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Recent studies have shown that individuals with sickle cell disease (SCD) exhibit greater vasoconstriction responses to physical autonomic stressors, such as heat pain and cold pain than normal individuals, but this is not the case for mental stress. We sought to determine whether this anomalous finding for mental stress is related to inter-group differences in baseline cardiac and vascular autonomic function. Fifteen subjects with SCD and 15 healthy volunteers participated in 3 mental stress tasks: N-back, Stroop, and pain anticipation. R-R interval, arterial blood pressure and finger photoplethysmogram (PPG) were continuously monitored before and during these mental stress tasks. The magnitude of vasoconstriction was quantified using change in PPG amplitude from the baseline period. To represent basal autonomic function, we assessed both cardiac and vascular arms of the baroreflex during the baseline period. Cardiac baroreflex sensitivity (BRSc) was estimated by applying both the “sequence” and “spectral” techniques to beat-to-beat measurements of systolic blood pressure and R-R intervals. The vascular baroreflex sensitivity (BRSv) was quantified using the same approaches, modified for application to beat-to-beat diastolic blood pressure and PPG amplitude (PPGa) measurements. Baseline BRSc was not different between SCD and non-SCD subjects, was not correlated with BRSv, and was not associated with the vasoconstriction responses to mental stress tasks. BRSv in both groups was correlated with mean PPGa, and since both baseline PPGa and BRSv were lower in SCD, these results suggested that the SCD subjects were in a basal state of higher sympathetically-mediated vascular tone. In both groups, baseline BRSv was positively correlated with the vasoconstriction responses to N-back, Stroop and pain anticipation. After adjusting for differences in BRSv within and between groups, we found no difference in the vasoconstriction responses to all 3 mental tasks between SCD and non-SCD subjects. The implications of these findings are significant in subjects with SCD since vasoconstriction reduces microvascular flow and prolongs capillary transit time, increasing the likelihood for VOC to be triggered by exposure to stressful events.

Noninvasive assessment of autonomic nervous system (ANS) activity is of great importance, but the accuracy of the method used, which is primarily based on electrocardiogram-derived heart rate variability (HRV), has long been suspected. We investigated the feasibility of photoplethysmography (PPG) in ANS evaluation. Data of 32 healthy young men under four different ANS activation patterns were recorded: baseline, slow deep breathing (parasympathetic activation), cold pressor test (peripheral sympathetic activation), and mental arithmetic test (cardiac sympathetic activation). We extracted 110 PPG-based features to construct classification models for the four ANS activation patterns. Using interpretable models based on random forest, the main PPG features related to ANS activation were obtained. Results showed that pulse rate variability (PRV) exhibited similar changes to HRV across the different experiments. The four ANS patterns could be better classified using more PPG-based features compared with using HRV or PRV features, for which the classification accuracies were 0.80, 0.56, and 0.57, respectively. Sensitive features of parasympathetic activation included features of nonlinear (sample entropy), frequency, and time domains of PRV. Sensitive features of sympathetic activation were features of the amplitude and frequency domain of PRV of the PPG derivatives. Subsequently, these sensitive PPG-based features were used to fit the improved HRV parameters. The fitting results were acceptable (p < 0.01), which might provide a better method of evaluating ANS activity using PPG.

Atrial fibrillation is often asymptomatic and intermittent making its detection challenging. A photoplethysmography (PPG) provides a promising option for atrial fibrillation detection. However, the shapes of pulse waves vary in atrial fibrillation decreasing pulse and atrial fibrillation detection accuracy. This study evaluated ten robust photoplethysmography features for detection of atrial fibrillation. The study was a national multi-center clinical study in Finland and the data were combined from two broader research projects (NCT03721601, URL: https://clinicaltrials.gov/ct2/show/NCT03721601 and NCT03753139, URL: https://clinicaltrials.gov/ct2/show/NCT03753139). A photoplethysmography signal was recorded with a wrist band. Five pulse interval variability, four amplitude features and a novel autocorrelation-based morphology feature were calculated and evaluated independently as predictors of atrial fibrillation. A multivariate predictor model including only the most significant features was established. The models were 10-fold cross-validated. 359 patients were included in the study (atrial fibrillation n = 169, sinus rhythm n = 190). The autocorrelation univariate predictor model detected atrial fibrillation with the highest area under receiver operating characteristic curve (AUC) value of 0.982 (sensitivity 95.1%, specificity 93.7%). Autocorrelation was also the most significant individual feature (p < 0.00001) in the multivariate predictor model, detecting atrial fibrillation with AUC of 0.993 (sensitivity 96.4%, specificity 96.3%). Our results demonstrated that the autocorrelation independently detects atrial fibrillation reliably without the need of pulse detection. Combining pulse wave morphology-based features such as autocorrelation with information from pulse-interval variability it is possible to detect atrial fibrillation with high accuracy with a commercial wrist band. Photoplethysmography wrist bands accompanied with atrial fibrillation detection algorithms utilizing autocorrelation could provide a computationally very effective and reliable wearable monitoring method in screening of atrial fibrillation.

Background: Induction of anesthesia with propofol is associated with a disturbance in hemodynamics, in part due to its effects on parasympathetic and sympathetic tone. The impact of propofol on autonomic function is unclear. In this study, we investigated in detail the changes in the cardiac autonomic nervous system (ANS) and peripheral sympathetic outflow that occur during the induction of anesthesia.Methods: Electrocardiography and pulse photoplethysmography (PPG) signals were recorded and analyzed from 30 s before to 120 s after propofol induction. The spectrogram was derived by continuous wavelet transform with the power of instantaneous high-frequency (HFi) and low-frequency (LFi) bands extracted at 1-s intervals. The wavelet-based parameters were then divided into the following segments: (1) baseline (30 s before administration of propofol), (2) early phase (first minute after administration of propofol), and (3) late phase (second minute after administration of propofol) and compared with the same time intervals of the Fourier-based spectrum [high-frequency (HF) and low-frequency (LF) bands]. Time-dependent effects were explored using fractional polynomials and repeated-measures analysis of variance.Results: Administration of propofol resulted in reductions in HFi and LFi and increases in the LFi/HFi ratio and PPG amplitude, which had a significant non-linear relationship. Significant between-group differences were found in the HFi, LFi, and LFi/HFi ratio and Fourier-based HF and LF after dividing the segments into baseline and early/late phases. On post hoc analysis, changes in HFi, LFi, and the LFi/HFi ratio were significant starting from the early phase. The corresponding effect size (partial eta squared) was > 0.3, achieving power over 90%; however, significant decreases in HF and LF were observed only in the late phase. The PPG amplitude was increased significantly in both the early and late phases.Conclusion: Propofol induction results in significant immediate changes in ANS activity that include temporally relative elevation of cardiac sympathovagal balance and reduced sympathetic activity.Clinical Trial Registration: The study was approved by the Institutional Review Board of Taipei Veterans General Hospital (No. 2017-07-009CC) and is registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03613961).

BackgroundTo increase the consultation rate of potential major depressive disorder (MDD) patients, we developed a contact-type fingertip photoplethysmography-based MDD screening system. With the outbreak of SARS-CoV-2, we developed an alternative to contact-type fingertip photoplethysmography: a novel web camera-based contact-free MDD screening system (WCF-MSS) for non-contact measurement of autonomic transient responses induced by a mental task.MethodsThe WCF-MSS measures time-series interbeat intervals (IBI) by monitoring color tone changes in the facial region of interest induced by arterial pulsation using a web camera (1920 × 1080 pixels, 30 frames/s). Artifacts caused by body movements and head shakes are reduced. The WCF-MSS evaluates autonomic nervous activation from time-series IBI by calculating LF (0.04–0.15 Hz) components of heart rate variability (HRV) corresponding to sympathetic and parasympathetic nervous activity and HF (0.15–0.4 Hz) components equivalent to parasympathetic activities. The clinical test procedure comprises a pre-rest period (Pre-R; 140 s), mental task period (MT; 100 s), and post-rest period (Post-R; 120 s). The WCF-MSS uses logistic regression analysis to discriminate MDD patients from healthy volunteers via an optimal combination of four explanatory variables determined by a minimum redundancy maximum relevance algorithm: HF during MT (HFMT), the percentage change of LF from pre-rest to MT (%ΔLF(Pre–R⇒MT)), the percentage change of HF from pre-rest to MT (%ΔHF(Pre–R⇒MT)), and the percentage change of HF from MT to post-rest (%ΔHF(MT⇒Post–R)). To clinically test the WCF-MSS, 26 MDD patients (16 males and 10 females, 20–58 years) were recruited from BESLI Clinic in Tokyo, and 27 healthy volunteers (15 males and 12 females, 18–60 years) were recruited from Tokyo Metropolitan University and RICOH Company, Ltd. Electrocardiography was used to calculate HRV variables as references.ResultThe WCF-MSS achieved 73% sensitivity and 85% specificity on 5-fold cross-validation. IBI correlated significantly with IBI from reference electrocardiography (r = 0.97, p < 0.0001). Logit scores and subjective self-rating depression scale scores correlated significantly (r = 0.43, p < 0.05).ConclusionThe WCF-MSS seems a promising contact-free MDD screening apparatus. This method enables web camera built-in smartphones to be used as MDD screening systems.

Introduction: Heart Rate Variability (HRV) and Pulse Rate Variability (PRV), are non-invasive techniques for monitoring changes in the cardiac cycle. Both techniques have been used for assessing the autonomic activity. Although highly correlated in healthy subjects, differences in HRV and PRV have been observed under various physiological conditions. The reasons for their disparities in assessing the degree of autonomic activity remains unknown.\ud \ud Methods: To investigate the differences between HRV and PRV, a whole-body cold exposure (CE) study was conducted on 20 healthy volunteers (11 male and 9 female, 30.3 ± 10.4 years old), where PRV indices were measured from red photoplethysmography signals acquired from central (ear canal, ear lobe) and peripheral sites (finger and toe), and HRV indices from the ECG signal. PRV and HRV indices were used to assess the effects of CE upon the autonomic control in peripheral and core vasculature, and on the relationship between HRV and PRV. The hypotheses underlying the experiment were that PRV from central vasculature is less affected by CE than PRV from the peripheries, and that PRV from peripheral and central vasculature differ with HRV to a different extent, especially during CE.\ud \ud Results: Most of the PRV time-domain and Poincaré plot indices increased during cold exposure. Frequency-domain parameters also showed differences except for relative-power frequency-domain parameters, which remained unchanged. HRV-derived parameters showed a similar behavior but were less affected than PRV. When PRV and HRV parameters were compared, time-domain, absolute-power frequency-domain, and non-linear indices showed differences among stages from most of the locations. Bland-Altman analysis showed that the relationship between HRV and PRV was affected by CE, and that it recovered faster in the core vasculature after CE. \ud \ud Conclusion: PRV responds to cold exposure differently to HRV, especially in peripheral sites such as the finger and the toe, and may have different information not available in HRV due to its non-localized nature. Hence, multi-site PRV shows promise for assessing the autonomic activity on different body locations and under different circumstances, which could allow for further understanding of the localized responses of the autonomic nervous system.

In sickle cell disease (SCD), prolonged capillary transit times, resulting from reduced peripheral blood flow, increase the likelihood of rigid red cells entrapment in the microvasculature, predisposing to vaso-occlusive crisis. Since changes in peripheral flow are mediated by the autonomic nervous system (ANS), we tested the hypothesis that the cardiac and peripheral vascular responses to head-up tilt (HUT) are abnormal in SCD. Heart rate, respiration, non-invasive continuous blood pressure and finger photoplethysmogram (PPG) were monitored before, during, and after HUT in SCD, anemic controls and healthy subjects. Percent increase in heart rate from baseline was used to quantify cardiac ANS response, while percent decrease in PPG amplitude represented degree of peripheral vasoconstriction. After employing cluster analysis to determine threshold levels, the HUT responses were classified into four phenotypes: (CP) increased heart rate and peripheral vasoconstriction; (C) increased heart rate only; (P) peripheral vasoconstriction only; and (ST) subthreshold cardiac and peripheral vascular responses. Multinomial logistic regression (MLR) was used to relate these phenotypic responses to various parameters representing blood properties and baseline cardiovascular activity. The most common phenotypic response, CP, was found in 82% of non-SCD subjects, including those with chronic anemia. In contrast, 70% of SCD subjects responded abnormally to HUT: C-phenotype = 22%, P-phenotype = 37%, or ST-phenotype = 11%. MLR revealed that the HUT phenotypes were significantly associated with baseline cardiac parasympathetic activity, baseline peripheral vascular variability, hemoglobin level and SCD diagnosis. Low parasympathetic activity at baseline dramatically increased the probability of belonging to the P-phenotype in SCD subjects, even after adjusting for hemoglobin level, suggesting a characteristic autonomic dysfunction that is independent of anemia. Further analysis using a mathematical model of heart rate variability revealed that the low parasympathetic activity in P-phenotype SCD subjects was due to impaired respiratory-cardiac coupling rather than reduced cardiac baroreflex sensitivity. By having strong peripheral vasoconstriction without compensatory cardiac responses, P-phenotype subjects may be at increased risk for vaso-occlusive crisis. The classification of autonomic phenotypes based on HUT response may have potential use for guiding therapeutic interventions to alleviate the risk of adverse outcomes in SCD.

Introduction: Photoplethysmography (PPG) has been widely used to assess cardiovascular function. However, few studies have comprehensively investigated the effect of measurement site on PPG waveform characteristics. This study aimed to provide a quantitative comparison on this.Methods: Thirty six healthy subjects participated in this study. For each subject, PPG signals were sequentially recorded for 1 min from six different body sites (finger, wrist under (anatomically volar), wrist upper (dorsal), arm, earlobe, and forehead) under both normal and deep breathing patterns. For each body site under a certain breathing pattern, the mean amplitude was firstly derived from recorded PPG waveform which was then normalized to derive several waveform characteristics including the pulse peak time (Tp), dicrotic notch time (Tn), and the reflection index (RI). The effects of breathing pattern and measurement site on the waveform characteristics were finally investigated by the analysis of variance (ANOVA) with post hoc multiple comparisons.Results: Under both breathing patterns, the PPG measurements from the finger achieved the highest percentage of analyzable waveforms for extracting waveform characteristics. There were significant effects of breathing pattern on Tn and RI (larger Tn and smaller RI with deep breathing on average, both p < 0.03). The effects of measurement site on mean amplitude, Tp, Tn, and RI were significant (all p < 0.001). The key results were that, under both breathing patterns, the mean amplitude from finger PPG was significantly larger and its Tp and RI were significantly smaller than those from the other five sites (all p < 0.001, except p = 0.04 for the Tp of “wrist under”), and Tn was only significantly larger than that from the earlobe (both p < 0.05).Conclusion: This study has quantitatively confirmed the effect of PPG measurement site on PPG waveform characteristics (including mean amplitude, Tp, Tn, and RI), providing scientific evidence for a better understanding of the PPG waveform variations between different body sites.

The differences in the degree of sympathetic nerve activity (SNA) over cutaneous blood vessels, although known to be more prominent in the periphery than the core vasculature, has not been thoroughly investigated quantitatively. Hence, two studies were carried out to investigate the differences in SNA between the periphery and the core during the cold pressor test (CPT) (right-hand immersion in ice water) and cold exposure (whole body exposed to cold air) using photoplethysmography (PPG). Two methods utilizing PPG, namely differential multi-site PTT measurements and low-frequency spectral analysis were explored for quantitative determination of SNA. Each study involved 12 healthy volunteers, and PPG signals were acquired from the right index finger (RIF), left index finger (LIF) (periphery) and the ear canal (core). During CPT, Pulse Transit Time (PTT) was measured to the respective locations and the mean percentage change in PTT during ice immersion at each location was used as an indicator for the extent of SNA. During cold exposure, the low-frequency spectral analysis was performed on the acquired raw PPGs to extract the power of the sympathetic [low-frequency (LF): 0.04–0.15 Hz] and parasympathetic components [high-frequency (HF): 0.15–0.4 Hz]. The ratio of LF/HF components was then used to quantify the differences in the influence of SNA on the peripheral and core circulation. PTT measured from the EC, and the LIF has dropped by 5 and 7%, respectively during ice immersion. The RIF PTT, on the other hand, has dropped significantly (P < 0.05) by 12%. During the cold exposure, the LF/HF power ratio at the finger has increased to 86.4 during the cold exposure from 19.2 at the baseline (statistically significant P = 0.002). While the ear canal LF/HF ratio has decreased to 1.38 during the cold exposure from 1.62 at baseline (P = 0.781). From these observations, it is evident that differential PTT measurements or low-frequency analysis can be used to quantify SNA. The results also demonstrate the effectiveness of the central auto-regulation during both short and long-term stress stimulus as compared to the periphery.

Objective: This study aimed to compare differences in cardiorespiratory function between untreated hypertensive subjects (UHS) and healthy subjects (HS) during cardiopulmonary exercise testing (CPET). Additionally, it also aimed to explore the potential mechanisms of different exercise responses in cardiorespiratory function before, during and after CPET. Methods: Thirty subjects (15 UHS and 15 HS) were enrolled. Photoplethysmography (PPG), respiratory signal, and ECG were simultaneously collected while subjects were performing CPET. Fiducial points (a, b, c, d, e) were extracted from the second derivative of the PPG (SDPPG), and the ratios b/a, c/a, d/a, e/a, and (b-c-d-e)/a (named Aging Index, AGI) were calculated as markers of systolic and diastolic function. Additionally, respiratory rate was calculated and analyzed. Results: Before CPET, there were no significant differences in b/a, d/a, and AGI between two groups. However, after CPET, b/a (-0.9 +/- 0.19 vs. -1.06 +/- 0.19, p-value = 0.03) and AGI (-0.49 +/- 0.75 vs. -1.15 +/- 0.59, p-value = 0.011) of the UHS group were significantly higher than those of the HS. The d/a (-0.32 +/- 0.24 vs. -0.14 +/- 0.17, p-value = 0.024), and c/a (-0.33 +/- 0.26 vs. -0.07 +/- 0.19, p-value = 0.004) were significantly lower in UHS than those in HS. In contrast, before CPET, e/a (0.22 +/- 0.11 vs. 0.32 +/- 0.09, p-value = 0.007) in UHS was significantly lower than that in HS, while after CPET there was no significant difference between the two groups in this variable. In addition, during CPET, AGI (p-value = 0.003), and respiratory rate (p-value = 0.000) in UHS were significantly higher in comparison with before CPET. Conclusions: Different exercise responses showed the differences of cardiorespiratory function between UHS and HS. These differences not only can highlight the CV risk of UHS, but also can predict the appearance of arterial stiffness in UHS. Additionally, during CPET, significant differences in AGI, autonomic nervous function and respiratory activity assessed by respiratory rate were found between the two groups in comparison with before CPET.

Perfusion at microvascular level involves the contribution of both local and central regulators, under a complex vascular signaling frame. The venoarteriolar reflex (VAR) is one of such regulatory responses, of particular relevance in the lower limb to prevent edema development. Although known for quite some time, many of the complex interactions involving all of these regulatory mechanisms still need clarification. Our objective was to look deeper into VAR through the Wavelet Transform (WT) spectral analysis of modern photoplethymography (PPG). Twelve healthy subjects (both sexes, 26.0 ± 5.0 y.o.) were enrolled in this study after informed written consent. Subjects were submitted to a leg lowering maneuver while lying supine to evoke the VAR, involving three phases – 10 minutes baseline register, both legs extended, 10 minutes challenge, with one randomly chosen leg (test) pending 50 cm below heart level, while the contralateral (control) remained in place, and 10 minutes recovery, resuming the initial position. PPG signals were collected from both feet and treated by the WT, revealing six spectral bands in frequency intervals comprising the cardiac [1.6-0.7 Hz], respiratory [0.4-0.26 Hz], myogenic [0.26-0.1 Hz], neurogenic / sympathetic [0.1-0.045 Hz], endothelial NO-dependent (NOd) [0.045-0.015 Hz] and NO-independent (NOi) [0.015-0.007 Hz] activities. For the first time, this approach revealed that, with VAR, perfusion significantly decreased in both limbs, although the change was more pronounced in the test foot. Here, a significant decrease in myogenic, neurogenic and NOd, were noted, while the control foot recorded a decrease in neurogenic and an increase in NOd. These results confirm the utility of WT spectral analysis for flowmotion. Further, it strongly suggests that VAR results from a complex cooperation between local myogenic-endothelial responses, where a central neurogenic reflex might also be involved.

In this study, we proposed a novel method for extracting the instantaneous respiratory rate (IRR) from the pulse oximeter photoplethysmogram (PPG). The method was performed in three main steps: (1) a time-frequency transform called synchrosqueezing transform (SST) was used to extract the respiratory-induced intensity, amplitude and frequency variation signals from PPG, (2) the second SST was applied to each extracted respiratory-induced variation signal to estimate the corresponding IRR, and (3) the proposed peak-conditioned fusion method then combined the IRR estimates to calculate the final IRR. We validated the implemented method with capnography and nasal/oral airflow as the reference RR using the limits of agreement (LOA) approach. Compared to simple fusion and single respiratory-induced variation estimations, peak-conditioned fusion shows better performance. It provided a bias of 0.28 bpm with the 95% LOAs ranging from -3.62 to 4.17, validated against capnography and a bias of 0.04 bpm with the 95% LOAs ranging from -5.74 to 5.82, validated against nasal/oral airflow. This algorithm would expand the functionality of a conventional pulse oximetry beyond the measurement of heart rate and oxygen saturation to measure the respiratory rate continuously and instantly.

The purpose of this study was to derive parameters that might reflect postoperative pain from photoplethysmography (PPG) and verify the derived parameters in postoperative pain assessment. We obtained preoperative and postoperative PPG and 100-mm visual analog scale (VAS) from 65 surgical patients and extracted a total of 51 PPG morphology-based parameters and their normalized parameters from these PPGs obtained. Pain discrimination performances of these derived parameters were assessed by statistical analyses, including Wilcoxon signed rank test with Bonferroni correction, classification accuracy based on logistic regression, and 4-fold cross validation. After comparing these parameters derived from PPG in pre- and post-operative conditions, statistically significant difference was found in 36 of the 51 parameters. Using logistic classification, dynamic between-pulse parameters such as normalized systolic amplitude variation and normalized diastolic amplitude variation showed better pain classification performance than the static within-pulse parameters. VAS score was 0 in every pre-operation condition, but >60 VAS was observed in the post-operative condition. Systolic peak amplitude variation normalized by PPG AC amplitude showed the best performance in classifying post-operative pain, with accuracy, sensitivity, specificity, and positive predictivity values of 79.5, 74.0, 86.0, and 84.5%, respectively. These results are superior to those of the surgical pleth index (SPI, GE Healthcare, Chicago, IL, United States) at 65.9, 65.9, 66.5, and 66.5%, respectively.

The sitting beach-chair position is regularly used for shoulder surgery and anesthesia may be induced in that position. We tested the hypothesis that the cardiovascular challenge induced by induction of anesthesia is attenuated if the patient is placed in a reclining beach-chair position. Anesthesia was induced with propofol in the sitting beach-chair (n = 15) or with the beach-chair tilted backwards to a reclining beach-chair position (n = 15). The last group was stepwise tilted to the sitting beach-chair position prior to surgery. Hypotension was treated with ephedrine. Continuous hemodynamic variables were recorded by photoplethysmography and frontal cerebral oxygenation (Sc02) by near infrared spectroscopy. Significant differences were only observed immediately after the induction when patients induced in a reclining beach-chair position had higher mean arterial pressure (MAP) (35 +/- 12 vs. 45 +/- 15 % reduction from baseline, p= 0.04) and ScO2 (7 +/- 6 vs. 1 +/- 8% increase from baseline, p= 0.02) and received less ephedrine (mean: 4 vs. 13 mg, p = 0.048). The higher blood pressure and lower need of vasopressor following induction of anesthesia in the reclining compared to the sitting beach-chair position indicate more stable hemodynamics with the clinical implication that anesthesia should not be induced with the patient in the sitting position