Abstract
BackgroundReduced 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.MethodsThis 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.ResultsLower 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.ConclusionsLoss 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.
Highlights
Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system associated with diffuse damage to white matter (WM) tracts
Lower fractional anisotropy (FA) was observed in the pediatric-onset multiple sclerosis (MS) group compared to healthy controls (HC) group within the entire WM skeleton, and the corpus callosum, posterior thalamic radiation, corona radiata and 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
Summary
Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system associated with diffuse damage to white matter (WM) tracts. Diffusion tensor imaging (DTI) is a technique that characterizes microstructural tissue integrity based on properties of diffusion, and this information is represented mathematically in a diffusion ellipsoid [4, 5]. AD represents diffusivity parallel to the main axis of WM tracts and higher values are considered to be indicative of axonal loss [6, 7]. RD represents diffusivity perpendicular to the main axis and higher values are more related to demyelination [8]. 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 pediatriconset MS to test the hypothesis that abnormalities in RSN reflects changes in structural integrity
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