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

Carlos Coronel-Oliveros, Raúl Gónzalez Gómez, Kamalini Ranasinghe, Agustín Sainz-Ballesteros, Agustina Legaz, Sol Fittipaldi, Josephine Cruzat, Rubén Herzog, Gorsev Yener, Mario Parra, David Aguillon, Francisco Lopera, Hernando Santamaria-Garcia, Sebastián Moguilner, Vicente Medel, Patricio Orio, Robert Whelan, Enzo Tagliazucchi, Pavel Prado, Agustín Ibañez

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3228-3250
Number of pages23
JournalAlzheimer's and Dementia
Volume20
Issue number5
DOIs
StatePublished - May 2024
Externally publishedYes

Keywords

  • Alzheimer's disease
  • electroencephalography
  • frontotemporal dementia
  • hypoexcitation
  • metaconnectivity
  • neurodegeneration
  • structural connectivity
  • whole-brain modeling

Fingerprint

Dive into the research topics of 'Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling'. Together they form a unique fingerprint.

Cite this