Biological theory proposes that autonomic nervous system (ANS) hypo-reactivity may be more specific to proactive aggression, while ANS hyper-reactivity may be specific to affective aggression. However, the literature finds mixed support, which may be because no study to date has concurrently examined emotion dysregulation, a highly related variable, as a potential moderator. The present study examined these relationships in 76 undergraduate participants (29 men, mean age = 21.49) who identified as Caucasian (51%), African-American (23%), Asian (21%), or Other (5%). Participants completed questionnaires, a resting state task, and a provocation task. Results found that blunted overall ANS reactivity was associated with proactive aggression. Emotion dysregulation moderated the relationship between parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) reactivity with both proactive (at a trending level for SNS reactivity) and affective aggression. Specifically, among those slightly above average and high on emotion dysregulation, PNS augmentation and blunted SNS reactivity were associated with proactive and affective aggression, respectively. In contrast, among those low on emotion dysregulation, PNS augmentation was associated with decreased affective aggression. Thus, among those elevated on emotion dysregulation, it may be beneficial to teach counter-regulatory strategies to reduce the impact of ANS hypo-reactivity on aggression (across function). / Psychology

The neurovisceral integration model (NVM) proposes that an organisms ability to flexibly adapt to their environment is related to biological flexibility within the central autonomic network. One important aspect of this flexibility is behavioral inhibition (Thayer and Friedman, 2002). During a behavioral inhibition task, the central autonomic network (CAN), which is comprised of a series of feedback loops, must be able to integrate information and react to these inputs flexibly to facilitate optimal performance. The functioning of the CAN is shown to be associated with respiratory sinus arrhythmia (RSA), as the vagus nerve is part of this feedback system. While the NVM has been examined through neural imaging and RSA, only a few studies have examined these measures simultaneously during the neuroimaging procedure. Furthermore, these studies were done at rest or used tasks that were not targeted at processes associated with the NVM, such as behavior inhibition and cognitive flexibility. For this reason, the present study assessed RSA and neural activation in the prefrontal cortex simultaneously while subjects completed a behavior inhibition task. Using a series of go/no-go tasks, RSA and functional near-infrared spectroscopy (fNIRS) were collected to investigate the relationship between prefrontal activation and vagal activity at rest and during behavioral inhibition. There are three primary aims of this study. First, examine prefrontal activation during various inhibition tasks through fNIRS. Second, evaluate the NVM during a cognitive task using simultaneous fNIRS and RSA analysis. Third, relate task performance, imaging, and RSA measures during behavioral inhibition to deficits in flexible everyday responding, as indicated by self-report measures of behavior. Doing so will elucidate the connection with prefrontal activation and RSA as proposed by the NVM model and determine whether neural and RSA metrics can be related to broader symptoms of inflexibility. / PHD / The neurovisceral integration model (NVM) proposes that the ability to adapt to the environment is related to biological flexibility within the brain. One important aspect of the ability to adapt to the environment is behavior inhibition (e.g., the ability to stop from engaging in a habitual response, Thayer & Friedman, 2002). During a behavior inhibition task, the brain must be able to integrate information and react to these inputs flexibly to facilitate optimal performance. The brain’s ability to do this is related to a measure of heart activity known as respiratory sinus arrhythmia (RSA). The present study assessed RSA and brain activity while subjects completed a behavior inhibition task. Neural activation was measured through functional near-infrared spectroscopy (fNIRS). fNIRS measures the amount of oxygenated blood in different areas of the brain. Greater concentrations of oxygenated blood indicated greater brain activity in an area. Through simultaneous fNIRS and RSA measurement the present study examined their relationship during various inhibition tasks. Doing so clarified the connection between brain activation and RSA as proposed by the NVM model.

Theories of emotion regulation and social engagement indicate that resting and reactive respiratory sinus arrhythmia (RSA), which reflect vagal activity, in early childhood can inform the development of social and emotional behaviors later in life. Low RSA at baseline and during a stressful task have been associated with symptoms of ED and disorders characterized by social impairments. The current study examined the mediating role of ED at 24-months-old (mo) on the prospective association between early infant resting and reactive RSA at 5 mo on social functioning outcomes at 48 mo, and the mediating role of social functioning at 24 mo on infant RSA at 5 mo and ED at 48 mo in 237 healthy children. It was hypothesized that ED would mediate the relationship between infant RSA and later childhood social function. Results largely indicated no support of the hypotheses and that there is no mediating effect of childhood ED on early RSA on later childhood social behavior; however, there was a significant relationship between infant resting and reactive RSA and later ED. Limitations and future directions for improving the methodology are addressed. / M.S. / Early childhood heart rate has been thought to influence the development of later child emotional and social development. The Polyvagal Theory suggests that low variability in heart rate, as measured by respiratory sinus arrhythmia (RSA), is related to greater difficulties in emotional and social behavior. Finding an underlying biological reason for emotional and social development can be important for understanding childhood psychological disorders. This research study examined healthy children at three different time points during development: 5 months old (mo), 24 mo, 48 mo. RSA was measured at 5 mo, and frustration levels and social abilities at 24 and 48 mo. It was hypothesized that low RSA at 5 mo predicts low social abilities at 48 mo because of high frustration levels at 24 mo. To rule out an alternate hypothesis, this study also tested if low RSA at 5 mo predicts high frustration levels at 48 mo because of low social abilities at 24 mo. The results of this study did not support the predictions and there was no evidence of emotional abilities affecting how RSA predicts later social abilities. Possible explanations for the lack of findings and ideas for future research were discussed.

Yes / Sublethal carbon monoxide (CO) exposure is frequently associated with myocardial arrhythmias, and our recent studies have demonstrated that these may be attributable to modulation of cardiac Na+ channels, causing an increase in the late current and an inhibition of the peak current. Using a recombinant expression system, we demonstrate that CO inhibits peak human Nav1.5 current amplitude without activation of the late Na+ current observed in native tissue. Inhibition was associated with a hyperpolarizing shift in the steady-state inactivation properties of the channels and was unaffected by modification of channel gating induced by anemone toxin (rATX-II). Systematic pharmacological assessment indicated that no recognized CO-sensitive intracellular signaling pathways appeared to mediate CO inhibition of Nav1.5. Inhibition was, however, markedly suppressed by inhibition of NO formation, but NO donors did not mimic or occlude channel inhibition by CO, indicating that NO alone did not account for the actions of CO. Exposure of cells to DTT immediately before CO exposure also dramatically reduced the magnitude of current inhibition. Similarly, L-cysteine and N-ethylmaleimide significantly attenuated the inhibition caused by CO. In the presence of DTT and the NO inhibitor Nω-nitro-L-arginine methyl ester hydrochloride, the ability of CO to inhibit Nav1.5 was almost fully prevented. Our data indicate that inhibition of peak Na+ current (which can lead to Brugada syndrome-like arrhythmias) occurs via a mechanism distinct from induction of the late current, requires NO formation, and is dependent on channel redox state. / This work was supported by the British Heart Foundation

The rise of machine learning has seen an increase in digital methods for use within health care. Arrythmia detection is one of the areas where this increase is obvious. However, many machine learning methods for arrythmia detection utilise models that are computationally expensive, such as convolutional neural networks, CNNs. This thesis examines whether it is viable to use the Fast Fourier Transform to transform an Electrocardiogram, ECG, signal into its frequency components before training a neural network, NN, on the data. This could allow for a lower computational cost and wider availability of arrythmia detection technology. The results from the model were compared to that of a CNN trained on time domain data. The results show that the CCN model outperforms the NN trained on FFT transformed data but the performance of the model still indicates that valuable information about heart arrythmias does exist within the frequency space. This suggests a potential for future work on the subject.

Voltage-gated sodium channels are composed of pore-forming α-subunits, and modulatory and multifunctional associated β subunits. While much of the field of cardiac electrophysiology and pathology has focused on treating and preventing cardiac arrhythmias by targeting the α subunit, there is also evidence that targeting the β subunits, particularly SCN1B, the gene that encodes β1 and an alternatively spliced variant β1B, has therapeutic potential. The first attempt at targeting the β1 subunit was with the generation of and treatment with an SCN1B Ig domain mimetic peptide βadp1. Here we describe further investigation into the function and mode-of-action of both βadp1 and novel peptides derived from the original βadp1 sequence. We find that in a heterologous expression system βadp1 initially disrupts β1-mediated trans-homophilic adhesion, but after approximately 30 hours eventually increases adhesion. Novel mimetic dimers increase β1 adhesion up to 48 hours post-treatment. Furthermore, it appears that βadp1 may increase β1 adhesion by upregulating the intramembrane proteolysis of β1, a process which has important downstream implications and effects on translation. Despite these exciting findings, we were unable to translate them into a primary culture of cardiac cells with endogenous expression of β1 because we found that both neonatal rat cardiomyocytes and isolated adult mouse cardiomyocytes do not express β1 at detectable levels, whereas they do appear to express β1B. In summary, we show exciting findings on the function and mode-of-action of SCN1B mimetic peptides and their therapeutic potential in targeting the β1 subunit, but further work is needed to determine the translatability of our findings to in vivo models and eventually to humans. / Doctor of Philosophy / Voltage-gated sodium channels have two main parts: the pore-forming α-subunits and the modulatory β subunits. Most research in heart function and issues has focused on fixing problems with the α subunit. However, there's evidence that working on the β subunits, specifically the SCN1B gene that makes β1 and another version called β1B, could be helpful. Previously, researchers used a peptide that is designed exactly like a part of β1, called βadp1, to target the β1 subunit. In our study, we explore more about how βadp1 works and test new peptides based on βadp1. We found that βadp1 initially disrupts trans-homophilic adhesion, where 2 β1 subunits interact with each other across the space between 2 cells, but after about 30 hours, it actually increases adhesion. New mimetic dimers also boost adhesion up to 48 hours later. It seems like βadp1 might enhance adhesion by triggering a process called intramembrane proteolysis of β1, which has important effects on translation. Despite these exciting findings, we couldn't confirm the presence of this protein in heart cells because we discovered that certain heart cells don't have enough β1, although they do have β1B. In conclusion, our study shows promising results about how SCN1B mimetic peptides work and their potential for treating arrhythmia. However, more research is needed to see if these findings apply to real-life situations and eventually to help people with cardiac conduction abnormalities.

Wong, Mei Fung Florence. / Thesis (D.Nurs.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 178-208). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Tolkningen av EKG är en viktig metod vid diagnostisering av onormala hjärttillstånd och kan användas i förebyggande syfte att upptäcka tidigare okända hjärtproblem. Att enkelt kunna mäta sitt EKG och få det analyserat och presenterat på ett pedagogiskt sätt utan att behöva rådfråga en läkare är något det finns ett konsumentbehov av. Denna rapport beskriver hur en EKG-signal behandlas med olika algoritmer och metoder i syfte att detektera hjärtslag och dess olika parametrar. Denna information används till att klassificera varje hjärtslag för sig och därmed avgöra om användaren har en normal eller onormal hjärtfunktion. För att nå dit har en mjukvaruprototyp utvecklats där algoritmerna implementerats. En enkätundersökning gjordes i syfte att undersöka hur utdata från mjukvaruprototypen skulle presenteras för en vanlig användare utan medicinsk utbildning. Sju filer med EKG-signaler från MIT-BIH Arrhythmia Database användes för testning av mjukvaruprototypen. Resultatet visade att prototypen kunde detektera en rad olika hjärtfel som låg till grund vid fastställning om hjärtat slog normalt eller onormalt. Resultatet presenterades på en mobilapp baserad på enkätundersökningen. / The interpretation of the ECG is an important method in the diagnosis of abnormal heart conditions and can be used proactively to discover previ-ously unknown heart problems. Being able to easily measure the ECG and get it analyzed and presented in a clear manner without having to consult a doctor is improtant to satisfy consumer needs. This report describes how an ECG signal is treated with different algo-rithms and methods to detect the heartbeat and its various parameters. This information is used to classify each heartbeat separately and thus determine whether the user has a normal or abnormal cardiac function. To achieve this a software prototype was developed in which the algorithms were implemented. A questionnaire survey was done in order to examine how the output of the software prototype should be presented for a user with no medical training. Seven ECG files from MIT-BIH Arrhythmia database were used for validation of the algorithms. The developed algorithms could detect of if any abnormality of heart function occurred and informed the users to consult a physician. The presentation of the heart function was based on the result from the questioner.

Identifying factors associated with appropriate and inappropriate therapies in patients with implantable cardioverter-defibrillator (ICD) could help to identify those at risk and reduce the incidence of this emergency situation which has detrimental effect on mortality and morbidity in patients with ICD. These studies were designed to find the prevalence and factors associated with appropriate and inappropriate therapies in patients with ICD.

The primary aim of this study was to investigate whether the joint action of the parasympathetic (PNS) and sympathetic nervous system (SNS) influenced three distinct indicators of child adjustment. Although evidence suggests that patterns of reactivity in the PNS and SNS each contribute to adjustment in youth, a paucity of work has examined the interaction between the two systems. Moreover, much of the research on children's autonomic reactivity has overly relied on variable-centered analytic approaches, which aim to predict variance and assume homogeneity in the relations between predictors and outcome. This project also incorporated a person-centered approach to systematically identify individual differences in the interrelation between PNS and SNS reactivity and to classify children into homogeneous autonomic reactivity groups. The person-centered results were then applied to variable-centered analyses to examine how adjustment varied across homogeneous autonomic reactivity groups. Thus, the goal of this study was to apply both variable-centered and person-centered analyses to investigate whether children's autonomic reactivity was related to child adjustment. Children (N = 64, 8-10 years, M = 9.06, SD = 0.81) and one parent completed a psychophysiological laboratory assessment at Wave 1 during which each child's respiratory sinus arrhythmia reactivity (RSAR; an index of PNS reactivity) and skin conductance level reactivity (SCLR; an index of SNS reactivity) was assessed in response to a mirror tracing challenge task. At both Wave 1 and Wave 2, each parent reported on their child's internalizing symptoms, externalizing symptoms, and social competence. The variable-centered analyses revealed that, consistent with hypotheses, the two-way RSAR x SCLR interaction was significant predicting internalizing symptoms at Time 1 and at Time 2. In both cases, RSA withdrawal was associated with fewer internalizing symptoms when coupled with low SCLR. When coupled with high SCLR, RSA withdrawal was associated with more internalizing symptoms at Time 1; however, RSAR was unrelated to Time 2 internalizing when coupled with high SCLR. In addition, SCLR was associated with more social competence and (marginally) fewer externalizing problems over time. The person-centered analyses (i.e., a model-based cluster analysis) identified two distinct clusters based on children's RSAR and SCLR. Children in Cluster 1 showed slight RSA withdrawal combined with SCL activation (modest reciprocal SNS activation) and exhibited marginally more internalizing and less social competence, as compared to children in Cluster 2 who, as a group, showed heightened RSAR (either withdrawal or augmentation) and SNS activation. When a 3-cluster model was examined, results indicated that children who showed modest reciprocal SNS activation (Cluster 1) showed marginally more internalizing symptoms then children who showed strong reciprocal SNS activation (Cluster 2A) and marginally less social competence then children who showed coactivation (Cluster 2B). This study offers important evidence that person-centered analyses can identify differences in autonomic reactivity that are relevant to children's adjustment. Cluster analysis identified only two (i.e., reciprocal SNS activation, coactivation) of the four autonomic profiles assumed to be represented in simple slope analyses in previous work. Thus, incorporating person-centered techniques in future research is an important and likely fruitful approach to investigating how autonomic reactivity contributes to child development.