Generative whole-brain dynamics models from healthy subjects predict functional alterations in stroke at the level of individual patients

Author:

Idesis Sebastian1ORCID,Allegra Michele23,Vohryzek Jakub14ORCID,Perl Yonatan Sanz1567,Metcalf Nicholas V8,Griffis Joseph C8ORCID,Corbetta Maurizio2891011,Shulman Gordon L810,Deco Gustavo112

Affiliation:

1. Center for Brain and Cognition (CBC), Department of Information Technologies and Communications (DTIC), Pompeu Fabra University, Edifici Mercè Rodoreda , Barcelona, Catalonia 08005 , Spain

2. Padova Neuroscience Center (PNC), University of Padova , Padova 35129 , Italy

3. Department of Physics and Astronomy ‘G. Galilei’, University of Padova , 35131 Padova , Italy

4. Centre for Eudaimonia and Human Flourishing, Linacre College, University of Oxford , OX3 9BX, Oxford , UK

5. Universidad de San Andrés , Centro de Neurociencias Cognitivias, NC1006ACC, Buenos Aires , Argentina

6. National Scientific and Technical Research Council , C1425FQB, Buenos Aires , Argentina

7. Institut du Cerveau et de la Moelle épinière, ICM , Hôpital Pitié Salpêtrière, 75013 Paris , France

8. Department of Neurology, Washington University School of Medicine , St. Louis, MO 63110 , USA

9. Department of Neuroscience (DNS), University of Padova , Padova 35128 , Italy

10. Department of Radiology, Washington University School of Medicine , St. Louis, MO 63110 , USA

11. VIMM, Venetian Institute of Molecular Medicine (VIMM), Biomedical Foundation , Padova 35129 , Italy

12. Institució Catalana de Recerca I Estudis Avançats (ICREA) , Barcelona, Catalonia 08010 , Spain

Abstract

Abstract Computational whole-brain models describe the resting activity of each brain region based on a local model, inter-regional functional interactions, and a structural connectome that specifies the strength of inter-regional connections. Strokes damage the healthy structural connectome that forms the backbone of these models and produce large alterations in inter-regional functional interactions. These interactions are typically measured by correlating the time series of the activity between two brain regions in a process, called resting functional connectivity. We show that adding information about the structural disconnections produced by a patient’s lesion to a whole-brain model previously trained on structural and functional data from a large cohort of healthy subjects enables the prediction of the resting functional connectivity of the patient and fits the model directly to the patient’s data (Pearson correlation = 0.37; mean square error = 0.005). Furthermore, the model dynamics reproduce functional connectivity-based measures that are typically abnormal in stroke patients and measures that specifically isolate these abnormalities. Therefore, although whole-brain models typically involve a large number of free parameters, the results show that, even after fixing those parameters, the model reproduces results from a population very different than that on which the model was trained. In addition to validating the model, these results show that the model mechanistically captures the relationships between the anatomical structure and the functional activity of the human brain.

Funder

Neurological Mechanisms

EU ERC Synergy Horizon Europe

Spanish National Research

Spanish Ministry of Science, Innovation, and Universities

Departments of Excellence Italian Ministry of Research

Fondazione Cassa di Risparmio di Padova e Rovigo

Ricerca Scientifica di Eccellenza 2018

Ministry of Health Italy

Celeghin Foundation Padova

H2020 European School of Network Neuroscience

H2020 Visionary Nature Based Actions For Heath

Wellbeing & Resilience in Cities

Publisher

Oxford University Press (OUP)

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