Abstract

The brain connectome of multiple sclerosis (MS) has been investigated by several previous studies; however, it is still unknown how the network changes in clinically isolated syndrome (CIS), the earliest stage of MS, and how network alterations on a functional level relate to the structural level in MS disease. Here, we investigated the topological alterations of both the structural and functional connectomes in 41 CIS and 32 MS patients, compared to 35 healthy controls, by combining diffusion tensor imaging and resting-state functional MRI with graph analysis approaches. We found that the structural connectome showed a deviation from the optimal pattern as early as the CIS stage, while the functional connectome only showed local changes in MS patients, not in CIS. When comparing two patient groups, the changes appear more severe in MS. Importantly, the disruptions of structural and functional connectomes in patients occurred in the same direction and locally correlated in sensorimotor component. Finally, the extent of structural network changes was correlated with several clinical variables in MS patients. Together, the results suggested early disruption of the structural brain connectome in CIS patients and provided a new perspective for investigating the relationship of the structural and functional alterations in MS.

Highlights

  • Network based on T1-weighted MRI images identified disrupted integration in Multiple sclerosis (MS), proportional to the white matter (WM) lesion load[23], while diffusion tensor imaging (DTI) network analysis showed decreased global and local efficiency in MS correlated with clinical disability[21]

  • The aim of this study was to provide a comprehensive view of the whole-brain structural and functional connectome and demonstrate its relationship based on DTI and resting-state functional MRI (rs-fMRI) in clinically isolated syndrome (CIS) and MS combined with graph theory analyses

  • Our study demonstrated disrupted structural connectome in the earliest stage of MS, while functional networks remain stable at that stage

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Summary

Introduction

Network based on T1-weighted MRI images identified disrupted integration in MS, proportional to the white matter (WM) lesion load[23], while diffusion tensor imaging (DTI) network analysis showed decreased global and local efficiency in MS correlated with clinical disability[21]. Network analysis based on resting-state functional MRI (rs-fMRI) found abnormal network properties in MS patients, which can contribute to distinguishing cognitively impaired MS patients from healthy controls[22]. The aim of this study was to provide a comprehensive view of the whole-brain structural and functional connectome and demonstrate its relationship based on DTI and rs-fMRI in CIS and MS combined with graph theory analyses. We set out to assess (i) whether structural and functional networks are affected in the earliest stage of MS (CIS), (ii) the changes of structural and functional networks from CIS to MS, and (iii) the relationship between structural and functional networks and its association with clinical disability and cognitive impairment

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