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

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  • dc.contributor.author Demirtaş, Muratca
  • dc.contributor.author Falcón, Carlesca
  • dc.contributor.author Tucholka, Alanca
  • dc.contributor.author Domingo Gispert, Juanca
  • dc.contributor.author Molinuevo, José Luisca
  • dc.contributor.author Deco, Gustavoca
  • dc.date.accessioned 2017-10-19T11:27:17Z
  • dc.date.available 2017-10-19T11:27:17Z
  • dc.date.issued 2017
  • dc.description.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.
  • dc.description.sponsorship GD is supported by the ERC Advanced Grant: DYSTRUCTURE (no. 295129), by the Spanish Research ProjectPSI2016-75688-P (AEI/FEDER) and by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 720270 (HBP SGA1).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Demirtaş M, Falcond C, Tucholka A, Domingo Gispert J, Molinuevo JL, Deco G. A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease. Neuroimage Clin. 2017;16:343-54. DOI: 10.1016/j.nicl.2017.08.006
  • dc.identifier.issn 2213-1582
  • dc.identifier.uri http://hdl.handle.net/10230/33048
  • dc.language.iso eng
  • dc.publisher Elsevierca
  • dc.relation.ispartof Neuroimage: Clinical. 2017;16:343-54.
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/295129
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/720270
  • dc.rights © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Resting state fMRI
  • dc.subject.keyword Dynamic functional connectivity
  • dc.subject.keyword Computational modeling
  • dc.subject.keyword Alzheimer's disease
  • dc.subject.keyword Biomarkers
  • dc.title A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's diseaseca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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