Deep learning-based sleep stage classification with cardiorespiratory and body movement activities in individuals with suspected sleep disorders.

Deep learning methods have gained significant attention in sleep science. This study aimed to assess the performance of a deep learning-based sleep stage classification model constructed using fewer physiological parameters derived from cardiorespiratory and body movement data. Overnight polysomnography (PSG) data from 123 participants (age: 19-82 years) with suspected sleep disorders were analyzed. Multivariate time series data, including heart rate, respiratory rate, cardiorespiratory coupling, and body movement frequency, were input into a bidirectional long short-term memory (biLSTM) network model to train and predict five-class sleep stages. The trained model's performance was evaluated using balanced accuracy, Cohen's κ coefficient, and F1 scores on an epoch-per-epoch basis and compared with the ground truth using the leave-one-out cross-validation scheme. The model achieved an accuracy of 71.2 ± 5.8%, Cohen's κ of 0.425 ± 0.115, and an F1 score of 0.650 ± 0.083 across all sleep stages, and all metrics were negatively correlated with the apnea-hypopnea index, as well as age, but positively correlated with sleep efficiency. Moreover, the model performance varied for each sleep stage, with the highest F1 score observed for N2 and the lowest for N3. Regression and Bland-Altman analyses between sleep parameters of interest derived from deep learning and PSG showed substantial correlations (r = 0.33-0.60) with low bias. The findings demonstrate the efficacy of the biLSTM deep learning model in accurately classifying sleep stages and in estimating sleep parameters for sleep structure analysis using a reduced set of physiological parameters. The current model without using EEG information may expand the application of unobtrusive in-home monitoring to clinically assess the prevalence of sleep disorders outside of a sleep laboratory.

Investigating the effect of cholinergic and adrenergic blocking agents on maternal-fetal heart rates and their interactions in mice fetuses.

This study examines the role of autonomic control of maternal and fetal heart rate variability (MHRV and FHRV) and their heartbeats phase coupling prevalence (CPheartbeat) in mice. The subjects are divided into three groups: control with saline, cholinergic blockade with atropine, and ß-adrenergic blockade with propranolol. Electrocardiogram signals of 27 anesthetized pregnant mice and 48 fetuses were measured for 20 min (drugs were administered after 10 min). For the coupling analysis, different maternal heartbeats were considered for one fetal beat. Results show that saline infusion did not produce any significant changes in MHRV and FHRV, as well as CPheartbeat. Atropine increased maternal HR (MHR) and decreased MHRV significantly without any considerable effect on fetal HR (FHR) and FHRV. Propranolol infusion did not produce any significant changes in MHR and MHRV, but significantly decreased FHR and increased FHRV. Moreover, atropine had led to a decrease in CPheartbeat when considering two and three maternal beats, and an increase for four beats; while propranolol resulted in a decrease for two heartbeats, but an increase for four and five beats. The proposed approach is useful for assessing the impact of maternal autonomic modulation activity on fetal distress and obstetric complications prevalent in pregnant mothers.

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.

Simple and affordable imaging of multiple physiological parameters with RGB camera-based diffuse reflectance spectroscopy.

We propose a simple and affordable imaging technique to evaluate transcutaneously multiple physiological parameters by using a digital red-green-blue camera. In this method, the RGB-values were converted into tristimulus values in the CIE (Commission Internationale de l'Eclairage) XYZ color space, which is compatible with the common color spaces. Monte Carlo simulation for light transport in biological tissue was then performed to specify the relationship among the XYZ-values and the concentrations of oxygenated hemoglobin, deoxygenated hemoglobin, bilirubin, and melanin. The concentration of total hemoglobin and tissue oxygen saturation were also calculated from the estimated concentrations of oxygenated and deoxygenated hemoglobin. In vivo experiments with bile duct ligation in rats demonstrated that the estimated bilirubin concentration increased after ligation of the bile duct and reached around 22 mg/dl at 116 h after the onset of ligation, which corresponds to the ground truth value of bilirubin measured by a commercially available transcutaneous bilirubinometer. Experiments with rats while varying the fraction of inspired oxygen demonstrated that oxygenated hemoglobin and deoxygenated hemoglobin decreased and increased, respectively, as the fraction of inspired oxygen decreased. Consequently, tissue oxygen saturation dramatically decreased. We further extended the method to a non-contact imaging photo-plethysmograph and estimation of the percutaneous oxygen saturation. An empirical formula to estimate percutaneous oxygen saturation was derived from the pulse wave amplitudes of oxygenated and deoxygenated hemoglobin. The estimated percutaneous oxygen saturation dropped remarkably when a faction of inspired oxygen was below 19%, indicating the onset of hypoxemia due to hypoxia, whereas the tissue oxygen saturation decreased gradually according to the reduction of the faction of inspired oxygen. The results in this study indicate the potential of this method for imaging of multiple physiological parameters in skin tissue and evaluating an optical biomedical imaging technique that enables cost-effective, easy-to-use, portable, remotely administered, and/or point-of-care solutions.

Effect of ß-blocker on maternal-fetal heart rates and coupling in pregnant mice and fetuses.

The aim of this preliminary study is to look how maternal-fetal heart rates and their coupling patterns are influenced by injection of ß blocker(propranolol) into pregnant mice. Total of 6 pregnant female mice were divided into two groups [control (N=3) and ß blockade (N=3)]. On 17.5-day mean heart rate of mothers and fetuses (MHR and FHR) were simultaneously measured for 20 minutes (10 minutes under normal condition and 10 minutes with saline (to control group) and propranolol (to the ß blockade group) solution by using an invasive maternal and fetal electrocardiogram techniques with needle electrodes. Results show that FHR decreased and maternal-fetal heart rate coupling (λ) patterns changed with propranolol infusion (no change with saline). Statistical test showed that changes (increase/decrease from pre to post values) in mean, rmssd and power spectral density (PSD) (2~4 Hz)) of MHR, short term variability of FHR, PSD (0.0~1.0 Hz) of FHR and λ were found to be significantly associated with treatment types (saline to propranolol). The presented results and protocol allow for assessment of ß adrenergic control of maternal and fetal heart, which will further enhance the value of the mouse as a model of heritable human pregnancy and hypertension.

Regulation of maternal-fetal heart rates and coupling in mice fetuses.

The aim of this preliminary study is to investigate if there is any evidence of maternal-fetal heart rate coupling in mice fetuses and how the coupling patterns are regulated by vagal nervous system on beat by beat. Total of 6 pregnant female mice were divided into two groups [control (N=3) and vagal blockade (N=3)]. On 17.5-day beat-to-beat heart rates of mothers and fetuses (MHR and FHR) were simultaneously measured for 20 minutes (10 minutes under normal condition and 10 minutes with saline (to control group) and atropine (to the vagal blockade group)) solution by using an invasive maternal and fetal electrocardiogram techniques with needle electrodes. Results show that occasional strong maternal-fetal heart rate coupling (strength was measured by $\lambda$) appeared and its patterns changed with atropine infusion (no change with saline). Additionally, fisher's exact test shows that changes (increase/decrease from pre to post injection values) in mean, rmssd and power spectral density (PSD) (2~4 Hz) of MHR, rmssd FHR and PSD (2~4 Hz) of${\lambda }$were found to be significantly (p<0.05) associated with treatment types (saline/ atropine). The presented results and protocol allow for the first time in the assessment of autonomic regulation of maternal and fetal heart and their interactions, which will further enhance the value of the mouse as a murine model of heritable human pregnancy and perinatal complications due to maternal conditions.

Association Between Phase Coupling of Respiratory Sinus Arrhythmia and Slow Wave Brain Activity During Sleep.

Phase coupling of respiratory sinus arrhythmia (RSA) has been proposed to be an alternative measure for evaluating autonomic nervous system (ANS) activity. The aim of this study was to analyze how phase coupling of RSA is altered during sleep, in order to explore whether this measure is a predictor of slow wave sleep (SWS). Overnight electroencephalograms (EEG), electrocardiograms (ECG), and breathing using inductance plethysmography were recorded from 30 healthy volunteers (six females, age range 21-64, 31.6 ± 14.7 years). Slow wave activity was evaluated by the envelope of the amplitude of the EEG δ-wave (0.5-4 Hz). The RSA was extracted from the change in the R-R interval (RRI) by band-pass filter, where pass band frequencies were determined from the profile of the power spectral density for respiration. The analytic signals of RSA and respiration were obtained by Hilbert transform, after which the amplitude of RSA (ARSA) and the degree of phase coupling (λ) were quantified. Additionally, the normalized high-frequency component (HFn) of the frequency-domain heart rate variability (HRV) was calculated. Using auto- and cross-correlation analyses, we found that overnight profiles of λ and δ-wave were correlated, with significant cross-correlation coefficients (0.461 ± 0.107). The δ-wave and HFn were also correlated (0.426 ± 0.115). These correlations were higher than that for the relationship between δ-wave and ARSA (0.212 ± 0.161). The variation of λ precedes the onset of the δ-wave by ~3 min, suggesting a vagal enhancement prior to the onset of SWS. Auto correlation analysis revealed that the periodicity of λ was quite similar to that of the δ-wave (88.3 ± 15.7 min vs. 88.6 ± 16.3 min, λ-cycle = 0.938 × Î´-cycle + 5.77 min, r = 0.902). These results suggest that phase coupling analysis of RSA appears to be a marker for predicting SWS intervals, thereby complementing other noninvasive tools and diagnostic efforts.

Analysis of cardiorespiratory phase coupling and cardiovascular autonomic responses during food ingestion.

The present study analyzed whether the phase coherency (λ) of respiratory sinus arrhythmia (RSA) is altered by food ingestion in healthy young subjects. After 5min of resting control, 13 healthy volunteers were asked to eat a solid meal with access to water at their own pace, followed by 5min of the postprandial state. The R-R interval (RRI), beat-to-beat blood pressure (BP), and respiratory activity were recorded using electrocardiography, a Finapres device, and inductance plethysmography, respectively. The stroke volume was calculated by the pulse-contour method from continuous BP measurement, and the cardiac output (CO) was obtained by multiplying the stroke volume by the heart rate. From the oscillatory signals of RSA and respiration, λ was computed; additionally, frequency domain indexes of the heart rate variability (HRV) were calculated using a short-time Fourier transform. A steady-state 3-min resting period (R), food ingestion period (FOOD), and the first 2-min and the last 3-min of the post prandial period were analyzed separately. We also compared the responses to gum chewing (GUM) and water intake (WATER) using the same protocol on separate days. A shortening of RRI and increases in BP and CO were observed in FOOD compared to R, suggesting a shift of sympathovagal balance toward sympathetic activation. Similar responses but smaller magnitudes were observed in the GUM condition, whereas only transient shortening of RRI was observed in the WATER condition. The HRV indexes did not show any significant changes in response to GUM and WATER but sympathovagal balance was shifted in favor of sympathetic dominance in FOOD. λ decreased during all of the conditions. There was a significant negative correlation between λ and the indirect measure of sympathovagal balance. These results suggest that ingestion of food induces enhanced cardiac sympathetic activity and that a phase coherence of RSA could provide a sensitive measure for evaluating the cardiac autonomic profile.

Estimation of melanin and hemoglobin using spectral reflectance images reconstructed from a digital RGB image by the Wiener estimation method.

A multi-spectral diffuse reflectance imaging method based on a single snap shot of Red-Green-Blue images acquired with the exposure time of 65 ms (15 fps) was investigated for estimating melanin concentration, blood concentration, and oxygen saturation in human skin tissue. The technique utilizes the Wiener estimation method to deduce spectral reflectance images instantaneously from an RGB image. Using the resultant absorbance spectrum as a response variable and the extinction coefficients of melanin, oxygenated hemoglobin and deoxygenated hemoglobin as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of melanin and total blood are then determined from the regression coefficients using conversion vectors that are numerically deduced in advance by the Monte Carlo simulations for light transport in skin. Oxygen saturation is obtained directly from the regression coefficients. Experiments with a tissue-like agar gel phantom validated the method. In vivo experiments on fingers during upper limb occlusion demonstrated the ability of the method to evaluate physiological reactions of human skin.

Visualization of peripheral vasodilative indices in human skin by use of red, green, blue images.

We propose a method to visualize the arterial inflow, the vascular resistance, and the venous capacitance in the skin tissue from red, green, blue (RGB) digital color images. The arterial inflow and the venous capacitance in the skin tissue are visualized based on an increase in the rate of change in the total blood concentration and the change of the total blood concentration during upper limb occlusion at a pressure of 50 mmHg. The resultant arterial inflow with the measured mean arterial pressure also provides an image of the vascular resistance in human skin. The arterial inflow, the vascular resistance, and the venous capacitance acquired by the method are well correlated with those obtained from the conventional strain-gauge plethysmograph. The correlation coefficients R between the estimated values by the method and the measurements by the SPG are calculated to be 0.83 (P<0.001) for the arterial inflow, 0.77 (P<0.01) for the vascular resistance, and 0.77 (P<0.01) for the venous capacitance. The arterial inflow and the venous capacitance in the skin tissue are significantly higher in active subjects compared with the sedentary subjects, whereas the vascular resistance was significantly lower in the active subjects compared with the sedentary subjects. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular functions in human skin.

Visualization of peripheral vasodilative indices in human skin by use of red, green, blue images.

We propose a method to visualize the arterial inflow, the vascular resistance, and the venous capacitance in the skin tissue from red, green, blue (RGB) digital color images. The arterial inflow and the venous capacitance in the skin tissue are visualized based on an increase in the rate of change in the total blood concentration and the change of the total blood concentration during upper limb occlusion at a pressure of 50 mmHg. The resultant arterial inflow with the measured mean arterial pressure also provides an image of the vascular resistance in human skin. The arterial inflow, the vascular resistance, and the venous capacitance acquired by the method are well correlated with those obtained from the conventional strain-gauge plethysmograph. The correlation coefficients R between the estimated values by the method and the measurements by the SPG are calculated to be 0.83 (P < 0.001) for the arterial inflow, 0.77 (P < 0.01) for the vascular resistance, and 0.77 (P < 0.01) for the venous capacitance. The arterial inflow and the venous capacitance in the skin tissue are significantly higher in active subjects compared with the sedentary subjects, whereas the vascular resistance was significantly lower in the active subjects compared with the sedentary subjects. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular functions in human skin.

Incoherent oscillations of respiratory sinus arrhythmia during acute mental stress in humans.

Respiratory sinus arrhythmia (RSA) has been widely used as a measure of the cardiac vagal control in response to stress. However, RSA seems not to be a generalized indicator because of its dependency on respiratory parameter and individual variations of RSA amplitude (A(RSA)). We hypothesized that phase-lag variations between RSA and respiration may serve as a normalized index of the degree of mental stress. Twenty healthy volunteers performed mental arithmetic task (ART) after 5 min of resting control followed by 5 min of recovery. Breathing pattern, beat-to-beat R-R intervals, and blood pressure (BP) were determined using inductance plethysmography, electrocardiography, and a Finapres device, respectively. The analytic signals of breathing and RSA were obtained by Hilbert transform and the degree of phase synchronization (λ) was quantified. With the use of spectral analysis, heart rate variability (HRV) was estimated for the low-frequency (LF) and high-frequency (HF) bands. A steady-state 3-min resting period (REST), the first 3 min (ART1), and the last 3 min (ART2) of the ART period (ranged from 6- to 19 min) and the last 3 min of the recovery period (RCV) were analyzed separately. Heart rate, systolic BP, and breathing frequency (f(R)) increased and λ, A(RSA), and HF power decreased from REST to ART (P < 0.01). The λ was correlated with normalized A(RSA) and the HF power. The decrease in λ could not be explained solely by the increase in f(R). We conclude that mental stress exerts an influence on RSA oscillations, inducing incoherent phase lag with respect to breathing, in addition to a decrease in RSA.

Noninvasive imaging of human skin hemodynamics using a digital red-green-blue camera.

In order to visualize human skin hemodynamics, we investigated a method that is specifically developed for the visualization of concentrations of oxygenated blood, deoxygenated blood, and melanin in skin tissue from digital RGB color images. Images of total blood concentration and oxygen saturation can also be reconstructed from the results of oxygenated and deoxygenated blood. Experiments using tissue-like agar gel phantoms demonstrated the ability of the developed method to quantitatively visualize the transition from an oxygenated blood to a deoxygenated blood in dermis. In vivo imaging of the chromophore concentrations and tissue oxygen saturation in the skin of the human hand are performed for 14 subjects during upper limb occlusion at 50 and 250 mm Hg. The response of the total blood concentration in the skin acquired by this method and forearm volume changes obtained from the conventional strain-gauge plethysmograph were comparable during the upper arm occlusion at pressures of both 50 and 250 mm Hg. The results presented in the present paper indicate the possibility of visualizing the hemodynamics of subsurface skin tissue.

Noninvasive spectral imaging of skin chromophores based on multiple regression analysis aided by Monte Carlo simulation.

In order to visualize melanin and blood concentrations and oxygen saturation in human skin tissue, a simple imaging technique based on multispectral diffuse reflectance images acquired at six wavelengths (500, 520, 540, 560, 580 and 600 nm) was developed. The technique utilizes multiple regression analysis aided by Monte Carlo simulation for diffuse reflectance spectra. Using the absorbance spectrum as a response variable and the extinction coefficients of melanin, oxygenated hemoglobin, and deoxygenated hemoglobin as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of melanin and total blood are then determined from the regression coefficients using conversion vectors that are deduced numerically in advance, while oxygen saturation is obtained directly from the regression coefficients. Experiments with a tissue-like agar gel phantom validated the method. In vivo experiments with human skin of the human hand during upper limb occlusion and of the inner forearm exposed to UV irradiation demonstrated the ability of the method to evaluate physiological reactions of human skin tissue.

Effects of lower-leg rhythmic cuff inflation on cardiovascular autonomic responses during quiet standing in healthy subjects.

To determine the effects of muscle pump function on cardiac autonomic activity in response to quiet standing, we simulated the muscle pump effect by rhythmic lower-leg cuff inflation (RCI) with four cuff pressures of 0 (sham), 40, 80, and 120 mmHg at 5 cycles/min. The R-R interval (RRI) and beat-to-beat blood pressure (BP) were acquired in healthy subjects (6 males and 5 females, aged 21-24 yr). From the continuous BP measurement, stroke volume (SV) was calculated by a pulse-contour method. Using spectral and cross-spectral analysis, RRI and systolic BP variability as well as the gain of spontaneous cardiac baroreflex sensitivity (sBRS) were estimated for the low- and high-frequency (HF) bands. Compared with the sham condition, RCI with cuff pressures of 80 and 120 mmHg led to increases in the mean RRI (P < 0.01) and HF power of RRI fluctuation (P < 0.05 for 80 mmHg and P < 0.01 for 120 mmHg) during quiet standing. Reduction in SV during standing was suppressed, and the sBRS of the HF band for standing were increased by RCI for either cuff pressure (P < 0.05 for 80 mmHg and P < 0.01 for 120 mmHg). However, at 40 mmHg RCI, these remained unchanged. These results suggest that, during standing, RCI of the lower leg increases cardiac vagal outflow when the cuff pressure is raised enough to oppose the hydrostatic-induced venous pressure in the calf.

Active muscle oxygenation dynamics measured during high-intensity exercise by using two near-infrared spectroscopy methods.

Near-infrared spectroscopy is a noninvasive optical technique used to monitor tissue oxygenation. Generally, the modified Beer-Lambert's law (MBL) using continuous-wave light has been used to measure active muscle oxygenation during exercise; however, it cannot measure absolute changes in the oxy- (oxy-[Hb + Mb]), deoxy- (deoxy-[Hb + Mb]), and total hemoglobin/myoglobin concentrations (total-[Hb + Mb]) because the pathlength and scattering coefficient are not measured. In contrast, the time-resolved spectroscopy (TRS) using a ultra short pulsed laser can be used to determine absolute changes in the concentration, although the temporal resolution is inferior to that in MBL. This study evaluated the absolute changes in active muscle oxygenation and the optical mean pathlength and scattering and absorption coefficient during high-intensity exercise by using the TRS system. In addition, the difference between the changes determined using TRS and MBL measurements was assessed. When the TRS and MBL measurements obtained during high-intensity exercise were compared, the total-[Hb + Mb] and oxy-[Hb + Mb] dynamics differed markedly during high-intensity exercise, while the deoxy-[Hb + Mb] dynamics and kinetics did not differ.

Visualizing of skin chromophore concentrations by use of RGB images.

A method is proposed for visualizing simply the concentrations of melanin, oxygenated blood, and deoxygenated blood in skin tissue using digital RGB images. The total blood concentration and oxygen saturation can also be reconstructed. Monte Carlo simulation of light transport specifies a relation between the chromophore concentrations and Commission Internationale de l'Eclairage XYZ, which are compatible with the common RGB working space. Experiments with a tissuelike agar gel phantom demonstrated the possibility of the method. In vivo imaging of a human hand during forearm occlusion demonstrated the ability of the method to evaluate hemodynamics of skin tissue.

Visualizing depth and thickness of a local blood region in skin tissue using diffuse reflectance images.

A method is proposed for visualizing the depth and thickness distribution of a local blood region in skin tissue using diffuse reflectance images at three isosbestic wavelengths of hemoglobin: 420, 585, and 800 nm. Monte Carlo simulation of light transport specifies a relation among optical densities, depth, and thickness of the region under given concentrations of melanin in epidermis and blood in dermis. Experiments with tissue-like agar gel phantoms indicate that a simple circular blood region embedded in scattering media can be visualized with errors of 6% for the depth and 22% for the thickness to the given values. In-vivo measurements on human veins demonstrate that results from the proposed method agree within errors of 30 and 19% for the depth and thickness, respectively, with values obtained from the same veins by the conventional ultrasound technique. Numerical investigation with the Monte Carlo simulation of light transport in the skin tissue is also performed to discuss effects of deviation in scattering coefficients of skin tissue and absorption coefficients of the local blood region from the typical values of the results. The depth of the local blood region is over- or underestimated as the scattering coefficients of epidermis and dermis decrease or increase, respectively, while the thickness of the region agrees well with the given values below 1.2 mm. Decreases or increases of hematocrit value give over- or underestimation of the thickness, but they have almost no influence on the depth.

Near-infrared laser tomographic imaging with right-angled scattered coherent light using an optical heterodyne-detection-based confocal scanning system.

We demonstrate, what is to the best of our knowledge, a novel optical tomographic method for the visualization of the inner structure of scattering media such as biological tissue in the near-infrared region. We constructed a scanning confocal imaging system with a cross-axes arrangement using optical fibers. This system is based on the optical heterodyne technique and enables the detection of very weak coherence photons that are generated in the spatially restricted confocal region and scattered laterally (90 degrees ) against an incident beam. To evaluate the fundamental imaging capabilities of the system, we assessed measurements from scattering phantoms composed of an Intralipid suspension with varying volume concentrations. The results of this study demonstrate that the right-angled scattered light adheres to the Lambert-Beer law and that the present system can detect light propagating through a distance of approximately 31l of the mean free path. An inclusion as small as 100 microm can be discriminated in a scattering media with an optical thickness of 4. We investigated the potential of the proposed system for imaging biological tissues in preliminary experiments using samples of chicken breast tissue.

Intramuscular pressure-induced inhibition of cardiac contraction: implications for cardiac-locomotor synchronization.

The synchronization of cardiac and locomotor rhythms has been suggested to enhance the efficiency of arterial delivery to active muscles during rhythmic exercise, but direct evidence showing such a functional role has not been provided. In this study, we tested the hypothesis that the heartbeat is coupled with intramuscular pressure (IMP) changes so as to time the delivery of blood through peripheral tissues when the IMP is lower. To this end, we developed a computer-controlled, dynamic, thigh cuff occlusion device that enables bilateral thigh cuffs to repeatedly inflate and deflate, one side after the other, to simulate rhythmic IMP changes during bipedal locomotion. Nine healthy subjects were examined, and three different occlusion pressures (50, 80, and 120 mmHg) were applied separately to the thigh cuffs of normal subjects while they were sitting. Alternate occlusions of the bilateral thigh cuffs administered at the frequency of the mean heart rate produced significant phase synchronization between the cardiac and cuff-occlusion rhythms when 120 mmHg pressure was applied. However, synchronization was not observed when the occlusion pressure was 50 or 80 mmHg. During synchronization, heartbeats were most likely to occur in phases that did not include overlap between the peak arterial flow velocity in the thigh and elevated cuff pressure. We believe that phase synchronization occurs so that the cardiac cycle is timed to deliver blood through the lower legs when IMP is not maximal. If this can be extrapolated to natural locomotion, synchronization between cardiac and locomotor activities may be associated with the improved perfusion of exercising muscles.