Uncertainties in the Analysis of Heart Rate Variability: A Systematic Review.

Heart rate variability (HRV) is an important metric with a variety of applications in clinical situations such as cardiovascular diseases, diabetes mellitus, and mental health. HRV data can be potentially obtained from electrocardiography and photoplethysmography signals, then computational techniques such as signal filtering and data segmentation are used to process the sampled data for calculating HRV measures. However, uncertainties arising from data acquisition, computational models, and physiological factors can lead to degraded signal quality and affect HRV analysis. Therefore, it is crucial to address these uncertainties and develop advanced models for HRV analysis. Although several reviews of HRV analysis exist, they primarily focus on clinical applications, trends in HRV methods, or specific aspects of uncertainties such as measurement noise. This paper provides a comprehensive review of uncertainties in HRV analysis, quantifies their impacts, and outlines potential solutions. To the best of our knowledge, this is the first study that presents a holistic review of uncertainties in HRV methods and quantifies their impacts on HRV measures from an engineer's perspective. This review is essential for developing robust and reliable models, and could serve as a valuable future reference in the field, particularly for dealing with uncertainties in HRV analysis.

Towards a Machine Learning-Based Digital Twin for Non-Invasive Human Bio-Signal Fusion.

Human bio-signal fusion is considered a critical technological solution that needs to be advanced to enable modern and secure digital health and well-being applications in the metaverse. To support such efforts, we propose a new data-driven digital twin (DT) system to fuse three human physiological bio-signals: heart rate (HR), breathing rate (BR), and blood oxygen saturation level (SpO2). To accomplish this goal, we design a computer vision technology based on the non-invasive photoplethysmography (PPG) technique to extract raw time-series bio-signal data from facial video frames. Then, we implement machine learning (ML) technology to model and measure the bio-signals. We accurately demonstrate the digital twin capability in the modelling and measuring of three human bio-signals, HR, BR, and SpO2, and achieve strong performance compared to the ground-truth values. This research sets the foundation and the path forward for realizing a holistic human health and well-being DT model for real-world medical applications.

Head hemodynamics and systemic responses during auditory stimulation.

The present study aims to analyze the systemic response to auditory stimulation by means of hemodynamic (cephalic and peripheral) and autonomic responses in a broad range of auditory intensities (70.9, 77.9, 84.5, 89.5, 94.5 dBA). This approach could help to understand the possible influence of the autonomic nervous system on the cephalic blood flow. Twenty-five subjects were exposed to auditory stimulation while electrodermal activity (EDA), photoplethysmography (PPG), electrocardiogram, and functional near-infrared spectroscopy signals were recorded. Seven trials with 20 individual tones, each for the five intensities, were presented. The results showed a differentiated response to the higher intensity (94.5 dBA) with a decrease in some peripheral signals such as the heart rate (HR), the pulse signal, the pulse transit time (PTT), an increase of the LFnu power in PPG, and at the head level a decrease in oxygenated and total hemoglobin concentration. After the regression of the visual channel activity from the auditory channels, a decrease in deoxyhemoglobin in the auditory cortex was obtained, indicating a likely active response at the highest intensity. Nevertheless, other measures, such as EDA (Phasic and Tonic), and heart rate variability (Frequency and time domain) showed no significant differences between intensities. Altogether, these results suggest a systemic and complex response to high-intensity auditory stimuli. The results obtained in the decrease of the PTT and the increase in LFnu power of PPG suggest a possible vasoconstriction reflex by a sympathetic control of vascular tone, which could be related to the decrease in blood oxygenation at the head level.

Non-contact imaging of peripheral hemodynamics during cognitive and psychological stressors.

Peripheral hemodynamics, measured via the blood volume pulse and vasomotion, provide a valuable way of monitoring physiological state. Camera imaging-based systems can be used to measure these peripheral signals without contact with the body, at distances of multiple meters. While researchers have paid attention to non-contact imaging photoplethysmography, the study of peripheral hemodynamics and the effect of autonomic nervous system activity on these signals has received less attention. Using a method, based on a tissue-like model of the skin, we extract melanin [Formula: see text] and hemoglobin [Formula: see text] concentrations from videos of the hand and face and show that significant decreases in peripheral pulse signal power (by 36% ± 29%) and vasomotion signal power (by 50% ± 26%) occur during periods of cognitive and psychological stress. Via three experiments we show that similar results are achieved across different stimuli and regions of skin (face and hand). While changes in peripheral pulse and vasomotion power were significant the changes in pulse rate variability were less consistent across subjects and tasks.

Different lasers reveal different skin microcirculatory flowmotion - data from the wavelet transform analysis of human hindlimb perfusion.

Laser Doppler flowmetry (LDF) and reflection photoplethysmography (PPG) are standard technologies to access microcirculatory function in vivo. However, different light frequencies mean different interaction with tissues, such that LDF and PPG flowmotion curves might have distinct meanings, particularly during adaptative (homeostatic) processes. Therefore, we analyzed LDF and PPG perfusion signals obtained in response to opposite challenges. Young healthy volunteers, both sexes, were assigned to Group 1 (n = 29), submitted to a normalized Swedish massage procedure in one lower limb, increasing perfusion, or Group 2 (n = 14), submitted to a hyperoxia challenge test, decreasing perfusion. LDF (Periflux 5000) and PPG (PLUX-Biosignals) green light sensors applied distally on both lower limbs recorded perfusion changes for each experimental protocol. Both techniques detected the perfusion increase with massage, and the perfusion decrease with hyperoxia, in both limbs. Further analysis with the wavelet transform (WT) revealed better depth-related discriminative ability for PPG (more superficial, less blood sampling) compared with LDF in both challenges. Spectral amplitude profiles consistently demonstrated better sensitivity for LDF, especially regarding the lowest frequency components. Strong correlations between components were not found. Therefore, LDF and PPG flowmotion curves are not equivalent, a relevant finding to better study microcirculatory physiology.

Assessing Pain Intensity Using Photoplethysmography Signals in Chronic Myofascial Pain Syndrome.

BACKGROUND: Efficacy of pain assessment is the basis for effective therapy. Clinically, assessing pain is by subjective scale, but these methods have some shortcomings. Therefore, studies have been conducted on assessment of pain using physiological signals. Photoplethysmography (PPG) signals provide much information about the cardiovascular system. PPG-derived parameters (PPG parameters) reflect nociceptive stimulation, and obtain an approximation of the R-R interval from the PPG period. The aim of this study was to evaluate PPG signals for assessment of pain intensity in chronic myofascial pain syndrome (MPS) patients. METHODS: This study recruited 37 patients with chronic MPS; all of them were treated with electrotherapy and thermotherapy. The difference between pre- and post-therapy PPG parameters, and the correlation between pulse rate variability (PRV) and heart rate variability (HRV) were determined. We also obtained patients' pain intensity scores by visual analog scale, visual rating scale, and Wong-Banker face pain rating scale. RESULTS: Photoplethysmography and PRV/HRV parameters showed significant differences between pre- and post-treatment. The variation trend of PRV was similar with HRV in heart rate, R-R interval, low frequency, high frequency, and LF/HF; in addition, a high correlation between the parameters was observed either in pre- or post-therapy. PPG parameters indicated increased sympathetic tone. CONCLUSION: The results of the study indicated that PRV substituted for HRV in assessment of pain intensity in chronic MPS reflected parasympathetic nervous tone increase, and PPG parameters might reflect stress stimulation on skin.

Imaging photoplethysmography for clinical assessment of cutaneous microcirculation at two different depths.

The feasibility of bispectral imaging photoplethysmography (iPPG) system for clinical assessment of cutaneous microcirculation at two different depths is proposed. The iPPG system has been developed and evaluated for in vivo conditions during various tests: (1) topical application of vasodilatory liniment on the skin, (2) skin local heating, (3) arterial occlusion, and (4) regional anesthesia. The device has been validated by the measurements of a laser Doppler imager (LDI) as a reference. The hardware comprises four bispectral light sources (530 and 810 nm) for uniform illumination of skin, video camera, and the control unit for triggering of the system. The PPG signals were calculated and the changes of perfusion index (PI) were obtained during the tests. The results showed convincing correlations for PI obtained by iPPG530 nm and LDI at (1) topical liniment (r = 0.98) and (2) heating (r = 0.98) tests. The topical liniment and local heating tests revealed good selectivity of the system for superficial microcirculation monitoring. It is confirmed that the iPPG system could be used for assessment of cutaneous perfusion at two different depths, morphologically and functionally different vascular networks, and thus utilized in clinics as a cost-effective alternative to the LDI.

Analysis of heart rate variability during auditory stimulation periods in patients with schizophrenia.

The vulnerability-stress model is a hypothesis for symptom development in schizophrenia patients who are generally characterized by cardiac autonomic dysfunction. Therefore, measures of heart rate variability (HRV) have been widely used in schizophrenics for assessing altered cardiac autonomic regulations. The goal of this study was to analyze HRV of schizophrenia patients and healthy control subjects with exposure to auditory stimuli. More specifically, this study examines whether schizophrenia patients may exhibit distinctive time and frequency domain parameters of HRV from control subjects during at rest and auditory stimulation periods. Photoplethysmographic signals were used in the analysis of HRV. Nineteen schizophrenic patients and twenty healthy control subjects were examined during rest periods, while exposed to periods of white noise (WN) and relaxing music. Results indicate that HRV in patients was lower than that of control subjects indicating autonomic dysfunction throughout the entire experiment. In comparison with control subjects, patients with schizophrenia exhibited lower high-frequency power and a higher low-frequency to high-frequency ratio. Moreover, while WN stimulus decreased parasympathetic activity in healthy subjects, no significant changes in heart rate and frequency-domain HRV parameters were observed between the auditory stimulation and rest periods in schizophrenia patients. We can conclude that HRV can be used as a sensitive index of emotion-related sympathetic activity in schizophrenia patients.

Accumulated mental stress study using the meridians of traditional Chinese medicine with photoplethysmography.

OBJECTIVES: To investigate accumulated mental stress according to the concept of the meridians of Traditional Chinese Medicine (TCM). This stress was quantified by using pulse spectrum analysis of finger-tip photoplethysmography (PPG). Stress accumulation is one of the main causes of cardiovascular disease and depression in humans, resulting in chronic physiologic malfunctions; however, few studies have thoroughly assessed the quantitative evaluation of accumulative stress using the concept of TCM. DESIGN: This study investigated accumulated mental stress from the perspective of TCM based on an 8-day experiment. The theory of organ resonance was integrated into the proposed PPG sensing instrument to capture the nine harmonics of TCM. Participants were given daily mental arithmetic tasks over 1 week to simulate stress accumulation, and trends in the proportion of the nine harmonics of TCM were extracted over several days and analyzed to identify the affective factors related to cumulative stress. RESULTS: The experimental results showed that the kidney harmonic proportion (C2) and stomach harmonic proportion (C5) were significant only on the first few days because of a physiologic phenomenon of temporary stimulation. Most important, the trend of the liver harmonic proportion (C1) from days 3 to 8 dramatically increased and became gradually saturated because of the influence of accumulated mental stress. CONCLUSIONS: The results strongly suggest that pulse spectrum analysis of the PPG signal provides physiologically and pathologically important information on accumulated mental stress and can be useful for TCM analysis.

Automatic stress-relieving music recommendation system based on photoplethysmography-derived heart rate variability analysis.

This paper presents an automatic stress-relieving music recommendation system (ASMRS) for individual music listeners. The ASMRS uses a portable, wireless photoplethysmography module with a finger-type sensor, and a program that translates heartbeat signals from the sensor to the stress index. The sympathovagal balance index (SVI) was calculated from heart rate variability to assess the user's stress levels while listening to music. Twenty-two healthy volunteers participated in the experiment. The results have shown that the participants' SVI values are highly correlated with their prespecified music preferences. The sensitivity and specificity of the favorable music classification also improved as the number of music repetitions increased to 20 times. Based on the SVI values, the system automatically recommends favorable music lists to relieve stress for individuals.

Chronic performance of a subcutaneous hemodynamic sensor.

BACKGROUND: A subcutaneous photoplethysmography (PPG) sensor uses light to detect changes in vascular volume from a location outside the bloodstream. Incorporation into a chronically implanted device, such as a pacemaker or an implantable cardioverter defibrillator, may facilitate therapy optimization and disease monitoring by providing continuous assessment of hemodynamic function and arterial oxygen saturation. However, performance of a chronically placed subcutaneous sensor has not been established. METHODS: Six dogs were implanted with 2-4 PPG sensors subcutaneously in the neck or posterior thorax. Half of the sensors were directed toward deep tissue and half toward overlying cutaneous tissue. Each sensor contained a red and an infrared light emitting diode, a photodetector, and supporting electronics, which were encapsulated in epoxy and attached to a transcutaneous connector. Data were collected at implant and every 3 ± 1 days for 4-9 months starting 3 weeks postimplant. At explant, the fibrous encapsulation was histologically analyzed. RESULTS: A minimally to moderately neovascularized encapsulation formed over all sensors, consisting of fibrous and granulation tissue. Higher cardiac pulse amplitudes and direct current (DC) components were recorded in sensors oriented toward deep tissue, but no significant difference between orientations was found in respiratory wave amplitude. Cardiac pulse amplitude, respiratory wave amplitude, and DC component amplitude, as recorded by the sensor, did not significantly change over time. CONCLUSIONS: Despite fibrous encapsulation of PPG sensors, cardiac pulses and respiratory waves could easily be measured throughout the study and remained constant over time. These results suggest suitability of subcutaneous PPG technology for chronic applications.

Contribución al estudio de los efectos sistémicos neurovegetativos del masaje terapéutico mediante el análisis espectral de la variabilidad de la frecuencia cardiaca / Contribution to the study of autonomic systemic effects of therapeutic massage by power spectral analysis of heart rate variability

Objetivo. Analizar las modificaciones que el masaje terapéutico produce en la actividad neurovegetativa sistémica del organismo a través del estudio de la modificación de la actividad autónoma cardiaca. Material y método. Estudio comparativo sobre 15 mujeres de la variabilidad de la frecuencia cardiaca (VFC) (intervalo R-R) obtenida mediante fotopletismografía durante 2 sesiones de 20 minutos de duración: control y masaje. Dicha VFC fue medida en 4 ocasiones diferentes sobre duraciones de 5 minutos cada una. La sesión de masaje consistió en effleurage superficial y presiones deslizadas de gran amplitud. Además, las participantes debían cumplimentar inmediatamente después de la sesión de control y de la de masaje el cuestionario de la escala visual analógica (EVA) de bienestar. Resultados. Para comparar los resultados obtenidos se ha utilizado el t-test pareado de Student y se ha empleado el coeficiente de correlación de Pearson para cuantificar la fuerza de la relación existente entre distintos tiempos en cada uno de los parámetros. Se observa un aumento estadísticamente significativo de la VFC (potencia total) y también un aumento de la actividad parasimpática en la sesión de masaje durante los 5 últimos minutos del mismo (respecto a valores basales), superior a la sesión control. Esta respuesta, sin embargo, tiende a disminuir 5 minutos después de la interrupción del mismo. Finalmente, la puntuación de la EVA de bienestar aumentó significativamente después del masaje, pero su ganancia no se correlaciona con la evolución de las variables fisiológicas. Conclusiones. El masaje aplicado sobre sujetos sanos tiene efecto sobre el sistema neurovegetativo (AU)

Goal: To analyze the changes produced by therapeutic massage on systemic autonomic activity by analyzing the modification of cardiac autonomic activity. Material and methods: A comparative study was performed on 15 women on the variability of heart rate variability (HRV) (RR interval) obtained by photoplethysmography for 2 20-minute sessions: control and massage. HRV was measured at 4 different times for periods of 5 minutes each. The massage session consisted of effleurage massage and wide-ranging sliding pressure. In addition, the participants had to fill out the well-being visual analogue scale (Well Being VAS) questionnaire immediately after the control and massage session. Results: The paired Student’s t-test was used to compare the results obtained. Pearson correlation coefficient was used to quantify the relationship existing between the different times in each one of the parameters. A statistically significant increase was observed in HRV (total power) as well as an increase in parasympathetic activity in the massage session during the last 5 minutes (relative to baseline) compared to control session. However, this response tends to decrease 5 minutes after its interruption/timeout. Finally, the Well Being VAS score shows a significant increase after the massage. However, its gain is not correlated to the changes in the physiological variables. Conclusions: The massage applied on healthy subjects affects the autonomic nervous system (AU)

A measurement of electrocardiography and photoplethesmography in obese children.

The purpose of this study was to establish heart rate variability normative data on obese children and to comparing the accuracy of two medical technologies photoplethesmography (PPG) with electrocardiography (ECG) while measuring heart rate variability (HRV). PPG is a relatively new technique that holds promise for health care practitioners as an evaluative tool and biofeedback instrument due to its cost and easy administration. This study involved ten children who were recruited for an after-school program designed to reduce obesity. Three-five-minute recordings of HRV were collected while the children were lying in the supine position on a therapy bed. PPG was measured from a thumb sensor and ECG from sensors placed under wristbands on both wrists. The results indicate that PPG is as effective as ECG in measuring the eleven parameters of heart rate variability.

Heart rate variability: an index of brain processing in vegetative state? An artificial intelligence, data mining study.

OBJECTIVE: Brain processing at varying levels of functional complexity has been documented in vegetative state. In this study, data mining procedures are applied to identify significant changes in heart rate variability (an emerging objective descriptor of autonomic correlates of brain activation) in response to complex auditory stimuli with emotional value (music). METHODS: The heart rate of subjects in vegetative state from brain damage (n=6) or spontaneous hemorrhage (n=3) and 16 healthy controls was recorded while they passively listened to four pre-selected music samples by different authors (mean recording time: 3m and 36s±24s). The parametric and non-parametric frequency spectra were computed on the heart rate, spectra were compared within/across subjects and music authors, and the spectra descriptors were entered into a 1-R rules data mining procedure (WEKA software Leave One Out and Ten Fold Cross validation). The procedure independently classified the heart rate spectral patterns of both patients and controls and the emotions reported by healthy subjects as "positive" or "negative". RESULTS: In both healthy controls and vegetative state subjects, the power spectra while passively listening to music differed from baseline when compared irrespective of the music authorship and from each other when compared across music samples. Data mining sorted the nu_LF (normalized parameter unit of the spectrum low frequency range) as the significant descriptor of heart rate variability in the conditions of the study. The nu_LF classification of the healthy controls' HRV changes in response to music replicated that based on subjective reports with 75-93.7% accuracy. CONCLUSIONS: Although preliminary, these findings suggest that autonomic changes with possible emotional value can be induced by complex stimuli also in vegetative state, with implications on the residual responsiveness of these subjects. SIGNIFICANCE: Heart rate variability descriptors and data mining methods appear applicable to investigate brain function in the absence of consciousness.

Multilaser photoplethysmography technique.

New technique for parallel recording of reflection photoplethysmography signals in broad spectral band (violet to NIR) has been developed based on fiber-coupled laser irradiation and time-resolved spectrometric detection. Differences in photoplethysmography waveforms that were recorded simultaneously at different wavelengths confirmed the depth variety of the skin blood pulsation dynamics, thus the proposed methodology has a potential for application in skin microcirculation studies.

Development of HIHM (Home Integrated Health Monitor) for ubiquitous home healthcare.

Home Integrated Health Monitor (HIHM) was developed for ubiquitous home healthcare. From quantitative analysis, we have elicited modal of chair. The HIHM could detect Electrocardiogram (ECG) and Photoplethysmography (PPG) non-intrusively. Also, it could estimate blood pressure (BP) non-intrusively, measure blood glucose and ear temperature. Detected signals and information were transmitted to home gateway and home server through Zigbee communication technology. Home server carried them to Healthcare Center, and specialists such as medical doctors could monitor by Internet. There was also feedback system. This device has a potential to study about ubiquitous home healthcare.

Coordination dynamics of circulatory and respiratory rhythms during psychomotor drive reduction.

A 0.15-Hz rhythm band in cutaneous blood oscillations in awake human subjects was studied in cardiovascular-respiratory time series of five subjects relaxing naïvely or practicing hypnoid relaxation (autogenic training, or AT). Time series analysis used nonlinear algorithms, time-frequency distribution (TFD), postevent scan (PES) method, and linear fast Fourier transform (FFT) algorithm. This 0.15-Hz rhythm band caused phase synchronization with respiration at 1:2, 1:1, and 2:1 integer number (n/m) ratios for extended periods. During wave epochs, the 0.15-Hz rhythm band was amplified, causing the 0.15-Hz rhythm band to also appear in interbeat intervals and arterial blood pressure fluctuations. If phase synchronization of the 0.15-Hz rhythm band with respiration was established at a 1:1 integer number ratio, it was maintained and resulted in consensualization of all cardiovascular-respiratory oscillations at this frequency. Simultaneous cardiovascular and respiratory oscillations at about 0.1 Hz did not affect the appearance of the 0.15-Hz rhythm band in the photoplethysmography (PPG) signal. Recent evidence suggests the emergence of the 0.15-Hz rhythm band and n/m phase synchronization to result from nonequilibrium phase transitions operational in the network of lower brainstem neurons and associated parasympathetic neuronal effectors. These findings corroborate our notion of the 0.15-Hz rhythm band as a marker of the trophotropic mode of operation.

[The re-evaluation of the vasodepressive component in the carotid sinus syndrome]. / Rivalutazione della componente vasodepressiva nella sindrome del seno carotideo.

BACKGROUND: The evaluation of the vasodepressor (VD) reflex of the carotid sinus syndrome is usually inaccurate, due to the difficulty in blood pressure measurement. AIM: To study the VD reflex with a beat-to-beat not invasive technique. METHODS: We investigated 68 patients (49 males, 19 females; mean age 70 +/- 11 years) affected by carotid sinus syndrome: cardioinhibitory (CI) form was present in 47 patients, mixed (M) form in 10 patients and VD form in 11 patients. The control group consisted of 9 patients (6 male, mean age 71 +/- 8 years) affected by third degree atrioventricular block who had received the implant of a permanent pacemaker and were pacemaker-dependent with a prolonged asystole at time of temporary inhibition of the pacemaker itself. The study of the VD reflex was performed in the supine position; beat-to-beat arterial systolic pressure was monitored by a photoplethysmographic method using a finger cuff (Finapres technique). RESULTS: In all the patients the carotid sinus massage caused a marked fall in systolic blood pressure which was greatest at the end of the massage: from 143 +/- 25 mm Hg to 74 +/- 20 mm Hg in the patients with CI form, from 144 +/- 14 mm Hg to 76 +/- 18 mm Hg in those with M form and from 125 +/- 26 mm Hg to 65 +/- 13 mm Hg in those with VD form. A decrease in systolic blood pressure > or = 50 mm Hg occurred in 84% of cases. Afterwards, the patients with CI form had a progressive increase of systolic blood pressure that reached the initial value after a mean of 27 seconds. In the patients with VD form systolic blood pressure was significantly (p < or = 0.5) lower than that observed in all the other groups, beginning from the third second after the end of the massage; mean systolic blood pressure value remained significantly lower than the initial value for more than 27 seconds. The patients with M form showed an intermediate pattern. Also control group patients showed a fall in systolic blood pressure immediately after pacemaker inhibition (from 152 +/- 29 mm Hg to 87 +/- 25 mm Hg) that was of similar extent than that observed in carotid sinus syndrome patients, but pressure returned to initial value within 9 seconds. CONCLUSIONS: An important VD reflex is present in most patients with carotid sinus syndrome. It lasts more than the CI reflex and it persists for several seconds after the end of the massage. The initial fall of systolic blood pressure is of similar extent in all the forms of carotid sinus syndrome, but the patients with the VD form are characterized by a longer duration and greater entity of the decrease. These results point out the importance of the VD reflex in patients with the carotid sinus syndrome.

Optical characteristics of human extracted teeth and the possible application of photoplethysmography to the human pulp.

In order to record pulp blood flow by photoplethysmography, the light transmission properties of extracted human teeth and human peripheral blood at wavelengths between 400 and 800 nm were first investigated. Transmission through peripheral blood and extracted teeth was lower at wavelengths shorter than 600 nm. Transmitted-light photoplethysmography (TLP) was applied to teeth in situ using a tungsten light, or one of two light-emitting diodes (LED) with peak wavelengths of 565 and 695 nm. A CdS-CdSe photoconductive cell was used as a detector. The LED with a peak intensity at 565 nm was the most efficient of the three light sources for recording the TLP. The results indicate that the TLP could be used to assess pulp vitality.