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Simulating the Evolution of Functional Brain Networks in Alzheimer's Disease: Exploring Disease Dynamics from the Perspective of Global Activity.

ABSTRACT: Functional brain connectivity is altered during the pathological processes of Alzheimer's disease (AD), but the specific evolutional rules are insufficiently understood. Resting-state functional magnetic resonance imaging indicates that the functional brain networks of individuals with AD tend to be disrupted in hub-like nodes, shifting from a small world architecture to a random profile. Here, we proposed a novel evolution model based on computational experiments to simulate the transition of functional brain networks from normal to AD. Specifically, we simulated the rearrangement of edges in a pathological process by a high probability of disconnecting edges between hub-like nodes, and by generating edges between random pair of nodes. Subsequently, four topological properties and a nodal distribution were used to evaluate our model. Compared with random evolution as a null model, our model captured well the topological alteration of functional brain networks during the pathological process. Moreover, we implemented two kinds of network attack to imitate the damage incurred by the brain in AD. Topological changes were better explained by 'hub attacks' than by 'random attacks', indicating the fragility of hubs in individuals with AD. This model clarifies the disruption of functional brain networks in AD, providing a new perspective on topological alterations.

SUBMITTER: Li W

PROVIDER: S-EPMC5039719 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Simulating the Evolution of Functional Brain Networks in Alzheimer's Disease: Exploring Disease Dynamics from the Perspective of Global Activity.

Li Wei W Wang Miao M Zhu Wenzhen W Qin Yuanyuan Y Huang Yue Y Chen Xi X

Scientific reports 20160928

Functional brain connectivity is altered during the pathological processes of Alzheimer's disease (AD), but the specific evolutional rules are insufficiently understood. Resting-state functional magnetic resonance imaging indicates that the functional brain networks of individuals with AD tend to be disrupted in hub-like nodes, shifting from a small world architecture to a random profile. Here, we proposed a novel evolution model based on computational experiments to simulate the transition of f ...[more]

PMID: 27677360

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Project description:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the "disconnection syndrome" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a "disconnection syndrome." Since only AD but not MCI patients were characterized by a significant decrease in structural connectivity, integrated structural/functional connectomics could provide a useful tool for assessing disease progression from MCI to AD.

Project description:Network-sensitive neuroimaging methods have been used to characterize large-scale brain network degeneration in Alzheimer's disease and its prodrome. However, few studies have investigated the combined effect of Alzheimer's disease and cerebrovascular disease on brain network degeneration. Our study sought to examine the intrinsic functional connectivity and structural covariance network changes in 235 prodromal and clinical Alzheimer's disease patients with and without cerebrovascular disease. We focused particularly on two higher-order cognitive networks-the default mode network and the executive control network. We found divergent functional connectivity and structural covariance patterns in Alzheimer's disease patients with and without cerebrovascular disease. Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's disease patients with cerebrovascular disease, showed reductions in posterior default mode network functional connectivity. By comparison, while both groups exhibited parietal reductions in executive control network functional connectivity, only Alzheimer's disease patients with cerebrovascular disease showed increases in frontal executive control network connectivity. Importantly, these distinct executive control network changes were recapitulated in prodromal Alzheimer's disease patients with and without cerebrovascular disease. Across Alzheimer's disease patients with and without cerebrovascular disease, higher default mode network functional connectivity z-scores correlated with greater hippocampal volumes while higher executive control network functional connectivity z-scores correlated with greater white matter changes. In parallel, only Alzheimer's disease patients without cerebrovascular disease showed increased default mode network structural covariance, while only Alzheimer's disease patients with cerebrovascular disease showed increased executive control network structural covariance compared to controls. Our findings demonstrate the differential neural network structural and functional changes in Alzheimer's disease with and without cerebrovascular disease, suggesting that the underlying pathology of Alzheimer's disease patients with cerebrovascular disease might differ from those without cerebrovascular disease and reflect a combination of more severe cerebrovascular disease and less severe Alzheimer's disease network degeneration phenotype.

Project description:Alzheimer's disease (AD) is a neurodegenerative disease that commonly affects the elderly; early diagnosis and timely treatment are very important to delay the course of the disease. In the past, most brain regions related to AD were identified based on imaging methods, and only some atrophic brain regions could be identified. In this work, the authors used mathematical models to identify the potential brain regions related to AD. In this study, 20 patients with AD and 13 healthy controls (non-AD) were recruited by the neurology outpatient department or the neurology ward of Peking University First Hospital from September 2017 to March 2019. First, diffusion tensor imaging (DTI) was used to construct the brain structural network. Next, the authors set a new local feature index 2hop-connectivity to measure the correlation between different regions. Compared with the traditional graph theory index, 2hop-connectivity exploits the higher-order information of the graph structure. And for this purpose, the authors proposed a novel algorithm called 2hopRWR to measure 2hop-connectivity. Then, a new index global feature score (GFS) based on a global feature was proposed by combing five local features, namely degree centrality, betweenness centrality, closeness centrality, the number of maximal cliques, and 2hop-connectivity, to judge which brain regions are related to AD. As a result, the top ten brain regions identified using the GFS scoring difference between the AD and the non-AD groups were associated to AD by literature verification. The results of the literature validation comparing GFS with the local features showed that GFS was superior to individual local features. Finally, the results of the canonical correlation analysis showed that the GFS was significantly correlated with the scores of the Mini-Mental State Examination (MMSE) scale and the Montreal Cognitive Assessment (MoCA) scale. Therefore, the authors believe the GFS can also be used as a new biomarker to assist in diagnosis and objective monitoring of disease progression. Besides, the method proposed in this paper can be used as a differential network analysis method for network analysis in other domains.

Dataset Information

Simulating the Evolution of Functional Brain Networks in Alzheimer's Disease: Exploring Disease Dynamics from the Perspective of Global Activity.

Publications

Simulating the Evolution of Functional Brain Networks in Alzheimer's Disease: Exploring Disease Dynamics from the Perspective of Global Activity.

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