A Singular-value-based Map to Highlight Abnormal Regions Associated with Atrial Fibrillation Using High-resolution Electrograms and Multi-lead ECG.

OBJECTIVE: The severity of atrial fibrillation (AF) can be assessed from intra-operative epicardial measurements (high-resolution electrograms), using metrics such as conduction block (CB) and continuous conduction delay and block (cCDCB). These features capture differences in conduction velocity and wavefront propagation, but ignore complementary properties such as the morphology of the action potentials. In this work, we focus on such complementary properties, and derive features to detect variations in the atrial potential waveforms. METHODS: We show that the spatial variation of atrial potential morphology during a single beat may be described by changes in the singular values of the epicardial measurement matrix. The method is non-parametric and requires little preprocessing. A corresponding singular value map points at areas subject to fractionation and block. Further, we developed an experiment where we simultaneously measure electrograms (EGMs) and a multi-lead ECG. RESULTS: The captured data showed that the normalized singular values of the heartbeats during AF are higher than during SR, and that this difference is more pronounced for the (non-invasive) ECG data than for the EGM data, if the electrodes are positioned at favorable locations. CONCLUSION: Overall, the singular value-based features are a useful indicator to detect and evaluate AF. SIGNIFICANCE: The proposed method might be beneficial for identifying electropathological regions in the tissue without estimating the local activation time.

Evoked Component Analysis (ECA): Decomposing the Functional Ultrasound Signal with GLM-Regularization.

Analysis of functional neuroimaging data aims to unveil spatial and temporal patterns of interest. Existing analysis methods fall into two categories: fully data-driven approaches and those reliant on prior information, e.g. the stimulus time course. While using the stimulus signal directly can help identify the activated brain areas, it is known that the relationship between stimuli and the brain's response exhibits nonlinear and time-varying characteristics. As such, relying completely on the stimulus signal to describe the brain's temporal response leads to a restricted interpretation of the brain function. In this paper, we present a new technique called Evoked Component Analysis (ECA), which leverages prior information up to a defined extent. This is achieved by including the general linear model (GLM) design matrix as a regulatory term and estimating the factor matrices in both space and time through an alternating minimization approach. We apply ECA to 2D and swept-3D functional ultrasound (fUS) experiments conducted with mice. When decomposing 2D fUS data, we employ GLM regularization at various intensities to emphasize the role of prior information. Furthermore, we show that incorporating multiple hemodynamic response functions within the design matrix can provide valuable insights into region-specific characteristics of evoked activity. Finally, we use ECA to analyze swept-3D fUS data recorded from five mice engaged in two distinct visual tasks. Swept-3D fUS images the 3D brain sequentially using a moving probe, resulting in different slice acquisition time instants. We show that ECA can estimate factor matrices with a fine resolution at each slice acquisition time instant and yield higher t-statistics compared to GLM and correlation analysis for all subjects.

Tensor Completion for Alzheimer's Disease Prediction From Diffusion Tensor Imaging.

OBJECTIVE: Alzheimer's disease (AD) is a slowly progressive neurodegenerative disorder with insidious onset. Accurate prediction of the disease progression has received increasing attention. Cognitive scores that reflect patients' cognitive status have become important criteria for predicting AD. Most existing methods consider the relationship between neuroimages and cognitive scores to improve prediction results. However, the inherent structure information in interrelated cognitive scores is rarely considered. METHOD: In this article, we propose a relation-aware tensor completion multitask learning method (RATC-MTL), in which the cognitive scores are represented as a third-order tensor to preserve the global structure information in clinical scores. We combine both tensor completion and linear regression into a unified framework, which allows us to capture both inter and intra modes correlations in cognitive tensor with a low-rank constraint, as well as incorporate the relationship between biological features and cognitive status by imposing a regression model on multiple cognitive scores. RESULT: Compared to the single-task and state-of-the-art multi-task algorithms, our proposed method obtains the best results for predicting cognitive scores in terms of four commonly used metrics. Furthermore, the overall performance of our method in classifying AD progress is also the best. CONCLUSION: Our results demonstrate the effectiveness of the proposed framework in fully exploring the global structure information in cognitive scores. SIGNIFICANCE: This study introduces a novel concept of leveraging tensor completion to assist in disease diagnoses, potentially offering a solution to the issue of data scarcity encountered in prolonged monitoring scenarios.

Deconvolution of the Functional Ultrasound Response in the Mouse Visual Pathway Using Block-Term Decomposition.

Functional ultrasound (fUS) indirectly measures brain activity by detecting changes in cerebral blood volume following neural activation. Conventional approaches model such functional neuroimaging data as the convolution between an impulse response, known as the hemodynamic response function (HRF), and a binarized representation of the input signal based on the stimulus onsets, the so-called experimental paradigm (EP). However, the EP may not characterize the whole complexity of the activity-inducing signals that evoke the hemodynamic changes. Furthermore, the HRF is known to vary across brain areas and stimuli. To achieve an adaptable framework that can capture such dynamics of the brain function, we model the multivariate fUS time-series as convolutive mixtures and apply block-term decomposition on a set of lagged fUS autocorrelation matrices, revealing both the region-specific HRFs and the source signals that induce the hemodynamic responses. We test our approach on two mouse-based fUS experiments. In the first experiment, we present a single type of visual stimulus to the mouse, and deconvolve the fUS signal measured within the mouse brain's lateral geniculate nucleus, superior colliculus and visual cortex. We show that the proposed method is able to recover back the time instants at which the stimulus was displayed, and we validate the estimated region-specific HRFs based on prior studies. In the second experiment, we alter the location of the visual stimulus displayed to the mouse, and aim at differentiating the various stimulus locations over time by identifying them as separate sources.

Classification of De novo post-operative and persistent atrial fibrillation using multi-channel ECG recordings.

Atrial fibrillation (AF) is the most sustained arrhythmia in the heart and also the most common complication developed after cardiac surgery. Due to its progressive nature, timely detection of AF is important. Currently, physicians use a surface electrocardiogram (ECG) for AF diagnosis. However, when the patient develops AF, its various development stages are not distinguishable for cardiologists based on visual inspection of the surface ECG signals. Therefore, severity detection of AF could start from differentiating between short-lasting AF and long-lasting AF. Here, de novo post-operative AF (POAF) is a good model for short-lasting AF while long-lasting AF can be represented by persistent AF. Therefore, we address in this paper a binary severity detection of AF for two specific types of AF. We focus on the differentiation of these two types as de novo POAF is the first time that a patient develops AF. Hence, comparing its development to a more severe stage of AF (e.g., persistent AF) could be beneficial in unveiling the electrical changes in the atrium. To the best of our knowledge, this is the first paper that aims to differentiate these different AF stages. We propose a method that consists of three sets of discriminative features based on fundamentally different aspects of the multi-channel ECG data, namely based on the analysis of RR intervals, a greyscale image representation of the vectorcardiogram, and the frequency domain representation of the ECG. Due to the nature of AF, these features are able to capture both morphological and rhythmic changes in the ECGs. Our classification system consists of a random forest classifier, after a feature selection stage using the ReliefF method. The detection efficiency is tested on 151 patients using 5-fold cross-validation. We achieved 89.07% accuracy in the classification of de novo POAF and persistent AF. The results show that the features are discriminative to reveal the severity of AF. Moreover, inspection of the most important features sheds light on the different characteristics of de novo post-operative and persistent AF.

The power of ECG in multimodal patient-specific seizure monitoring: Added value to an EEG-based detector using limited channels.

OBJECTIVE: Wearable seizure detection devices could provide more reliable seizure documentation outside the hospital compared to seizure self-reporting by patients, which is the current standard. Previously, during the SeizeIT1 project, we studied seizure detection based on behind-the-ear electroencephalography (EEG). However, the obtained sensitivities were too low for practical use, because not all seizures are associated with typical ictal EEG patterns. Therefore, in this paper, we aim to develop a multimodal automated seizure detection algorithm integrating behind-the-ear EEG and electrocardiography (ECG) for detecting focal seizures. In this framework, we quantified the added value of ECG to behind-the-ear EEG. METHODS: This study analyzed three multicenter databases consisting of 135 patients having focal epilepsy and a total of 896 seizures. A patient-specific multimodal automated seizure detection algorithm was developed using behind-the-ear/temporal EEG and single-lead ECG. The EEG and ECG data were processed separately using machine learning methods. A late integration approach was applied for fusing those predictions. RESULTS: The multimodal algorithm outperformed the EEG-based algorithm in two of three databases, with an increase of 11% and 8% in sensitivity for the same false alarm rate. SIGNIFICANCE: ECG can be of added value to an EEG-based seizure detection algorithm using only behind-the-ear/temporal lobe electrodes for patients with focal epilepsy.

Augmenting interictal mapping with neurovascular coupling biomarkers by structured factorization of epileptic EEG and fMRI data.

EEG-correlated fMRI analysis is widely used to detect regional BOLD fluctuations that are synchronized to interictal epileptic discharges, which can provide evidence for localizing the ictal onset zone. However, the typical, asymmetrical and mass-univariate approach cannot capture the inherent, higher order structure in the EEG data, nor multivariate relations in the fMRI data, and it is nontrivial to accurately handle varying neurovascular coupling over patients and brain regions. We aim to overcome these drawbacks in a data-driven manner by means of a novel structured matrix-tensor factorization: the single-subject EEG data (represented as a third-order spectrogram tensor) and fMRI data (represented as a spatiotemporal BOLD signal matrix) are jointly decomposed into a superposition of several sources, characterized by space-time-frequency profiles. In the shared temporal mode, Toeplitz-structured factors account for a spatially specific, neurovascular 'bridge' between the EEG and fMRI temporal fluctuations, capturing the hemodynamic response's variability over brain regions. By analyzing interictal data from twelve patients, we show that the extracted source signatures provide a sensitive localization of the ictal onset zone (10/12). Moreover, complementary parts of the IOZ can be uncovered by inspecting those regions with the most deviant neurovascular coupling, as quantified by two entropy-like metrics of the hemodynamic response function waveforms (9/12). Hence, this multivariate, multimodal factorization provides two useful sets of EEG-fMRI biomarkers, which can assist the presurgical evaluation of epilepsy. We make all code required to perform the computations available at https://github.com/svaneynd/structured-cmtf.

Personalizing Heart Rate-Based Seizure Detection Using Supervised SVM Transfer Learning.

Objective: Automated seizure detection is a key aspect of wearable seizure warning systems. As a result, the quality of life of refractory epilepsy patients could be improved. Most state-of-the-art algorithms for heart rate-based seizure detection use a so-called patient-independent approach, which do not take into account patient-specific data during algorithm training. Although such systems are easy to use in practice, they lead to many false detections as the ictal heart rate changes are patient-dependent. In practice, only a limited amount of accurately annotated patient data is typically available, which makes it difficult to create fully patient-specific algorithms. Methods: In this context, this study proposes for the first time a new transfer learning approach that allows to personalize heart rate-based seizure detection by using only a couple of days of data per patient. The algorithm was evaluated on 2,172 h of single-lead ECG data from 24 temporal lobe epilepsy patients including 227 focal impaired awareness seizures. Results: The proposed personalized approach resulted in an overall sensitivity of 71% with 1.9 false detections per hour. This is an average decrease in false detection rate of 37% compared to the reference patient-independent algorithm using only a limited amount of personal seizure data. The proposed transfer learning approach adapts faster and more robustly to patient-specific characteristics than other alternatives for personalization in the literature. Conclusion: The proposed method allows an easy implementable solution to personalize heart rate-based seizure detection, which can improve the quality of life of refractory epilepsy patients when used as part of a multimodal seizure detection system.

Visual seizure annotation and automated seizure detection using behind-the-ear electroencephalographic channels.

OBJECTIVE: Seizure diaries kept by patients are unreliable. Automated electroencephalography (EEG)-based seizure detection systems are a useful support tool to objectively detect and register seizures during long-term video-EEG recording. However, this standard full scalp-EEG recording setup is of limited use outside the hospital, and a discreet, wearable device is needed for capturing seizures in the home setting. We are developing a wearable device that records EEG with behind-the-ear electrodes. In this study, we determined whether the recognition of ictal patterns using only behind-the-ear EEG channels is possible. Second, an automated seizure detection algorithm was developed using only those behind-the-ear EEG channels. METHODS: Fifty-four patients with a total of 182 seizures, mostly temporal lobe epilepsy (TLE), and 5284 hours of data, were recorded with a standard video-EEG at University Hospital Leuven. In addition, extra behind-the-ear EEG channels were recorded. First, a neurologist was asked to annotate behind-the-ear EEG segments containing selected seizure and nonseizure fragments. Second, a data-driven algorithm was developed using only behind-the-ear EEG. This algorithm was trained using data from other patients (patient-independent model) or from the same patient (patient-specific model). RESULTS: The visual recognition study resulted in 65.7% sensitivity and 94.4% specificity. By using those seizure annotations, the automated algorithm obtained 64.1% sensitivity and 2.8 false-positive detections (FPs)/24 hours with the patient-independent model. The patient-specific model achieved 69.1% sensitivity and 0.49 FPs/24 hours. SIGNIFICANCE: Visual recognition of ictal EEG patterns using only behind-the-ear EEG is possible in a significant number of patients with TLE. A patient-specific seizure detection algorithm using only behind-the-ear EEG was able to detect more seizures automatically than what patients typically report, with 0.49 FPs/24 hours. We conclude that a large number of refractory TLE patients can benefit from using this device.

Zebrafish-Based Screening of Antiseizure Plants Used in Traditional Chinese Medicine: Magnolia officinalis Extract and Its Constituents Magnolol and Honokiol Exhibit Potent Anticonvulsant Activity in a Therapy-Resistant Epilepsy Model.

With the aim to discover interesting lead compounds that could be further developed into compounds active against pharmacoresistant epilepsies, we first collected 14 medicinal plants used in traditional Chinese medicine (TCM) against epilepsy. Of the six extracts that tested positive in a pentylenetetrazole (PTZ) behavioral zebrafish model, only the ethanol and acetone extracts from Magnolia officinalis (M. officinalis) also showed effective antiseizure activity in the ethylketopentenoate (EKP) zebrafish model. The EKP model is regarded as an interesting discovery platform to find mechanistically novel antiseizure drugs, as it responds poorly to a large number of marketed anti-epileptics. We then demonstrated that magnolol and honokiol, two major constituents of M. officinalis, displayed an effective behavioral and electrophysiological antiseizure activity in both the PTZ and the EKP models. Out of six structural analogues tested, only 4-O-methylhonokiol was active and to a lesser extent tetrahydromagnolol, whereas the other analogues (3,3'-dimethylbiphenyl, 2,2'-biphenol, 2-phenylphenol, and 3,3',5,5'-tetra-tert-butyl-[1,1'-biphenyl]-2,2'-diol) were not consistently active in the aforementioned assays. Finally, magnolol was also active in the 6 Hz psychomotor mouse model, an acute therapy-resistant rodent model, thereby confirming the translation of the findings from zebrafish larvae to mice in the field of epilepsy. We also developed a fast and automated power spectral density (PSD) analysis of local field potential (LFP) recordings. The PSD results are in agreement with the visual analysis of LFP recordings using Clampfit software and manually counting the epileptiform events. Taken together, screening extracts of single plants employed in TCM, using a combination of zebrafish- and mouse-based assays, allowed us to identify allyl biphenol as a chemical scaffold for the future development of compounds with potential activity against therapy-resistant epilepsies.

Nonconvulsive epileptic seizure monitoring with incremental learning.

Nonconvulsive epileptic seizures (NCSz) and nonconvulsive status epilepticus (NCSE) are two neurological entities associated with increment in morbidity and mortality in critically ill patients. In a previous work, we introduced a method which accurately detected NCSz in EEG data (referred here as 'Batch method'). However, this approach was less effective when the EEG features identified at the beginning of the recording changed over time. Such pattern drift is an issue that causes failures of automated seizure detection methods. This paper presents a support vector machine (SVM)-based incremental learning method for NCSz detection that for the first time addresses the seizure evolution in EEG records from patients with epileptic disorders and from ICU having NCSz. To implement the incremental learning SVM, three methodologies are tested. These approaches differ in the way they reduce the set of potentially available support vectors that are used to build the decision function of the classifier. To evaluate the suitability of the three incremental learning approaches proposed here for NCSz detection, first, a comparative study between the three methods is performed. Secondly, the incremental learning approach with the best performance is compared with the Batch method and three other batch methods from the literature. From this comparison, the incremental learning method based on maximum relevance minimum redundancy (MRMR_IL) obtained the best results. MRMR_IL method proved to be an effective tool for NCSz detection in a real-time setting, achieving sensitivity and accuracy values above 99%.

Semi-automated EEG Enhancement Improves Localization of Ictal Onset Zone With EEG-Correlated fMRI.

Objective: To improve the accuracy of detecting the ictal onset zone, we propose to enhance the epilepsy-related activity present in the EEG signals, before mapping their BOLD correlates through EEG-correlated fMRI analysis. Methods: Based solely on a segmentation of interictal epileptic discharges (IEDs) on the EEG, we train multi-channel Wiener filters (MWF) which enhance IED-like waveforms, and suppress background activity and noisy influences. Subsequently, we use EEG-correlated fMRI to find the brain regions in which the BOLD signal fluctuation corresponds to the filtered signals' time-varying power (after convolving with the hemodynamic response function), and validate the identified regions by quantitatively comparing them to ground-truth maps of the (resected or hypothesized) ictal onset zone. We validate the performance of this novel predictor vs. that of commonly used unitary or power-weighted predictors and a recently introduced connectivity-based metric, on a cohort of 12 patients with refractory epilepsy. Results: The novel predictor, derived from the filtered EEG signals, allowed the detection of the ictal onset zone in a larger percentage of epileptic patients (92% vs. at most 83% for the other predictors), and with higher statistical significance, compared to existing predictors. At the same time, the new method maintains maximal specificity by not producing false positive activations in healthy controls. Significance: The findings of this study advocate for the use of the MWF to maximize the signal-to-noise ratio of IED-like events in the interictal EEG, and subsequently use time-varying power as a sensitive predictor of the BOLD signal, to localize the ictal onset zone.

Development of temporal lobe epilepsy during maintenance electroconvulsive therapy: A case of human kindling?

We describe a patient with new-onset temporal lobe epilepsy during prolonged maintenance electroconvulsive therapy. We suggest a possible causal relationship with maintenance electroconvulsive therapy through electrical kindling of the temporal lobe.

Nonconvulsive Epileptic Seizure Detection in Scalp EEG Using Multiway Data Analysis.

Nonconvulsive status epilepticus is a condition where the patient is exposed to abnormally prolonged epileptic seizures without evident physical symptoms. Since these continuous seizures may cause permanent brain damage, it constitutes a medical emergency. This paper proposes a method to detect nonconvulsive seizures for a further nonconvulsive status epilepticus diagnosis. To differentiate between the normal and seizure electroencephalogram (EEG), a K-Nearest Neighbor, a Radial Basis Support Vector Machine, and a Linear Discriminant Analysis classifier are used. The classifier features are obtained from the Canonical Polyadic Decomposition (CPD) and Block Term Decomposition of the EEG data represented as third order tensor. To expand the EEG into a tensor, Wavelet or Hilbert-Huang transform are used. The algorithm is tested on a scalp EEG database of 139 seizures of different duration. The experimental results suggest that a Hilbert-Huang tensor representation and the CPD analysis provide the most suitable framework for nonconvulsive seizure detection. The Radial Basis Support Vector Machine classifier shows the best performance with sensitivity, specificity, and accuracy values over 98%. A rough comparison with other methods proposed in the literature shows the superior performance of the proposed method for nonconvulsive epileptic seizure detection.

A foldable electrode array for 3D recording of deep-seated abnormal brain cavities.

OBJECTIVE: This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. APPROACH: A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. MAIN RESULTS: Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. SIGNIFICANCE: The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

Testing for the Presence of Correlation Changes in a Multivariate Time Series: A Permutation Based Approach.

Detecting abrupt correlation changes in multivariate time series is crucial in many application fields such as signal processing, functional neuroimaging, climate studies, and financial analysis. To detect such changes, several promising correlation change tests exist, but they may suffer from severe loss of power when there is actually more than one change point underlying the data. To deal with this drawback, we propose a permutation based significance test for Kernel Change Point (KCP) detection on the running correlations. Given a requested number of change points K, KCP divides the time series into K + 1 phases by minimizing the within-phase variance. The new permutation test looks at how the average within-phase variance decreases when K increases and compares this to the results for permuted data. The results of an extensive simulation study and applications to several real data sets show that, depending on the setting, the new test performs either at par or better than the state-of-the art significance tests for detecting the presence of correlation changes, implying that its use can be generally recommended.

Automated Epileptic Seizure Detection Based on Wearable ECG and PPG in a Hospital Environment.

Electrocardiography has added value to automatically detect seizures in temporal lobe epilepsy (TLE) patients. The wired hospital system is not suited for a long-term seizure detection system at home. To address this need, the performance of two wearable devices, based on electrocardiography (ECG) and photoplethysmography (PPG), are compared with hospital ECG using an existing seizure detection algorithm. This algorithm classifies the seizures on the basis of heart rate features, extracted from the heart rate increase. The algorithm was applied to recordings of 11 patients in a hospital setting with 701 h capturing 47 (fronto-)temporal lobe seizures. The sensitivities of the hospital system, the wearable ECG device and the wearable PPG device were respectively 57%, 70% and 32%, with corresponding false alarms per hour of 1.92, 2.11 and 1.80. Whereas seizure detection performance using the wrist-worn PPG device was considerably lower, the performance using the wearable ECG is proven to be similar to that of the hospital ECG.

Automated analysis of brain activity for seizure detection in zebrafish models of epilepsy.

BACKGROUND: Epilepsy is a chronic neurological condition, with over 30% of cases unresponsive to treatment. Zebrafish larvae show great potential to serve as an animal model of epilepsy in drug discovery. Thanks to their high fecundity and relatively low cost, they are amenable to high-throughput screening. However, the assessment of seizure occurrences in zebrafish larvae remains a bottleneck, as visual analysis is subjective and time-consuming. NEW METHOD: For the first time, we present an automated algorithm to detect epileptic discharges in single-channel local field potential (LFP) recordings in zebrafish. First, candidate seizure segments are selected based on their energy and length. Afterwards, discriminative features are extracted from each segment. Using a labeled dataset, a support vector machine (SVM) classifier is trained to learn an optimal feature mapping. Finally, this SVM classifier is used to detect seizure segments in new signals. RESULTS: We tested the proposed algorithm both in a chemically-induced seizure model and a genetic epilepsy model. In both cases, the algorithm delivered similar results to visual analysis and found a significant difference in number of seizures between the epileptic and control group. COMPARISON WITH EXISTING METHODS: Direct comparison with multichannel techniques or methods developed for different animal models is not feasible. Nevertheless, a literature review shows that our algorithm outperforms state-of-the-art techniques in terms of accuracy, precision and specificity, while maintaining a reasonable sensitivity. CONCLUSION: Our seizure detection system is a generic, time-saving and objective method to analyze zebrafish LPF, which can replace visual analysis and facilitate true high-throughput studies.

Online Automated Seizure Detection in Temporal Lobe Epilepsy Patients Using Single-lead ECG.

Automated seizure detection in a home environment has been of increased interest the last couple of decades. The electrocardiogram is one of the signals that is suited for this application. In this paper, a new method is described that classifies different heart rate characteristics in order to detect seizures from temporal lobe epilepsy patients. The used support vector machine classifier is trained on data from other patients, so that the algorithm can be used directly from the start of each new recording. The algorithm was tested on a dataset of more than 918[Formula: see text]h of data coming from 17 patients containing 127 complex partial and generalized partial seizures. The algorithm was able to detect 81.89% of the seizures, with on average 1.97 false alarms per hour. These results show a strong drop in the number of false alarms of more than 50% compared to other heart rate-based patient-independent algorithms from the literature, at the expense of a slightly higher detection delay of 17.8s on average.