EEG sleep stages identification based on weighted undirected complex networks

Sleep scoring is important in sleep research because any errors in the scoring of the patient's sleep electroencephalography (EEG) recordings can cause serious problems such as incorrect diagnosis, medication errors, and misinterpretations of patient's EEG recordings. The aim of this research is to develop a new automatic method for EEG sleep stages classification based on a statistical model and weighted brain networks. Methods each EEG segment is partitioned into a number of blocks using a sliding window technique. A set of statistical features are extracted from each block. As a result, a vector of features is obtained to represent each EEG segment. Then, the vector of features is mapped into a weighted undirected network. Different structural and spectral attributes of the networks are extracted and forwarded to a least square support vector machine (LS-SVM) classifier. At the same time the network's attributes are also thoroughly investigated. It is found that the network's characteristics vary with their sleep stages. Each sleep stage is best represented using the key features of their networks. Results In this paper, the proposed method is evaluated using two datasets acquired from different channels of EEG (Pz-Oz and C3-A2) according to the R&K and the AASM without pre-processing the original EEG data. The obtained results by the LS-SVM are compared with those by Naïve, k-nearest and a multi-class-SVM. The proposed method is also compared with other benchmark sleep stages classification methods. The comparison results demonstrate that the proposed method has an advantage in scoring sleep stages based on single channel EEG signals. Conclusions An average accuracy of 96.74% is obtained with the C3-A2 channel according to the AASM standard, and 96% with the Pz-Oz channel based on the R&K standard

Genomic and phenotypic signatures of climate adaptation in an Anolis lizard

Integrated knowledge on phenotype, physiology and genomic adaptations is required to understand the effects of climate on evolution. The functional genomic basis of organismal adaptation to changes in the abiotic environment, its phenotypic consequences, and its possible convergence across vertebrates, are still understudied. In this study, we use a comparative approach to verify predicted gene functions for vertebrate thermal adaptation with observed functions underlying repeated genomic adaptations in response to elevation in the lizard Anolis cybotes. We establish a direct link between recurrently evolved phenotypes and functional genomics of altitude-related climate adaptation in three highland and lowland populations in the Dominican Republic. We show that across vertebrates, genes contained in this interactome are expressed within the brain and during development. These results are relevant to elucidate the effect of global climate change across vertebrates, and might aid in furthering insight into gene-environment relationships under disturbances to external homeostasis

Disentangling causal webs in the brain using functional Magnetic Resonance Imaging: A review of current approaches

In the past two decades, functional Magnetic Resonance Imaging has been used to relate neuronal network activity to cognitive processing and behaviour. Recently this approach has been augmented by algorithms that allow us to infer causal links between component populations of neuronal networks. Multiple inference procedures have been proposed to approach this research question but so far, each method has limitations when it comes to establishing whole-brain connectivity patterns. In this work, we discuss eight ways to infer causality in fMRI research: Bayesian Nets, Dynamical Causal Modelling, Granger Causality, Likelihood Ratios, LiNGAM, Patel's Tau, Structural Equation Modelling, and Transfer Entropy. We finish with formulating some recommendations for the future directions in this area

Latent Factor Analysis of High-Dimensional Brain Imaging Data

Recent advances in neuroimaging study, especially functional magnetic resonance imaging (fMRI), has become an important tool in understanding the human brain. Human cognitive functions can be mapped with the brain functional organization through the high-resolution fMRI scans. However, the high-dimensional data with the increasing number of scanning tasks and subjects pose a challenge to existing methods that wasn’t optimized for high-dimensional imaging data. In this thesis, I develop advanced data-driven methods to help utilize more available sources of information in order to reveal more robust brain-behavior relationship. In the first chapter, I provide an overview of the current related research in fMRI and my contributions to the field. In the second chapter, I propose two extensions to the connectome-based predictive modeling (CPM) method that is able to combine multiple connectomes when building predictive models. The two extensions are both able to generate higher prediction accuracy than using the single connectome or the average of multiple connectomes, suggesting the advantage of incorporating multiple sources of information in predictive modeling. In the third chapter, I improve CPM from the target behavioral measure’s perspective. I propose another two extensions for CPM that are able to combine multiple available behavioral measures into a composite measure for CPM to predict. The derived composite measures are shown to be predicted more accurately than any other single behavioral measure, suggesting a more robust brainbehavior relationship. In the fourth chapter, I propose a nonlinear dimensionality reduction framework to embed fMRI data from multiple tasks into a low-dimensional space. This framework helps reveal the common brain state in the multiple available tasks while also help discover the differences among these tasks. The results also provide valuable insights into the various prediction performance based on connectomes from different tasks. In the fifth chapter, I propose an another hyerbolic geometry-based brain graph edge embedding framework. The framework is based on Poincar´e embedding and is able to more accurately represent edges in the brain graph in a low-dimensional space than traditional Euclidean geometry-based embedding. Utilizing the embedding, we are able to cluster edges of the brain graph into disjoint clusters. The edge clusters can then be used to define overlapping brain networks and the derived metrics like network overlapping number can be used to investigate functional flexibility of each brain region. Overall, these work provide rich data-driven methods that help understand the brain-behavioral relationship through predictive modeling and low-dimensional data representation

Analysis of large-scale molecular biological data using self-organizing maps

Modern high-throughput technologies such as microarrays, next generation sequencing and mass spectrometry provide huge amounts of data per measurement and challenge traditional analyses. New strategies of data processing, visualization and functional analysis are inevitable. This thesis presents an approach which applies a machine learning technique known as self organizing maps (SOMs). SOMs enable the parallel sample- and feature-centered view of molecular phenotypes combined with strong visualization and second-level analysis capabilities. We developed a comprehensive analysis and visualization pipeline based on SOMs. The unsupervised SOM mapping projects the initially high number of features, such as gene expression profiles, to meta-feature clusters of similar and hence potentially co-regulated single features. This reduction of dimension is attained by the re-weighting of primary information and does not entail a loss of primary information in contrast to simple filtering approaches. The meta-data provided by the SOM algorithm is visualized in terms of intuitive mosaic portraits. Sample-specific and common properties shared between samples emerge as a handful of localized spots in the portraits collecting groups of co-regulated and co-expressed meta-features. This characteristic color patterns reflect the data landscape of each sample and promote immediate identification of (meta-)features of interest. It will be demonstrated that SOM portraits transform large and heterogeneous sets of molecular biological data into an atlas of sample-specific texture maps which can be directly compared in terms of similarities and dissimilarities. Spot-clusters of correlated meta-features can be extracted from the SOM portraits in a subsequent step of aggregation. This spot-clustering effectively enables reduction of the dimensionality of the data in two subsequent steps towards a handful of signature modules in an unsupervised fashion. Furthermore we demonstrate that analysis techniques provide enhanced resolution if applied to the meta-features. The improved discrimination power of meta-features in downstream analyses such as hierarchical clustering, independent component analysis or pairwise correlation analysis is ascribed to essentially two facts: Firstly, the set of meta-features better represents the diversity of patterns and modes inherent in the data and secondly, it also possesses the better signal-to-noise characteristics as a comparable collection of single features. Additionally to the pattern-driven feature selection in the SOM portraits, we apply statistical measures to detect significantly differential features between sample classes. Implementation of scoring measurements supplements the basal SOM algorithm. Further, two variants of functional enrichment analyses are introduced which link sample specific patterns of the meta-feature landscape with biological knowledge and support functional interpretation of the data based on the ‘guilt by association’ principle. Finally, case studies selected from different ‘OMIC’ realms are presented in this thesis. In particular, molecular phenotype data derived from expression microarrays (mRNA, miRNA), sequencing (DNA methylation, histone modification patterns) or mass spectrometry (proteome), and also genotype data (SNP-microarrays) is analyzed. It is shown that the SOM analysis pipeline implies strong application capabilities and covers a broad range of potential purposes ranging from time series and treatment-vs.-control experiments to discrimination of samples according to genotypic, phenotypic or taxonomic classifications

Analysis of EEG signals using complex brain networks

The human brain is so complex that two mega projects, the Human Brain Project and the BRAIN Initiative project, are under way in the hope of answering important questions for peoples' health and wellbeing. Complex networks become powerful tools for studying brain function due to the fact that network topologies on real-world systems share small world properties. Examples of these networks are the Internet, biological networks, social networks, climate networks and complex brain networks. Complex brain networks in real time biomedical signal processing applications are limited because some graph algorithms (such as graph isomorphism), cannot be solved in polynomial time. In addition, they are hard to use in single-channel EEG applications, such as clinic applications in sleep scoring and depth of anaesthesia monitoring. The first contribution of this research is to present two novel algorithms and two graph models. A fast weighted horizontal visibility algorithm (FWHVA) overcoming the speed limitations for constructing a graph from a time series is presented. Experimental results show that the FWHVA can be 3.8 times faster than the Fast Fourier Transfer (FFT) algorithm when input signals exceed 4000 data points. A linear time graph isomorphism algorithm (HVGI) can determine the isomorphism of two horizontal visibility graphs (HVGs) in a linear time domain. This is an efficient way to measure the synchronized index between two time series. Difference visibility graphs (DVGs) inherit the advantages of horizontal visibility graphs. They are noise-robust, and they overcome a pitfall of visibility graphs (VG): that the degree distribution (DD) doesn't satisfy a pure power-law. Jump visibility graphs (JVGs) enhance brain graphs allowing the processing of non-stationary biomedical signals. This research shows that the DD of JVGs always satisfies a power-lower if the input signals are purely non-stationary. The second highlight of this work is the study of three clinical biomedical signals: alcoholic, epileptic and sleep EEGs. Based on a synchronization likelihood and maximal weighted matching method, this work finds that the processing repeated stimuli and unrepeated stimuli in the controlled drinkers is larger than that in the alcoholics. Seizure detections based on epileptic EEGs have also been investigated with three graph features: graph entropy of VGs, mean strength of HVGs, and mean degrees of JVGs. All of these features can achieve 100% accuracy in seizure identification and differentiation from healthy EEG signals. Sleep EEGs are evaluated based on VG and DVG methods. It is shown that the complex brain networks exhibit more small world structure during deep sleep. Based on DVG methods, the accuracy peaks at 88:9% in a 5-state sleep stage classification from 14; 943 segments from single-channel EEGs. This study also introduces two weighted complex network approaches to analyse the nonlinear EEG signals. A weighted horizontal visibility graph (WHVG) is proposed to enhance noise-robustness properties. Tested with two Chaos signals and an epileptic EEG database, the research shows that the mean strength of the WHVG is more stable and noise-robust than those features from FFT and entropy. Maximal weighted matching algorithms have been applied to evaluate the difference in complex brain networks of alcoholics and controlled drinkers. The last contribution of this dissertation is to develop an unsupervised classifier for biomedical signal pattern recognition. A Multi-Scale Means (MSK-Means) algorithm is proposed for solving the subject-dependent biomedical signals classification issue. Using JVG features from the epileptic EEG database, the MSK-Means algorithm is 4:7% higher in identifying seizures than those by the K-means algorithm and achieves 92:3% accuracy for localizing the epileptogenic zone. The findings suggest that the outcome of this thesis can improve the performance of complex brain networks for biomedical signal processing and nonlinear time series analysis