Evaluación no invasiva del impulso neural respiratorio y su relación con la respuesta mecánica mediante el análisis de señales electromiográficas de músculos respiratorios

Respiratory muscle contraction occurs in response to the electrical stimulation of the muscles. These electrical stimuli originate in the respiratory neurons of the brainstem, are transmitted via motor nerves to the neuromuscular junctions and propagate along muscle fibers. Respiratory electromyography measures the electrical activity of respiratory muscles in response to this nerve stimulation. The neural respiratory drive (NRD) is best expressed in a phrenic neurogram, but this is not feasible in humans. Alternatively, measurements of the diaphragm electromyographic signal (EMGdi) would most likely reflect phrenic neurogram activity. EMGdi signal can be recorded using invasive methods, involving the use of needle electrodes or electrodes positioned in the esophagus at the level of the diaphragm. As a non-invasive alternative, the study of respiratory muscle activity can be addressed by surface electromyography. The onset and offset of the neural inspiratory time (nton and ntoff, respectively) are fundamentally important measurements in studies of patient-ventilator interaction, where the level of assistance delivered by the ventilator is controlled by patient demand. Cardiac artifacts (ECG) often make it difficult to utilize EMGdi. To overcome the shortcoming of the ECG, in this thesis is proposed to use sample entropy with fixed tolerance values (fSampEn), a robust technique against impulsive noise. To evaluate nton and ntoff estimation it has been carried out an experimental study with surface EMGdi signals recorded in healthy subjects during two respiratory protocols designed to evaluate the influence of different breathing patterns on the EMGdi. These protocols consisted of a stepwise increase in respiratory rate (RR) with constant fractional inspiratory time (Ti/Ttot) and a stepwise decrement in the Ti/Ttot with constant RR, respectively. The developed algorithms allowed to determine the nton and ntoff and derive the RR, Ti and Ti/Ttot neural ventilatory parameters. The EMGdi amplitude provides a real-time indirect measure of the NRD, which reflects the load on the respiratory muscles. The NRD, assessed by normalized EMGdi signals, is higher in patients with respiratory disease than in healthy subjects. To evaluate the behavior of the fSamp En, as a method for improving the measurement of NRD from EMGdi signals in the presence of cardiac activity, compared to the average rectified value and root mean square value approaches, first, these methods have been applied to synthetic EMGdi signals . Secondly, we tested the proposed methods in an experimental study with EMGdi signals recorded in healthy subjects during an incremental inspiratory load test. The EMGdi amplitude allowed to evaluate changes in the respiratory muscle activation patterns and estimate the NRD. Also, this thesis contributes to the study of the respiratory activity by the non-invasive recording of mechanomyographic low frequency (BF) activity in healthy subjects and in patients with chronic obstructive pulmonary disease, allowing the study of bilateral asynchrony of the diaphragm and the RR. Finally, we have proposed the use of concentric ring electrodes as an alternative to improve the spatial resolution of electromyographic recordings, and eliminate the problems associated with the location and orientation of the bipolar configuration. The approaches presented in this doctoral thesis based on the analysis of electromyographic and mechanomyographic signals of respiratory museles allow to extract complementary information to current use techniques of and contribute to the study of respiratory function in the clinical setting .La contracción de los músculos respiratorios se produce en respuesta a la estimulación eléctrica. Estos estímulos se originan en las neuronas respiratorias del tronco del encéfalo, se transmiten a través de los nervios motores a las uniones neuromusculares y se propagan a lo largo de las fibras musculares. La electromiografía respiratoria mide la actividad eléctrica de los músculos respiratorios en respuesta a esta estimulación nerviosa. El impulso neural respiratorio (NRD) se expresa mejor a través del neurograma frénico, pero esto no es factible en los seres humanos. Como alternativa, la medida de la señal electromiográfica del diafragma (EMGdi) refleja de forma indirecta la actividad frénica. La señal EMGdi puede registrarse utilizando métodos invasivos, lo que implica el uso de electrodos de aguja o electrodos colocados en el esófago a nivel del diafragma . Como alternativa no invasiva, el estudio de la actividad muscular respiratoria puede abordarse mediante la electromiografía de superficie. El inicio y fin del tiempo neural inspiratorio (nton y ntoff, respectivamente) son medidas de importancia en los estudios de interacción paciente-ventilador, donde el nivel de la asistencia proporcionada por el ventilador es controlado por la demanda del paciente. Los artefactos cardíacos (ECG) a menudo hacen que sea difícil de utilizar la señal EMGdi. Para superar el inconveniente de la interferencia ECG, en la presente tesis se propone utilizar la entropía muestra! con valores de tolerancia fijos (fSampEn), una técnica que es robusta contra el ruido de tipo impulsivo. Para evaluar la estimación del nton y ntoff se ha realizado un estudio experimental con señales EMGdi superficie registrada en sujetos sanos durante dos protocolos respiratorios, diseñados para evaluar la influencia de los diferentes patrones respiratorios sobre la señal EMGdi. Estos protocolos consistieron en un aumento gradual de la frecuencia respiratoria (RR) con un tiempo inspiratorio (Ti) fracciona! constante (Ti!Ttot) y en una disminución gradual en el Ti!Ttot con una RR constante, respectivamente. Los algoritmos desarrollados han permitido determinar el nton y el ntoff y derivar los parámetros ventilatorios RR, Ti, y TifTtot neurales. La amplitud de la EMGdi proporciona una medida indirecta del NRD, que refleja la carga sobre los músculos respiratorios. El NRD, evaluado en señales EMGdi normalizadas, es mayor en pacientes con enfermedades respiratorias que en sujetos sanos. Para evaluar el comportamiento de la fSampEn, como un método para mejorar la medición del NRD a partir de señales EMGdi en presencia de ECG, en comparación con los enfoques basados en el uso del valor rectificado medio y valor cuadrático medio, primero, se han aplicado estos métodos a señales EMGdi sintéticas . En segundo lugar, hemos probado los métodos propuestos en un estudio experimental con señales EMGdi registradas en sujetos sanos durante una prueba de carga inspiratoria incremental. La amplitud de la EMGdi permitió evaluar los cambios en el patrón de activación de los músculos respiratorios y estimar el NRO. Asimismo, esta tesis doctoral contribuye al estudio de la actividad respiratoria mediante el registro no invasivo de actividad mecanomiográfica de baja frecuencia (BF) en sujetos sanos y en pacientes con enfermedad obstructiva crónica, permitiendo el estudio de la asincronía bilateral del diafragma y la RR. Finalmente, hemos propuesto el uso de electrodos de anillos concéntricos como una alternativa para mejorar la resolución espacial de los registros electromiográficos, y eliminar los problemas asociados a la localización y orientación de la configuración bipolar. Los enfoques presentados en esta tesis doctoral basados en el análisis de señales electromiográficas y mecanomiográficas de los músculo

Assessment of the non-linear response of the fSampEn on simulated EMG signals

© 2021 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other worksFixed 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.Peer ReviewedPostprint (author's final draft

Características de los electrodos de tatuaje y electrónica flexible y sus aplicaciones en la adquisición de señales biomédicas

Focused on solving the problem of adherence to the skin and the quality of the bioelectrical recordings, new devices that have emerged such as tattoo electrodes and flexible electronics, which prove to be a novel and viable technology, capable of improving the quality in electrophysiological signal studies and patient comfort. The use of electrodes or medical patches to capture bioelectrical signals is of utmost importance for the diagnostic of different pathologies, as is the need for devices that are biocompatible with human skin and are effective when capturing these signals. This article presents a study of the state of the art on the main characteristics and applications of tattoo electrodes and flexible electronics in biomedical signal measurement processes and the benefits, it offers compared to used medical electrodes

Noninvasive assessment of inspiratory muscle neuromechanical coupling during inspiratory threshold loading

Diaphragm neuromechanical coupling (NMC), which reflects the efficiency of conversion of neural activation to transdiaphragmatic pressure (Pdi), is increasingly recognized to be a useful clinical index of diaphragm function and respiratory mechanics in neuromuscular weakness and cardiorespiratory disease. However, the current gold standard assessment of diaphragm NMC requires invasive measurements of Pdi and crural diaphragm electromyography (oesEMGdi), which complicates the measurement of diaphragm NMC in clinical practice. This is the first study to compare invasive measurements of diaphragm NMC (iNMC) using the relationship between Pdi and oesEMGdi, with noninvasive assessment of NMC (nNMC) using surface mechanomyography (sMMGlic) and electromyography (sEMGlic) of lower chest wall inspiratory muscles. Both invasive and noninvasive measurements were recorded in twelve healthy adult subjects during an inspiratory threshold loading protocol. A linear relationship between noninvasive sMMGlic and sEMGlic measurements was found, resulting in little change in nNMC with increasing inspiratory load. By contrast, a curvilinear relationship between invasive Pdi and oesEMGdi measurements was observed, such that there was a progressive increase in iNMC with increasing inspiratory threshold load. Progressive recruitment of lower ribcage muscles, serving to enhance the mechanical advantage of the diaphragm, may explain the more linear relationship between sMMGlic and sEMGlic (both representing lower intercostal plus costal diaphragm activity) than between Pdi and crural oesEMGdi. Noninvasive indices of NMC derived from sEMGlic and sMMGlic may prove to be useful indices of lower chest wall inspiratory muscle NMC, particularly in settings that do not have access to invasive measures of diaphragm function.Peer ReviewedPostprint (published version

Evaluation of a wearable device to determine cardiorespiratory parameters from surface diaphragm electromyography

Using 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 capability of a Shimmer3 wearable device 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), the inspiratory mouth pressure (Pmouth) and the lead-I electrocardiogram (ECG) were recorded via a standard wired laboratory acquisition system. Different cardiorespiratory parameters have been 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 ambulatory monitoring of respiratory muscle function in chronic respiratory diseases.Postprint (author's final draft

Noninvasive assessment of neuromechanical coupling and mechanical efficiency of parasternal intercostal muscle during inspiratory threshold loading

This study aims to investigate noninvasive indices of neuromechanical coupling (NMC) and mechanical efficiency (MEff) of parasternal intercostal muscles. Gold standard assessment of diaphragm NMC requires using invasive techniques, limiting the utility of this procedure. Noninvasive NMC indices of parasternal intercostal muscles can be calculated using surface mechanomyography (sMMGpara) and electromyography (sEMGpara). However, the use of sMMGpara as an inspiratory muscle mechanical output measure, and the relationships between sMMGpara, sEMGpara, and simultaneous invasive and noninvasive pressure measurements have not previously been evaluated. sEMGpara, sMMGpara, and both invasive and noninvasive measurements of pressures were recorded in twelve healthy subjects during an inspiratory loading protocol. The ratios of sMMGpara to sEMGpara, which provided muscle-specific noninvasive NMC indices of parasternal intercostal muscles, showed nonsignificant changes with increasing load, since the relationships between sMMGpara and sEMGpara were linear (R2 = 0.85 (0.75–0.9)). The ratios of mouth pressure (Pmo) to sEMGpara and sMMGpara were also proposed as noninvasive indices of parasternal intercostal muscle NMC and MEff, respectively. These indices, similar to the analogous indices calculated using invasive transdiaphragmatic and esophageal pressures, showed nonsignificant changes during threshold loading, since the relationships between Pmo and both sEMGpara (R2 = 0.84 (0.77–0.93)) and sMMGpara (R2 = 0.89 (0.85–0.91)) were linear. The proposed noninvasive NMC and MEff indices of parasternal intercostal muscles may be of potential clinical value, particularly for the regular assessment of patients with disordered respiratory mechanics using noninvasive wearable and wireless devices.Peer ReviewedPostprint (published version

Noninvasive assessment of neuromechanical and neuroventilatory coupling in COPD

This study explored the use of parasternal second intercostal space and lower intercostal space surface electromyogram (sEMG) and surface mechanomyogram (sMMG) recordings (sEMG para and sMMG para , and sEMG lic and sMMG lic , respectively) to assess neural respiratory drive (NRD), neuromechanical (NMC) and neuroventilatory (NVC) coupling, and mechanical efficiency (MEff) noninvasively in healthy subjects and chronic obstructive pulmonary disease (COPD) patients. sEMG para , sMMG para , sEMG lic , sMMG lic , mouth pressure (P mo ), and volume (V i ) were measured at rest, and during an inspiratory loading protocol, in 16 COPD patients (8 moderate and 8 severe) and 9 healthy subjects. Myographic signals were analyzed using fixed sample entropy and normalized to their largest values (fSEsEMG para%max , fSEsMMG para%max , fSEsEMG lic%max , and fSEsMMG lic%max ). fSEsMMG para%max , fSEsEMG para%max , and fSEsEMG lic%max were significantly higher in COPD than in healthy participants at rest. Parasternal intercostal muscle NMC was significantly higher in healthy than in COPD participants at rest, but not during threshold loading. P mo -derived NMC and MEff ratios were lower in severe patients than in mild patients or healthy subjects during threshold loading, but differences were not consistently significant. During resting breathing and threshold loading, V i -derived NVC and MEff ratios were significantly lower in severe patients than in mild patients or healthy subjects. sMMG is a potential noninvasive alternative to sEMG for assessing NRD in COPD. The ratios of P mo and V i to sMMG and sEMG measurements provide wholly noninvasive NMC, NVC, and MEff indices that are sensitive to impaired respiratory mechanics in COPD and are therefore of potential value to assess disease severity in clinical practice.Peer ReviewedPostprint (published version

Evaluación no invasiva del impulso neural respiratorio y su relación con la respuesta mecánica mediante el análisis de señales electromiográficas de músculos respiratorios

Aplicat embargament des de la data de defensa fins 1/11/2018Respiratory muscle contraction occurs in response to the electrical stimulation of the muscles. These electrical stimuli originate in the respiratory neurons of the brainstem, are transmitted via motor nerves to the neuromuscular junctions and propagate along muscle fibers. Respiratory electromyography measures the electrical activity of respiratory muscles in response to this nerve stimulation. The neural respiratory drive (NRD) is best expressed in a phrenic neurogram, but this is not feasible in humans. Alternatively, measurements of the diaphragm electromyographic signal (EMGdi) would most likely reflect phrenic neurogram activity. EMGdi signal can be recorded using invasive methods, involving the use of needle electrodes or electrodes positioned in the esophagus at the level of the diaphragm. As a non-invasive alternative, the study of respiratory muscle activity can be addressed by surface electromyography. The onset and offset of the neural inspiratory time (nton and ntoff, respectively) are fundamentally important measurements in studies of patient-ventilator interaction, where the level of assistance delivered by the ventilator is controlled by patient demand. Cardiac artifacts (ECG) often make it difficult to utilize EMGdi. To overcome the shortcoming of the ECG, in this thesis is proposed to use sample entropy with fixed tolerance values (fSampEn), a robust technique against impulsive noise. To evaluate nton and ntoff estimation it has been carried out an experimental study with surface EMGdi signals recorded in healthy subjects during two respiratory protocols designed to evaluate the influence of different breathing patterns on the EMGdi. These protocols consisted of a stepwise increase in respiratory rate (RR) with constant fractional inspiratory time (Ti/Ttot) and a stepwise decrement in the Ti/Ttot with constant RR, respectively. The developed algorithms allowed to determine the nton and ntoff and derive the RR, Ti and Ti/Ttot neural ventilatory parameters. The EMGdi amplitude provides a real-time indirect measure of the NRD, which reflects the load on the respiratory muscles. The NRD, assessed by normalized EMGdi signals, is higher in patients with respiratory disease than in healthy subjects. To evaluate the behavior of the fSamp En, as a method for improving the measurement of NRD from EMGdi signals in the presence of cardiac activity, compared to the average rectified value and root mean square value approaches, first, these methods have been applied to synthetic EMGdi signals . Secondly, we tested the proposed methods in an experimental study with EMGdi signals recorded in healthy subjects during an incremental inspiratory load test. The EMGdi amplitude allowed to evaluate changes in the respiratory muscle activation patterns and estimate the NRD. Also, this thesis contributes to the study of the respiratory activity by the non-invasive recording of mechanomyographic low frequency (BF) activity in healthy subjects and in patients with chronic obstructive pulmonary disease, allowing the study of bilateral asynchrony of the diaphragm and the RR. Finally, we have proposed the use of concentric ring electrodes as an alternative to improve the spatial resolution of electromyographic recordings, and eliminate the problems associated with the location and orientation of the bipolar configuration. The approaches presented in this doctoral thesis based on the analysis of electromyographic and mechanomyographic signals of respiratory museles allow to extract complementary information to current use techniques of and contribute to the study of respiratory function in the clinical setting .La contracción de los músculos respiratorios se produce en respuesta a la estimulación eléctrica. Estos estímulos se originan en las neuronas respiratorias del tronco del encéfalo, se transmiten a través de los nervios motores a las uniones neuromusculares y se propagan a lo largo de las fibras musculares. La electromiografía respiratoria mide la actividad eléctrica de los músculos respiratorios en respuesta a esta estimulación nerviosa. El impulso neural respiratorio (NRD) se expresa mejor a través del neurograma frénico, pero esto no es factible en los seres humanos. Como alternativa, la medida de la señal electromiográfica del diafragma (EMGdi) refleja de forma indirecta la actividad frénica. La señal EMGdi puede registrarse utilizando métodos invasivos, lo que implica el uso de electrodos de aguja o electrodos colocados en el esófago a nivel del diafragma . Como alternativa no invasiva, el estudio de la actividad muscular respiratoria puede abordarse mediante la electromiografía de superficie. El inicio y fin del tiempo neural inspiratorio (nton y ntoff, respectivamente) son medidas de importancia en los estudios de interacción paciente-ventilador, donde el nivel de la asistencia proporcionada por el ventilador es controlado por la demanda del paciente. Los artefactos cardíacos (ECG) a menudo hacen que sea difícil de utilizar la señal EMGdi. Para superar el inconveniente de la interferencia ECG, en la presente tesis se propone utilizar la entropía muestra! con valores de tolerancia fijos (fSampEn), una técnica que es robusta contra el ruido de tipo impulsivo. Para evaluar la estimación del nton y ntoff se ha realizado un estudio experimental con señales EMGdi superficie registrada en sujetos sanos durante dos protocolos respiratorios, diseñados para evaluar la influencia de los diferentes patrones respiratorios sobre la señal EMGdi. Estos protocolos consistieron en un aumento gradual de la frecuencia respiratoria (RR) con un tiempo inspiratorio (Ti) fracciona! constante (Ti!Ttot) y en una disminución gradual en el Ti!Ttot con una RR constante, respectivamente. Los algoritmos desarrollados han permitido determinar el nton y el ntoff y derivar los parámetros ventilatorios RR, Ti, y TifTtot neurales. La amplitud de la EMGdi proporciona una medida indirecta del NRD, que refleja la carga sobre los músculos respiratorios. El NRD, evaluado en señales EMGdi normalizadas, es mayor en pacientes con enfermedades respiratorias que en sujetos sanos. Para evaluar el comportamiento de la fSampEn, como un método para mejorar la medición del NRD a partir de señales EMGdi en presencia de ECG, en comparación con los enfoques basados en el uso del valor rectificado medio y valor cuadrático medio, primero, se han aplicado estos métodos a señales EMGdi sintéticas . En segundo lugar, hemos probado los métodos propuestos en un estudio experimental con señales EMGdi registradas en sujetos sanos durante una prueba de carga inspiratoria incremental. La amplitud de la EMGdi permitió evaluar los cambios en el patrón de activación de los músculos respiratorios y estimar el NRO. Asimismo, esta tesis doctoral contribuye al estudio de la actividad respiratoria mediante el registro no invasivo de actividad mecanomiográfica de baja frecuencia (BF) en sujetos sanos y en pacientes con enfermedad obstructiva crónica, permitiendo el estudio de la asincronía bilateral del diafragma y la RR. Finalmente, hemos propuesto el uso de electrodos de anillos concéntricos como una alternativa para mejorar la resolución espacial de los registros electromiográficos, y eliminar los problemas asociados a la localización y orientación de la configuración bipolar. Los enfoques presentados en esta tesis doctoral basados en el análisis de señales electromiográficas y mecanomiográficas de los músculo

Neural respiratory drive estimation in respiratory sEMG with cardiac arrhythmias

© 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other worksNeural respiratory drive as measured by the electromyography allows the study of the imbalance between the load on respiratory muscles and its capacity. Surface respiratory electromyography (sEMG) is a non-invasive tool used for indirectly assessment of NRD. It also provides a way to evaluate the level and pattern of respiratory muscle activation. The prevalence of electrocardiographic activity (ECG) in respiratory sEMG signals hinders its proper evaluation. Moreover, the occurrence of abnormal heartbeats or cardiac arrhythmias in respiratory sEMG measures can make even more challenging the NRD estimation. Respiratory sEMG can be evaluated using the fixed sample entropy (fSampEn), a technique which is less affected by cardiac artefacts. The aim of this work was to investigate the performance of the fSampEn, the root mean square (RMS) and the average rectified value (ARV) on respiratory sEMG signals with supraventricular arrhythmias (SVA) for NRD estimation. fSampEn, ARV and RMS parameters increased as the inspiratory load increased during the test. fSampEn was less influenced by ECG with SVAs for the NRD estimation showing a greater response to respiratory sEMG, reflected with a higher percentage increase with increasing load (228 % total increase, compared to 142 % and 135 % for ARV and RMS, respectively).Peer ReviewedPostprint (author's final draft

Neural offset time evaluation in surface respiratory signals during controlled respiration

The electrical activity of the diaphragm measured by surface electromyography (sEMGdi) provides indirect information on neural respiratory drive. Moreover, it allows evaluating the ventilatory pattern from the onset and offset (ntoff) estimation of the neural inspiratory time. sEMGdi amplitude variation was quantified using the fixed sample entropy (fSampEn), a less sensitive method to the interference from cardiac activity. The detection of the ntoff is controversial, since it is located in an intermediate point between the maximum value and the cessation of sEMGdi inspiratory activity, evaluated by the fSampEn. In this work ntoff detection has been analyzed using thresholds between 40% and 100 % of the fSampEn peak. Furthermore, fSampEn was evaluated analyzing the r parameter from 0.05 to 0.6, using a m equal to 1 and a sliding window size equal to 250 ms. The ntoff has been compared to the offset time (toff) obtained from the airflow during a controlled respiratory protocol varying the fractional inspiratory time from 0.54 to 0.18 whilst the respiratory rate was constant at 16 bpm. Results show that the optimal threshold values were between 66.0 % to 77.0 % of the fSampEn peak value. r values between 0.25 to 0.50 were found suitable to be used with the fSampEn