Topological classifier for detecting the emergence of epileptic seizures

Objective An innovative method based on topological data analysis is introduced for classifying EEG recordings of patients affected by epilepsy. We construct a topological space from a collection of EEGs signals using Persistent Homology; then, we analyse the space by Persistent entropy, a global topological feature, in order to classify healthy and epileptic signals. Results The performance of the resulting one-feature-based linear topological classifier is tested by analysing the Physionet dataset. The quality of classification is evaluated in terms of the Area Under Curve (AUC) of the receiver operating characteristic curve. It is shown that the linear topological classifier has an AUC equal to 97.2% while the performance of a classifier based on Sample Entropy has an AUC equal to 62.0%

Topological biomarkers for real-time detection of epileptic seizures

Automated seizure detection is a fundamental problem in computational neuroscience towards diagnosis and treatment's improvement of epileptic disease. We propose a real-time computational method for automated tracking and detection of epileptic seizures from raw neurophysiological recordings. Our mechanism is based on the topological analysis of the sliding-window embedding of the time series derived from simultaneously recorded channels. We extract topological biomarkers from the signals via the computation of the persistent homology of time-evolving topological spaces. Remarkably, the proposed biomarkers robustly captures the change in the brain dynamics during the ictal state. We apply our methods in different types of signals including scalp and intracranial EEG and MEG, in patients during interictal and ictal states, showing high accuracy in a range of clinical situations.Comment: 21 pages, 12 figure

The Value of Seizure Semiology in Epilepsy Surgery: Epileptogenic-Zone Localisation in Presurgical Patients using Machine Learning and Semiology Visualisation Tool

Background Eight million individuals have focal drug resistant epilepsy worldwide. If their epileptogenic focus is identified and resected, they may become seizure-free and experience significant improvements in quality of life. However, seizure-freedom occurs in less than half of surgical resections. Seizure semiology - the signs and symptoms during a seizure - along with brain imaging and electroencephalography (EEG) are amongst the mainstays of seizure localisation. Although there have been advances in algorithmic identification of abnormalities on EEG and imaging, semiological analysis has remained more subjective. The primary objective of this research was to investigate the localising value of clinician-identified semiology, and secondarily to improve personalised prognostication for epilepsy surgery. Methods I data mined retrospective hospital records to link semiology to outcomes. I trained machine learning models to predict temporal lobe epilepsy (TLE) and determine the value of semiology compared to a benchmark of hippocampal sclerosis (HS). Due to the hospital dataset being relatively small, we also collected data from a systematic review of the literature to curate an open-access Semio2Brain database. We built the Semiology-to-Brain Visualisation Tool (SVT) on this database and retrospectively validated SVT in two separate groups of randomly selected patients and individuals with frontal lobe epilepsy. Separately, a systematic review of multimodal prognostic features of epilepsy surgery was undertaken. The concept of a semiological connectome was devised and compared to structural connectivity to investigate probabilistic propagation and semiology generation. Results Although a (non-chronological) list of patients’ semiologies did not improve localisation beyond the initial semiology, the list of semiology added value when combined with an imaging feature. The absolute added value of semiology in a support vector classifier in diagnosing TLE, compared to HS, was 25%. Semiology was however unable to predict postsurgical outcomes. To help future prognostic models, a list of essential multimodal prognostic features for epilepsy surgery were extracted from meta-analyses and a structural causal model proposed. Semio2Brain consists of over 13000 semiological datapoints from 4643 patients across 309 studies and uniquely enabled a Bayesian approach to localisation to mitigate TLE publication bias. SVT performed well in a retrospective validation, matching the best expert clinician’s localisation scores and exceeding them for lateralisation, and showed modest value in localisation in individuals with frontal lobe epilepsy (FLE). There was a significant correlation between the number of connecting fibres between brain regions and the seizure semiologies that can arise from these regions. Conclusions Semiology is valuable in localisation, but multimodal concordance is more valuable and highly prognostic. SVT could be suitable for use in multimodal models to predict the seizure focus

Graph analysis of functional brain networks: practical issues in translational neuroscience

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires a know-how of all the methodological steps of the processing pipeline that manipulates the input brain signals and extract the functional network properties. On the other hand, a knowledge of the neural phenomenon under study is required to perform physiological-relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes

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

Promises and pitfalls of topological data analysis for brain connectivity analysis

Acknowledgment The authors thank Jakub Kopal for sharing the preprocessed fMRI time series and Barbora Bučková for sharing scripts for classification pipelinePeer reviewedPublisher PD

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

Network-based brain computer interfaces: principles and applications

Brain-computer interfaces (BCIs) make possible to interact with the external environment by decoding the mental intention of individuals. BCIs can therefore be used to address basic neuroscience questions but also to unlock a variety of applications from exoskeleton control to neurofeedback (NFB) rehabilitation. In general, BCI usability critically depends on the ability to comprehensively characterize brain functioning and correctly identify the user s mental state. To this end, much of the efforts have focused on improving the classification algorithms taking into account localized brain activities as input features. Despite considerable improvement BCI performance is still unstable and, as a matter of fact, current features represent oversimplified descriptors of brain functioning. In the last decade, growing evidence has shown that the brain works as a networked system composed of multiple specialized and spatially distributed areas that dynamically integrate information. While more complex, looking at how remote brain regions functionally interact represents a grounded alternative to better describe brain functioning. Thanks to recent advances in network science, i.e. a modern field that draws on graph theory, statistical mechanics, data mining and inferential modelling, scientists have now powerful means to characterize complex brain networks derived from neuroimaging data. Notably, summary features can be extracted from these networks to quantitatively measure specific organizational properties across a variety of topological scales. In this topical review, we aim to provide the state-of-the-art supporting the development of a network theoretic approach as a promising tool for understanding BCIs and improve usability

Towards personalized diagnosis of Glioblastoma in Fluid-attenuated inversion recovery (FLAIR) by topological interpretable machine learning

Glioblastoma multiforme (GBM) is a fast-growing and highly invasive brain tumour, it tends to occur in adults between the ages of 45 and 70 and it accounts for 52 percent of all primary brain tumours. Usually, GBMs are detected by magnetic resonance images (MRI). Among MRI, Fluid-attenuated inversion recovery (FLAIR) sequence produces high quality digital tumour representation. Fast detection and segmentation techniques are needed for overcoming subjective medical doctors (MDs) judgment. In the present investigation, we intend to demonstrate by means of numerical experiments that topological features combined with textural features can be enrolled for GBM analysis and morphological characterization on FLAIR. To this extent, we have performed three numerical experiments. In the first experiment, Topological Data Analysis (TDA) of a simplified 2D tumour growth mathematical model had allowed to understand the bio-chemical conditions that facilitate tumour growth: the higher the concentration of chemical nutrients the more virulent the process. In the second experiment topological data analysis was used for evaluating GBM temporal progression on FLAIR recorded within 90 days following treatment (e.g., chemo-radiation therapy - CRT) completion and at progression. The experiment had confirmed that persistent entropy is a viable statistics for monitoring GBM evolution during the follow-up period. In the third experiment we had developed a novel methodology based on topological and textural features and automatic interpretable machine learning for automatic GBM classification on FLAIR. The algorithm reached a classification accuracy up to the 97%.Comment: 22 pages; 16 figure

Visualising 2-simplex formation in metabolic reactions

Understanding in silico the dynamics of metabolic reactions made by a large number of molecules has led to the development of different tools for visualising molecular interactions. However, most of them are mainly focused on quantitative aspects. We investigate the potentiality of the topological interpretation of the interaction-as-perception at the basis of a multiagent system, to tackle the complexity of visualising the emerging behaviour of a complex system. We model and simulate the glycolysis process as a multiagent system, and we perform topological data analysis of the molecular perceptions graphs, gained during the formation of the enzymatic complexes, to visualise the set of emerging patterns. Identifying expected patterns in terms of simplicial structures allows us to characterise metabolic reactions from a qualitative point of view and conceivably reveal the simulation reactivity trend