Abstract
Recent evidence increasingly associates network disruption in brain organization with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), a rare terminal disease. However, the comparability of brain network characteristics across different studies remains a challenge for conventional graph theoretical methods. One suggested method to address this issue is minimum spanning tree (MST) analysis, which provides a less biased comparison. Here, we assessed the novel application of MST network analysis to hemodynamic responses recorded by functional near-infrared spectroscopy (fNIRS) neuroimaging modality, during an activity-based paradigm to investigate hypothetical disruptions in frontal functional brain network topology as a marker of the executive dysfunction, one of the most prevalent cognitive deficit reported across ALS studies. We analyzed data recorded from nine participants with ALS and ten age-matched healthy controls by first estimating functional connectivity, using phase-locking value (PLV) analysis, and then constructing the corresponding individual and group MSTs. Our results showed significant between-group differences in several MST topological properties, including leaf fraction, maximum degree, diameter, eccentricity, and degree divergence. We further observed a global shift toward more centralized frontal network organizations in the ALS group, interpreted as a more random or dysregulated network in this cohort. Moreover, the similarity analysis demonstrated marginally significantly increased overlap in the individual MSTs from the control group, implying a reference network with lower topological variation in the healthy cohort. Our nodal analysis characterized the main local hubs in healthy controls as distributed more evenly over the frontal cortex, with slightly higher occurrence in the left prefrontal cortex (PFC), while in the ALS group, the most frequent hubs were asymmetrical, observed primarily in the right prefrontal cortex. Furthermore, it was demonstrated that the global PLV (gPLV) synchronization metric is associated with disease progression, and a few topological properties, including leaf fraction and tree hierarchy, are linked to disease duration. These results suggest that dysregulation, centralization, and asymmetry of the hemodynamic-based frontal functional network during activity are potential neuro-topological markers of ALS pathogenesis. Our findings can possibly support new bedside assessments of the functional status of ALS’ brain network and could hypothetically extend to applications in other neurodegenerative diseases.
Highlights
In recent years, there has been growing interest in associations between disruptions in brain network topology and a range of neurodegenerative diseases (Stam et al, 2009; Stam, 2014; McMackin et al, 2019), including amyotrophic lateral sclerosis (ALS) (Zhou et al, 2016; Sorrentino et al, 2018), a rare terminal neurodegenerative condition generally characterized by progressive deficits in motor neurons
The global Phase-locking value (PLV) that were calculated by averaging the PLVs over all channel pairs for each subject within each group were given to Wilcoxon rank sum statistical analysis
We have shown the links with weights greater than 15% of the maximum normalized PLVs in each group
Summary
There has been growing interest in associations between disruptions in brain network topology and a range of neurodegenerative diseases (Stam et al, 2009; Stam, 2014; McMackin et al, 2019), including amyotrophic lateral sclerosis (ALS) (Zhou et al, 2016; Sorrentino et al, 2018), a rare terminal neurodegenerative condition generally characterized by progressive deficits in motor neurons This tendency stems from a conceptual shift from a reductionist view of brain organization as a mere sum of independent constituent regions toward a more integrative network view, which has been propelled to applying network science in neuroimaging studies (Bullmore and Sporns, 2012; Olde Dubbelink et al, 2014). As executive dysfunctions are generally related to deficits in the frontal cortex (Alvarez and Emory, 2006), recognizing the underlying structural and functional neurocorrelates of these type of impairments in the frontal regions of the cortex would advance our understanding of the pathological and prognostic patterns of the disease and lead to more efficient diagnostic and treatment methods
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
