Dynamic Changes in Functional Network Connectivity Involving Amyotrophic Lateral Sclerosis and Its Correlation With Disease Severity

Abstract

Aberrant static functional connectivity (FC) has been well demonstrated in amyotrophic lateral sclerosis (ALS); however, ALS-related alterations in FC dynamic properties remain unclear, although dynamic FC analyses contribute to uncover mechanisms underlying neurodegenerative disorders. To explore dynamic functional network connectivity (dFNC) in ALS and its correlation with disease severity. Prospective. Thirty-two ALS patients and 45 healthy controls. Multiband resting-state functional images using gradient echo echo-planar imaging and T1-weighted images were acquired at 3.0T. Disease severity was evaluated with the revised ALS Functional Rating Scale (ALSFRS-R) and patients were stratified according to diagnostic category. Independent component analysis was conducted to identify the components of seven intrinsic brain networks (ie, visual/sensorimotor (SMN)/auditory/cognitive-control (CCN)/default-mode (DMN)/subcortical/cerebellar networks). A sliding-window correlation approach was used to compute dFNC. FNC states were determined by k-mean clustering, and state-specific FNC and dynamic indices (fraction time/mean dwell time/transition number) were calculated. Two-sample t test used for comparisons on dynamic measures and Spearman's correlation analysis. ALS patients showed increased FNC between DMN-SMN in state 1 and between CCN-SMN in state 4. Patients remained in state 2 (showing the weakest FNC) for a significantly longer time (mean dwell time: 49.8 ± 40.1 vs. 93.6 ± 126.3; P < 0.05) and remained in state 1 (showing a relatively strong FNC) for a shorter time (fraction time: 0.27 ± 0.25 vs. 0.13 ± 0.20; P < 0.05). ALS patients exhibited less temporal variability in their FNC (transition number: 10.2 ± 4.4 vs. 7.8 ± 3.8; P < 0.05). A significant correlation was observed between ALSFRS-R and mean dwell time in state 2 (r=-0.414, P < 0.05) and transition number (r=0.452, P < 0.05). No significant between-subgroup difference in dFNC properties was found (all P > 0.05). Our findings suggest aberrant dFNC properties in ALS, which is associated with disease severity. 2 TECHNICAL EFFICACY: Stage 3.