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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.

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 (A?1 - 42) total tau (t-tau) and phosphorylated tau (p-tau). CSF A?1 - 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 A?1 - 42. APOE4 carriership showed no significant correlations with the connectivity measures.

SUBMITTER: Demirtas M

PROVIDER: S-EPMC5568172 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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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 Murat M Falcon Carles C Tucholka Alan A Gispert Juan Domingo JD Molinuevo José Luis JL Deco Gustavo G

NeuroImage. Clinical 20170808

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 ...[more]

PMID: 28861336

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Project description:BackgroundPrevious neuroimaging studies have extensively demonstrated many signs of functionally spontaneous local neural activity abnormalities in bipolar disorder (BD) patients using resting-state functional magnetic resonance imaging (rs-fMRI). However, how to identify the changes of voxel-wise whole-brain functional connectivity pattern and its corresponding functional connectivity changes remain largely unclear in BD patients. The current study aimed to investigate the voxel-wise changes of functional connectivity patterns in BD patients using publicly available data from the UCLA CNP LA5c Study.MethodsA total of 45 BD patients and 115 healthy control subjects were finally included and whole-brain functional connectivity homogeneity (FcHo) was calculated from their rs-fMRI. Moreover, the alterations of corresponding functional connectivity were subsequently identified using seed-based resting-state functional connectivity analysis.ResultsIndividuals with BD exhibited significantly lower FcHo values in the left middle temporal gyrus (MTG) when compared with controls. Functional connectivity findings further indicated decreased functional connectivities between left MTG and cluster 1 (left superior temporal gyrus, extend to middle temporal gyrus, rolandic operculum), cluster 2 (right postcentral, extend to right precentral) in BD patients. The mean FcHo values of left MTG were positively correlated with insomnia, middle scores and appetite increase scores. The mean functional connectivities of left MTG to cluster 1 were negatively correlated with grandiose delusions scores. While the functional connections between left MTG with cluster 2 were negatively correlated with delusions of reference and positively correlated with insomnia, middle scores in BD patients.ConclusionsOur findings suggested that abnormal FcHo and functional connections in those areas of the brain involving DMN and SMN networks might play a crucial role in the neuropathology of BD.

Dataset Information

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

Publications

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

Similar Datasets

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