Model-based whole-brain perturbational landscape of neurodegenerative diseases

Yonatan Sanz Perl, Sol Fittipaldi, Cecilia Gonzalez Campo, Sebastián Moguilner, Josephine Cruzat, Matias E. Fraile-Vazquez, Rubén Herzog, Morten L. Kringelbach, Gustavo Deco, Pavel Prado, Agustin Ibanez, Enzo Tagliazucchi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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 repro-ducing 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.

Original languageEnglish
Article numbere83970
StatePublished - 2023
Externally publishedYes


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