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Updated: Jan 4, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Morphological MRI phenotypes of multiple sclerosis differ in resting-state brain function
Daniela Pinter1,2, Christian F Beckmann3, Franz Fazekas1
1Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, Graz, Austria.
Abstract:
We aimed to assess differences in resting-state functional connectivity (FC) between distinct morphological MRI-phenotypes in multiple sclerosis (MS). Out of 180 MS patients, we identified those with high T2-hyperintense lesion load (T2-LL) and high normalized brain volume (NBV; a predominately white matter damage group, WMD; N = 37) and patients with low T2-LL and low NBV (N = 37; a predominately grey matter damage group; GMD). Independent component analysis of resting-state fMRI was used to test for differences in the sensorimotor network (SMN) between MS MRI-phenotypes and compared to 37 age-matched healthy controls (HC). The two MS groups did not differ regarding EDSS scores, disease duration and distribution of clinical phenotypes. WMD compared to GMD patients showed increased FC in all sub-units of the SMN (sex- and age-corrected). WMD patients had increased FC compared to HC and GMD patients in the central SMN (leg area). Only in the WMD group, higher EDSS scores and T2-LL correlated with decreased connectivity in SMN sub-units. MS patients with distinct morphological MRI-phenotypes also differ in brain function. The amount of focal white matter pathology but not global brain atrophy affects connectivity in the central SMN (leg area) of the SMN, consistent with the notion of a disconnection syndrome.
Insights
Multiple sclerosis patients with distinct MRI phenotypes show altered brain connectivity. White matter damage, not global atrophy, impacts sensorimotor network function, suggesting a disconnection syndrome in MS.
Area of Science:
- Neuroimaging
- Neurology
- Functional Connectivity
Background:
- Multiple sclerosis (MS) is characterized by diverse pathological changes, including white matter lesions and grey matter damage.
- Distinct MRI-defined phenotypes in MS may exhibit differential impacts on brain function and connectivity.
Purpose of the Study:
- To investigate resting-state functional connectivity (FC) differences in the sensorimotor network (SMN) across distinct multiple sclerosis (MS) MRI-phenotypes.
- To compare FC between MS groups with predominant white matter damage (WMD) and grey matter damage (GMD), and healthy controls (HC).
Main Methods:
- Utilized resting-state functional MRI (fMRI) and independent component analysis (ICA) to analyze FC in the SMN.
- Categorized 180 MS patients into WMD (high T2-lesion load, high normalized brain volume) and GMD (low T2-lesion load, low normalized brain volume) groups.
- Compared FC patterns between WMD, GMD, and 37 age-matched HC.
Main Results:
- WMD patients exhibited increased FC across all SMN sub-units compared to GMD patients.
- WMD patients showed increased FC in the central SMN (leg area) compared to both GMD patients and HC.
- In the WMD group, higher Expanded Disability Status Scale (EDSS) scores and T2-lesion load correlated with reduced SMN connectivity.
Conclusions:
- Distinct morphological MRI-phenotypes in MS are associated with significant differences in brain functional connectivity.
- Focal white matter pathology, rather than global brain atrophy, appears to be a key determinant of altered connectivity in the central SMN.
- Findings support the concept of a disconnection syndrome in MS, where white matter integrity influences network function.
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