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京都大学 / 新制・論文博士 / 博士(人間健康科学) / 乙第13483号 / 論人健博第9号 / 新制||人健||7(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 藤井 康友, 教授 澤本 伸克, 教授 長尾 美紀 / 学位規則第4条第2項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

An emerging diagnostic tool for detecting heart and physiological conditions is heart rate variability (HRV). Copious research continuously discovers relationships between heart rate variability metrics and physiological functions and cardiac health. The first step in calculating HRV metrics is calculating heart rate. Heart rate is typically calculated using the interval between R peaks in an EKG signal. Consequently, heart rate measurements rely on the presence of distinctive R peaks and the accurate detection of them. The study is motivated by the drawbacks associated with using R peaks to calculate instantaneous heart rate. In this study we present an alternative method (that does not rely on R peaks) based on the concept of instantaneous frequency to estimate heart rate from electrocardiogram (EKG) signals. The EKG signal is filtered to extract constituent frequency components that correlate with the instantaneous heart rate. The filtered signal is then fed into an algorithm that outputs a signal that shows the variation of the instantaneous heart rate with time. This output signal contains noise due to the behavior of the algorithm at zero crossings of the filtered EKG signal. Two methods for filtering the output signal are also presented in the study. The proposed method was able to successfully estimate the instantaneous heart rate and allowed the subsequent calculation of frequency domain HRV metrics. This method potentially provides more information for HRV analysis and addresses the drawbacks associated with methods based on R peak detection. / Master of Science / Heart disease is the leading cause of death in America accounting for about 20% of all deaths. Consequently, both the public and the medical community are engrossed in cardiovascular health, research that enables early detection of heart disease and novel treatments for cardiac conditions. An emerging diagnostic tool for detecting heart and physiological conditions is heart rate variability (HRV). Copious research continuously discovers relationships between heart rate variability metrics and physiological functions and cardiac health. The first step in calculating HRV metrics is calculating heart rate. With the rise in popularity and improvement of wearable technologies, it has become easier than ever to collect data and perform diagnostics, often in real time. As such the need for robust methods and algorithms to perform these calculations are ever more important. The study is motivated by drawbacks associated with the conventional method used to calculate heart rate from electrocardiogram signals. In this study we present a more robust method to calculate heart rate from EKG signals allowing more accurate HRV metrics to be calculated. In this study we present an alternative method based on the concept of instantaneous frequency to estimate heart rate from electrocardiogram (EKG) signals. We identify the shortcomings of the conventional method of estimating heart rate and discuss the strengths and weaknesses of the alternative method introduced. We then calculate and compare the HRV metrics calculated from the proposed method and the conventional method. The method presented also has the potential to be used on other signals that measure the heart's activity such as Photoplethysmography signals (PPG) allowing it to be used on wearable devices. We hope that the information provided, and the findings presented in this study will be utilized by the medical community and researchers for future research related to heart rate variability.

Obstructive sleep apnea (OSA) is a serious disorder that affects up to 24% of middle-aged males. The substantial cost and inconvenience associated with polysomnography limits the number of people who seek treatment. Therefore, information concerning exercise tolerance and hemodynamic function in obstructive sleep apnea (OSA) patients may add new and clinically meaningful information to the process of grading disease severity and/or assessing treatment outcomes. Objectives: The primary objective of this study was to explore relationships between polysomnography (PSG) markers of sleep function and resting and exercise measures of hemodynamic function in patients diagnosed with mild-to-severe OSA. A family of clinical markers including heart rate (HR), blood pressure (BP), cardiac index (CI), stroke volume index (SVI), total peripheral resistance (TPR), and oxygen uptake (VO2) were assessed in this study. A second objective was to explore differences in hemodynamic function at rest and during graded exercise in OSA patients versus control subjects matched for age and body mass index (BMI). A final objective was to evaluate the extent that treatment with nCPAP alone, or combined with a moderate aerobic exercise training program impacted markers of hemodynamic function (results not reported here). Methods: Eleven newly diagnosed OSA patients [5 male, 6 female; age: 46.5 + 12.0 yrs; respiratory disturbance index (RDI) = 30.2 + 15.0] and 10 apparently healthy control subjects (4 male, 6 female; age: 39.8 + 6.9 yrs) completed daytime resting measurements of heart rate variability (HRV) and blood pressure (BP); and underwent a maximal cycle ergometer exercise test at baseline and 6 wk post-treatment initiation. Pearson product moment correlations were calculated between PSG markers of sleep function and: (1) daytime measures of HRV; (2) BP; and (3) submaximal and peak exercise measures of hemodynamic function. Independent t tests were used to explore differences between OSA patients and controls. Results: Stage 1 sleep duration was significantly related to daytime SBP (r = 0.69; P < 0.05) and MAP (r = 0.72; P < 0.05). Daytime MAP (P = 0.01) and DBP (P = 0.02) were significantly different between groups. Exercise testing yielded the following results: RDI was significantly related to HR at 60 watts (r = -0.70; P = 0.02) and 100 watts (r = -0.69; P = 02); stage 2 sleep duration was inversely related to CI at 60 (r = -0.76; P = 0.03) and 100 watts. In addition, stage 1 sleep duration was significantly correlated with TPR at 60 watts (r = 0.70; P = 0.06) and 100 watts (r = 0.71; P = 0.05). At peak exercise, a significant relationship was noted between peak HR and stage 2 sleep duration (r = -0.73; P = 0.02); and RDI (r = -0.66; P = 0.03). Furthermore, relative VO2pk was positively correlated to REM sleep duration (r = 0.62; P = 0.04). Conclusions: Distinct patterns exist in measures of daytime HRV and BP may provide physicians unique and clinically useful information. In addition, peak exercise capacity is reduced in the OSA patient and may be related to a blunted HR response to graded exercise. / Ph. D.

Heart Rate Variability (HRV) currently is utilized when assessing the risk of mortality in individuals suffering from coronary heart disease or diabetic neuropathy. Research has shown that patients with Obstructive Sleep Apnea (OSA) also show a decrease in HRV, as well as an increase in sympathetic drive characterized by an increase in the low-frequency component of HRV. HRV, in conjunction with other indicators, may represent a non-invasive, low cost method for the confirmation of severity of OSA in some patients and therefore may represent an additional tool for the assessment of risk in these individuals. This becomes especially true when urinary catecholamines, fitness level, and quality of life (QOL) assessment are included. The purpose of this study was to determine if a correlation exists between severity of OSA as assessed by respiratory distress index (RDI) and the selected measures HRV, fitness, QOL, and catecholamine output. Subjects were 6 men and 5 women who were recently diagnosed with OSA by polysomnographic (PSG) study. HRV and blood pressure was measured during two consecutive trials consisting of 512 heartbeats. Catecholamine levels were determined by HPLC following 24-hour urine collection. Fitness levels were established following cycle ergometer testing and QOL following questionnaire completion. Subjects with lower weight, BMI, and neck circumference had significantly higher parasympathetic influence as analyzed through the amount of high frequency component of HRV (r =.738, .726, .789, respectively; p<0.05). Respiratory distress index (RDI) was negatively related to the average heart rate (HR=RR average, r = -.610, p<0.05), while the amount of total sleep (r = .657, p<0.05) and REM sleep (r = .739, p<0.01) increased as HR increased. The average HR was correlated to the predicted VO2max (r = .677, p<0.05). When the frequency components of HRV, fitness, QOL, and catecholamines were combined, the association to RDI increased dramatically (r = .984, p = .02). The results indicate that as the severity of OSA increases, markers of fitness, QOL, and sleep decrease. There is also an inverse relationship between autonomic function and severity of OSA. It is concluded that HRV and fitness levels are inversely related to the severity of OSA, and that these measures may be developed into a risk assessment tool for use in OSA patient evaluatio / Master of Science

The current study aimed to test sensation seeking as a mediator in the relationship between arousal and aggression. In addition, an experimental design was used to test whether arousal can be manipulated to alter levels of sensation seeking and aggression, both measured behaviorally. A sample of 128 undergraduate students completed state and trait measures of sensation seeking and aggression, and baseline measures of physiology. It was hypothesized that trait sensation seeking would mediate the relationship between baseline physiology and trait aggression. Also, state sensation seeking would mediate the relationship between an arousal manipulation and state aggression. The results failed to support the proposed mediation models. Furthermore, the arousal manipulation was insufficient to result in sustained heart rate differences, and therefore the malleability of state sensation seeking and aggression could not truly be tested. Exploratory analyses supported an interaction between arousal and sensation seeking, such that in individuals low on experience seeking, disinhibition and boredom susceptibility, low heart rate was associated with greater aggression. These findings suggest that arousal and sensation seeking may conjointly predict aggression through moderation rather than mediation, though future studies with improved experimental designs are needed. / Ph. D.

Deficits in social functioning in individuals with autism spectrum disorder (ASD) may be explained in part by the limited salience of or reward value associated with the social world, relative to individuals with typical development (e.g., Jones and Klin, 2008; Mundy, 1995; Mundy and Neal, 2005). However, despite many calls for the use of ecologically valid, rich, complex stimuli when investigating deficits in social attention and interest in ASD, few studies have adopted these recommendations. The current study investigated social interest in a non-clinical college student population (n = 78; 72% female; M age = 20.41 years) by analyzing participants' verbal descriptions of dynamic film clips. It was predicted that as level of self-reported ASD characteristics increased, proportions of verbal descriptions devoted to higher-level social information (e.g., relationships, mental or emotional states) would decrease, while holding self-reported social anxiety, autonomic flexibility (i.e., heart rate variability), and verbal ability constant. In other words, self-reported ASD characteristics were hypothesized to impact social interest above and beyond the effects of other predicted covariates. Results, however, did not reveal significant differences in social interest across varying levels of ASD characteristics, and neither social anxiety nor autonomic flexibility served as a moderator of this association. Variations of the current study and the inclusion of a clinical population are discussed as possible future directions to refine the study and better target intervention efforts aimed at ameliorating social deficits in ASD. / Ph. D.

Anxiety is an area of documented challenge for people with Autism Spectrum Disorder (ASD). Despite this, some studies state that those with ASD and language deficits have lower reported anxiety than those without language deficits. This effect may be due to the complicated task of appropriately evaluating anxiety in those with compromised language. Using biomarkers of anxiety, such as reduced Heart Rate Variability (HRV) and increased Heart Rate (HR), may improve anxiety assessment but more research is necessary. Specifically, it would be helpful to understand if the relationship between HRV/HR and anxiety is moderated by language abilities in children with ASD, and whether HRV/HR can discriminate between anxiety and other emotions, like anger, in children with ASD. This study examined the relationship between baseline HRV/HR, language ability, and different emotional states (i.e., anxiety and anger) in a sample of 23 children with ASD. It was hypothesized that receptive language would moderate the relationship between decreased HRV/increased HR and increased anxiety but not the relationship between decreased HRV/increased HR and increased anger. Multiple regression analyses indicated that HRV and HR were not significant predictors of anxiety or anger, and language was not a significant moderator. Future studies may wish to take new approaches to determining the role of language in the relationship between HRV/HR and anxiety. / Master of Science / Anxiety is an area of documented challenge for people with Autism Spectrum Disorder (ASD). Despite this, some studies state that those with ASD and language deficits have lower reported anxiety than those without language deficits. This effect may be due to the complicated task of appropriately evaluating anxiety in those with compromised language. Using biomarkers of anxiety, such as reduced Heart Rate Variability (HRV) and increased Heart Rate (HR), may improve anxiety assessment but more research is necessary. Specifically, it would be helpful to understand if the relationship between HRV/HR and anxiety is moderated by language abilities in children with ASD, and whether HRV/HR can discriminate between anxiety and other emotions, like anger, in children with ASD. This study examined the relationship between baseline HRV/HR, language ability, and different emotional states (i.e., anxiety and anger) in a sample of 23 children with ASD. It was hypothesized that receptive language would moderate the relationship between decreased HRV/increased HR and increased anxiety but not the relationship between decreased HRV/increased HR and increased anger. Multiple regression analyses indicated that HRV and HR were not significant predictors of anxiety or anger, and language was not a significant moderator. Future studies may wish to take new approaches to determining the role of language in the relationship between HRV/HR and anxiety.

Heart rate variability (HRV) and personality are related to both physical and mental health outcomes. Previous research has found a relationship between neuroticism and distress while the findings on the relationship between neuroticism and HRV are mixed. Studying the facets of neuroticism may provide a more nuanced view of the effects of personality on HRV and distress. Previous research has suggested that the vulnerability facet of neuroticism appears to be uniquely related to the cardiovascular response to stress. This study's first hypothesis is that individuals with higher scores on the vulnerability facet will have lower heart rate variability. The second hypothesis is that individuals with higher vulnerability facet scores will report higher levels of distress. Using SEM, this study evaluated the measurement model of the facets of neuroticism as well as the structural relationships between these facets and HRV as well as psychological distress. Our study's sample consisted of 374 college students, the majority of whom were young adults. The SEM results indicated that there was no significant relationship between vulnerability and HRV or psychological distress. The lack of a significant association among any of the facets of neuroticism with HRV in this study further supports the notion that the non-significant relationship between neuroticism and HRV extends even when examining neuroticism at the facet level.