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Chronic loneliness and low perceived social support have been recognized as risk factors for both mental and cardiovascular disorders. It has been proposed that their link to psychophysiological problems may involve changes in parasympathetic activity. However, the exact underlying psychopathological mechanisms and the moderating effects of gender are still not thoroughly examined. Thus, the present study investigated associations between perceived social functioning and resting vagal tone in the context of potential cognitive and subclinical mediators and gender differences. Three hundred twenty‐five young adults (aged 18–35, 180 women) underwent an electrocardiogram measurement of 6‐minute resting heart rate variability (HRV). They also completed questionnaires assessing loneliness, perceived social support, social cognitive biases, depressive and social anxiety symptoms, and general mental health. In men, HRV was significantly and negatively associated with poorer perceived social functioning, depressive symptoms, and self‐reported social cognitive biases, while in women, there was a quadratic link between HRV and depressive symptoms and HRV and general mental health. Moderated mediation analysis revealed that depressive symptoms fully mediated the relationship between perceived social functioning and HRV in men. The results suggest that decreased resting vagal tone in lonely individuals is linked to depressive symptomatology rather than to specific social cognitive biases and that this association is significant only in men. [ABSTRACT FROM AUTHOR]

Historically, studies on the neural basis of fear conditioning have emphasized the role of the central nervous system. However, there is growing evidence for the role of the autonomic nervous system in human fear conditioning. Here, we provide an overview of the sophisticated anatomical–functional interplay between the prefrontal cortex and heart-related dynamics in human fear conditioning and propose a theoretical model to conceptualize these psychophysiological processes, the neurovisceral integration model of fear (NVI-f). A richer understanding of the neurovisceral concomitants of this functional interplay will have both theoretical and clinical implications. [ABSTRACT FROM AUTHOR]

Darwin emphasized the intimate relationship between the brain and the heart over 150 years ago. Healthy aging is associated with significant changes in both the brain and the heart. The changes between these, the two most important organs of the body, are linked via the vagus nerve. In this review, we examine the normative changes with aging and the effect that stress may have on how the brain–heart connection changes with age. We provide a framework based on the concept of neurovisceral integration and propose that stress regulation is emotion regulation. As such, studies that have investigated emotion regulation may yield insights into successful stress regulation that helps protect people from age‐related decline. In addition, interventions that improve brain health also improve heart health and vice versa. We conclude by noting that significant sex and ethnic differences exist but that future studies are needed to more fully explicate how they may moderate the associations between stress and aging. Impact Statement: A framework is provided, proposing that stress regulation is emotion regulation. Studies that have investigated emotion regulation may yield insights into successful stress regulation that helps protect people from age‐related decline in brain‐heart connections. Future studies are needed to explicate how associations between stress and aging are moderated by third factors. [ABSTRACT FROM AUTHOR]

Elevated blood pressure is a risk factor for increased cardiovascular morbidity and mortality. Decreased vagally-mediated heart rate variability has previously been prospectively linked with increased blood pressure; however, to date, no such prospective data exist regarding this relationship among Blacks. We examined this association in 387 normotensive young adults (mean age, 23 years, 52% female, 54% Black) who participated in two laboratory evaluations spanning approximately six years. Blood pressure was measured at both timepoints with a non-invasive oscillometric device and heart rate variability was assessed via bio-impedance. In the total sample, heart rate variability significantly predicted systolic (p =.022) and diastolic (p <.001) blood pressure increases six years into the future. However, this pattern varied as a function of ethnicity and sex with the effect of heart rate variability on Time 2 systolic blood pressure only significant among White males (p =.007). Heart rate variability was also predictive of Time 2 diastolic blood pressure in White males (p =.038) as well as among both White (p =.032) and Black (p =.015) females, but was not related to blood pressure among Black males. We report for the first time significant ethnic and sex differences in the prospective relationship between heart rate variability and blood pressure change. These findings may give clues as to the underlying mechanisms that are involved in the well-known health disparities in blood pressure and hypertension-related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

African American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared with European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178 EAs; mean age 23.16 ± 2.9 yr). Individuals participated in two laboratory evaluations spanning approximately 6 yr. Bioimpedance was used to assess HRV at time 1 and cardiac output at both time 1 and time 2. Mean arterial pressure (MAP) was measured at both time points via an automated BP machine. TPR was calculated as MAP divided by cardiac output. Results showed AAs to have higher BP and higher TPR at time 2 compared with EAs, independent of several important covariates. Also, higher HRV at time 1 significantly predicted both lower TPR and BP at time 2 among EAs only; these associations were attenuated and not significant in AAs. HRV did not significantly predict cardiac output at time 2 in the full sample or split by ethnicity. Our findings highlight that AAs show TPR mediated long-term increases in BP irrespective of resting HRV, providing a physiological pathway linking AAs with a greater risk for mortality and morbidity from hypertension and potentially other cardiovascular disease. [ABSTRACT FROM AUTHOR]

Non‐medical prescription opioid use (NMPOU) is at the heart of the opioid epidemic in the United States. Although chronic opioid use is commonly accompanied by deficits in social functioning, little is known about the impact of chronic NMPOU on social cognitive functions. Social neuroscience models suggest that empathy activates similar or even equivalent neural structures as those underpinning the first‐hand experience in that emotional state (e.g., pain). Therefore, we measured subjective and psychophysiological responses during an empathy‐for‐pain task in 23 individuals with NMPOU, objectively confirmed by hair and urine testing, and compared them with 29 opioid‐naïve healthy controls. NMPOU individuals showed lower other‐related and self‐related unpleasantness ratings when seeing others in pain than controls. No differences between the control and NMPOU group were found in skin conductance responses and heart rate variability (HRV) assessed by root mean square of successive differences (RMSSD) in response to the task. However, RMSSD‐HRV was strongly negatively correlated with self‐related unpleasantness and craving in the NMPOU group. A subsequent mediation analysis showed a total effect of RMSSD‐HRV on self‐related unpleasantness with no mediation of craving. This indicates that stronger emotion regulation indexed by high RMSSD‐HRV might have downregulating effects on sharing others' pain in NMPOU individuals but not in healthy controls, which was further accompanied by decreased ratings of personal distress and empathetic concern. These results contribute to a better understanding of social functioning in chronic opioid users, suggesting adequate emotion regulation and empathy trainings as therapeutic targets for future interventions of opioid use disorders and long‐term pain treatment with opioids. Our study provides novel insights into empathy for pain in individuals with non‐medical prescription opioid use (NMPOU) supporting social neuroscience models of empathy. Furthermore, the association with empathy for pain and heart rate variability in the NMPOU group suggests new implications for improved interventions of opioid dependence and long‐term opioid treatment for pain. [ABSTRACT FROM AUTHOR]

The cumulative science linking stress to negative health outcomes is vast. Stress can affect health directly, through autonomic and neuroendocrine responses, but also indirectly, through changes in health behaviors. In this review, we present a brief overview of (a) why we should be interested in stress in the context of health; (b) the stress response and allostatic load; (c) some of the key biological mechanisms through which stress impacts health, such as by influencing hypothalamic-pituitary-adrenal axis regulation and cortisol dynamics, the autonomic nervous system, and gene expression; and (d) evidence of the clinical relevance of stress, exemplified through the risk of infectious diseases. The studies reviewed in this article confirm that stress has an impact on multiple biological systems. Future work ought to consider further the importance of early-life adversity and continue to explore how different biological systems interact in the context of stress and health processes. [ABSTRACT FROM AUTHOR]

Background: African Americans have the highest rates of hypertension-related disease of any ethnic group in the USA. Importantly, racism and discrimination have been linked to these higher rates of morbidity and mortality. Discrimination is deleterious not only to those that are the recipients of this unfair treatment but also to the partners and family members of those affected as well to those that perpetrate this bias.Purpose: In this paper, we identify a unique pattern of physiological response to unfair treatment, we have called the "cardiovascular conundrum." This pattern is characterized by greater heart rate variability and greater total peripheral resistance in African Americans compared to their European American counterparts.Methods and Results: We review the evidence supporting the existence of this pattern and propose several physiological and psychological factors that might underpin it. We also propose a number of factors that might help to mitigate the deleterious effects associated with it.Conclusions: Whereas the context of the current review is on Black/White disparities the framework we propose may be relevant to others exposed to unfair treatment. Ultimately, the systemic factors that perpetuate these inequalities will require that we first acknowledge and then face the challenges they present if we are to address the wealth and health disparities in our country. [ABSTRACT FROM AUTHOR]

The neurovisceral integration (NVI) model was originally proposed to account for observed relationships between peripheral physiology, cognitive performance, and emotional/physical health. This model has also garnered a considerable amount of empirical support, largely from studies examining cardiac vagal control. However, recent advances in functional neuroanatomy, and in computational neuroscience, have yet to be incorporated into the NVI model. Here we present an updated/expanded version of the NVI model that incorporates these advances. Based on a review of studies of structural/functional anatomy, we first describe an eight - level hierarchy of nervous system structures, and the contribution that each level plausibly makes to vagal control. Second, we review recent work on a class of computational models of brain function known as “predictive coding” models. We illustrate how the computational dynamics of these models, when implemented within our proposed vagal control hierarchy, can increas e understanding of the relationship between vagal control and both cognitive performance and emotional/physical health. We conclude by discussing novel implications of this updated NVI model for future research. [ABSTRACT FROM AUTHOR]

Given the intrinsic connection between the brain and the heart, a recent body of research emerged with the aim to influence cardiovascular system functioning by non-invasive brain stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Despite the implications of cardiovascular activity modulation for therapeutic purposes, such effects of NIBS have not yet been quantified. The aim of this study was to meta-analyze studies on NIBS effects on blood pressure (BP), heart rate (HR) and its variability (HRV). PubMed and Scopus databases were searched for English language studies conducted in humans. Twenty-nine studies were eligible for the analyses. Pooled effect sizes (Hedges’ g ) were compared. Random effect models were used. NIBS was effective in reducing HR ( g = 0.17) and enhancing HRV ( g = 0.30). A marginal effect emerged for BP ( g = 0.21). Significant moderators were the stimulation technique and the site of stimulation. Results show that NIBS affects cardiovascular and autonomic nervous system activity, confirming a potential pathogenic brain-heart pathway to cardiovascular disease. [ABSTRACT FROM AUTHOR]

Intraindividual reaction time variability (IIV), defined as the variability in trial-to-trial response times, is thought to serve as an index of central nervous system function. As such, greater IIV reflects both poorer executive brain function and cognitive control, in addition to lapses in attention. Resting-state vagally mediated heart rate variability (vmHRV), a psychophysiological index of self-regulatory abilities, has been linked with executive brain function and cognitive control such that those with greater resting-state vmHRV often perform better on cognitive tasks. However, research has yet to investigate the direct relationship between resting vmHRV and task IIV. The present study sought to examine this relationship in a sample of 104 young and healthy participants who first completed a 5-min resting-baseline period during which resting-state vmHRV was assessed. Participants then completed an attentional (target detection) task, where reaction time, accuracy, and trial-to-trial IIV were obtained. Results showed resting vmHRV to be significantly related to IIV, such that lower resting vmHRV predicted higher IIV on the task, even when controlling for several covariates (including mean reaction time and accuracy). Overall, our results provide further evidence for the link between resting vmHRV and cognitive control, and extend these notions to the domain of lapses in attention, as indexed by IIV. Implications and recommendations for future research on resting vmHRV and cognition are discussed. [ABSTRACT FROM AUTHOR]

The present meta-analysis aimed to quantify current evidence on sex differences in the autonomic control of the heart, indexed by measures of heart rate variability (HRV) in healthy human subjects. An extensive search of the literature yielded 2020 titles and abstracts, of which 172 provided sufficient reporting of sex difference in HRV. Data from 63,612 participants (31,970 females) were available for analysis. Meta-analysis yielded a total of 1154 effect size estimates ( k ) across 50 different measures of HRV in a cumulated total of 296,247 participants. Females showed a significantly lower mean RR interval and standard deviation of RR intervals (SDNN). The power spectral density of HRV in females is characterized by significantly less total power that contains significantly greater high- (HF) and less low-frequency (LF) power. This is further reflected by a lower LF/HF ratio. Meta-regression revealed significant effects of age, respiration control and the length of recording available for analysis. Although women showed greater mean heart rate, they showed greater vagal activity indexed by HF power of HRV. Underlying mechanisms of these findings are discussed. [ABSTRACT FROM AUTHOR]

Patients with high cervical complete spinal cord injuries (tetraplegia) sustain damage to the autonomic neural pathways that influence cardiovascular functioning and produce variability in the heart rate (HR) and blood pressure (BP). In non-injured individuals, an inverse relationship exists between resting autonomic control of the heart (as evidenced by HR variability (HRV)) and BP variability (BPV). This study examined the relationship between HRV, BP and BPV in individuals with tetraplegic ( n = 10) and paraplegic ( n = 10) spinal cord injuries, and a group of healthy controls ( n = 14). Resting HRV at baseline and 24-hour ambulatory BP measurements were collected from electrocardiogram measures of each participant. HRV was quantified using time- and frequency-domain measures. The standard deviation of the BP measurements was used as an index of BPV. Multivariate analyses of variance were performed to examine group differences for laboratory-based and 24-h dependent variables. The MANOVAs for HRV parameters (λ (14,50) = .352, p = .010, η 2 = .407) and for BP indices and HR (λ (16,48) = .318, p = .013, η 2 = .436) were significant. Furthermore, in line with existing evidence, we found that vagally mediated HRV was inversely related to BPV in healthy controls. However, this relationship did not hold for the tetraplegia group (ρ < |.42 |), and mixed results were found for the paraplegia group (e.g., ρ < |.29 | for time domain HRV, ρ > |.65 | for low-frequency power). These results support the conclusion that the damage to the spinal sympathetic pathways to the heart found in people with tetraplegia causes a significant disruption in baroreflex control of BP. [ABSTRACT FROM AUTHOR]

The study explored the relationship between time- and frequency-domain indices of cardiac autonomic control and 24 h blood pressure variability (BPV) in a sample of healthy men and women. Vagally mediated cardiac control was inversely related to 24 h BPV, and measures of cardiac autonomic control were better predictors of systolic BPV in men and better predictors of diastolic BPV in women. These findings may help researchers to understand the disparity in cardiovascular disease morbidity and mortality between men and women. [ABSTRACT FROM AUTHOR]

The Research Domain Criteria (RDoC), developed by the National Institute of Mental Health as a neuroscience-informed alternative to traditional psychiatric nosology, is an explicitly dimensional system in which classification of psychopathology is derived inductively (i.e., from basic science), across multiple levels of analysis (e.g., genetic, neural, psychophysiological, and behavioral). Although RDoC is often presented as paradigmatically revolutionary, a review of the history of psychophysiology suggests that roots of RDoC thinking extend at least as far back as the mid-20th Century. In this paper, we briefly and selectively review the historical emergence of neurobiologically-informed dimensional trait models of psychopathology, and we summarize our thinking regarding high frequency heart rate variability (HF-HRV) as a transdiagnostic biomarker of self-regulation and cognitive control. When functional interactions between HF-HRV and systems of behavioral approach and avoidance are considered, diverse patterns of behavioral maladjustment can be subsumed into a single model. This model accommodates the general bifactor structure of psychopathology, and suggests that HF-HRV can be viewed as an autonomic, transdiagnostic biomarker of mental illness. [ABSTRACT FROM AUTHOR]

Following a stressful life event, there is considerable variation in how individuals respond and adapt. Multiple models of risk and resilience show that adverse childhood experiences may be associated with an individual's response to stress later in life. While there is considerable support that early adversity can sensitize the stress response system and lead to adverse outcomes later in life, there is mounting evidence that in adolescence and young adulthood, certain biological predispositions to stress may be associated with resilience in the context of subsequent stressors. In this study, we evaluated how individual differences in vagally mediated heart rate variability moderated the relationship between childhood maltreatment and grief among a sample of individuals experiencing a stressful life event (i.e., spousal bereavement) over time. Data were collected at approximately 3, 4.5, and 6.5 months after the death of a spouse (n = 130). Heart rate variability moderated the relationship between childhood maltreatment and grief symptoms over time (b = −0.03, p <.001), such that among individuals with more severe experiences of childhood maltreatment, those with higher heart rate variability had a faster recovery from grief than those with low heart rate variability. This research highlights an overall pattern of resilience among older adult's following spousal bereavement, as well as the relationships between childhood maltreatment, heart rate variability, and differential responses to grief following the loss of a spouse. Public Significance Statement: Childhood maltreatment and heart rate variability may be related to differential responses to grief among bereaved spouses over time. Among bereaved spouses with a history of childhood maltreatment, those with higher heart rate variability experienced faster recovery from grief symptoms than bereaved spouses with lower heart rate variability. These findings suggest a pathway to intervention may include increased heart rate variability to mitigate the relationship between adverse childhood experiences and adjustment to stressors later in life, particularly among older adults. [ABSTRACT FROM AUTHOR]

We have previously shown that persons with low HRV showed potentiated startle responses to neutral stimuli. In the present study we replicated our prior findings and extended them to examine the effects of HRV on the startle magnitude to pictures that were presented outside of conscious awareness. A total of 85 male and female students were stratified via median split on their resting HRV. They were presented pictures for 6 s or for 30 ms. Results indicated that the high HRV group showed the context appropriate startle magnitude increase to unpleasant foreground. The low HRV group showed startle magnitude increase from pleasant to neutral pictures but no difference between the neutral and unpleasant pictures. This pattern of results was similar for the 30 ms and the 6 s conditions. These results suggest that having high HRV may allow persons to more efficiently process emotional stimuli and to better recognize threat and safety signals. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to assess the relationship between autonomic nervous system activity as indexed by measures of heart rate variability and overnight urinary norepinephrine, and plasma cholesterol levels in a large sample of working adults. Methods: The study population comprised 611 apparently healthy employees of an airplane manufacturing plant in Southern Germany. Heart rate variability was calculated as beat-to-beat intervals over the course of one 24-hour weekday measured with an ambulatory ECG recorder. Overnight urine collection and blood samples were also obtained. Results: We found an inverse association between indices of vagally-mediated heart rate variability and plasma levels of total cholesterol, low density lipoprotein (LDL), and the ratio of LDL to high density lipoprotein (HDL) that remained significant in multivariate models after controlling for relevant covariates including norepinephrine. Urinary norepinephrine was not significantly related to any measure of cholesterol in multivariate models. Conclusions: We report here for the first time, in a large sample of healthy human adults, evidence supporting the hypothesis of a clinically relevant inverse relationship between measures of plasma cholesterol and vagally-mediated heart rate variability after controlling for sympathetic nervous system activity. This suggests an important role for the vagal control of plasma cholesterol levels in cardiovascular disease. [Copyright &y& Elsevier]

The last decade has seen significant progress in identifying sleep mechanisms that support cognition. Most of these studies focus on the link between electrophysiological events of the central nervous system during sleep and improvements in different cognitive domains, while the dynamic shifts of the autonomic nervous system across sleep have been largely overlooked. Recent studies, however, have identified significant contributions of autonomic inputs during sleep to cognition. Yet, there remain considerable gaps in understanding how central and autonomic systems work together during sleep to facilitate cognitive improvement. In this article we examine the evidence for the independent and interactive roles of central and autonomic activities during sleep and wake in cognitive processing. We specifically focus on the prefrontal-subcortical structures supporting working memory and mechanisms underlying the formation of hippocampal-dependent episodic memory. Our Slow Oscillation Switch Model identifies separate and competing underlying mechanisms supporting the two memory domains at the synaptic, systems, and behavioral levels. We propose that sleep is a competitive arena in which both memory domains vie for limited resources, experimentally demonstrated when boosting one system leads to a functional trade-off in electrophysiological and behavioral outcomes. As these findings inevitably lead to further questions, we suggest areas of future research to better understand how the brain and body interact to support a wide range of cognitive domains during a single sleep episode. [ABSTRACT FROM AUTHOR]

Abstract: The intimate connection between the brain and the heart was enunciated by Claude Bernard over 150 years ago. In our neurovisceral integration model we have tried to build on this pioneering work. In the present paper we further elaborate our model and update it with recent results. Specifically, we performed a meta-analysis of recent neuroimaging studies on the relationship between heart rate variability and regional cerebral blood flow. We identified a number of regions, including the amygdala and ventromedial prefrontal cortex, in which significant associations across studies were found. We further propose that the default response to uncertainty is the threat response and may be related to the well known negativity bias. Heart rate variability may provide an index of how strongly ‘top–down’ appraisals, mediated by cortical-subcortical pathways, shape brainstem activity and autonomic responses in the body. If the default response to uncertainty is the threat response, as we propose here, contextual information represented in ‘appraisal’ systems may be necessary to overcome this bias during daily life. Thus, HRV may serve as a proxy for ‘vertical integration’ of the brain mechanisms that guide flexible control over behavior with peripheral physiology, and as such provides an important window into understanding stress and health. [Copyright &y& Elsevier]

Previous research investigating the emotion recognition ability in patients with schizophrenia has mainly focused on the recognition of facial expressions. To broaden our understanding of emotional processes in patients with schizophrenia, this study aimed to investigate whether these patients experience and process other emotionally evocative stimuli differently from healthy participants. To investigate this, we measured the cardiac and subjective responses of 33 male patients (9 with and 24 without antipsychotic medication) and 40 male control subjects to emotion-eliciting pictures. Cardiac responses were chosen as an outcome measure because previous research has indicated that these are linked with attentional and emotional processes and provide a more objective measure than self-report measures alone. The differences in cardiac responses between patients and controls were limited to medicated patients: only the medicated patients showed significantly decreased cardiac orienting responses compared with control subjects, regardless of picture contents. These results indicate that medicated patients directed less attention towards emotion-eliciting pictures than controls. Decreased attentional resources while processing emotional evocative stimuli could lead to incorrect appraisals of the environment and may have detrimental emotional and social consequences, contributing to chronic stress levels and an increased risk for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract: Inflammation and immunity have been implicated in a wide variety of diseases and disorders ranging from asthma to cardiovascular disease to hemorrhagic shock. In this review we will briefly consider the evidence for the neural concomitants of immunomodulation. First, we will briefly review the anatomy and physiology of the cardiorespiratory system. Then we will review the anatomy and physiology of neural–immune communication. The nucleus of the solitary tract is a site of integration of both the afferent and efferent neural regulation of the cardiorespiratory as well as the immune system. Then we will provide an overview of what is known about neuroimmunomodulation from both animal and human studies including neuroimaging and clinical studies. Finally, we will discuss a possible role of this neural circuitry in asthma related health disparities. [Copyright &y& Elsevier]

Abstract: Inflammation and immunity have been implicated in a wide variety of diseases and disorders ranging from Alzheimer’s disease to cardiovascular disease to hemorrhagic shock. In this review, we will briefly consider the evidence for the neural concomitants of immunomodulation. First, we will briefly review the anatomy and physiology of neural-immune communication. Evidence for the somatotopic organization of the vagus nerve and for pain processes suggests that such an organization may be relevant for the investigation of the neural concomitants of immunity. Then we will provide an overview of what is known from both animal and human studies including neuroimaging and clinical studies. Finally, we will discuss some of the challenges and opportunities in this exciting area of investigation. [ABSTRACT FROM AUTHOR]

Abstract: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The understanding of the risk factors for CVD may yield important insights into the prevention, etiology, course, and treatment of this major public health concern. Autonomic imbalance, characterized by a hyperactive sympathetic system and a hypoactive parasympathetic system, is associated with various pathological conditions. Over time, excessive energy demands on the system can lead to premature aging and diseases. Therefore, autonomic imbalance may be a final common pathway to increased morbidity and mortality from a host of conditions and diseases, including cardiovascular disease. Heart rate variability (HRV) may be used to assess autonomic imbalances, diseases and mortality. Parasympathetic activity and HRV have been associated with a wide range of conditions including CVD. Here we review the evidence linking HRV to established and emerging modifiable and non-modifiable CVD risk factors such as hypertension, obesity, family history and work stress. Substantial evidence exists to support the notion that decreased HRV precedes the development of a number of risk factors and that lowering risk profiles is associated with increased HRV. We close with a suggestion that a model of autonomic imbalance may provide a unifying framework within which to investigate the impact of risk factors, including psychosocial factors and work stress, on cardiovascular disease. [Copyright &y& Elsevier]

Reduced heart rate variability (HRV) and delayed blood pressure recovery are associated with increased cardiovascular risk. Besides this evident link, the vagus is thought to play an inhibitory role in the regulation of other allostatic systems, including inflammation and the hypothalamic-pituitary-adrenal (HPA) axis. However, human evidence is scarce. To further explore these associations and with special regard to the postulated mediating role of the vagus, we hypothesised that subjects with low vagal tone as indexed by reduced resting HRV would show impaired post-stress recovery of cardiovascular, endocrine and immune system markers involved in cardiovascular pathology. 44 healthy men underwent a standardised mental stress test. Besides continuous measurement of systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and HRV serum cortisol, tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured before, after, 20, and 60 min after stress. Low versus high HRV groups was defined by median split on resting HRV (RMSSD). The task elicited significant time effects for SBP, DBP, HR, HRV, cortisol, and TNF-alpha. Subjects with low baseline HRV showed almost no modulation of HRV coupled with overall reduced HRV levels, and impaired recovery of DBP, cortisol, and TNF-alpha. Confirming our hypothesis, low vagal tone was associated with impaired recovery of cardiovascular, endocrine, and immune markers in healthy males. The data support an inhibitory role of the vagus in the regulation of allostatic systems as described in the neurovisceral integration model. We posit reduced resting HRV as a risk marker for future cardiovascular and other stress-related disease. [ABSTRACT FROM AUTHOR]

DESPITE A WEALTH OF EVIDENCE FOR THE INVOLVEMENT of the autonomic nervous system (ANS) in health and disease and the ability of music to affect ANS activity, few studies have systematically explored the therapeutic effects of music on ANS dysfunction. Furthermore, whep ANS activity is quantified and analyzed, it is usually from a point of convenience rather than from an understanding of its physiological basis. After a review of the experimental and therapeutic literatures exploring music and the ANS, a "Neurovisceral Integration" perspective on the interplay between the central and autonomic nervous systems is introduced, and the associated implications for physiological, emotional, and cognitive health are explored. The construct of heart rate variability is discussed both as an example of this complex interplay and as a useful metric for exploring the sometimes subtle effect of music on autonomic response. Suggestions for future investigations using musical interventions are offered based on this integrative account. [ABSTRACT FROM AUTHOR]

Abstract: The Neurovisceral Integration Model is based on the premise of significant central nervous system–peripheral nervous system interactions. In support of this model we have previously shown that the prefrontal cortex tonically inhibits cardioacceleratory circuits as evidenced by increased heart rate (HR) when the prefrontal cortex is inactivated by injections of sodium amobarbitol (ISA) into the internal carotid artery. In this report we re-examine these data to investigate possible age-related differences in the prefrontal control of HR in humans. Seventy-three patients were divided into three groups based on a tertile split with mean ages of 20, 34, and 47, respectively. There were significant age-related differences in cortical control of HR as evidenced by a significant three way interaction of age (young, middle, old) by side (left versus right) by time (baseline and epochs 1–10 of inactivation) [Roy''s Root (10,59)=0.378, p =0.028]. Results showed significant HR increases that did not differ between hemispheres in the youngest age group, significant increases in the middle age group that were larger in the right hemisphere than in the left, and significant HR increases in the oldest group in the right hemisphere only. The findings suggest important age-related differences in cortical inhibitory control of HR that appear less lateralized in the youngest group and significantly attenuated in the oldest age group. These results have important implications for the understanding of age-related differences in cognitive, affective, behavioral, and physiological functioning. In addition they support the importance of investigating central nervous system–peripheral nervous system relationships. [Copyright &y& Elsevier]

An introduction to the journal is presented in which the author discusses an article on the role of executive functioning (EF) in relation with the maintenance and change of health behavior, stress regulation and developmental trajectories of aging and mortality.

In the present paper, we describe a model of neurovisceral integration in which a set of neural structures involved in cognitive, affective, and autonomic regulation are related to heart rate variability (HRV) and cognitive performance. We detail the pathways involved in the neural regulation of the cardiovascular system and provide pharmacological and neuroimaging data in support of the neural structures linking the central nervous system to HRV in humans. We review a number of studies from our group showing that individual differences in HRV are related to performance on tasks associated with executive function and prefrontal cortical activity. These studies include comparisons of executive- and nonexecutive-function tasks in healthy participants, in both threatening and nonthreatening conditions. In addition, we show that manipulating resting HRV levels is associated with changes in performance on executive-function tasks. We also examine the relationship between HRV and cognitive performance in ecologically valid situations using a police shooting simulation and a naval navigation simulation. Finally, we review our studies in anxiety patients, as well as studies examining psychopathy. These findings in total suggest an important relationship among cognitive performance, HRV, and prefrontal neural function that has important implications for both physical and mental health. Future studies are needed to determine exactly which executive functions are associated with individual differences in HRV in a wider range of situations and populations. [ABSTRACT FROM AUTHOR]

Abstract: The intimate connection between the brain and the heart was enunciated by Claude Bernard over 150 years ago. In our neurovisceral integration model we have tried to build on this pioneering work. In the present paper we further elaborate our model. Specifically we review recent neuroanatomical studies that implicate inhibitory GABAergic pathways from the prefrontal cortex to the amygdala and additional inhibitory pathways between the amygdala and the sympathetic and parasympathetic medullary output neurons that modulate heart rate and thus heart rate variability. We propose that the default response to uncertainty is the threat response and may be related to the well known negativity bias. We next review the evidence on the role of vagally mediated heart rate variability (HRV) in the regulation of physiological, affective, and cognitive processes. Low HRV is a risk factor for pathophysiology and psychopathology. Finally we review recent work on the genetics of HRV and suggest that low HRV may be an endophenotype for a broad range of dysfunctions. [Copyright &y& Elsevier]

Research suggests equivocal findings on associations of catecholamines and mood. Our study investigated the associations of emotional state, blood pressure and catecholamines in 55 healthy males undergoing mental stress. We especially checked the reported link between norepinephrine (NE) and emotional irritation. Blood pressure (SBP, DBP) and heart rate (HR) were continuously monitored. NE and epinephrine (EPI) were measured before, after, and 20 minutes after stress. Participants were divided into irritated versus non-irritated and anxious versus non-anxious subjects by median split on their baseline questionnaires. The task elicited significant cardiovascular, hormonal, and psychological stress responses. NE levels were significantly correlated with irritation before stress. Irritated subjects showed significantly higher DBP and NE than non-irritated subjects. The higher NE and DBP levels in the irritated participants suggest detrimental psycho-physiological interrelations promoting the development of stress-mediated cardiovascular diseases. Heightened emotional irritation before stress may be regarded as a psychological risk factor. [ABSTRACT FROM AUTHOR]

Abstract: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The understanding of the risk factors for CVD may yield important insights into the prevention, etiology, course, and treatment of this major public health concern. We review the evidence for the role of vagal function in the risk for cardiovascular disease and mortality. Using a broad range of indicators of vagal function including resting heart rate, heart rate recovery, heart rate variability, and baroreflex sensitivity we show that decreased vagal function is associated with an increased risk for morbidity and mortality. These effects are independent of traditional risk factors. Moreover, we show that decreased vagal function is associated with both traditional and emerging risk factors as well as modifiable and non-modifiable risk factors. Most importantly, we provide evidence to support the notion that decreased vagal function precedes the development of a number of risk factors and that modification of risk profiles in the direction of lower risk is associated with increased vagal function. We close with a brief overview of the neural concomitants of vagal function and suggest that a model of neurovisceral integration may provide a unifying framework within which to investigate the impact of risk factors, including psychosocial factors, on cardiovascular disease. [Copyright &y& Elsevier]

The autonomic nervous system (ANS) plays a role in a wide range of somatic and mental diseases. Whereas the role of the ANS in the regulation of the cardiovascular system seems evident, its role in the regulation of other systems associated with allostasis is less clear. Using a model of neurovisceral integration we describe how the ANS and parasympathetic tone in particular may be associated with the regulation of allostatic systems associated with glucose regulation, hypothalamic-pituitary-adrenal (HPA) axis function, and inflammatory processes. Decreased vagal function and heart rate variability (HRV) were shown to be associated with increased fasting glucose and hemoglobin A1c levels, increased overnight urinary cortisol, and increased proinflammatory cytokines and acute-phase proteins. All of these factors have been associated with increased allostatic load and poor health. Thus, vagal activity appears to play an inhibitory function in the regulation of allostatic systems. The prefrontal cortex and the amygdala are important central nervous system structures linked to the regulation of these allostatic systems via the vagus nerve. Finally, the identification of this neurovisceral regulatory system may help to illuminate the pathway via which psychosocial factors may influence health and disease. [ABSTRACT FROM AUTHOR]

Abstract: Associations of inter- and intra-individual differences in anxiety and fear with within subject variability in breathing parameters were explored. Timing and volume components of respiration and FETCO2 were measured non-intrusively before and during anxious and fearful imagery in 98 young women. Trait anxiety was associated with less variability in several breathing parameters during baseline preceding imagery. Significant decreases in the variability of expiratory time and inspiratory drive were also observed during anxious imagery. During fearful imagery, however, the variability of FETCO2 increased compared to baseline. Results on anxiety are largely in agreement with models that posit that healthy systems are characterized by variability and flexibility. The paradoxical findings for fearful imagery enhance the importance of a distinction between fearful and anxious affects. [Copyright &y& Elsevier]

Abstract: In the present paper we describe a model of neurovisceral integration in which a set of neural structures involved in cognitive, affective and autonomic regulation are related to heart rate variability (HRV) and health. We show that autonomic imbalance is associated with increased morbidity and mortality. We also provide evidence that this autonomic imbalance can be indexed by HRV. We then provide pharmacological and neuroimaging data in support of the neural structures linking the central nervous system to HRV. Next, in an experiment investigating emotional regulation we showed that resting levels of HRV were related to emotion modulated startle responses such that those with higher HRV produced context appropriate responses compared with those with low HRV. We then show that stimuli presented outside of conscious awareness lead to potentiated startle responses and undifferentiated phasic HR responses. These results suggest that the prefrontal cortex may modulate responses to threat via a top-down regulation of sympathoexcitatory circuits. We propose that these findings have important implications for the understanding of the two-way communication between the heart and the brain, and provide a connection among negative emotions and negative health consequences via the common mechanism of autonomic imbalance and low parasympathetic activity. [Copyright &y& Elsevier]

Abstract: Alcoholism and heavy drinking are associated with a number of physiological, behavioral, affective, and cognitive problems. One such problem involves dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, with alcoholics showing higher basal cortisol levels and reduced inhibitory feedback control. In addition, alcohol consumption is associated with decreased heart rate variability (HRV). In the present study we examined the relationships among alcohol consumption, cortisol excretion, and HRV in 542 apparently healthy men. Men in the top tertile of self-reported alcohol consumption had higher cortisol levels and lower HRV compared to men in the lower two tertiles of alcohol consumption. In addition, the inverse relationship between cortisol and HRV was greatly attenuated in the heavy drinking group even after accounting for a number of potential confounding factors. These results support prior research on the HPA axis dysregulation in alcoholics and suggest impaired inhibitory control of the HPA axis in heavy drinkers. The findings are consistent with the neurovisceral integration model, which links central and peripheral processes, and may provide a comprehensive framework for the future investigation of the complex mix of physiological, behavioral, affective, and cognitive factors which comprise the heavy drinking phenotype. [Copyright &y& Elsevier]

Inhibitory processes provide for the sculpting of neural action at all levels of the neuraxis. Importantly, it appears that this inhibitory function may be decidedly nonlinear in nature such that a little inhibition goes a long way in guiding the behavior of neural systems. The neural control of the heart is used as a model system to illustrate the nature of this nonlinear inhibitory control. Similar inhibitory processes function in the prefrontal cortex, in the amygdala, and between the prefrontal cortex and the amygdala in the service of organism flexibility, adaptability, and health. It is suggested that a dynamical systems perspective of neural regulation involving nonlinear inhibitory processes may be a useful framework within which to investigate the complex behavior associated with health and disease. [ABSTRACT FROM AUTHOR]

Summary: The autonomic nervous system (ANS) plays a role in a wide range of somatic and mental diseases. Using a model of neurovisceral integration, this article describes how autonomic imbalance and decreased parasympathetic tone in particular may be the final common pathway linking negative affective states and conditions to ill health. The central nervous system (CNS) network that regulates autonomic balance (central autonomic network, CAN) is closely related and partially overlaps with networks serving executive, social, affective, attentional, and motivated behavior (anterior executive region, AER; and Damasio''s [Damasio, A.R., 1998. Emotion in the perspective of an integrated nervous system. Brain Res. Rev. 26, 83–86.] ‘emotion circuit’). A common reciprocal inhibitory cortico-subcortical neural circuit serves to regulate defensive behavior, including autonomic, emotional and cognitive features. This inhibitory cortico-subcortical circuit may structurally, as well as functionally, link psychological processes with health-related physiology. When the prefrontal cortex is taken ‘offline’ for whatever reason, parasympathetic inhibitory action is withdrawn and a relative sympathetic dominance associated with disinhibited defensive circuits is released, which can be pathogenic when sustained for long periods. This state is indicated by low heart rate variability (HRV), which is a marker for low parasympathetic activation and prefrontal hypoactivity. Consistent with this, HRV is associated with a range of psychological and somatic pathological conditions, including immune dysfunction. Finally, we discuss supportive evidence from recent studies of the reflexive startle blink, attention and working memory, which shows that low HRV predicts hypervigilance and inefficient allocation of attentional and cognitive resources. [Copyright &y& Elsevier]

This study investigated whether heart rate variability (HRV) in young African-Americans differed from that in young European Americans. It further examined the genetic and/or environmental sources of HRV variance and to what extent they depend on ethnicity or gender in young twins. Subjects were available from 1 data set including 166 subjects (mean age 16 ± 2 years; 63 African-Americans) and another including 219 twins (11 singletons [4 African-Americans] and 104 pairs [42 African-Americans]; mean age 15 ± 2 years). HRV was measured over 256 RR intervals in a supine position. Two time-domain variables, the SD of normal RR intervals (SDNN) and the root-mean-square of successive differences (RMSSD) of normal RR intervals, and 3 frequency-domain variables, high-frequency (HF) power, low-frequency (LF) power, and the LF power/HF power ratio, were used. African-Americans had higher RMSSDs (p <0.01) and HF power (p = 0.047) and lower LF power/HF power ratios (p <0.01) than European Americans. These differences remained significant after adjusting for covariates. All HRV parameters were heritable; estimated heritability ranged from 32% to 71%. Model fitting showed no ethnic or gender differences for any measure. SDNN, RMSSD, and HF power were strongly correlated (r values >0.8). One factor explaining >90% of the variance for all 3 measures was identified. The heritability of this combined HRV score was 70%. In conclusion, this study suggests that ethnic differences in HRV already exist in youth, with African-Americans having greater HRV than European Americans. High heritability estimates for HRV measures were observed, and no differences in HRV heritability estimates were noted for ethnicity or gender. [Copyright &y& Elsevier]

Seventy-nine African-American participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) pilot study were genotyped for the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and had spectral power of their high-frequency (HF) heart rate variability (HRV) determined by fast-Fourier transformation. HF HRV was highest in II, intermediate in ID, and lowest in DD (II vs DD, p <0.043) genotypes, thus making an association of the ACE I/D DD genotype with decreased HF HRV that is consistent with the hypothesis that the DD genotype confers susceptibility to increased cardiovascular risk. The urban African-American population we studied had a particularly high cardiovascular risk, and these findings suggest that ACE I/D genotypes may modify that risk. [Copyright &y& Elsevier]

Summary. Recent ambulatory findings showing comparable cardiovascular effects of positive and negative emotions are not consistent with the assumed etiological role of negative affect in stress-related diseases. We tested the hypothesis that regardless of initial reactivity, responses associated with negative emotions would be prolonged compared to responses associated with positive emotions. During 8 h, 33 healthy subjects from a general population reported their emotional arousal, emotional valence and physical activity and recorded their heart rates (HR) after a beep at each 60th min (‘initial HR’; T0), followed by two ‘prolonged activation’ recordings, respectively 5 min later (T1) and 10 min later (T2). While emotional arousal and activity predicted initial HR, prolonged activation at T1 was solely predicted by emotional valence (negative affect) at T0, independent of emotional recovery. The results lend support to the hypothesis that cardiovascular activation after negative emotions last longer than after positive emotions. This finding is consistent with the view that prolonged activation, and not so much reactivity, might be a mechanism underlying the etiological role of negative emotions (‘stress’) in somatic disease. Perseverative cognition (worry, rumination) might be responsible for this prolonged activation. [Copyright &y& Elsevier]

The present study was designed to test the hypothesis of unconscious attending to alcohol-related information in alcoholics experiencing a high level of craving for alcohol. Subjects included a group of alcoholics (n=34) divided by a median split on a craving measure into two groups labeled as ‘high craving’ (n=18) and ‘low craving’ (n=16) alcoholics, and a non-alcoholic control group (n=39). The cardiovascular reactions of these groups were compared after their exposure to masked and unmasked alcohol and control stimuli. As expected the ‘high craving’ alcoholics showed an immediate heart rate deceleration after exposure to masked and non-consciously accessible alcohol pictures. The ‘high craving’ alcoholics reported a small but significant increase in difficulty resisting a drink after exposure to masked alcohol pictures. When the alcohol pictures were presented unmasked a significant increase was found in both high and low craving alcoholics on consciously expressed urges, fidgeting and reduced coping with temptation to drink. The ‘high craving’ alcoholics had lower tonic heart rate variability compared to the control group and the level of craving was positively associated with salivation during the exposure to all picture types. The findings generally support the psychobiological theory of craving, which suggests that the uncontrollability of the craving experience is rooted in unconscious processing of drug-related information. [Copyright &y& Elsevier]

An experiment was conducted to test the automatic analysis of briefly presented alcohol stimuli in alcohol-dependent individuals. Alcoholics and controls were exposed to four different conditions: two brief (30 ms) and two long (130 ms) exposure conditions, each containing alcoholic and non-alcoholic pictures. Heart rate (HR) interbeat intervals were recorded and phasic cardiac responses assessed. Alcoholics had a stronger initial HR deceleration after exposure to masked alcohol slides compared with masked control slides, indicating a preattentive analysis of alcohol stimuli. This initial HR deceleration in the masked condition suggests an automatic attentional focusing to degraded alcohol cues. No such attentional effect was found when the pictures were presented unmasked and were clearly perceived. The implication of these results for the understanding of relapse in addictive behavior is discussed. [ABSTRACT FROM AUTHOR]

Twenty patients with dental anxiety were investigated while seated in a dental chair in a dental clinic. Heart rate (HR), heart rate variability (HRV), and skin conductance level (SCL) were recorded while the patients were exposed to scenes of dental treatment as well as a Stroop attentional task. Results showed an attentional bias with longer manual reaction times (RT’s) to the incongruent compared to the congruent color words as well as the threat compared to the neutral words. Longer RT’s to the incongruent and the threat words were found in the low HRV patients compared to the high HRV patients. Furthermore, all patients showed an increase in HR during exposure and the Stroop task compared to baseline. The HRV showed a decrease during the exposure and the Stroop task compared to baseline. HR and HRV did not differ between exposure and the Stroop task. Moreover, HR and HRV did not return to baseline levels during the recovery period. The SCL showed an increase from baseline to exposure, from exposure to the Stroop task and a decrease in the recovery phase. Results showed the importance of vagal cardiac control in attentional, emotional, and physiological processes in patients suffering from dental fear. [Copyright &y& Elsevier]

Proposes a model that relates perseverative thinking to poor health via a network of neural structures that relates attention, emotion and autonomic activity. Nature of perseverative thinking; Relation of automatic control of the heart to perseverative thinking and cerebral blood flow; Functional units within the central nervous system that appear to support goal-directed behavior and adaptability.

Recent research on brain asymmetry and emotion treated measures of resting electroencephalograph (EEG) asymmetry as genuine trait variables, but inconsistency in reported findings and modest retest correlations of baseline asymmetry are not consistent with this practice. The present study examined the alternative hypothesis that resting EEG asymmetry represents a superimposition of a traitlike activation asymmetry with substantial state-dependent fluctuations. Resting EEG was collected from 59 participants on 4 occasions of measurement, and data were analyzed in terms of latent state-trait theory. For most scalp regions, about 60% of the variance of the asymmetry measure was due to individual differences on a temporally stable latent trait, and 40% of the variance was due to occasion-specific fluctuations, but measurement errors were negligible. Further analyses indicated that these fluctuations might be efficiently reduced by aggregation across several occasions. [ABSTRACT FROM AUTHOR]

There is increasing evidence that the behavior of living systems can be conceptualized as a self-organizing dynamical system. Moreover, evidence suggests that inhibitory processes give these systems the flexibility that is necessary for efficient functioning in the face of changing environmental demands. The process of sensitization can be conceived as a breakdown of inhibitory neural processes that can lead to maladaptive, perseverative behavior. In this paper we describe a model of inhibition and sensitization from a dynamical systems perspective. We show that inhibition is important for adaptive behavior across a number of levels of system functioning. Using our work on attention, emotion, and anxiety disorders we show the importance of both central - for example gamma-aminobutyric acid (GABA)-ergic - and peripheral - for example heart rate variability (HRV) - inhibitory processes and how they may be linked by a network of neural structures that guide the organism from one state of relative stability to another. [ABSTRACT FROM AUTHOR]

Presents a study which investigated the context of two studies on memory bias in generalized anxiety disorder (GAD). Methodology; Results; Discussion.

Details a study conducted to bridge the attentional and physiological underpinnings of generalized anxiety disorder (GAD) by examining phasic heart period responses to cued threat and nonthreat stimuli. Cardiac-autonomic underpinnings of GAD appearing to rigidly maintain precognitive defensive responses against threat.

Background: Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. Methods: Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aβ42, Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed. Results: All autonomic networks were positively associated with Aβ42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P =.004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. Conclusion: The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aβ42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications. [ABSTRACT FROM AUTHOR]