Mechanisms of Network Changes in Cognitive Impairment in Multiple Sclerosis

Danka Jandric, Ilona Lipp, David Paling, David Rog, Gloria Castellazzi, Hamied Haroon, Laura Parkes, Geoff JM Parker, Valentina Tomassini, Nils Muhlert

Research output: Contribution to journalArticlepeer-review


Background and Objectives: Cognitive impairment in multiple sclerosis (MS) is associated with functional connectivity abnormalities. While there have been calls to use functional connectivity measures as biomarkers there remains to be a full understanding of why they are affected in MS. In this cross-sectional study we tested the hypothesis that functional network regions may be susceptible to disease-related ‘wear-and-tear’ and that this can be observable on co-occuring abnormalities on other MR metrics. We tested whether functional connectivity abnormalities in cognitively impaired MS patients co-occur with either 1) overlapping, 2) local, or 3) distal changes in anatomical connectivity and cerebral blood flow abnormalities.

Methods: Multimodal MRI and neuropsychological assessments were performed in all participants. Functional connectivity was assessed with Independent Component Analysis of resting state fMRI images. Cerebral blood flow maps were estimated and anatomical connectivity was assessed with anatomical connectivity mapping and fractional anisotropy of diffusion-weighted MRI. Changes in cerebral blood flow and anatomical connectivity were assessed within resting state networks that showed functional connectivity abnormalities in cognitively impaired MS patients.

Results: The study included 102 relapsing-remitting MS patients and 27 healthy controls. Fifty-five patients were cognitively impaired and 47 cognitively preserved. We found significantly decreased functional connectivity in the anterior and posterior default mode networks and significant increases in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved MS patients. Networks showing functional abnormalities showed altered cerebral blood flow and anatomical connectivity locally and distally but not in overlapping locations.

Discussion: We provide the first evidence that FC abnormalities are accompanied with local cerebral blood flow and structural connectivity abnormalities but also demonstrate that these effects do not occur in exactly the same location. Our findings suggest a possibly shared pathological mechanism for altered functional connectivity in brain networks in MS.
Original languageEnglish
Publication statusAccepted/In press - 25 Aug 2021


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