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Background: 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. Purpose: To explore dynamic functional network connectivity (dFNC) in ALS and its correlation with disease severity. Study Type: Prospective. Subjects: Thirty-two ALS patients and 45 healthy controls. Field Strength/Sequence: Multiband resting-state functional images using gradient echo echo-planar imaging and T1weighted images were acquired at 3.0 T. Assessment: 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. Statistical Tests: Two-sample t test used for comparisons on dynamic measures and Spearman's correlation analysis. Results: 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 AE 40.1 vs. 93.6 AE 126.3; P < 0.05) and remained in state 1 (showing a relatively strong FNC) for a shorter time (fraction time: 0.27 AE 0.25 vs. 0.13 AE 0.20; P < 0.05). ALS patients exhibited less temporal variability in their FNC (transition number: 10.2 AE 4.4 vs. 7.8 AE 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). Data Conclusion: Our findings suggest aberrant dFNC properties in ALS, which is associated with disease severity. Level of Evidence: 2 Technical Efficacy: Stage 3

Purpose: Static and dynamic analyses for identifying functional connectivity (FC) have demonstrated brain dysfunctions in amyotrophic lateral sclerosis (ALS). However, few studies on the stability of dynamic FC have been conducted among ALS patients. This study explored the change of functional stability in ALS and how it correlates with disease severity.Methods: We gathered resting-state functional magnetic resonance data from 20 patients with ALS and 22 healthy controls (HCs). The disease severity was assessed with the Revised ALS Functional Rating Scale (ALSFRS-R). We used a sliding window correlation approach to identify dynamic FC and measured the concordance of dynamic FC over time to obtain the functional stability of each voxel. We assessed the between-group difference in functional stability by voxel-wise two-sample t-test. The correlation between the functional stability index and ALSFRS-R in ALS patients was evaluated using Spearman's correlation analysis.Results: Compared with the HC group, the ALS group had significantly increased functional stability in the left pre-central and post-central gyrus and right temporal pole while decreased functional stability in the right middle and inferior frontal gyrus. The results revealed a significant correlation between ALSFRS-R and the mean functional stability in the right temporal pole (r = −0.452 and P = 0.046) in the ALS patients.Conclusions: ALS patients have abnormal stability of brain functional architecture, which is associated with the severity of the disease.

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