Large‐scale collaboration in ENIGMA‐EEG: A perspective on the meta‐analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity.

Background and purpose The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. Methods We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. Results We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. Conclusion The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

BACKGROUND AND PURPOSE: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. METHODS: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. RESULTS: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. CONCLUSION: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability

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

Developing artificial intelligence models for classification of brain disorder diseases based on statistical techniques

The Abstract is currently unavailable, due to the thesis being under Embargo

High-performance detection of epilepsy in seizure-free EEG recordings: A novel machine learning approach using very specific epileptic EEG sub-bands

We applied machine learning to diagnose epilepsy based on the fine-graded spectral analysis of seizure-free (resting state) EEG recordings. Despite using unspecific agglomerated EEG spectra, our fine-graded spectral analysis specifically identified the two EEG resting state sub-bands differentiating healthy people from epileptics (1.5-2 Hz and 11-12.5 Hz). The rigorous evaluation of completely unseen data of 100 EEG recordings (50 belonging to epileptics and the other 50 to healthy people) shows that the approach works successfully, achieving an outstanding accuracy of 99 percent, which significantly outperforms the current benchmark of 70% to 95% by a panel of up to three experienced neurologists. Our epilepsy diagnosis classifier can be implemented in modern EEG analysis devices, especially in intensive care units where early diagnosis and appropriate treatment are decisive in life and death scenarios and where physicians’ error rates are particularly high. Our approach is accurate, robust, fast, and cost-efficient and substantially contributes to Information Systems research in healthcare. The approach is also of high practical and theoretical relevance

Data selection in EEG signals classification

The alcoholism can be detected by analyzing electroencephalogram (EEG) signals. However, analyzing multi-channel EEG signals is a challenging task, which often requires complicated calculations and long execution time. This paper proposes three data selection methods to extract representative data from the EEG signals of alcoholics. The methods are the principal component analysis based on graph entropy (PCA-GE), the channel selection based on graph entropy (GE) difference, and the mathematic combinations channel selection, respectively. For comparison purposes, the selected data from the three methods are then classified by three classifiers: the J48 decision tree, the K-nearest neighbor and the Kstar, separately. The experimental results show that the proposed methods are successful in selecting data without compromising the classification accuracy in discriminating the EEG signals from alcoholics and non-alcoholics. Among them, the proposed PCA-GE method uses only 29.69 % of the whole data and 29.5 % of the computation time but achieves a 94.5 % classification accuracy. The channel selection method based on the GE difference also gains a 91.67 % classification accuracy by using only 29.69 % of the full size of the original data. Using as little data as possible without sacrificing the final classification accuracy is useful for online EEG analysis and classification application design

Coherence analysis: Methods, solutions and problems

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.A coherence function is a measure of the correlation of two signals and may be used as a measure for functional relationship between brain areas. In studying functional relationships, referenced EEG (REEG) coherence analysis yields important new aspects of brain activities, which complement the data obtained by power spectral analysis. However, REEG-based coherence tends to show a false high value due to volume conduction from un correlated sources (VCUS). Existing signal processing methods address this issue using a Fourier coherence function of scalp Laplacian. Although this method has been proved useful to reveal correlation between EEG signals with minimum VCUS effects, it only provides frequency-domain analysis. Since EEG signals are highly non-stationary, it is more appropriate to use time-frequency methods for coherence analysis of scalp Laplacian. Thus this research applies the wavelet transform on coherence analysis of scalp Laplacian. To verify our technique, already recorded EEG data of event related potentials were obtained from a study of two large groups of alcoholic and abstinent alcoholic subjects, performing visual picture-recognition tasks. The proposed coherence method successfully detected time-frequency correlation between EEG signals with minimum VCUS effects. It showed significant spatial specificity and revealed detailed coherence patterns. Some new important results regarding time-frequency characteristics of VCUS effects on wavelet and short-time Fourier transform (STFT) coherence analysis of REEG signals were deduced. The proposed coherence method was also compared to a conventional wavelet coherence method of REEG signals in the study of coherence difference between coherences of alcoholic and abstinent alcoholic EEG signals. Results of this study provided substantial evidence that VCUS effects are not additive and therefore can not be ignored in comparison of different brain states between groups of subjects