Energy landscape of resting magnetoencephalography reveals frontoparietal network impairments in epilepsy

Juvenile myoclonic epilepsy (JME) is a form of idiopathic generalized epilepsy. It is yet unclear to what extent JME leads to abnormal network activation patterns. Here, we characterised statistical regularities in MEG resting-state networks and their differences between JME patients and controls, by combining a pairwise maximum entropy model (pMEM) and novel energy landscape analyses for MEG. First, we fitted the pMEM to the MEG oscillatory power in the frontoparietal network (FPN) and other resting-state networks, which provided a good estimation of the occurrence probability of network states. Then, we used energy values derived from the pMEM to depict an energy landscape, with a higher energy state corresponding to a lower occurrence probability. JME patients showed fewer local energy minima than controls and had elevated energy values for the FPN within the theta, beta and gamma-bands. Furthermore, simulations of the fitted pMEM showed that the proportion of time the FPN was occupied within the basins of energy minima was shortened in JME patients. These network alterations were highlighted by significant classification of individual participants employing energy values as multivariate features. Our findings suggested that JME patients had altered multi-stability in selective functional networks and frequency bands in the frontoparietal cortices

Permutation entropy applied to the characterization of the clinical evolution of epileptic patients under pharmacological treatment

Different techniques originated in information theory and tools from nonlinear systems theory have been applied to the analysis of electro-physiological time series. Several clinically relevant results have emerged from the use of concepts, such as entropy, chaos and complexity, in analyzing electrocardiograms and electroencephalographic (EEG) records. In this work, we develop a method based on permutation entropy (PE) to characterize EEG records from different stages in the treatment of a chronic epileptic patient. Our results show that the PE is useful for clearly quantifying the evolution of the patient along a certain lapse of time and allows visualizing in a very convenient way the effects of the pharmacotherapy.publishedVersionFil: Mateos, Diego. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Díaz, Juan Manuel. Instituto Privado de Neurociencias; Argentina.Fil: Lamberti, Pedro Walter. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Lamberti, Pedro Walter. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaOtras Ciencias Física

EEG complexity as a biomarker for autism spectrum disorder risk

BACKGROUND: Complex neurodevelopmental disorders may be characterized by subtle brain function signatures early in life before behavioral symptoms are apparent. Such endophenotypes may be measurable biomarkers for later cognitive impairments. The nonlinear complexity of electroencephalography (EEG) signals is believed to contain information about the architecture of the neural networks in the brain on many scales. Early detection of abnormalities in EEG signals may be an early biomarker for developmental cognitive disorders. The goal of this paper is to demonstrate that the modified multiscale entropy (mMSE) computed on the basis of resting state EEG data can be used as a biomarker of normal brain development and distinguish typically developing children from a group of infants at high risk for autism spectrum disorder (ASD), defined on the basis of an older sibling with ASD. METHODS: Using mMSE as a feature vector, a multiclass support vector machine algorithm was used to classify typically developing and high-risk groups. Classification was computed separately within each age group from 6 to 24 months. RESULTS: Multiscale entropy appears to go through a different developmental trajectory in infants at high risk for autism (HRA) than it does in typically developing controls. Differences appear to be greatest at ages 9 to 12 months. Using several machine learning algorithms with mMSE as a feature vector, infants were classified with over 80% accuracy into control and HRA groups at age 9 months. Classification accuracy for boys was close to 100% at age 9 months and remains high (70% to 90%) at ages 12 and 18 months. For girls, classification accuracy was highest at age 6 months, but declines thereafter. CONCLUSIONS: This proof-of-principle study suggests that mMSE computed from resting state EEG signals may be a useful biomarker for early detection of risk for ASD and abnormalities in cognitive development in infants. To our knowledge, this is the first demonstration of an information theoretic analysis of EEG data for biomarkers in infants at risk for a complex neurodevelopmental disorder.This research was supported by a grant from Autism Speaks (to HTF), National Institute on Deafness and Other Communication Disorders (NIDCD) grant R21 DC08647 (to HTF), NIDCD grant R01 DC 10290 (to HTF and CAN) and a grant from the Simons Foundation (to CAN and WJB). We thank the following people for their help in data collection: Tara Augenstein, Leah Casner, Laura Kasparian, Nina Leezenbaum, Vanessa Vogel-Farley and Annemarie Zuluaga. We are especially grateful to the families who participated in this study. (Autism Speaks; R21 DC08647 - National Institute on Deafness and Other Communication Disorders (NIDCD); R01 DC 10290 - National Institute on Deafness and Other Communication Disorders (NIDCD); Simons Foundation

Diagnosing epilepsy using entropy measures and embedding parameters of EEG signals

Epilepsy is a neurological disorder that affects normal neural activity. These electrical activities can be recorded as signals containing information about the brain known as Electroencephalography (EEG) signals. Analysis of the EEG signals by individuals for epilepsy diagnosis is subjective and time-consuming. So, an automatic classification system with high detection accuracy is required to overcome possible errors. In this study, the discrete wavelet transform has been applied to EEG signals. Then, entropy measures and embedding parameters have been extracted. These features have been investigated individually to find the most discriminating ones. The significance level of each feature was evaluated by statistical analysis. Consequently, LDA and SVM algorithms have been employed to categorize the EEG signals. The results have indicated that the features of Embedding parameters, PermutationEntropy, FuzzyEntropy, SampleEntropy, NormEntropy, SureEntropy, LogEntropy, and ThresholdEntropy have the potential to discriminate epileptic patients from healthy subjects significantly. Also, SVM classifier has achieved the highest classification accuracy. In this study, we could find effective embedding-based and entropy-based features as appropriate single measures for identifying abnormal activities that can efficiently discriminate the EEG signals of epileptics from healthy individuals. According to the results, they can be used for automatic classification of epileptic EEG signals that are difficult to examine visually

Informatics for EEG biomarker discovery in clinical neuroscience

Neurological and developmental disorders (NDDs) impose an enormous burden of disease on children throughout the world. Two of the most common are autism spectrum disorder (ASD) and epilepsy. ASD has recently been estimated to affect 1 in 68 children, making it the most common neurodevelopmental disorder in children. Epilepsy is also a spectrum disorder that follows a developmental trajectory, with an estimated prevalence of 1%, nearly as common as autism. ASD and epilepsy co-occur in approximately 30% of individuals with a primary diagnosis of either disorder. Although considered to be different disorders, the relatively high comorbidity suggests the possibility of common neuropathological mechanisms. Early interventions for NDDs lead to better long-term outcomes. But early intervention is predicated on early detection. Behavioral measures have thus far proven ineffective in detecting autism before about 18 months of age, in part because the behavioral repertoire of infants is so limited. Similarly, no methods for detecting emerging epilepsy before seizures begin are currently known. Because atypical brain development is likely to precede overt behavioral manifestations by months or even years, a critical developmental window for early intervention may be opened by the discovery of brain based biomarkers. Analysis of brain activity with EEG may be under-utilized for clinical applications, especially for neurodevelopment. The hypothesis investigated in this dissertation is that new methods of nonlinear signal analysis, together with methods from biomedical informatics, can extract information from EEG data that enables detection of atypical neurodevelopment. This is tested using data collected at Boston Children’s Hospital. Several results are presented. First, infants with a family history of ASD were found to have EEG features that may enable autism to be detected as early as 9 months. Second, significant EEG-based differences were found between children with absence epilepsy, ASD and control groups using short 30-second EEG segments. Comparison of control groups using different EEG equipment supported the claim that EEG features could be computed that were independent of equipment and lab conditions. Finally, the potential for this technology to help meet the clinical need for neurodevelopmental screening and monitoring in low-income regions of the world is discussed

Permutation entropy and its main biomedical and econophysics applications: a review

Entropy is a powerful tool for the analysis of time series, as it allows describing the probability distributions of the possible state of a system, and therefore the information encoded in it. Nevertheless, important information may be codified also in the temporal dynamics, an aspect which is not usually taken into account. The idea of calculating entropy based on permutation patterns (that is, permutations defined by the order relations among values of a time series) has received a lot of attention in the last years, especially for the understanding of complex and chaotic systems. Permutation entropy directly accounts for the temporal information contained in the time series; furthermore, it has the quality of simplicity, robustness and very low computational cost. To celebrate the tenth anniversary of the original work, here we analyze the theoretical foundations of the permutation entropy, as well as the main recent applications to the analysis of economical markets and to the understanding of biomedical systems.Facultad de Ingenierí

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

Energy landscape of resting magnetoencephalography reveals fronto-parietal network impairments in epilepsy

Juvenile myoclonic epilepsy (JME) is a form of idiopathic generalized epilepsy. It is yet unclear to what extent JME leads to abnormal network activation patterns. Here, we characterized statistical regularities in magnetoencephalograph (MEG) resting-state networks and their differences between JME patients and controls by combining a pairwise maximum entropy model (pMEM) and novel energy landscape analyses for MEG. First, we fitted the pMEM to the MEG oscillatory power in the front-oparietal network (FPN) and other resting-state networks, which provided a good estimation of the occurrence probability of network states. Then, we used energy values derived from the pMEM to depict an energy landscape, with a higher energy state corresponding to a lower occurrence probability. JME patients showed fewer local energy minima than controls and had elevated energy values for the FPN within the theta, beta, and gamma bands. Furthermore, simulations of the fitted pMEM showed that the proportion of time the FPN was occupied within the basins of energy minima was shortened in JME patients. These network alterations were highlighted by significant classification of individual participants employing energy values as multivariate features. Our findings suggested that JME patients had altered multistability in selective functional networks and frequency bands in the fronto-parietal cortices