Cacao Polyphenol-Rich Dark Chocolate Intake Contributes to Efficient Brain Activity during Cognitive Tasks: A Randomized, Single-Blinded, Crossover, and Dose-Comparison fMRI Study.

Cacao polyphenol-enriched dark chocolate may have beneficial effects on human health, such as facilitating maintaining good performance in long-lasting cognitive tasks. This study examined the effects of dark chocolate intake on improving brain function during cognitive tasks using functional magnetic resonance imaging (fMRI). In this randomized, single-blinded, crossover, and dose-comparison study, 26 healthy middle-aged participants ingested dark chocolate (25 g) either with a low concentration (LC) (211.7 mg) or a high concentration (HC) (635 mg) of cacao polyphenols. Thereafter, their brain activities were analyzed during continuous and effortful cognitive tasks relevant to executive functioning using fMRI in two consecutive 15 min sessions (25 and 50 min after ingestion). We observed significant interaction effects between chocolate consumption and brain activity measurement sessions in the left dorsolateral prefrontal cortex and left inferior parietal lobule. After HC chocolate ingestion, these areas showed lower brain activity in the second session than in the first session; however, these areas showed higher activity in the second session after LC chocolate ingestion. These results suggest that cacao polyphenol-enriched dark chocolate enhances the efficient use of cognitive resources by reducing the effort of brain activity.

Acute effects of regional heat stimulation by indirect moxibustion on cardiovascular responses.

Moxibustion is a traditional East Asian medicine treatment that involves burning moxa directly or indirectly on or near the skin at a specific site of the body, called an acupoint. However, whether moxibustion induces cardiovascular responses by modulating autonomic nervous activity remains unknown. The purpose of this study was to elucidate the effects of indirect moxibustion on cardiovascular responses and autonomic nervous activity. Fifteen healthy volunteers participated in the study. Each subject received regional heat stimulation by indirect moxibustion at the lower leg acupoint. Heart rate, RR intervals, blood pressure and skin temperature were measured continuously for 3 min at rest and 5 min during indirect moxibustion. Local skin temperature increased reaching a peak (45.3 ± 3.3 °C) at 2 min after moxibustion was started, and was accompanied by a significant decrease in heart rate (63.0 ± 7.8 to 60.8 ± 7.8 bpm, p < 0.05) together with a significant increase in root mean square difference of successive RR intervals. Regional heat stimulation by indirect moxibustion induced bradycardic response, which was modulated by autonomic nervous system.

Physiological role of anticipatory cardiorespiratory responses to exercise.

This study aimed to investigate whether anticipatory cardiorespiratory responses vary depending on the intensity of the subsequent exercise bout, and whether anticipatory cardiorespiratory adjustments contribute importantly to enhancing exercise performance during high-intensity exercise. Eleven healthy men were provided advance notice of the exercise intensity and a countdown to generate anticipation during 10 min prior to exercise at 0, 50, 80 or 95% maximal work-rate (Experiment 1). A different group of subjects (n = 15) performed a time to exhaustion trial with or without anticipatory countdown (Experiment 2). In Experiment 1, heart rate (HR), oxygen uptake (VO2 ) and minute ventilation (VE ) during pre-exercise resting period increased over time and depended on the subsequent exercise intensity. Specifically, there was already a 7.4% increase in HR from more than 5 min prior to the start of exercise at 95% maximal work-rate, followed by progressively augmented increases of 12.5% between 2 and 3 min before exercise, 24.4% between 0 and 1 min before exercise. In Experiment 2, the initial HR for the first 10 s of exercise in the task with anticipation was 11.4% larger compared to without anticipation (p < 0.01), and the difference in HR between the two conditions decreased in a time-dependent manner. In contrast, the initial increases in VO2 and VE were significantly lower in the task with anticipation than that without anticipation. The time to exhaustion during high-intensity exercise was 14.6% longer under anticipation condition compared to no anticipation (135 ± 26 s vs. 119 ± 26 s, p = 0.003). In addition, the enhanced exercise performance correlated positively with increased HR response just before and immediately after exercise onset (p < 0.01). These results showed that anticipatory cardiorespiratory adjustments (feedforward control) via the higher brain that operate before starting exercise may play an important role in minimizing the time delay of circulatory response and enhancing performance after onset of high-intensity exercise in man.

Effects of pre-exercise acupuncture stimulation on heart rate response during short-duration exercise.

BACKGROUND: The purpose of the present study was to investigate the effects of bradycardia induced by pre-exercise acupuncture on heart rate responses during short-duration exercise. METHODS: A total of 29 healthy subjects underwent two protocols: protocol 1 assessed the effects of manual acupuncture on heart rate response during rest, and protocol 2 tested the hypothesis that the bradycardic effects induced by pre-exercise acupuncture continue during low- and high-intensity exercise. Their average age, height, weight, and body mass index were 21.2 ± 2.0 years, 167.2 ± 8.8 cm, 63.8 ± 12.8 kg, and 22.7 ± 3.5 kg/m2, respectively. In acupuncture stimulations for protocols 1 and 2, an acupuncture needle was inserted into the lower leg and manual acupuncture stimulation was performed at 1 Hz. RESULTS: In protocol 1 (resting condition), acupuncture stimulation induced a bradycardic response, which continued for 4 min after the cessation of acupuncture stimulation (p < 0.05). In protocol 2, the bradycardic response induced by pre-exercise acupuncture stimulation remained during low-intensity exercise and in the beginning of high-intensity exercise performed immediately after the cessation of acupuncture stimulation (p < 0.05). However, the effects disappeared when post-acupuncture exercise was performed when the heart rate was approximately 140 beats/min during high-intensity exercise. The rating of perceived exertion after exercise differed significantly between the acupuncture stimulation task (7.9 ± 1.6) and no-stimulation task (8.5 ± 2.0) (p = 0.03) only in the low intensity group. CONCLUSION: This study may provide new insights into the effect of acupuncture stimulation on psycho-physiological conditions during exercise.

Increase in diastolic blood pressure induced by fragrance inhalation of grapefruit essential oil is positively correlated with muscle sympathetic nerve activity.

Fragrance inhalation of essential oils is widely used in aromatherapy, and it is known to affect blood pressure (BP) and heart rate (HR) via autonomic control of circulation. In this study, we aimed to test the hypothesis that the changes in hemodynamics with fragrance inhalation were observed along with changes in muscle sympathetic nerve activity (MSNA). In study 1, thirteen healthy men were exposed to fragrance stimulation of grapefruit essential oil for 10 min, and BP, HR, and MSNA were continuously measured. In study 2, another nine healthy men were exposed to the same fragrance stimulation; responses in BP and HR were continuously measured, and plasma noradrenaline and cortisol concentrations were determined. We found that diastolic BP increased significantly during fragrance inhalation, while the other variables remained unchanged in both studies. Although MSNA burst frequency, burst incidence, and total activity remained unchanged during fragrance inhalation, we found a significant linear correlation between changes in diastolic BP in the last 5 min of fragrance inhalation and changes in MSNA burst frequency. The plasma cortisol concentration decreased significantly at 10 min of fragrance inhalation, though the noradrenaline concentration remained unchanged. These results suggest, for the first time, that changes in BP with fragrance inhalation of essential oil are associated with changes in MSNA even with decreased stress hormone.

Acupoint dependence of depressor and bradycardic responses elicited by manual acupuncture stimulation in humans.

The cardiovascular effects of the autonomic nervous system (ANS) are modulated by inputs from peripheral sensors and other brain regions. However, it currently remains unknown whether the manual acupuncture (MA) stimulation of different acupuncture points evokes different responses by the heart and vasculature, a phenomenon known as "site specificity". Sixty healthy subjects were randomly divided into a control group and MA stimulation groups at the lower leg, ear, abdomen, and forearm. MA was performed at 1 Hz for 2 min. A depressor response was observed only in the lower leg stimulation group, in which mean blood pressure significantly decreased from 83.4 ± 10.1 to 80.9 ± 11.7 mmHg (p < 0.003). A bradycardic response was elicited in all MA stimulation groups. There was no significant differences in the magnitude of the bradycardic response between groups. MA-induced cardiovascular responses, which may be mediated by the modulation of ANS, differ depending on acupuncture points.

Aerobic Exercise Training with Brisk Walking Increases Intestinal Bacteroides in Healthy Elderly Women.

This study examined the effect of an exercise intervention on the composition of the intestinal microbiota in healthy elderly women. Thirty-two sedentary women that were aged 65 years and older participated in a 12-week, non-randomized comparative trial. The subjects were allocated to two groups receiving different exercise interventions, trunk muscle training (TM), or aerobic exercise training (AE). AE included brisk walking, i.e., at an intensity of ≥ 3 metabolic equivalents (METs). The composition of the intestinal microbiota in fecal samples was determined before and after the training period. We also assessed the daily physical activity using an accelerometer, trunk muscle strength by the modified Kraus-Weber (K-W) test, and cardiorespiratory fitness by a 6-min. walk test (6MWT). K-W test scores and distance achieved during the 6MWT (6MWD) improved in both groups. The relative abundance of intestinal Bacteroides only significantly increased in the AE group, particularly in subjects showing increases in the time spent in brisk walking. Overall, the increases in intestinal Bacteroides following the exercise intervention were associated with increases in 6MWD. In conclusion, aerobic exercise training that targets an increase of the time spent in brisk walking may increase intestinal Bacteroides in association with improved cardiorespiratory fitness in healthy elderly women.

The effects of aging on the distribution of cerebral blood flow with postural changes and mild hyperthermia.

PURPOSE: Cerebral blood flow (CBF) would be impaired with dual stresses of heat and orthostatic changes, even if those stresses are mild, in the elderly with declined cardio- and cerebrovascular functions with aging. To test the hypothesis, we compared the response of blood flow in the internal carotid artery (ICA) and vertebral artery (VA) to dual stresses of heat and orthostatic changes between the elderly and young individuals. METHODS: Nine elderly and eight young healthy men (71.3 ± 3.0 and 23.3 ± 3.1 years, mean ± SD, respectively) underwent measurements of blood flow in the ICA, VA and external carotid artery (ECA) via ultrasonography. The measurements were obtained in sitting and supine positions under normothermic (NT) and mildly hyperthermic (HT) conditions (ambient temperature 28 °C). Esophageal temperatures increased from NT (36.4 ± 0.2 °C, mean ± SE) to HT (37.4 ± 0.2 °C) with lower legs immersion in 42 °C water. RESULTS: With heat stress, ECA blood flow increased in both postures in both age groups (effect of heat, p < 0.001), whereas ICA blood flow remained unchanged. With postural changes from supine to sitting, ECA blood flow remained unchanged whereas ICA blood flow decreased (effect of posture, p = 0.027) by 18% in NT in the young and by 20% in HT in the elderly. VA blood flow remained unchanged under both heat stress and postural changes. CONCLUSIONS: The CBF is impaired under dual stresses of heat and orthostatic changes in healthy aged individuals, even if the levels of the stresses are mild.

Inhibitory Effects of Intranasal Administration of Insulin on Fat Oxidation during Exercise Are Diminished in Young Overweight Individuals.

It remains unknown whether the high insulin (INS) levels in the brain affect fat oxidation during exercise. We examined the effects of the intranasal administration of INS, which increases the INS concentration in the cerebrospinal fluid when peripheral effects are lacking, on the maximum fat oxidation rate (maxFOR) and its intensity (FATmax) during exercise in 15 young normal-weight (N group) and eight young overweight (O group) individuals. On two separate days, either INS or placebo (PL) was randomly administered intranasally before a graded exercise test. Indirect calorimetry was used to assess maxFOR and FATmax during exercise. Blood INS and glucose levels did not change after INS administration. In the N group, maxFOR and FATmax were significantly smaller in the INS trial than in the PL trial. MaxFOR was significantly smaller in the O group than in the N group and was not influenced by INS administration. Exercise-induced elevation in blood epinephrine levels tended to be reduced by INS administration only in the N group. Intranasal INS administration reduces fat oxidation during exercise without any peripheral effects, possibly by suppressing sympathetic nerve activity. This inhibitory effect is diminished in overweight subjects, suggesting that cerebral insulin effects are attenuated in this population.

Effects of 2-Year Cognitive⁻Motor Dual-Task Training on Cognitive Function and Motor Ability in Healthy Elderly People: A Pilot Study.

We aimed to examine the effect of 2-year cognitive⁻motor dual-task (DT) training on cognitive functions and motor ability of healthy elderly people without marked cognitive impairment. From the 25 participants of our 12-week DT trial conducted in 2014, we recruited 8 subjects who voluntarily participated in a new DT training program once a week for 2 years (exercise (EX) group). Their cognitive functions were evaluated by the Modified Mini-Mental State (3MS) examination and the Trail Making Test, and results were compared with those of the 11 subjects who discontinued the training and did not perform any types of exercise for 2 years (non-exercise (NO) group). Subjects in the NO group showed deterioration in the 3MS examination results, especially in the cognitive domain of attention. Meanwhile, participation in DT training maintained the scores in almost all domains of cognitive function, as well as the total 3MS scores. However, both groups had impaired quadriceps muscle strength and motor ability after the 2-year observation period. These results suggest that participating in exercise program comprising DT training for 2 years may be beneficial for maintaining the broad domains of cognitive function in healthy elderly people, although further verification is needed.

Effects of walking in water on gut hormone concentrations and appetite: comparison with walking on land.

The effects of water exercise on gut hormone concentrations and appetite currently remain unclear. The aim of the present study was to investigate the effects of treadmill walking in water on gut hormone concentrations and appetite. Thirteen men (mean ± s.d. age: 21.6 ± 2.2 years, body mass index: 22.7 ± 2.8 kg/m2, peak oxygen uptake (VO2peak): 49.8 ± 7.8 mL/kg per min) participated in the walking in water and on land challenge. During the study period, ratings of subjective feelings of hunger, fullness, satiety and motivation to eat were reported on a 100-mm visual analog scale. A test meal was presented after walking, and energy intake (EI) was calculated. Blood samples were obtained during both trials to measure glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and acylated ghrelin (AG) concentrations. Hunger scores (How hungry do you feel?) were significantly lower during the water trial than during the land trial (P < 0.05). No significant differences were observed in EI between water and land trials. GLP-1 concentrations were significantly higher in the water trial than in the land trial (P < 0.05). No significant differences were observed in PYY concentrations between water and land trials. AG concentrations were significantly lower in the water trial than in the land trial (P < 0.01). In conclusion, changes in gut hormone concentrations during walking in water contribute to the exercise-induced suppression of appetite and provide novel information on the influence of walking in water on the acute regulation of appetite.

A novel approach for evaluating the effects of odor stimulation on dynamic cardiorespiratory functions.

We aimed to develop a novel method to quantitatively evaluate the effects of odor stimulation on cardiorespiratory functions over time, and to examine the potential usefulness of clinical aromatherapy. Eighteen subjects participated. Nine people were assigned to each of the two resting protocols. Protocol 1: After resting for 2 min in a sitting position breathing room air, the subject inhaled either air or air containing sweet marjoram essential oil from the Douglas bag for 6 min, Protocol 2: After resting for 5 min in a supine position, the subject inhaled the essential oil for 10 min, and then recovered for 10 min breathing room air. All subjects inhaled the essential oil through a face mask attached to one-way valve, and beat-to-beat heart rate (HR) and arterial blood pressure (BP) as well as breath-by-breath respiratory variables were continuously recorded. In both protocols, during fragrance inhalation of the essential oil, time-dependent decrease in mean BP and HR were observed (P<0.05). During post-inhalation recovery, the significant fragrance-induced bradycardic effect lasted at least 5 min (- 3.1 ± 3.9% vs. pre-inhalation baseline value, p<0.05). The mean BP response at the start of odor stimulation was approximated by a first-order exponential model. However, such fragrance-induced changes were not observed in the respiratory variables. We established a novel approach to quantitatively and accurately evaluate the effects of quantitative odor stimulation on dynamic cardiorespiratory functions, and the duration of the effect. This methodological approach may be useful for scientific evaluation of aromatherapy as an approach to integrated medicine, and the mechanisms of action of physiological effects in fragrance compounds.

Electroacupuncture most effectively elicits depressor and bradycardic responses at 1 Hz in humans.

PURPOSE: Acupuncture stimulation is known to act on the autonomic nervous system and elicits depressor and bradycardic effects. However, previous studies on humans did not conduct quantitative analyses on optimal acupuncture conditions such as the stimulation frequency and duration to achieve maximum depressor and bradycardic effects. The aim of the present study was to investigate the effects of varying stimulation frequencies of electroacupuncture on time-dependent changes in blood pressure and heart rate in humans. METHODS: Twelve healthy volunteers participated in the study. An acupuncture needle was inserted at the Ximen acupoint (PC4 according to WHO nomenclature), located at the anterior aspect of the forearm. An electrical stimulation was delivered through the acupuncture needle at an intensity of 1 V, pulse width of 5 ms, and stimulation frequencies of 0.5, 1, 5, and 10 Hz in a random order. The duration of electroacupuncture was 6 min, during which blood pressure and heart rate responses were monitored. RESULTS: Group-averaged data indicated that 1-Hz electroacupuncture decreased blood pressure and heart rate. Blood pressure was significantly decreased from the prestimulation baseline value of 86.6 ± 2.9 to 81.4 ± 2.3 mmHg during 4-6 min of 1-Hz electroacupuncture (mean ± SE, P < 0.01). Heart rate was also significantly decreased (from 66.2 ± 2.0 to 62.7 ± 1.7 beats/min, P < 0.01). CONCLUSIONS: These results provide fundamental evidence that bradycardiac and depressor responses are effectively produced by electrical acupuncture in humans.

Periodic Breathing in Heart Failure Explained by Dynamic and Static Properties of Respiratory Control.

OBJECTIVE: The respiratory operating point is determined by the interplay between the controller and plant subsystem elements within the respiratory chemoreflex feedback system. This study aimed to establish the methodological basis for quantitative analysis of the open-loop dynamic properties of the human respiratory control system and to apply the results to explore detailed mechanisms of the regulation of respiration and the possible mechanism of periodic breathing in chronic heart failure. METHODS AND RESULTS: In healthy volunteers, we measured arterial CO2 partial pressure (PaCO2) and minute ventilation [Formula: see text] to estimate the dynamic properties of the controller ( [Formula: see text] relation) and plant ( [Formula: see text] relation). The dynamic properties of the controller and plant approximated first- and second-order exponential models, respectively, and were described using parameters including gain, time constant, and lag time. We then used the open-loop transfer functions to simulate the closed-loop respiratory response to an exogenous disturbance, while manipulating the parameter values to deviate from normal values but within physiological ranges. By increasing both the product of gains of the two subsystem elements (total loop gain) and the lag time, the condition of system oscillation (onset of periodic breathing) was satisfied. CONCLUSION: When abnormality occurs in a part of the respiratory chemoreflex system, instability of the control system is amplified and may result in the manifestation of respiratory abnormalities such as periodic breathing.

Image analysis of skin color heterogeneity focusing on skin chromophores and the age-related changes in facial skin.

BACKGROUND/PURPOSE: Heterogeneity with respect to skin color tone is one of the key factors in visual perception of facial attractiveness and age. However, there have been few studies on quantitative analyses of the color heterogeneity of facial skin. The purpose of this study was to develop image evaluation methods for skin color heterogeneity focusing on skin chromophores and then characterize ethnic differences and age-related changes. METHODS: A facial imaging system equipped with an illumination unit and a high-resolution digital camera was used to develop image evaluation methods for skin color heterogeneity. First, melanin and/or hemoglobin images were obtained using pigment-specific image-processing techniques, which involved conversion from Commission Internationale de l'Eclairage XYZ color values to melanin and/or hemoglobin indexes as measures of their contents. Second, a spatial frequency analysis with threshold settings was applied to the individual images. Cheek skin images of 194 healthy Asian and Caucasian female subjects were acquired using the imaging system. Applying this methodology, the skin color heterogeneity of Asian and Caucasian faces was characterized. RESULTS: The proposed pigment-specific image-processing techniques allowed visual discrimination of skin redness from skin pigmentation. In the heterogeneity analyses of cheek skin color, age-related changes in melanin were clearly detected in Asian and Caucasian skin. Furthermore, it was found that the heterogeneity indexes of hemoglobin were significantly higher in Caucasian skin than in Asian skin. CONCLUSION: We have developed evaluation methods for skin color heterogeneity by image analyses based on the major chromophores, melanin and hemoglobin, with special reference to their size. This methodology focusing on skin color heterogeneity should be useful for better understanding of aging and ethnic differences.

Skin surface electrical potential as an indicator of skin condition: observation of surfactant-induced dry skin and middle-aged skin.

We previously reported that skin surface electrical potential might be a good parameter of skin pathophysiology. To examine the potential availability of skin surface electrical potential measurement for diagnostic purposes, we measured the change of the potential in surfactant-induced dry skin and we compared the values of the potential in volunteers of different age groups. We also measured trans-epidermal water loss (TEWL) in the same groups. The skin surface electrical potential was significantly increased after sodium dodecyl sulphate treatment, and the alteration was much more marked than that of TEWL. Further, a significant difference in skin surface electrical potential was observed between young- and middle-aged volunteers, although there was no significant difference in TEWL between the two groups. These results suggest that skin surface electrical potential may be a good indicator of the pathophysiological state of the living layer of epidermis.

Skin surface electric potential as an indicator of skin condition: a new, non-invasive method to evaluate epidermal condition.

We previously demonstrated that the skin surface electric potential, which has been long recognized as a parameter of emotional or physiological state, is generated by epidermal keratinocytes and is strongly associated with the ion concentration gradient in the epidermis. Thus, at temperatures below the threshold of sweating, the potential provides a measure of the epidermal ion concentration gradient, which in turn is related to epidermal homeostasis and pathology. In the present study, we established a new, non-invasive method to measure skin surface electric potential. In healthy skin, calcium ion was localized in the uppermost epidermis and the gradation disappeared by tape stripping. Skin surface potential was also disappeared by tape stripping. Moreover, environmental humidity affected the potential, whereas temporary hydration of the stratum corneum did not affect it. These results suggest that the skin surface electric potential may be an indicator of the pathophysiology of the living layer of epidermis, and thus may be useful as a new parameter to evaluate skin condition.

Urokinase-type plasminogen activator is activated in stratum corneum after barrier disruption.

The plasminogen/plasmin system in epidermis is thought to be the major protease involved in the delay of barrier recovery. However, little is known about the mechanism through which this system is activated. In order to clarify this mechanism, we first determined the distribution of proteolytic activity by using in situ zymography. As a result, plasminogen-activator activity was found to be present in the stratum corneum (SC) after barrier disruption. Next, SC subjected to repeated barrier disruption was collected to identify the protease. The protease was identified as urokinase-type plasminogen activator, because flybrinolytic activity of the collected SC was abolished by addition of anti-urokinase antibody. Urokinase activation in SC was confirmed by means of an in vitro assay, in which the precursor of urokinase (pro-uPA) became active after incubation with the insoluble component of SC homogenate. These findings indicated that urokinase-type plasminogen activator is activated in SC after barrier disruption and this activation might trigger the plasminogen/plasmin system in the epidermis.