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  A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease

Demirtaş, M., Falcon, C., Tucholka, A., Gispert, J. D., Molinuevo, J. L., & Deco, G. (2017). A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease. NeuroImage: Clinical, 16, 343-354. doi:10.1016/j.nicl.2017.08.006.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002E-2923-B Version Permalink: https://hdl.handle.net/21.11116/0000-0005-51D2-2
Genre: Journal Article

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 Creators:
Demirtaş, Murat1, 2, Author
Falcon, Carles3, 4, Author
Tucholka, Alan3, Author
Gispert, Juan Domingo3, 4, Author
Molinuevo, José Luis3, Author
Deco, Gustavo1, 5, 6, 7, Author           
Affiliations:
1Center for Brain and Cognition, University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
2Department of Psychiatry, Yale University, New Haven, CT, USA, ou_persistent22              
3Pasqual Maragall Foundation, Barcelonabeta Brain Research Center, Barcelona, Spain, ou_persistent22              
4CIBER-BBN: Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, Zaragoza, Spain, ou_persistent22              
5Catalan Institution for Research and Advanced Studies (ICREA), University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
6Department Neuropsychology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634551              
7School of Psychological Sciences, Monash University, Melbourne, Australia, ou_persistent22              

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Free keywords: Resting state fMRI; Dynamic functional connectivity; Computational modeling; Alzheimer's disease; Biomarkers
 Abstract: Alzheimer's disease (AD) is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC) of the subjects with preclinical Alzheimer's disease (PAD), mild cognitive impairment due to AD (MCI) and mild dementia due to Alzheimer's disease (AD), the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers. The synchronization in the whole-brain was monotonously decreasing during the course of the disease progression. Furthermore, in AD patients we found widespread significant decreases in functional connectivity (FC) strengths particularly in the brain regions with high global connectivity. We employed a whole-brain computational modeling approach to study the mechanisms underlying these alterations. To characterize the causal interactions between brain regions, we estimated the effective connectivity (EC) in the model. We found that the significant EC differences in AD were primarily located in left temporal lobe. Then, we systematically manipulated the underlying dynamics of the model to investigate simulated changes in FC based on the healthy control subjects. Furthermore, we found distinct patterns involving CSF biomarkers of amyloid-beta (Aβ1 − 42) total tau (t-tau) and phosphorylated tau (p-tau). CSF Aβ1 − 42 was associated to the contrast between healthy control subjects and clinical groups. Nevertheless, tau CSF biomarkers were associated to the variability in whole-brain synchronization and sensory integration regions. These associations were robust across clinical groups, unlike the associations that were found for CSF Aβ1 − 42. APOE4 carriership showed no significant correlations with the connectivity measures.

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Language(s): eng - English
 Dates: 2017-07-222017-03-242017-08-072017-08-08
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.nicl.2017.08.006
Other: eCollection 2017
PMID: 28861336
PMC: PMC5568172
 Degree: -

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Project name : The Dynamical and Structural Basis of Human Mind Complexity: Segregation and Integration of Information and Processing in the Brain / DYSTRUCTURE
Grant ID : 295129
Funding program : Funding Programme 7
Funding organization : European Commission (EC)
Project name : Spanish National Project Complexity of Brain States
Grant ID : PSI2016-75688-P
Funding program : -
Funding organization : Spanish Research Agency (AEI) and the European Regional Development Fund (ERDF)
Project name : Human Brain Project Specific Grant Agreement 1 / HBP SGA1
Grant ID : 720270
Funding program : Horizon 2020
Funding organization : European Commission (EC)

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Title: NeuroImage: Clinical
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Elsevier
Pages: - Volume / Issue: 16 Sequence Number: - Start / End Page: 343 - 354 Identifier: ISSN: 2213-1582
CoNE: https://pure.mpg.de/cone/journals/resource/2213-1582