Alterations in Functional and Structural Connectivity in Pediatric-Onset Multiple SclerosisReport as inadecuate

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Reduced white matter WM integrity is a fundamental aspect of pediatric multiple sclerosis MS, though relations to resting-state functional MRI fMRI connectivity remain unknown. The objective of this study was to relate diffusion-tensor imaging DTI measures of WM microstructural integrity to resting-state network RSN functional connectivity in pediatric-onset MS to test the hypothesis that abnormalities in RSN reflects changes in structural integrity.


This study enrolled 19 patients with pediatric-onset MS mean age = 19, range 13–24 years, 14 female, mean disease duration = 65 months, mean age of disease onset = 13 years and 16 age- and sex-matched healthy controls HC. All subjects underwent 3.0T anatomical and functional MRI which included DTI and resting-state acquisitions. DTI processing was performed using Tract-Based Spatial Statistics TBSS. RSNs were identified using Independent Components Analysis, and a dual regression technique was used to detect between-group differences in the functional connectivity of RSNs. Correlations were investigated between DTI measures and RSN connectivity.


Lower fractional anisotropy FA was observed in the pediatric-onset MS group compared to HC group within the entire WM skeleton, and particularly the corpus callosum, posterior thalamic radiation, corona radiata and sagittal stratum all p < .01, corrected. Relative to HCs, MS patients showed higher functional connectivity involving the anterior cingulate cortex and right precuneus of the default-mode network, as well as involving the anterior cingulate cortex and left middle frontal gyrus of the frontoparietal network all p < .005 uncorrected, k≥30 voxels. Higher functional connectivity of the right precuneus within the default-mode network was associated with lower FA of the entire WM skeleton r = -.525, p = .02, genu of the corpus callosum r = -.553, p = .014, and left r = -.467, p = .044 and right r = -.615, p = .005 sagittal stratum.


Loss of WM microstructural integrity is associated with increased resting-state functional connectivity in pediatric MS, which may reflect a diffuse and potentially compensatory activation early in MS.

Author: Nadine Akbar , Antonio Giorgio, Christine Till, John G. Sled, Sam M. Doesburg, Nicola De Stefano, Brenda Banwell



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