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

Coronel-Oliveros, Carlos; Gomez, Raul Gonzalez; Ranasinghe, Kamalini; Sainz-Ballesteros, Agustin; Legaz, Agustina; Fittipaldi, Sol; Cruzat, Josephine; Herzog, Ruben; Yener, Gorsev; Parra, Mario; Aguillon, David; Lopera, Francisco; Santamaria-Garcia, Hernando; Moguilner, Sebastian; Medel, Vicente; et. al.

Abstract

INTRODUCTIONAlzheimer'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.METHODSWe 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).RESULTSMetaconnectivity 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.DISCUSSIONThe results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.

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Título según WOS: ID WOS:001187045800001 Not found in local WOS DB
Título de la Revista: ALZHEIMERS & DEMENTIA
Editorial: Wiley
Fecha de publicación: 2024
DOI:

10.1002/alz.13788

Notas: ISI