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  Mechanisms of network changes in cognitive impairment in multiple sclerosis

Jandric, D., Lipp, I., Paling, D., Rog, D., Castellazzi, G., Haroon, H., et al. (2021). Mechanisms of network changes in cognitive impairment in multiple sclerosis. Neurology, 97(19), e1886-e1897. doi:10.1212/WNL.0000000000012834.

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 Creators:
Jandric, Danka, Author
Lipp, Ilona1, Author           
Paling, David, Author
Rog, David, Author
Castellazzi, Gloria, Author
Haroon, Hamied, Author
Parkes, Laura, Author
Parker, Geoff J.M., Author
Tomassini, Valentina, Author
Muhlert, Nils, Author
Affiliations:
1Department Neurophysics (Weiskopf), MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_2205649              

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 Abstract: 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-occurring abnormalities on other magnetic resonance metrics. We tested whether functional connectivity abnormalities in cognitively impaired patients with MS co-occur with (1) overlapping, (2) local, or (3) distal changes in anatomic connectivity and cerebral blood flow abnormalities.

Methods: Multimodal 3T MRI and assessment with the Brief Repeatable Battery of Neuropsychological tests were performed in 102 patients with relapsing-remitting MS and 27 healthy controls. Patients with MS were classified as cognitively impaired if they scored ≥1.5 SDs below the control mean on ≥2 tests (n = 55) or as cognitively preserved (n = 47). Functional connectivity was assessed with Independent Component Analysis and dual regression of resting-state fMRI images. Cerebral blood flow maps were estimated, and anatomic connectivity was assessed with anatomic connectivity mapping and fractional anisotropy of diffusion-weighted MRI. Changes in cerebral blood flow and anatomic connectivity were assessed within resting-state networks that showed functional connectivity abnormalities in cognitively impaired patients with MS.

Results: Functional connectivity was significantly decreased in the anterior and posterior default mode networks and significantly increased in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients with MS (threshold-free cluster enhancement corrected at p ≤ 0.05, 2 sided). Networks showing functional abnormalities showed altered cerebral blood flow and anatomic connectivity locally and distally but not in overlapping locations.

Discussion: We provide the first evidence that functional connectivity abnormalities are accompanied by 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 pathologic mechanism for altered functional connectivity in brain networks in MS.

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Language(s): eng - English
 Dates: 2021-10-142021-11-09
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1212/WNL.0000000000012834
Other: epub 2021
PMID: 34649879
PMC: PMC8601205
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Grant ID : MR/N013751/11
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Funding organization : MS Society UK and Medical Research Council (MRC)

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Title: Neurology
Source Genre: Journal
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Publ. Info: Cleveland, Ohio [etc.] : Advanstar Communications [etc.]
Pages: - Volume / Issue: 97 (19) Sequence Number: - Start / End Page: e1886 - e1897 Identifier: ISSN: 0028-3878
CoNE: https://pure.mpg.de/cone/journals/resource/954925246073