ArticlePloS one2022
Network diffusion model predicts neurodegeneration in limb-onset Amyotrophic Lateral Sclerosis.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 7 citations in OpenAlex.
- Molecular, cellular and network mapping of brain structural deviations in patients with Post-COVID19 syndrome.Brain, behavior, & immunity - health · 2026Article
- Diffusion network model analysis of multimodal neuroimaging reveals differential patterns of brain disease propagation in four subgroups of ALS patients.Brain imaging and behavior · 2026Article
- Network spreading and local biological vulnerability in amyotrophic lateral sclerosis.Communications biology · 2025Article
- Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Molecular neurodegeneration · 2025Review
- Pathological laugher and crying in motor neuron diseases: a matter of bulbar and neurobehavioral involvement with sex imbalance.Journal of neurology · 2025Article
- Structural and Functional Brain Network Connectivity at Different King's Stages in Patients With Amyotrophic Lateral Sclerosis.Neurology · 2024Observational
- Evidence based on Mendelian randomization and colocalization analysis strengthens causal relationships between structural changes in specific brain regions and risk of amyotrophic lateral sclerosis.Frontiers in neuroscience · 2024Article
- Harmonized multi-metric and multi-centric assessment of EEG source space connectivity for dementia characterization.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveEmerging evidences suggest that the trans-neural propagation of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43) contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). We investigated whether Network Diffusion Model (NDM), a biophysical model of spread of pathology via the brain connectome, could capture the severity and progression of neurodegeneration (atrophy) in ALS.
methodsWe measured degeneration in limb-onset ALS patients (n = 14 at baseline, 12 at 6-months, and 9 at 12 months) and controls (n = 12 at baseline) using FreeSurfer analysis on the structural T1-weighted Magnetic Resonance Imaging (MRI) data. The NDM was simulated on the canonical structural connectome from the IIT Human Brain Atlas. To determine whether NDM could predict the atrophy pattern in ALS, the accumulation of pathology modelled by NDM was correlated against atrophy measured using MRI. In order to investigate whether network spread on the brain connectome derived from healthy individuals were significant findings, we compared our findings against network spread simulated on random networks.
resultsThe cross-sectional analyses revealed that the network diffusion seeded from the inferior frontal gyrus (pars triangularis and pars orbitalis) significantly predicts the atrophy pattern in ALS compared to controls. Whereas, atrophy over time with-in the ALS group was best predicted by seeding the network diffusion process from the inferior temporal gyrus at 6-month and caudal middle frontal gyrus at 12-month. Network spread simulated on the random networks showed that the findings using healthy brain connectomes are significantly different from null models.
interpretationOur findings suggest the involvement of extra-motor regions in seeding the spread of pathology in ALS. Importantly, NDM was able to recapitulate the dynamics of pathological progression in ALS. Understanding the spatial shifts in the seeds of degeneration over time can potentially inform further research in the design of disease modifying therapeutic interventions in ALS.
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