Brain Network Modeling Based on Mutual Information and Graph Theory for Predicting the Connection Mechanism in the Development of Alzheimer's Disease

Abstract

Abnormal connections in brain networks of healthy people always bring the problems of cognitive impairments and degeneration of specific brain circuits, which may finally result in Alzheimer's disease (AD). Exploring the development of the brain from normal controls (NC) to AD is an essential part of human research. Although connections changes have been found in the development, the connection mechanism that drives these changes remain incompletely understood. The purpose of this study is to explore the connection changes in brain networks in the process from NC to AD, and uncover the underlying connection mechanism that shapes the topologies of AD brain networks. In particular, we propose a model named MINM from the perspective of topology-based mutual information to achieve our aim. MINM concerns the question of estimating the connection probability between two cortical regions with the consideration of both the mutual information of their observed network topologies and their Euclidean distance in anatomical space. In addition, MINM considers establishing and deleting connections, simultaneously, during the networks modeling from the stage of NC to AD. Experiment results show that MINM is sufficient to capture an impressive range of topological properties of real brain networks such as characteristic path length, network efficiency, and transitivity, and it also provides an excellent fit to the real brain networks in degree distribution compared to experiential models. Thus, we anticipate that MINM may explain the connection mechanism for the formation of the brain network organization in AD patients.topological properties for evaluating the characteristics of human brain networks [8][9][10][11][12]. Taking the form of a graph, people can learn the alterations of brain network properties in terms of network connectivity, transitivity, efficiency, degree distribution, modularity, and small-world-ness between normal controls (NC) and AD patients [13][14][15]. Particularly, graph theory also provides numerous methods of network modeling for simulating the evolution processes of real complex networks [16][17][18][19]. Through network modeling, one can surmise the fundamental causes that result in the existence of connections among nodes, and explain the underlying mechanisms of networks organization [20]. Previous studies have reported that network modelings could be effectively applied in various science fields to help explore the dynamic connection schemes in networks of real-world systems [21][22][23][24][25], i.e., friendships recommendation in social networks [21,22], spurious links identification in biological networks [23,24]. We can generate network topologies that incorporate desired properties by employing suitable network models. Network modeling is viewed as a promising way to help us understand how the inter-connection mechanism affects the topological structures in complex networks.It is worth mentioning that network modeling has made some significant advances, particularly in the study of brain net...