TY - JOUR
T1 - Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling
AU - Coronel-Oliveros, Carlos
AU - Gómez, Raúl Gónzalez
AU - Ranasinghe, Kamalini
AU - Sainz-Ballesteros, Agustín
AU - Legaz, Agustina
AU - Fittipaldi, Sol
AU - Cruzat, Josephine
AU - Herzog, Rubén
AU - Yener, Gorsev
AU - Parra, Mario
AU - Aguillon, David
AU - Lopera, Francisco
AU - Santamaria-Garcia, Hernando
AU - Moguilner, Sebastián
AU - Medel, Vicente
AU - Orio, Patricio
AU - Whelan, Robert
AU - Tagliazucchi, Enzo
AU - Prado, Pavel
AU - Ibañez, Agustín
N1 - Publisher Copyright:
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2024/5
Y1 - 2024/5
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - electroencephalography
KW - frontotemporal dementia
KW - hypoexcitation
KW - metaconnectivity
KW - neurodegeneration
KW - structural connectivity
KW - whole-brain modeling
UR - http://www.scopus.com/inward/record.url?scp=85188537152&partnerID=8YFLogxK
U2 - 10.1002/alz.13788
DO - 10.1002/alz.13788
M3 - Article
C2 - 38501336
AN - SCOPUS:85188537152
SN - 1552-5260
VL - 20
SP - 3228
EP - 3250
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 5
ER -