Frontiers in Neurology, 9, 690. http://doi.org/10.3389/fneur.2018.00690en
dc.identifier.doihttps://doi.org/10.3389/fneur.2018.00690
dc.identifier.issn1664-2295
dc.identifier.urihttp://hdl.handle.net/10092/16059
dc.language.isoen
dc.rightsCreative Commons Attribution Licenseen
dc.subjectrelapsing remitting multiple sclerosisen
dc.subjectresting state fMRIen
dc.subjectfunctional connectivityen
dc.subjectfunctional impairmenten
dc.subjectresting state networksen
dc.subject.anzsrcField of Research::11 - Medical and Health Sciences::1109 - Neurosciences::110903 - Central Nervous Systemen
dc.subject.anzsrcField of Research::11 - Medical and Health Sciences::1103 - Clinical Sciences::110320 - Radiology and Organ Imagingen
dc.titleFunctional connectivity alterations reveal complex mechanisms based on clinical and radiological status in mild relapsing remitting multiple sclerosisen
dc.typeJournal Articleen
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
fneur-09-00690-2.pdf
Size:
1.96 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Engineering: Journal Articles