Publications

The severe neurological disorder epilepsy affects almost 1% of the world population. For patients who suffer from pharmacoresistant focal-onset epilepsy, electroencephalographic (EEG) recordings are essential for the localization of the brain area where seizures start. Apart from the visual inspection of the recordings, quantitative EEG signal analysis techniques proved to be useful for this purpose. Among other features, regularity versus irregularity and phase coherence versus phase independence allowed characterizing brain dynamics from the measured EEG signals. Can phase irregularities also characterize brain dynamics? To address this question, we use the univariate coefficient of phase velocity variation, defined as the ratio of phase velocity standard deviation and the mean phase velocity. Beyond that, as a bivariate measure we use the classical mean phase coherence to quantify the degree of phase locking. All phase-based measures are combined with surrogates to test null hypotheses about the dynamics underlying the signals. In the first part of our analysis, we use the Rössler model system to study our approach under controlled conditions. In the second part, we use the Bern-Barcelona EEG database which consists of focal and nonfocal signals extracted from seizure-free recordings. Focal signals are recorded from brain areas where the first seizure EEG signal changes can be detected, and nonfocal signals are recorded from areas that are not involved in the seizure at its onset. Our results show that focal signals have less phase variability and more phase coherence than nonfocal signals. Once combined with surrogates, the mean phase velocity proved to have the highest discriminative power between focal and nonfocal signals. In conclusion, conceptually simple and easy to compute phase-based measures can help to detect features induced by epilepsy from EEG signals. This holds not only for the classical mean phase coherence but even more so for univariate measures of phase irregularity. © 2022 American Physical Society.

JTD Keywords: brain, entropy, epileptogenic networks, functional connectivity, hilbert transform, seizure onset, surrogate data, synchronization, time-series, Biomedical signal processing, Brain areas, Brain dynamics, Dynamics, Electroencephalographic signals, Electroencephalography, Electrophysiology, Intracranial eeg signals, Localisation, Neurological disorders, Neurology, Phase based, Phase coherence, Signal detection, Simple++, Univariate, Velocity, World population

Fixed sample entropy (fSampEn) is a promising technique for the analysis of respiratory electromyographic (EMG) signals. Its use has shown outperformance of amplitude-based estimators such as the root mean square (RMS) in the evaluation of respiratory EMG signals with cardiac noise and a high correlation with respiratory signals, allowing changes in respiratory muscle activity to be tracked. However, the relationship between the fSampEn response to a given muscle activation has not been investigated. The aim of this study was to analyze the nature of the fSampEn measurements that are produced as the EMG activity increases linearly. Simulated EMG signals were generated and increased linearly. The effect of the parameters r and the size of the moving window N of the fSampEn were evaluated and compared with those obtained using the RMS. The RMS showed a linear trend throughout the study. A non-linear, sigmoidal-like behavior was found when analyzing the EMG signals using the fSampEn. The lower the values of r, the higher the non-linearity observed in the fSampEn results. Greater moving windows reduced the variation produced by too small values of r.Clinical Relevance - Understanding the inherent non-linear relationship produced when using the fSampEn in EMG recordings will contribute to the improvement of the respiratory muscle activation assessment at different levels of respiratory effort in patients with respiratory conditions, particularly during the inspiratory phase © 2021 IEEE.

JTD Keywords: Breathing muscle, Breathing rate, Electromyography, Entropy, Heart, Human, Humans, Respiratory muscles, Respiratory rate

Lung sound (LS) signals are often contaminated by impulsive artifacts that complicate the estimation of lung sound intensity (LSI) using conventional amplitude estimators. Fixed sample entropy (fSampEn) has proven to be robust to cardiac artifacts in myographic respiratory signals. Similarly, fSampEn is expected to be robust to artifacts in LS signals, thus providing accurate LSI estimates. However, the choice of fSampEn parameters depends on the application and fSampEn has not previously been applied to LS signals. This study aimed to perform an evaluation of the performance of the most relevant fSampEn parameters on LS signals, and to propose optimal fSampEn parameters for LSI estimation. Different combinations of fSampEn parameters were analyzed in LS signals recorded in a heterogeneous population of healthy subjects and chronic obstructive pulmonary disease patients during loaded breathing. The performance of fSampEn was assessed by means of its cross-covariance with flow signals, and optimal fSampEn parameters for LSI estimation were proposed.

JTD Keywords: Large scale integration, Lung, Estimation, Entropy, Loading, Robustness, Diseases

The use of wearable devices in clinical routines could reduce healthcare costs and improve the quality of assessment in patients with chronic respiratory diseases. The purpose of this study is to evaluate the capacity of a Shimmer3 wearable device to extract reliable cardiorespiratory parameters from surface diaphragm electromyography (EMGdi). Twenty healthy volunteers underwent an incremental load respiratory test whilst EMGdi was recorded with a Shimmer3 wearable device (EMGdiW). Simultaneously, a second EMGdi (EMGdiL), inspiratory mouth pressure (Pmouth) and lead-I electrocardiogram (ECG) were recorded via a standard wired laboratory acquisition system. Different cardiorespiratory parameters were extracted from both EMGdiW and EMGdiL signals: heart rate, respiratory rate, respiratory muscle activity and mean frequency of EMGdi signals. Alongside these, similar parameters were also extracted from reference signals (Pmouth and ECG). High correlations were found between the data extracted from the EMGdiW and the reference signal data: heart rate (R = 0.947), respiratory rate (R = 0.940), respiratory muscle activity (R = 0.877), and mean frequency (R = 0.895). Moreover, similar increments in EMGdiW and EMGdiL activity were observed when Pmouth was raised, enabling the study of respiratory muscle activation. In summary, the Shimmer3 device is a promising and cost-effective solution for the ambulatory monitoring of respiratory muscle function in chronic respiratory diseases.

JTD Keywords: Cardiorespiratory monitoring, Chronic respiratory diseases, Fixed sample entropy, Non-invasive respiratory monitoring, Surface diaphragm electromyography, Wearable wireless device

Obstructive sleep apnea (OSA) is a prevalent disease, but most patients remain undiagnosed and untreated. Here we propose analyzing smartphone audio signals for screening OSA patients at home. Our objectives were to: (1) develop an algorithm for detecting silence events and classifying them into apneas or hypopneas; (2) evaluate the performance of this system; and (3) compare the information provided with a type 3 portable sleep monitor, based mainly on nasal airflow. Overnight signals were acquired simultaneously by both systems in 13 subjects (3 healthy subjects and 10 OSA patients). The sample entropy of audio signals was used to identify apnea/hypopnea events. The apnea-hypopnea indices predicted by the two systems presented a very high degree of concordance and the smartphone correctly detected and stratified all the OSA patients. An event-by-event comparison demonstrated good agreement between silence events and apnea/hypopnea events in the reference system (Sensitivity = 76%, Positive Predictive Value = 82%). Most apneas were detected (89%), but not so many hypopneas (61%). We observed that many hypopneas were accompanied by snoring, so there was no sound reduction. The apnea/hypopnea classification accuracy was 70%, but most discrepancies resulted from the inability of the nasal cannula of the reference device to record oral breathing. We provided a spectral characterization of oral and nasal breathing to correct this effect, and the classification accuracy increased to 82%. This novel knowledge from acoustic signals may be of great interest for clinical practice to develop new non-invasive techniques for screening and monitoring OSA patients at home.

JTD Keywords: Sleep apnea, Acoustics, Monitoring, Entropy, Sensors, Microphones, Acoustics, Biomedical signal processing, mHealth, Monitoring, Sleep apnea, Smartphone

To optimize long-term nocturnal non-invasive ventilation in patients with chronic obstructive pulmonary disease, surface diaphragm electromyography (EMGdi) might be helpful to detect patient-ventilator asynchrony. However, visual analysis is labor-intensive and EMGdi is heavily corrupted by electrocardiographic (ECG) activity. Therefore, we developed an automatic method to detect inspiratory onset from EMGdi envelope using fixed sample entropy (fSE) and a dynamic threshold based on kernel density estimation (KDE). Moreover, we combined fSE with adaptive filtering techniques to reduce ECG interference and improve onset detection. The performance of EMGdi envelopes extracted by applying fSE and fSE with adaptive filtering was compared to the root mean square (RMS)-based envelope provided by the EMG acquisition device. Automatic onset detection accuracy, using these three envelopes, was evaluated through the root mean square error (RMSE) between the automatic and mean visual onsets (made by two observers). The fSE-based method provided lower RMSE, which was reduced from 298 ms to 264 ms when combined with adaptive filtering, compared to 301 ms provided by the RMS-based method. The RMSE was negatively correlated with the proposed EMGdi quality indices. Following further validation, fSE with KDE, combined with adaptive filtering when dealing with low quality EMGdi, indicates promise for detecting the neural onset of respiratory drive.

JTD Keywords: Fixed sample entropy, Adaptive filtering, Root mean square, Diaphragm electromyography, Non-invasive mechanical ventilation, Chronic obstructive pulmonary disease

Fixed sample entropy (fSampEn) has been successfully applied to myographic signals for inspiratory muscle activity estimation, attenuating interference from cardiac activity. However, several values have been suggested for fSampEn parameters depending on the application, and there is no consensus standard for optimum values. This study aimed to perform a thorough evaluation of the performance of the most relevant fSampEn parameters in myographic respiratory signals, and to propose, for the first time, a set of optimal general fSampEn parameters for a proper estimation of inspiratory muscle activity. Different combinations of fSampEn parameters were used to calculate fSampEn in both non-invasive and the gold standard invasive myographic respiratory signals. All signals were recorded in a heterogeneous population of healthy subjects and chronic obstructive pulmonary disease patients during loaded breathing, thus allowing the performance of fSampEn to be evaluated for a variety of inspiratory muscle activation levels. The performance of fSampEn was assessed by means of the cross-covariance of fSampEn time-series and both mouth and transdiaphragmatic pressures generated by inspiratory muscles. A set of optimal general fSampEn parameters was proposed, allowing fSampEn of different subjects to be compared and contributing to improving the assessment of inspiratory muscle activity in health and disease.

JTD Keywords: Electromyography, Fixed sample entropy, Mechanomyography, Non-invasive physiological measurements, Oesophageal electromyography, Respiratory muscle

This study evaluates the onset and offset of neural inspiratory time estimated from surface diaphragm electromyographic (EMGdi) recordings. EMGdi and airflow signals were recorded in ten healthy subjects according to two respiratory protocols based on respiratory rate (RR) increments, from 15 to 40 breaths per minute (bpm), and fractional inspiratory time (Ti/Ttot) decrements, from 0.54 to 0.18. The analysis of diaphragm electromyographic (EMGdi) signal amplitude is an alternative approach for the quantification of neural respiratory drive (NRD). The EMGdi amplitude was estimated using the fixed sample entropy computed over a 250 ms moving window of the EMGdi signal (EMGdifse). The neural onset was detected through a dynamic threshold over the EMGdifse using the kernel density estimation method, while neural offset was detected by finding when the EMGdifse had decreased to 70 % of the peak value reached during inspiration. The Bland-Altman analysis between airflow and neural onsets showed a global bias of 46 ms in the RR protocol and 22 ms in the Ti/Ttot protocol. The Bland-Altman analysis between airflow and neural offsets reveals a global bias of 11 ms in the RR protocol and -2 ms in the Ti/Ttot protocol. The relationship between pairs of RR values (Pearson’s correlation coefficient of 0.99, Bland- Altman limits of -2.39 to 2.41 bpm, and mean bias of 0.01 bpm) and between pairs of Ti/Ttot values (Pearson’s correlation coefficient of 0.86, Bland-Altman limits of -0.11 to 0.10, and mean bias of -0.01) showed a good agreement. In conclusion, we propose a method for determining neural onset and neural offset based on non-invasive recordings of the electrical activity of the diaphragm that requires no filtering of cardiac muscle interference.

JTD Keywords: Kernel density estimation (KDE),, Surface diaphragm electromyographic,, (EMGdi) signal,, Inspiratory time,, Neural respiratory drive (NRD),, Neural inspiratory time,, Fixed sample entropy (fSampEn)

Fixed sample entropy (fSampEn) is a robust technique that allows the evaluation of inspiratory effort in diaphragm electromyography (EMGdi) signals, and has potential utility in sleep studies. To appropriately estimate respiratory effort, fSampEn requires the adjustment of several parameters. The aims of the present study were to evaluate the influence of the embedding dimension m, the tolerance value r, the size of the moving window, and the sampling frequency, and to establish recommendations for estimating the respiratory activity when using the fSampEn on surface EMGdi recorded for different inspiratory efforts. Values of m equal to 1 and r ranging from 0.1 to 0.64, and m equal to 2 and r ranging from 0.13 to 0.45, were found to be suitable for evaluating respiratory activity. fSampEn was less affected by window size than classical amplitude parameters. Finally, variations in sampling frequency could influence fSampEn results. In conclusion, the findings suggest the potential utility of fSampEn for estimating muscle respiratory effort in further sleep studies.

JTD Keywords: Fixed sample entropy (fSampEn), Non-invasive respiratory monitoring, Respiratory activity, Respiratory effort, Surface diaphragm electromyography

Extracting clinical information from one single measurement represents a step forward in the assessment of the respiratory muscle function. This attracting idea entails the reduction of the instrumentation and fosters to develop new medical integrated technologies. We present the use of the fixed sample entropy (fSampEn) as a more direct method to non-invasively derive the breathing activity from the diaphragm electromyographic (EMGdi) signal, and thus to extract the respiratory rate, an important vital sign which is cumbersome and time-consuming to be measured by clinicians. fSampEn is a method to evaluate the EMGdi activity that is less sensitive to the cardiac activity (ECG) and its application has proven to be useful to evaluate the load of the respiratory muscles. The behavior of the proposed method was tested in signals from two subjects that performed an inspiratory load protocol, which consists of increments in the inspiratory mouth pressure (P_mouth). Two respiratory signals were derived and compared to the P_mouth signal: the ECG-derived respiration (EDR) signal from the lead-I configuration, and the EMG-derived respiration (EMGDR) signal by applying the fSampEn method over the EMGdi signal. The similitude and the lag between signals were calculated through the cross-correlation between each derived respiratory signal and the P_mouth. The EMGDR signal showed higher correlation and lower lag values (≥ 0.91 and ≤ 0.70 s, respectively) than the EDR signal (≥ 0.83 and ≤0.99 s, respectively). Additionally, the respiratory rate was estimated with the P_mouth, EDR and EMGDR signals showing very similar values. The results from this preliminary work suggest that the fSampEn method can be used to derive the respiration waveform from the respiratory muscle electrical activity.

JTD Keywords: Band-pass filters, Electrocardiography, Electromyography, Entropy, Mouth, Muscles, Protocols

A correntropy-based technique is proposed for the characterization and classification of respiratory flow signals in chronic heart failure (CHF) patients with periodic or nonperiodic breathing (PB or nPB, respectively) and healthy subjects. The correntropy is a recently introduced, generalized correlation measure whose properties lend themselves to the definition of a correntropy-based spectral density (CSD). Using this technique, both respiratory and modulation frequencies can be reliably detected at their original positions in the spectrum without prior demodulation of the flow signal. Single-parameter classification of respiratory patterns is investigated for three different parameters extracted from the respiratory and modulation frequency bands of the CSD, and one parameter defined by the correntropy mean. The results show that the ratio between the powers in the modulation and respiratory frequency bands provides the best result when classifying CHF patients with either PB or nPB, yielding an accuracy of 88.9%. The correntropy mean offers excellent performance when classifying CHF patients versus healthy subjects, yielding an accuracy of 95.2% and discriminating nPB patients from healthy subjects with an accuracy of 94.4%.

JTD Keywords: Autoregressive (AR) modeling, Chronic heart failure (CHF), Correntropy spectral density (CSD), Linear classification, Periodic breathing (PB)

In this study we propose the correntropy function as a discriminative measure for detecting nonlinearities in the respiratory pattern of chronic heart failure (CHF) patients with periodic or nonperiodic breathing pattern (PB or nPB, respectively). The complexity seems to be reduced in CHF patients with higher risk level. Correntropy reflects information on both, statistical distribution and temporal structure of the underlying dataset. It is a suitable measure due to its capability to preserve nonlinear information. The null hypothesis considered is that the analyzed data is generated by a Gaussian linear stochastic process. Correntropy is used in a statistical test to reject the null hypothesis through surrogate data methods. Various parameters, derived from the correntropy and correntropy spectral density (CSD) to characterize the respiratory pattern, presented no significant differences when extracted from the iteratively refined amplitude adjusted Fourier transform (IAAFT) surrogate data. The ratio between the powers in the modulation and respiratory frequency bands R was significantly different in nPB patients, but not in PB patients, which reflects a higher presence of nonlinearities in nPB patients than in PB patients.

JTD Keywords: Practical, Theoretical or Mathematical, Experimental/cardiology diseases, Fourier transforms, Medical signal processing, Pattern classification, Pneumodynamics, Spectral analysis, Statistical analysis, Stochastic processes/ correntropy based nonlinearity test, Chronic heart failure, Correntropy function, Respiratory pattern nonlinearities, CHF patients, Nonperiodic breathing pattern, Dataset statistical distribution, Dataset temporal structure, Nonlinear information, Null hypothesis, Gaussian linear stochastic process, Statistical test, Correntropy spectral density, Iteratively refined amplitude adjusted Fourier transform, Surrogate data, Periodic breathing pattern

A new method for the quantification of amplitude variations in biomedical signals through moving approximate entropy is presented. Unlike the usual method to calculate the approximate entropy (ApEn), in which the tolerance value (r) varies based on the standard deviation of each moving window, in this work ApEn has been computed using a fixed value of r. We called this method, moving approximate entropy with fixed tolerance values: ApEn/sub f/. The obtained results indicate that ApEn/sub f/ allows determining amplitude variations in biomedical data series. These amplitude variations are better determined when intermediate values of tolerance are used. The study performed in diaphragmatic mechanomyographic signals shows that the ApEn/sub f/ curve is more correlated with the respiratory effort than the standard RMS amplitude parameter. Furthermore, it has been observed that the ApEn/sub f/ parameter is less affected by the existence of impulsive, sinusoidal, constant and Gaussian noises in comparison with the RMS amplitude parameter.

JTD Keywords: Practical, Theoretical or Mathematical/ biomechanics, Entropy, Gaussian noise, Medical signal processing, Muscle, Random processes/ approximate entropy interpretation, Fixed tolerance values, Diaphragmatic mechanomyographic signals, ApEnf curve, Respiratory effort, Gaussian noises