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Increased default-mode network centrality in cognitively impaired multiple sclerosis patients.
Neurology 2017; 88(10):952-960Neur

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.

Authors+Show Affiliations

Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK. a.eijlers@vumc.nl.Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.Departments of Anatomy and Neurosciences (A.J.C.E., K.A.M., T.M.W., M.D.S., J.J.G.G., M.M.S.), Neurology (M.D.S., B.M.J.U.), and Radiology and Nuclear Medicine (F.B., A.M.W.), Neuroscience Campus Amsterdam, MS Center Amsterdam, VU University Medical Center, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28179464

Citation

Eijlers, Anand J C., et al. "Increased Default-mode Network Centrality in Cognitively Impaired Multiple Sclerosis Patients." Neurology, vol. 88, no. 10, 2017, pp. 952-960.
Eijlers AJ, Meijer KA, Wassenaar TM, et al. Increased default-mode network centrality in cognitively impaired multiple sclerosis patients. Neurology. 2017;88(10):952-960.
Eijlers, A. J., Meijer, K. A., Wassenaar, T. M., Steenwijk, M. D., Uitdehaag, B. M., Barkhof, F., ... Schoonheim, M. M. (2017). Increased default-mode network centrality in cognitively impaired multiple sclerosis patients. Neurology, 88(10), pp. 952-960. doi:10.1212/WNL.0000000000003689.
Eijlers AJ, et al. Increased Default-mode Network Centrality in Cognitively Impaired Multiple Sclerosis Patients. Neurology. 2017 Mar 7;88(10):952-960. PubMed PMID: 28179464.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2017/02/08/ PY - 2016/07/25/received PY - 2016/12/12/accepted PY - 2017/2/10/pubmed PY - 2017/5/23/medline PY - 2017/2/10/entrez SP - 952 EP - 960 JF - Neurology JO - Neurology VL - 88 IS - 10 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. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/28179464/Increased_default_mode_network_centrality_in_cognitively_impaired_multiple_sclerosis_patients_ L2 - http://www.neurology.org/cgi/pmidlookup?view=long&pmid=28179464 DB - PRIME DP - Unbound Medicine ER -