Global functional connectivity reorganization reflects cognitive processing speed deficits and fatigue in multiple...

Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (k_D) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis.

Differentiation between PwMS and healthy controls (HCs) using k_D and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability.

Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower k_D in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). k_D and degree in medial prefrontal cortex (MPFC) correlated with CI (k_D/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). k_D also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability.

k_D is a potential biomarker of CI and fatigue warranting further validation.