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.
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 language | English |
|---|---|
| Pages (from-to) | 3228-3250 |
| Number of pages | 23 |
| Journal | Alzheimer's & Dementia: The Journal of the Alzheimer's Association |
| Volume | 20 |
| Issue number | 5 |
| Early online date | 19 Mar 2024 |
| DOIs | |
| Publication status | Published - May 2024 |
Funding
C.C.O. is an Atlantic Fellow of the Global Brain Health Institute (GBHI) at Trinity College Dublin and is also supported by a postdoctoral grant from BrainLat. A.I. is supported by grants from ReD‐Lat (National Institutes of Health and the Fogarty International Center [FIC], National Institutes of Aging [R01 AG057234, R01 AG075775, R01 AG021051, R01 AG083799, CARDS‐NIH], Alzheimer's Association [SG‐20‐725707], Rainwater Charitable Foundation – The Bluefield project to cure FTD, and Global Brain Health Institute), ANID/FONDECYT Regular (1210195, 1210176 and 1220995), and ANID/FONDAP/15150012. The contents of this publication are solely the author's responsibility and do not represent the official views of these institutions.
Keywords
- Alzheimer’s disease
- electroencephalography
- frontotemporal dementia
- hypoexcitation
- meta-connectivity
- neurodegeneration
- structural connectivity
- whole-brainmodeling