Heart rate variability (HRV) has been used to evaluate cardiac autonomic function by measuring variations in electrocardiographic R-R intervals between cardiac cycles. HRV was first used to associate decreases in autonomic nervous system (ANS) control with an increased risk of mortality in coronary heart disease and in the diagnosis of diabetes (1). Current clinical research interest has extended to investigate uses of HRV to evaluate changes in the cardiovascular system due to disease, aging, physical activity, and cardiac rehabilitation treatment (2, 5). HRV scores are derivatives of R-R intervals and these may be represented as a function of either time or frequency domain parameters. Time domain analysis is the simplest and includes: the standard deviation of R-R intervals and the number of adjacent RR intervals that differ by >50ms (dRR50). Frequency domain measures involve more elaborate calculation and have been applied in studies to evaluate sympathetic and parasympathetic autonomic balance. The latter include: Low Frequency Power (LF), High Frequency Power (HF), and LF/HF ratio. HRV has been measured in a variety of ways, the most common being a continuous 24-hour collection of R-R data. In recent years, several investigators have sought to assess HRV by utilizing brief collection periods. Controversy exists about the potential of these short-term sampling intervals to yield reproducible and meaningful measurements of HRV. Many confounders such as respiration, stress, and body positioning can influence HRV, which is why a longer collection period has been accepted as the standard for providing a stable index of ANS function. However, short sampling periods would be useful to evaluate HRV when faced with time constraints. The purpose of the current study was to evaluate the reproducibility of HRV using 8-hour daytime measures with the Polar R-R RecorderTM (Polar Electro Oy, Kempele, Finland) and with short sampling duration of 512 cardiac cycles, using the Schiller AT-10TM device (Schiller AG, Baar, Switzerland). Methods: 10 apparently healthy adult volunteers participated in the study, which was conducted at the Sleep Disorders Clinic in Christiansburg, VA. Each subject performed two HRV trials with the Cardiovit AT-10TM device using recordings of 512 cardiac cycles. Within one or two days following the Schiller, the same subjects wore a Polar R-R RecorderTM device to obtain an 8-hour recording of HRV during waking hours; 24-hour urine samples were collected on the same day. Urine was analyzed for catecholamine levels, including norepinephrine and epinephrine in order to evaluate sympathetic nervous system globally. Each subject recorded their personal impressions of unavoidable physical activity and daytime stress demands on the day of the 8-hour recording and urine collection. This entire protocol was repeated one week later. On one of the days of the short sampling recording, VO2pk also was evaluated for each subject using a ramp protocol on the cycle ergometer and a metabolic cart. Results: The correlation analysis for the HRV response variables using the Schiller method indicated a high-to-very high correlation between trials within a day for the time domain measures (r = 0.75-0.99). The frequency domain measures, however, were low-to-moderately correlated (r = 0.24-0.66) between trials within a day for the Schiller method. Correlations between days for HRV response variables using the Schiller method were similarly low for both time (r < 0.5) and (r < 0.4) frequency domain measures. Correlation coefficients between days for the HRV response variables using the Polar method were moderate (r = 0.59-0.67) for the time domain and only low-moderate for the frequency domain measures (r = 0.37-0.69). However, an important finding was that Polar R-R data for two of the subjects contained excessive signal artifact, which affected the fidelity of the HRV scores. When these two cases were excluded from the group analyses, the resulting correlations were high-very high for all time and frequency domain measures (r = 0.70-0.93). The means for each response HRV time and frequency domain variable between the Polar method and Schiller method were significantly different (P < 0.05). Additional correlational analyses did not reveal any systematic associations between HRV measures and simple markers of sympathetic activity (urinary NE or E) and aerobic fitness (VO2pk) in this small sample of subjects. Conclusions: Due to this important change in reproducibility with the Polar method, the consequence of artifact-free recordings is unmistakable. Within the limitations of this small study sample it is concluded that, while HRV in apparently healthy adults may not be measured reliably with brief data collection periods, longer daytime sampling periods of 8 hours (e.g. Polar device) yields acceptable reliability for both time and frequency domain parameters of HRV. / Master of Science

There is clear evidence that the autonomic nervous system (ANS) is lateralized at both the peripheral as well as the central levels of the nervous system. Both the vagus and the sympathetic ganglia asymmetrically innervate the sino-atrial node and the myocardium of the heart. This lateralization has also been observed in afferent as well as efferent projections to nuclei in the brainstem, hypothalamus, and amygdala. Where laterality has not been as clear is in regions of the frontal lobe dedicated to the regulation of autonomic nervous system responses. This study addressed that issue via the implementation of lateralized autonomic response-evoking tasks. With the use of cardiovascular and electrodermal measures, the present study indexed autonomic responses to lateralized stimuli. This study also explored the role of lateralization within sex as well as in relation to reported gender identity. The findings lend support to the right hemisphere as serving a dominant role in regulating sympathetic nervous system activity, while lending less conclusive support for lateralization of parasympathetic nervous system regulation. Men demonstrated greater lateralization for sympathetic nervous system responses across several different metrics of autonomic indices. The exploration of gender variables in relation to lateralization of autonomic responses was generally not supported. / Master of Science

Major depressive disorder (MDD) features symptoms spanning cognitive, affective, behavioral, and physiological domains. While many of the neural circuit disruptions mediating emotional and cognitive disturbances in depression have been described, far fewer studies have explored neurobiological mechanisms underlying its associated motor or physiological impairments. Emotionally motivated behaviors, including responses to stress, are characterized by concomitant somatomotor actions and autonomic changes that require intricate coordination of the motor and autonomic systems. Prior investigations by our group used a pseudorabies virus (PRV)-mediated retrograde tract-tracing approach to identify brain regions with parallel descending premotor and presympathetic efferents that play a role in integrating somatomotor and sympathetic functions. Several nodes of this circuitry, including the hypothalamic paraventricular nucleus (PVN), locus coeruleus (LC), and periaqueductal gray (PAG), are implicated in responses to stressful and emotionally salient stimuli. Based on this observation, it was hypothesized that these parallel descending circuits shape responses to diverse stressors and are altered in clinical depression and comorbid anxiety disorders. To explore this possibility, the experiments in this dissertation used two recombinant PRV strains to trace polysynaptic premotor and presympathetic pathways innervating sympathectomized skeletal muscle and adrenal gland, respectively, in two rat models with heritable differences in emotionality and stress reactivity: the Wistar-Kyoto (WKY) rat and the selectively bred Low Novelty Responder (bLR) rat. During our initial neuroanatomical investigations in the PVN, we observed that both WKY and bLR rats displayed significant decreases in the quantity of PVN neurons with premotor projections to skeletal muscle compared to their respective control strains. Labeling of neurons with presympathetic projections to adrenal gland or dual-labeled polysynaptic projections to both motor and sympathetic targets was not altered in either model. Our subsequent neuroanatomical studies focused on comparing premotor efferent projections from LC and PAG. In LC, fewer premotor efferent projections to skeletal muscle were observed in both models. There were also reductions in the number of premotor efferents in the four subdivisions of the PAG. WKY rats had significantly fewer premotor projections in the dorsomedial (DMPAG), lateral (LPAG), and ventrolateral (VLPAG) subdivisions, while bLR rats had significantly fewer premotor efferents in dorsolateral (DL)PAG. The final experiments in this dissertation sought to determine whether one potential therapeutic intervention, environmental enrichment during late childhood and adolescence, can improve emotional behavior disturbances and reverse premotor circuit alterations in bLR rats. Rearing young bLR rats in conditions with increased environmental complexity partially but incompletely improved aspects of depression- and anxiety-relevant behaviors and their corresponding PVN premotor circuit abnormalities. Cumulatively, these findings highlight somatomotor circuits in several brain structures involved in responses to stress and emotional stimuli that could be implicated in mediating motor-related impairments in clinical depression. / Doctor of Philosophy / Depression is a common and complex illness that features many types of impairing symptoms. Some of these symptoms involve functions regulated by the somatic motor system, which controls movement, and the autonomic nervous system, which regulates many basic bodily functions (for example, heart rate and blood pressure) that occur outside of our conscious control. The ability to coordinate the actions of these two systems is important for many behaviors, including how we respond to emotional or stressful situations. Past experiments in our laboratory used a type of virus (pseudorabies virus, PRV) that travels backwards through neural circuits containing multiple neurons and allows us to label parts of the brain that project to peripheral areas regulated by the somatic motor system (i.e., hindlimb skeletal muscle), the autonomic nervous system (i.e., adrenal gland), or both. These labeling experiments identified neurons in these motor and autonomic circuits in several parts of the brain, including the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus (LC), and periaqueductal gray (PAG). Of note, all of these structures are involved in regulating responses to stressful or emotional situations. This observation led us to hypothesize that motor and autonomic projections from these areas of the brain are important for regulating how we respond to stress and might be altered in individuals suffering from depression. To test this idea, we labeled motor- and autonomic-projections with PRV in two separate rat models with a genetic disposition for emotional behaviors that resemble symptoms of clinical depression or anxiety. When we analyzed the PVN, LC, and PAG of rats with depression-relevant behaviors, we discovered that each of these brain areas contained fewer labeled neurons with motor projections to skeletal muscle. Based on these findings, we were interested in exploring whether enriching or stimulating experiences during early life had the potential to reverse deficits in the PVN motor projections and improve emotional behavior in one of our rat models for depression. Although enrichment partially improved behavioral and circuit-level outcomes, it was not fully effective. Taken together, our experimental findings highlight disruptions of motor projecting circuits in several brain structures implicated in mediating responses to stressful or emotional stimuli in two rat models relevant to depression and anxiety disorders. These motor circuit disruptions could be implicated in mediating motor-related symptoms observed in clinically depressed patients.

Understanding physiological responses to threat can inform therapeutic interventions for phobias, anxieties, and PTSD. The defense cascade is reviewed as a theoretical model that predicts behavioral and physiological responses to threats. Nineteen undergraduates (five male), average age 19.4 experienced a novel virtual reality (VR) threat scenario while their physiology was measured. The Subjective Units of Distress Scale (SUDS) was used as a self-report indicator of distress in the research setting. Averaged SUDS reports suggested that the VR stimulus was experienced as threatening for most participants, but their autonomic response patterns did not fit those predicted by the defense cascade. Participants who had scored high on adaptive response questionnaires tended to show uncoupled ANS activation during baseline, but varied across the stimulus condition. Nearly all participants showed either coactivation or reciprocal activation during the stimulus period except those reporting the most dissociative trauma experiences, who mostly showed uncoupled ANS activation. / M.S. / The more we understand about how people’s bodies and their energies act when they feel threatened, the better we can find help for folks who struggle with anxiety, trauma or other challenging conditions. This research uses a theoretical model called the defense cascade to explore how people respond mentally and physically to threatening situations. Nineteen undergraduates went through a virtual reality (VR) experience that was designed to feel threatening while their body and its energy systems were measured. A scale was introduced called the Subjective Units of Distress Scale (SUDS) and was used to help the researchers understand how distressed people felt while they were in the VR experience. Averaged SUDS reports suggested that the VR stimulus was experienced as threatening for most participants, but their body response patterns did not fit those predicted by the defense cascade. Participants whose questionnaire responses suggested they were not anxiety-prone or traumatized, tended to show bodily activation that uncoupled their two autonomic bodily systems during a baseline period before the threatening stimulus. However, their autonomic responses during the stimulus period varied. Nearly all participants showed either both autonomic systems acting together or only one system acting in a mutually exclusive way to the other system during the stimulus period. This was the case for most participants except those reporting the most trauma involving dissociative experiences. This latter group mostly showed uncoupled autonomic bodily patterns.

<p>A2B Electronics AB is a company that develops and manufactures products and technology for digital cable television. A2B's new EXM-product family translates digital television channels from multiple source networks into a single destination network. Multiple EXM-units are connected in a system to provide a custom set of TV channels. To minimize the administrative effort, the units in a system should be able to interact and collaborate without manual intervention. The purpose of this thesis is to propose an underlying system that supports seamless interaction and collaboration between units.</p><p>The autonomic system concept has served as a foundation for the proposed solution. The requirements for the EXM-system proved to be similar to many properties of an autonomic system. The proposed solution was elaborated by answering five reseach questions. The answers describe how an autonomic system can be implemented with the prerequisites of the EXM-system. Solutions for service availability, configuration preservation, system state changes and automatic addressing and communication are provided.</p><p>The project has resulted in a proposal of a general autonomic system. The solution has also been implemented as prototype that runs both in a simulator and on the EXM-hardware. The simulator was also developed in the scope of this project as a side-effect of the limited access to EXM-hardware.</p><p>The proposed solution together with the prototype can hopefully serve as a base for projects with prerequisites similar to the project described in this thesis.</p>

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Auburn University. / Abstract. Includes bibliographical references.

A2B Electronics AB is a company that develops and manufactures products and technology for digital cable television. A2B's new EXM-product family translates digital television channels from multiple source networks into a single destination network. Multiple EXM-units are connected in a system to provide a custom set of TV channels. To minimize the administrative effort, the units in a system should be able to interact and collaborate without manual intervention. The purpose of this thesis is to propose an underlying system that supports seamless interaction and collaboration between units. The autonomic system concept has served as a foundation for the proposed solution. The requirements for the EXM-system proved to be similar to many properties of an autonomic system. The proposed solution was elaborated by answering five reseach questions. The answers describe how an autonomic system can be implemented with the prerequisites of the EXM-system. Solutions for service availability, configuration preservation, system state changes and automatic addressing and communication are provided. The project has resulted in a proposal of a general autonomic system. The solution has also been implemented as prototype that runs both in a simulator and on the EXM-hardware. The simulator was also developed in the scope of this project as a side-effect of the limited access to EXM-hardware. The proposed solution together with the prototype can hopefully serve as a base for projects with prerequisites similar to the project described in this thesis.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第22888号 / 社医博第112号 / 新制||社医||11(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 川上 浩司, 教授 今中 雄一, 教授 稲垣 暢也 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Purpose: This study will identify that patients with chronic neck pain have an altered autonomic functioning compared to a control group, and that manipulation might directly influence the autonomic nervous system as measured by using a fully automated pupillometry system. Subjects: 100 chronic pain patients and 50 control subjects participated in this study to achieve a power of 0.80, effect size of 0.5, and a type I error rate of 0.05 for two-tailed hypothesis testing. Method: A quasi-experimental design was be used. The ANOVA and Chi square test were used to establish homogeneity of baseline characteristics. The Mann-Whitney U test was performed to compare the pre-intervention pupil diameter amongst the groups. The Friedman's test was used to determine the pupil diameter change during the three measurements. The Wilcoxen Signed-ranks test was used to analyze the difference in pupil size between the pre- and post-intervention measures and to determine if there was a difference in pupil diameter between the two groups undergoing the thoracic manipulation. The Kruskal-Wallis test was used to compare the pupil diameter change to the presence of joint sounds. And the Fisher's Exact test was used to determine the relationship between the number of pops and the VAS change score > 13mm. Results: This study demonstrated that the chronic pain group had a statistically significant smaller pupil diameter than the healthy control group (P=0.022). Manipulation resulted in a relative increase in pupil diameter following the manipulation, however this was not statistical significant. There was a statistical significant decrease in pupil diameter in the placebo group (pConclusions: It appears that a T3-T4 manipulation results in a relative non-specific increase in sympathetic activity. Recommendations: Manipulation may be used by physical therapists to affect the autonomic nervous system. Visual pupil assessment may become part of the evaluation process to identify patients that might present with autonomic dysfunction and to determine the effect of treatment modalities.