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

Abstract

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

Flexibility of brain dynamics predicts clinical impairment in Amyotrophic Lateral Sclerosis

“…In particular, reduced temporal variability in network dynamics was found in ALS patients as compared to healthy controls. These changes significantly correlated with disease severity, in accordance with our results 67 .…”

Abnormal Stability of Dynamic Functional Architecture in Amyotrophic Lateral Sclerosis: A Preliminary Resting-State fMRI Study

“…In accordance with our findings, several studies from a dynamic perspective have found a reduction in ReHo (regional homogeneity, a functional index reflecting the regional coherence of brain activity) in bilateral sensorimotor cortices in ALS ( 36 , 37 ). From the perspective of static FC, previous studies have reported decreased connectivity in SMN ( 9 , 10 , 38 , 39 ); moreover, from a dynamic point of view, a recent FC study based on resting-state fMRI also found that SMN was involved in ALS ( 13 ). These reports in static and dynamic FC studies are in keeping with our findings.…”

“…The FC alterations in ALS are in keeping with the change of structural connections in the motor system and extra-motor systems ( 12 ). In addition, a recent study has revealed the alteration of dynamic FC properties in ALS, which is correlative with the severity of motor dysfunction ( 13 ). Taken together, both static and dynamic FC analyses hold great promise to explain the mechanisms underlying ALS.…”

Brain Connectivity and Network Analysis in Amyotrophic Lateral Sclerosis

“…In contrast to these findings, more studies have shown increased functional connectivity in ALS patients, even in regions with reduced structural connectivity [40,[53][54][55][56][57][58]. Dynamic connectivities of default motor networks and sensorimotor networks have increased connectivity in ALS [59]. Functional MRI (fMRI) studies using motor task activation have shown increased activation clusters in ALS patients compared to controls for the same task.…”

“…Studies interrogating specific resting-state networks of the brain have identified increased connectivity in the default mode network and reduced connectivity in sensorimotor network at the same time and both these correlated to the severity of the disease process [74,75]. While there are regions of increased and decreased regional functional connectivity in ALS, the global pattern across various studies leans towards increased functional connectivity, suggestive of the hyperexcitable cortex [59]. Despite several different studies, the functional connectivity changes in ALS remain complex and poorly defined.…”