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Investigating Functional Network Abnormalities and Associations With Disability in Multiple Sclerosis.
Antonio Carotenuto1, Paola Valsasina1, Menno M Schoonheim1
1From the Neuroimaging Research Unit (A.C., P.V., M.F., M.A.R.), Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Department of Anatomy and Neurosciences (M.M.S., J.J.G.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, The Netherlands; Radiology and Nuclear Medicine (F.B.), MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, The Netherlands; Institutes of Neurology & Healthcare Engineering (F.B.), UCL, London, United Kingdom; National Institute for Health Research (NIHR) (F.B.), University College London Hospitals (UCLH), Biomedical Research Centre, London, United Kingdom; Division of Neurology and 3T MRI Research Center (A.G.,G.T.), Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; Department of Human Neurosciences (S.T., P.P), Sapienza University, Rome, Italy; IRCCS NEUROMED (P.P.), Pozzilli (IS), Italy; Neurology Unit (M.F., M.A.R.), IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit (M.F.), IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurophysiology Service (M.F.), IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University (M.F., M.A.R.), Milan, Italy.
Multiple sclerosis (MS) patients exhibit altered brain network centrality, with reduced salience and sensorimotor networks and increased default-mode networks. These changes correlate with disease progression and disability.
Area of Science:
- Neuroimaging
- Network Neuroscience
- Multiple Sclerosis Research
Background:
- Multiple sclerosis (MS) is characterized by dynamic functional network reconfigurations and topographical changes.
- Understanding these network alterations is crucial for assessing disease progression and disability.
Purpose of the Study:
- To investigate functional network topography abnormalities in MS.
- To associate these abnormalities with disease phenotype, clinical/cognitive disability, and structural MRI damage.
Main Methods:
- A multicenter, cross-sectional study involving 971 MS patients and 330 healthy controls.
- Resting-state fMRI was used to assess network topography via degree centrality.
- Statistical analyses included ANOVA and multivariable regressions, corrected for multiple comparisons (FWE).
Main Results:
- MS patients showed reduced centrality in salience and sensorimotor networks and increased centrality in the default-mode network compared to controls.
- Abnormalities were present even in early MS (clinically isolated syndrome) and worsened with disease progression (SPMS, PPMS).
- Cognitive impairment correlated with altered centrality in salience and default-mode networks; disability correlated with right precuneus centrality.
Conclusions:
- Functional network centrality alterations are evident in MS, varying by disease phenotype.
- These network changes are associated with clinical and cognitive disability.
- Voxel-wise centrality analysis may serve as a biomarker for pathological substrates underlying disability in MS.
