Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling


Coronel-Oliveros C., Gómez R. G., Ranasinghe K., Sainz-Ballesteros A., Legaz A., Fittipaldi S., ...Daha Fazla

Alzheimer's and Dementia, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/alz.13788
  • Dergi Adı: Alzheimer's and Dementia
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Alzheimer's disease, electroencephalography, frontotemporal dementia, hypoexcitation, metaconnectivity, neurodegeneration, structural connectivity, whole-brain modeling
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS: We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION: The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.