Increased default-mode network centrality in cognitively impaired multiple sclerosis patients

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: To investigate how changes in functional network hierarchy determine cognitive impairment in multiple sclerosis (MS).

METHODS: A cohort consisting of 332 patients with MS (age 48.1 ± 11.0 years, symptom duration 14.6 ± 8.4 years) and 96 healthy controls (HCs; age 45.9 ± 10.4 years) underwent structural MRI, fMRI, and extensive neuropsychological testing. Patients were divided into 3 groups: cognitively impaired (CI; n = 87), mildly cognitively impaired (MCI; n = 65), and cognitively preserved (CP; n = 180). The functional importance of brain regions was quantified with degree centrality, the average strength of the functional connections of a brain region with the rest of the brain, and eigenvector centrality, which adds to this concept by adding additional weight to connections with brain hubs because these are known to be especially important. Centrality values were calculated for each gray matter voxel based on resting-state fMRI data, registered to standard space. Group differences were assessed with a cluster-wise permutation-based method corrected for age, sex, and education.

RESULTS: CI patients demonstrated widespread centrality increases compared to both HCs and CP patients, mainly in regions making up the default-mode network. Centrality decreases were similar in all patient groups compared to HCs, mainly in occipital and sensorimotor areas. Results were robust across centrality measures.

CONCLUSIONS: Patients with MS with cognitive impairment show hallmark alterations in functional network hierarchy with increased relative importance (centrality) of the default-mode network.

Original languageEnglish
Pages (from-to)952-960
Number of pages9
JournalNeurology
Volume88
Issue number10
DOIs
Publication statusPublished - 7 Mar 2017

Cite this

@article{5fcb5f022f9b41eeb952f73059ed6a61,
title = "Increased default-mode network centrality in cognitively impaired multiple sclerosis patients",
abstract = "OBJECTIVE: To investigate how changes in functional network hierarchy determine cognitive impairment in multiple sclerosis (MS).METHODS: A cohort consisting of 332 patients with MS (age 48.1 ± 11.0 years, symptom duration 14.6 ± 8.4 years) and 96 healthy controls (HCs; age 45.9 ± 10.4 years) underwent structural MRI, fMRI, and extensive neuropsychological testing. Patients were divided into 3 groups: cognitively impaired (CI; n = 87), mildly cognitively impaired (MCI; n = 65), and cognitively preserved (CP; n = 180). The functional importance of brain regions was quantified with degree centrality, the average strength of the functional connections of a brain region with the rest of the brain, and eigenvector centrality, which adds to this concept by adding additional weight to connections with brain hubs because these are known to be especially important. Centrality values were calculated for each gray matter voxel based on resting-state fMRI data, registered to standard space. Group differences were assessed with a cluster-wise permutation-based method corrected for age, sex, and education.RESULTS: CI patients demonstrated widespread centrality increases compared to both HCs and CP patients, mainly in regions making up the default-mode network. Centrality decreases were similar in all patient groups compared to HCs, mainly in occipital and sensorimotor areas. Results were robust across centrality measures.CONCLUSIONS: Patients with MS with cognitive impairment show hallmark alterations in functional network hierarchy with increased relative importance (centrality) of the default-mode network.",
keywords = "Adult, Aged, Brain, Cognition Disorders, Cohort Studies, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Neural Networks (Computer), Neural Pathways, Neuropsychological Tests, Journal Article",
author = "Eijlers, {Anand J C} and Meijer, {Kim A.} and Wassenaar, {Thomas M.} and Steenwijk, {Martijn D.} and Uitdehaag, {Bernard M J} and Frederik Barkhof and Wink, {Alle M.} and Geurts, {Jeroen J G} and Schoonheim, {Menno M.}",
note = "{\circledC} 2017 American Academy of Neurology.",
year = "2017",
month = "3",
day = "7",
doi = "10.1212/WNL.0000000000003689",
language = "English",
volume = "88",
pages = "952--960",
journal = "Neurology",
issn = "0028-3878",
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Increased default-mode network centrality in cognitively impaired multiple sclerosis patients. / Eijlers, Anand J C; Meijer, Kim A.; Wassenaar, Thomas M.; Steenwijk, Martijn D.; Uitdehaag, Bernard M J; Barkhof, Frederik; Wink, Alle M.; Geurts, Jeroen J G; Schoonheim, Menno M.

In: Neurology, Vol. 88, No. 10, 07.03.2017, p. 952-960.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Increased default-mode network centrality in cognitively impaired multiple sclerosis patients

AU - Eijlers, Anand J C

AU - Meijer, Kim A.

AU - Wassenaar, Thomas M.

AU - Steenwijk, Martijn D.

AU - Uitdehaag, Bernard M J

AU - Barkhof, Frederik

AU - Wink, Alle M.

AU - Geurts, Jeroen J G

AU - Schoonheim, Menno M.

N1 - © 2017 American Academy of Neurology.

PY - 2017/3/7

Y1 - 2017/3/7

N2 - OBJECTIVE: To investigate how changes in functional network hierarchy determine cognitive impairment in multiple sclerosis (MS).METHODS: A cohort consisting of 332 patients with MS (age 48.1 ± 11.0 years, symptom duration 14.6 ± 8.4 years) and 96 healthy controls (HCs; age 45.9 ± 10.4 years) underwent structural MRI, fMRI, and extensive neuropsychological testing. Patients were divided into 3 groups: cognitively impaired (CI; n = 87), mildly cognitively impaired (MCI; n = 65), and cognitively preserved (CP; n = 180). The functional importance of brain regions was quantified with degree centrality, the average strength of the functional connections of a brain region with the rest of the brain, and eigenvector centrality, which adds to this concept by adding additional weight to connections with brain hubs because these are known to be especially important. Centrality values were calculated for each gray matter voxel based on resting-state fMRI data, registered to standard space. Group differences were assessed with a cluster-wise permutation-based method corrected for age, sex, and education.RESULTS: CI patients demonstrated widespread centrality increases compared to both HCs and CP patients, mainly in regions making up the default-mode network. Centrality decreases were similar in all patient groups compared to HCs, mainly in occipital and sensorimotor areas. Results were robust across centrality measures.CONCLUSIONS: Patients with MS with cognitive impairment show hallmark alterations in functional network hierarchy with increased relative importance (centrality) of the default-mode network.

AB - OBJECTIVE: To investigate how changes in functional network hierarchy determine cognitive impairment in multiple sclerosis (MS).METHODS: A cohort consisting of 332 patients with MS (age 48.1 ± 11.0 years, symptom duration 14.6 ± 8.4 years) and 96 healthy controls (HCs; age 45.9 ± 10.4 years) underwent structural MRI, fMRI, and extensive neuropsychological testing. Patients were divided into 3 groups: cognitively impaired (CI; n = 87), mildly cognitively impaired (MCI; n = 65), and cognitively preserved (CP; n = 180). The functional importance of brain regions was quantified with degree centrality, the average strength of the functional connections of a brain region with the rest of the brain, and eigenvector centrality, which adds to this concept by adding additional weight to connections with brain hubs because these are known to be especially important. Centrality values were calculated for each gray matter voxel based on resting-state fMRI data, registered to standard space. Group differences were assessed with a cluster-wise permutation-based method corrected for age, sex, and education.RESULTS: CI patients demonstrated widespread centrality increases compared to both HCs and CP patients, mainly in regions making up the default-mode network. Centrality decreases were similar in all patient groups compared to HCs, mainly in occipital and sensorimotor areas. Results were robust across centrality measures.CONCLUSIONS: Patients with MS with cognitive impairment show hallmark alterations in functional network hierarchy with increased relative importance (centrality) of the default-mode network.

KW - Adult

KW - Aged

KW - Brain

KW - Cognition Disorders

KW - Cohort Studies

KW - Female

KW - Humans

KW - Image Processing, Computer-Assisted

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis

KW - Neural Networks (Computer)

KW - Neural Pathways

KW - Neuropsychological Tests

KW - Journal Article

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U2 - 10.1212/WNL.0000000000003689

DO - 10.1212/WNL.0000000000003689

M3 - Article

VL - 88

SP - 952

EP - 960

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 10

ER -