Brain functional networks become more connected as amyotrophic lateral sclerosis progresses: a source level magnetoencephalographic study

Abstract

This study hypothesizes that the brain shows hyper connectedness as amyotrophic lateral sclerosis (ALS) progresses. 54 patients (classified as “early stage” or “advanced stage”) and 25 controls underwent magnetoencephalography and MRI recordings. The activity of the brain areas was reconstructed, and the synchronization between them was estimated in the classical frequency bands using the phase lag index. Brain topological metrics such as the leaf fraction (number of nodes with degree of 1), the degree divergence (a measure of the scale-freeness) and the degree correlation (a measure of disassortativity) were estimated. Betweenness centrality was used to estimate the centrality of the brain areas.In all frequency bands, it was evident that, the more advanced the disease, the more connected, scale-free and disassortative the brain networks. No differences were evident in specific brain areas. Such modified brain topology is sub-optimal as compared to controls. Within this framework, our study shows that brain networks become more connected according to disease staging in ALS patients.

Mutations in the SPAST gene causing hereditary spastic paraplegia are related to global topological alterations in brain functional networks

“…In the present work, we set out to study the functional alterations linked to mutations in the SPAST gene. More specifically, accordingly to ours [ 18 ] and other authors’ [ 19 ] previous studies, we hypothesized that the pathological process induces a global reorganization of the brain functional networks. To test our hypothesis, we applied the phase lag index (PLI), which quantifies synchronization between time series, followed by the minimum spanning tree (MST) algorithm, which allows the computation of statistically comparable metrics [ 20 ], to magnetoencephalography (MEG) data obtained from a cohort of SPG4 patients and healthy controls.…”

Patterned functional network disruption in amyotrophic lateral sclerosis

“…To date, however, there have been limited attempts to localise abnormal EEG patterns to specific brain regions. Moreover, although source-space studies that use frequency-specific analysis have also been performed in ALS (Fraschini et al, 2018;Sorrentino et al, 2018), the phase-and amplitude-based connectivity profiles of specific brain networks affected by ALS remain to be established. However, because network interactions are often marked by narrow band cortical oscillations (Buzsáki & Draguhn, 2004), it has not been possible to address the spectral aspects of ALS-specific changes in brain networks using broadband signals.…”

“…However, because network interactions are often marked by narrow band cortical oscillations (Buzsáki & Draguhn, 2004), it has not been possible to address the spectral aspects of ALS-specific changes in brain networks using broadband signals. Moreover, although source-space studies that use frequency-specific analysis have also been performed in ALS (Fraschini et al, 2018;Sorrentino et al, 2018), the phase-and amplitude-based connectivity profiles of specific brain networks affected by ALS remain to be established.…”

Extensive functional repertoire underpins complex behaviours: insights from Parkinson’s disease

“…In fact, excessive synchronization reduces the variability of the behaviour of the system, hence narrowing the number of states that are readily accessible (54,73,74). Hypersynchronization and hyperconnected topology have been associated with a variety of neurological diseases (75,76), as well as in preclinical conditions that carry an increased risk of neurodegeneration (77) hence investigations of the functional repertoires in these diseases and conditions could provide answers to this question.…”