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.

Validation of Photoplethysmography Using a Mobile Phone Application for the Assessment of Heart Rate Variability in the Context of Heart Rate Variability-Biofeedback.

OBJECTIVE: Heart rate variability-biofeedback (HRV-BF) is an effective intervention to reduce stress and anxiety and requires accurate measures of real-time HRV. HRV can be measured through photoplethysmography (PPG) using the camera of a mobile phone. No studies have directly compared HRV-BF supported through PPG against classical electrocardiogram (ECG). The current study aimed to validate PPG HRV measurements during HRV-BF against ECG. METHODS: Fifty-seven healthy participants (70% women) with a mean (standard deviation) age of 26.70 (9.86) years received HRV-BF in the laboratory. Participants filled out questionnaires and performed five times a 5-minute diaphragmatic breathing exercise at different paces (range, ~6.5 to ~4.5 breaths/min). Four HRV indices obtained through PPG, using the Happitech software development kit, and ECG, using the validated NeXus apparatus, were calculated and compared: RMSSD, pNN50, LFpower, and HFpower. Resonance frequency (i.e., optimal breathing pace) was also compared between methods. RESULTS: All intraclass correlation coefficient values of the five different breathing paces were "near perfect" (>0.90) for all HRV indices: lnRMSSD, lnpNN50, lnLFpower, and lnHFpower. All Bland-Altman analyses (with just three incidental exceptions) showed good interchangeability of PPG- and ECG-derived HRV indices. No systematic evidence for proportional bias was found for any of the HRV indices. In addition, correspondence in resonance frequency detection was good with 76.6% agreement between PPG and ECG. CONCLUSIONS: PPG is a potentially reliable and valid method for the assessment of HRV. PPG is a promising replacement of ECG assessment to measure resonance frequency during HRV-BF.

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.

Novel Method to Assess Endothelial Function via Monitoring of Perfusion Response to Local Heating by Imaging Photoplethysmography.

Endothelial dysfunction is one of the most important markers of the risk of cardiovascular complications. This study is aimed to demonstrate the feasibility of imaging photoplethysmography to assess microcirculation response to local heating in order to develop a novel technology for assessing endothelial function. As a measure of vasodilation, we used the relative dynamics of the pulsatile component of the photoplethysmographic waveform, which was assessed in a large area of the outer surface of the middle third of the subject's forearm. The perfusion response was evaluated in six healthy volunteers during a test with local skin heating up to 40-42 °C and subsequent relaxation. The proposed method is featured by accurate control of the parameters affecting the microcirculation during the prolonged study. It was found that in response to local hyperthermia, a multiple increase in the pulsation component, which has a biphasic character, was observed. The amplitude of the first phase of the perfusion reaction depends on both the initial skin temperature and the difference between the basal and heating temperatures. The proposed method allows the assessment of a reproducible perfusion increase in response to hyperthermia developed due to humoral factors associated with the endothelium, thus allowing detection of its dysfunction.

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.

Blue as an Underrated Alternative to Green: Photoplethysmographic Heartbeat Intervals Estimation under Two Temperature Conditions.

Since photoplethysmography (PPG) sensors are usually placed on open skin areas, temperature interference can be an issue. Currently, green light is the most widely used in the reflectance PPG for its relatively low artifact susceptibility. However, it has been known that hemoglobin absorption peaks at the blue part of the spectrum. Despite this fact, blue light has received little attention in the PPG field. Blue wavelengths are commonly used in phototherapy. Combining blue light-based treatments with simultaneous blue PPG acquisition could be potentially used in patients monitoring and studying the biological effects of light. Previous studies examining the PPG in blue light compared to other wavelengths employed photodetectors with inherently lower sensitivity to blue, thereby biasing the results. The present study assessed the accuracy of heartbeat intervals (HBIs) estimation from blue and green PPG signals, acquired under baseline and cold temperature conditions. Our PPG system is based on TCS3472 Color Sensor with equal sensitivity to both parts of the light spectrum to ensure unbiased comparison. The accuracy of the HBIs estimates, calculated with five characteristic points (PPG systolic peak, maximum of the first PPG derivative, maximum of the second PPG derivative, minimum of the second PPG derivative, and intersecting tangents) on both PPG signal types, was evaluated based on the electrocardiographic values. The statistical analyses demonstrated that in all cases, the HBIs estimation accuracy of blue PPG was nearly equivalent to the G PPG irrespective of the characteristic point and measurement condition. Therefore, blue PPG can be used for cardiovascular parameter acquisition. This paper is an extension of work originally presented at the 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

Continuous Blood Pressure Estimation Using Exclusively Photopletysmography by LSTM-Based Signal-to-Signal Translation.

Monitoring continuous BP signal is an important issue, because blood pressure (BP) varies over days, minutes, or even seconds for short-term cases. Most of photoplethysmography (PPG)-based BP estimation methods are susceptible to noise and only provides systolic blood pressure (SBP) and diastolic blood pressure (DBP) prediction. Here, instead of estimating a discrete value, we focus on different perspectives to estimate the whole waveform of BP. We propose a novel deep learning model to learn how to perform signal-to-signal translation from PPG to arterial blood pressure (ABP). Furthermore, using a raw PPG signal only as the input, the output of the proposed model is a continuous ABP signal. Based on the translated ABP signal, we extract the SBP and DBP values accordingly to ease the comparative evaluation. Our prediction results achieve average absolute error under 5 mmHg, with 70% confidence for SBP and 95% confidence for DBP without complex feature engineering. These results fulfill the standard from Association for the Advancement of Medical Instrumentation (AAMI) and the British Hypertension Society (BHS) with grade A. From the results, we believe that our model is applicable and potentially boosts the accuracy of an effective signal-to-signal continuous blood pressure estimation.

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.

Benefits of dry needling of myofascial trigger points on autonomic function and photoelectric plethysmography in patients with fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is a condition characterised by the presence of chronic, widespread musculoskeletal pain, low pain threshold and hyperalgesia. Myofascial trigger points (MTrPs) may worsen symptoms in patients with FMS. OBJECTIVE: The purpose of this randomised controlled trial was to compare the effects of dry needling and transcutaneous electrical nerve stimulation (TENS) on pain intensity, heart rate variability, galvanic response and oxygen saturation (SpO2). METHODS: 74 subjects with FMS were recruited and randomly assigned to either the dry needling group or the TENS group. Outcomes measures (pain intensity, heart rate variability, galvanic skin response, SpO2 and photoplethysmography) were evaluated at baseline and after 6 weeks of treatment. 2×2 mixed-model analyses of variance (ANOVAs) were performed. RESULTS: The mixed-model ANOVAs showed significant differences between groups for the sensory dimension of pain, affective dimension of pain, total dimension of pain, visual analogue scale (VAS) and present pain intensity (PPI) (P=0.001). ANOVAs also showed that significant differences between groups were achieved for very low frequency power of heart rate variability (P=0.008) and low frequency power (P=0.033). There were no significant differences in dry needling versus TENS groups on the spectral analysis of the photoplethysmography and SpO2. CONCLUSIONS: This trial showed that application of dry needling therapy and TENS reduced pain attributable to MTrPs in patients with FMS, with greater improvements reported in the dry needling group across all dimensions of pain. Additionally, there were between-intervention differences for several parameters of heart rate variability and galvanic skin responses. TRIAL REGISTRATION NUMBER: NCT02393352.

Estimation of Arterial Blood Pressure Based on Artificial Intelligence Using Single Earlobe Photoplethysmography during Cardiopulmonary Resuscitation.

This study investigates the feasibility of estimation of blood pressure (BP) using a single earlobe photoplethysmography (Ear PPG) during cardiopulmonary resuscitation (CPR). We have designed a system that carries out Ear PPG for estimation of BP. In particular, the BP signals are estimated according to a long short-term memory (LSTM) model using an Ear PPG. To investigate the proposed method, two statistical analyses were conducted for comparison between BP measured by the micromanometer-based gold standard method (BPMEAS) and the Ear PPG-based proposed method (BPEST) for swine cardiac model. First, Pearson's correlation analysis showed high positive correlations (r = 0.92, p < 0.01) between BPMEAS and BPEST. Second, the paired-samples t-test on the BP parameters (systolic and diastolic blood pressure) of the two methods indicated no significant differences (p > 0.05). Therefore, the proposed method has the potential for estimation of BP for CPR biofeedback based on LSTM using a single Ear PPG.

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.

A Low-Power Dynamic-Range Relaxed Analog Front End for Photoplethysmogram Acquisition.

This paper presents a low-power analog front-end that enables photoplethysmographic signals acquisition, the dynamic range for AC component exaction is relaxed with simple high-pass implementation. The chopping modulation ensures the low-noise operation. The circuit is fabricated in a 0.18-um CMOS technology. Measurements show that the consuming current is approximately 72 uA at a supply of 2.5 V. The circuit achieves a input noise of 6.45 $\mathrm{pA}/\sqrt{Hz}$. The calibred algorithm is implemented by means of MCU, and the demonstration that is compared with the Fluck Simulator used as the reference shows the heart rate is accurately detected, and the error of the measured blood oxygen saturation is less than 1.5%.

Genital lubrication: A cue-specific sexual response?

Women's genital responses are sensitive to the presence and intensity of sexual cues, yet some stimulus features (e.g., male vs. female actors, consensual vs. non-consensual interactions) have little influence on the magnitude of response-a phenomenon called low cue-specificity. Genital responses are typically assessed using vaginal photoplethysmography, a measure of vaginal vasocongestion, itself a precursor to lubrication. One explanation for low cue-specificity is the preparation hypothesis: Women genitally respond to almost all sexual cues because lubrication functions to protect genital organs from potential injury should vaginal penetration occur. In order to test the preparation hypothesis, both vaginal vasocongestion and introital lubrication were assessed in a sample of 20 women in response to sexually explicit films. While patterns of vasocongestion were consistent with low cue-specificity for gender cues and type of sexual activity, lubrication was specific to women's most preferred sexual stimulus categories. These results are inconsistent with the preparation hypothesis.

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.

The SPLENDID chewing detection challenge.

Monitoring of eating behavior using wearable technology is receiving increased attention, driven by the recent advances in wearable devices and mobile phones. One particularly interesting aspect of eating behavior is the monitoring of chewing activity and eating occurrences. There are several chewing sensor types and chewing detection algorithms proposed in the bibliography, however no datasets are publicly available to facilitate evaluation and further research. In this paper, we present a multi-modal dataset of over 60 hours of recordings from 14 participants in semi-free living conditions, collected in the context of the SPLENDID project. The dataset includes raw signals from a photoplethysmography (PPG) sensor and a 3D accelerometer, and a set of extracted features from audio recordings; detailed annotations and ground truth are also provided both at eating event level and at individual chew level. We also provide a baseline evaluation method, and introduce the "challenge" of improving the baseline chewing detection algorithms. The dataset can be downloaded from http: //dx.doi.org/10.17026/dans-zxw-v8gy, and supplementary code can be downloaded from https://github. com/mug-auth/chewing-detection-challenge.git.

Advanced Uses of Pulse Oximetry for Monitoring Mechanically Ventilated Patients.

Pulse oximetry is an undisputable standard of care in clinical monitoring. It combines a spectrometer to detect hypoxemia with a plethysmograph for the diagnosis, monitoring, and follow-up of cardiovascular diseases. These pulse oximetry capabilities are extremely useful for assessing the respiratory and circulatory status and for monitoring of mechanically ventilated patients. On the one hand, the key spectrography-derived function of pulse oximetry is to evaluate a patient's gas exchange that results from a particular ventilatory treatment by continuously and noninvasively measuring arterial hemoglobin saturation (SpO2). This information helps to maintain patients above the hypoxemic levels, leading to appropriate ventilator settings and inspired oxygen fractions. However, whenever higher than normal oxygen fractions are used, SpO2 can mask existing oxygenation defects in ventilated patients. This limitation, resulting from the S shape of the oxyhemoglobin saturation curve, can be overcome by reducing the oxygen fraction delivered to the patient in a controlled and stepwise manner. This results in a SpO2/FIO2 diagram, which allows a rough characterization of a patient's gas exchange, shunt, and the amount of lung area with a low ventilation/perfusion ratio without the need of blood sampling. On the other hand, the photoplethysmography-derived oximeter function has barely been exploited for the purpose of monitoring hemodynamics in mechanically ventilated patients. The analysis of the photoplethysmography contour provides useful real-time and noninvasive information about the interaction of heart and lungs during positive pressure ventilation. These hemodynamic monitoring capabilities are related to both the assessment of preload dependency-mainly by analyzing the breath-by-breath variation of the photoplethysmographic signals-and the analysis of arterial impedance, which examines the changes in the plethysmographic amplitude, contour, and derived indexes. In this article, we present and describe these extended monitoring capabilities and propose a more holistic monitoring concept that takes advantage of these advanced uses of pulse oximetry in the monitoring of ventilated patients. Today's monitors need to be improved if such novel functionalities were to be offered for clinical use. Future developments and clinical evaluations are needed to establish the true potential of these advanced monitoring uses of pulse oximetry.

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.

Evaluation of acute effect of light-emitting diode (LED) phototherapy on muscle deoxygenation and pulmonary oxygen uptake kinetics in patients with diabetes mellitus: study protocol for a randomized controlled trial.

BACKGROUND: Type 2 diabetes mellitus (DM) is responsible for a significant reduction in the quality of life due to its negative impact on functional capacity. Cardiopulmonary fitness impairment in DM patients has been associated with limited tissue oxygenation. Phototherapy is widely utilized to treat several disorders due to expected light-tissue interaction. This type of therapy may help to improve muscular oxygenation, thereby increasing aerobic fitness and functional capacity. METHODS/DESIGN: This study is a randomized, double-blind, placebo-controlled crossover trial approved by the Ethics Committee of the Federal University of São Carlos and registered at ClinicalTrials.gov. Four separate tests will be performed to evaluate the acute effect of phototherapy. All participants will receive both interventions in random order: light-emitting diode therapy (LEDT) and placebo, with a minimum 14-day interval between sessions (washout period). Immediately after the intervention, participants will perform moderate constant workload cycling exercise corresponding to 80 % of the pulmonary oxygen uptake [Formula: see text] during the gas exchange threshold (GET). LEDT will be administered with a multidiode cluster probe (50 GaAIA LEDs, 850 ηm, 75 mW each diode, and 3 J per point) before each exercise session. Pulmonary oxygen uptake, muscle oxygenation, heart rate, and arterial pressure will be measured using a computerized metabolic cart, a near-infrared spectrometer, an electrocardiogram, and a photoplethysmography system, respectively. DISCUSSION: The main objective of this study is to evaluate the acute effects of muscular pre-conditioning using LED phototherapy on pulmonary oxygen uptake, muscle oxygenation, heart rate, and arterial pressure dynamics during dynamic moderate exercise. We hypothesize that phototherapy may be beneficial to optimize aerobic fitness in the DM population. Data will be published after the study is completed. TRIAL REGISTRATION: Registered at ClinicalTrials.gov under trial number NCT01889784 (date of registration 5 June 2013).

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.