Model-based whole-brain perturbational landscape of neurodegenerative diseases
Open Access
- 30 March 2023
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
The treatment of neurodegenerative diseases is hindered by lack of interventions capable of steering multimodal whole-brain dynamics towards patterns indicative of preserved brain health. To address this problem, we combined deep learning with a model capable of reproducing whole-brain functional connectivity in patients diagnosed with Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD). These models included disease-specific atrophy maps as priors to modulate local parameters, revealing increased stability of hippocampal and insular dynamics as signatures of brain atrophy in AD and bvFTD, respectively. Using variational autoencoders, we visualized different pathologies and their severity as the evolution of trajectories in a low-dimensional latent space. Finally, we perturbed the model to reveal key AD- and bvFTD-specific regions to induce transitions from pathological to healthy brain states. Overall, we obtained novel insights on disease progression and control by means of external stimulation, while identifying dynamical mechanisms that underlie functional alterations in neurodegeneration.Funding Information
- Marie Skłodowska-Curie Actions (896354)
- Fondo Nacional de Desarrollo Científico y Tecnológico (1210195)
- Fondo Nacional de Desarrollo Científico y Tecnológico (1210176)
- Fondo Nacional de Desarrollo Científico y Tecnológico (1220995)
- Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (15150012)
- Comisión Nacional de Investigación Científica y Tecnológica (ACT210096)
- Comisión Nacional de Investigación Científica y Tecnológica (ID20I10152)
- Comisión Nacional de Investigación Científica y Tecnológica (ID22I10029)
- Takeda (CW2680521)
- National Institute on Aging (Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat) R01 AG057234)
- Alzheimer's Association (20-725707)
- Rainwater Charitable Foundation
- Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (PICT-2019-02294)
- Tau Consortium
- Global Brain Health Institute
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