Julian F. Thayer

A model of neurovisceral integration in emotion regulation and dysregulation

In the present paper we present the outlines of a model that integrates autonomic, attentional, and affective systems into a functional and structural network that may help to guide us in our understanding of emotion regulation and dysregulation. We will emphasize the relationship between attentional regulation and affective processes and propose a group of underlying physiological systems that serve to integrate these functions in the service of self-regulation and adaptability of the organism. We will attempt to place this network in the context of dynamical systems models which involve feedback and feedforward circuits with special attention to negative feedback mechanisms, inhibitory processes, and their role in response selection. From a systems perspective, inhibitory processes can be viewed as negative feedback circuits that allow for the interruption of ongoing behavior and the re-deployment of resources to other tasks. When these negative feedback mechanisms are compromised, positive feedback loops may develop as a result (of dis-inhibition). From this perspective, the relative sympathetic activation seen in anxiety disorders may represent dis-inhibition due to faulty inhibitory mechanisms.

The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors

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.

Claude Bernard and the heart-brain connection : Further elaboration of a model of neurovisceral integration

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.

Autonomic characteristics of generalized anxiety disorder and worry

Autonomic characteristics of generalized anxiety disorder (GAD) and worry were examined using measures of heart period variability. The cardiorespiratory responses of 34 GAD clients and 32 nonanxious control subjects were recorded during resting baseline, relaxation, and worry periods. Results indicated differences between GAD subjects and controls as well as among baseline, relaxation, and worry periods. GAD clients exhibited shorter cardiac interbeat intervals (IBIs) and lower high frequency spectral power across all task conditions. Relative to baseline and relaxation conditions, worry was associated with (1) shorter IBIs, (2) smaller mean successive differences (MSD) of the cardiac IBIs, and (3) lower high frequency spectral power. These findings suggest that GAD and its cardinal feature (worry), are associated with lower cardiac vagal control. The findings of the present study provide evidence for the utility of further exploration of the role of autonomic nervous system activity in GAD.

The role of vagal function in the risk for cardiovascular disease and mortality.

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.

Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health.

BackgroundIn 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.MethodsWe 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.ConclusionThese 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.

Autonomic balance revisited: Panic anxiety and heart rate variability.

The analysis of heart rate variability (HRV) is becoming widely used in clinical research to provide a window into autonomic control of HR. This technique has been valuable in elucidating the autonomic underpinnings of panic disorder (PD), a condition that is marked by reports of heart palpitations. A body of research has emerged that implicates a relative reduction in HRV and cardiac vagal tone in PD, as indicated by various HRV measures. These data are consistent with the cardiac symptoms of panic attacks, as well as with developmental evidence that links high vagal tone with enhanced attention, effective emotion regulation, and organismic responsivity. Implications of these findings for nosology and pathophysiology are discussed. Reports of reduced HRV in PD contrast with portrayals of excess autonomic lability in anxiety. This contradiction is addressed in the context of traditional homeostatic models versus a systems perspective that views physiologic variability as essential to overall stability.

Vagal influence on working memory and attention

The aim of the present study was to investigate the effect of vagal tone on performance during executive and non-executive tasks, using a working memory and a sustained attention test. Reactivity to cognitive tasks was also investigated using heart rate (HR) and heart rate variability (HRV). Fifty-three male sailors from the Royal Norwegian Navy participated in this study. Inter-beat-intervals were recorded continuously for 5 min of baseline, followed by randomized presentation of a working memory test (WMT) based on Baddeley and Hitchs research (1974) and a continuous performance test (CPT). The session ended with a 5-min recovery period. High HRV and low HRV groups were formed based on a median split of the root mean squared successive differences during baseline. The results showed that the high HRV group showed more correct responses than the low HRV group on the WMT. Furthermore, the high HRV group showed faster mean reaction time (mRT), more correct responses and less error, than the low HRV group on the CPT. Follow-up analysis revealed that this was evident only for components of the CPT where executive functions were involved. The analyses of reactivity showed a suppression of HRV and an increase in HR during presentation of cognitive tasks compared to recovery. This was evident for both groups. The present results indicated that high HRV was associated with better performance on tasks involving executive function.

Neural correlates of heart rate variability during emotion.

The vagal (high frequency [HF]) component of heart rate variability (HRV) predicts survival in post-myocardial infarction patients and is considered to reflect vagal antagonism of sympathetic influences. Previous studies of the neural correlates of vagal tone involved mental stress tasks that included cognitive and emotional elements. To differentiate the neural substrates of vagal tone due to emotion, we correlated HF-HRV with measures of regional cerebral blood flow (rCBF) derived from positron emission tomography (PET) and (15)O-water in 12 healthy women during different emotional states. Happiness, sadness, disgust and three neutral conditions were each induced by film clips and recall of personal experiences (12 conditions). Inter-beat intervals derived from electrocardiographic recordings during the 60-second scans were spectrally-analyzed, generating 12 separate measures of HF-HRV in each subject. The six emotion and six neutral conditions were grouped together and contrasted. We observed substantial overlap between emotion-specific rCBF and the correlation between emotion-specific rCBF and HF-HRV, particularly in the medial prefrontal cortex. Emotion-specific rCBF also correlated with HF-HRV in the caudate nucleus, periacqueductal gray and left mid-insula. We also observed that the elements of cognitive control inherent in this experiment (that involved focusing on the target mental state) had definable neural substrates that correlated with HF-HRV and to a large extent differed from the emotion-specific correlates of HF-HRV. No statistically significant asymmetries were observed. Our findings are consistent with the view that the medial visceromotor network is a final common pathway by which emotional and cognitive functions recruit autonomic support.

A meta-analysis of fibromyalgia treatment interventions.

Objective: To evaluate and compare the efficacy of pharmacological and nonpharmacological treatments of fibromyalgia syndrome (FMS). Methods: This meta-analysis of 49 fibromyalgia treatment outcome studies assessed the efficacy of pharmacological and nonpharmacological treatment across four types of outcome measures—physical status, self-report of FMS symptoms, psychological status, and daily functioning. Results: After controlling for study design, antidepressants resulted in improvements on physical status and self-report of FMS symptoms. All nonpharmacological treatments were associated with significant improvements in all four categories of outcome measures with the exception that physically-based treatment (primarily exercise) did not significantly improve daily functioning. When compared, nonpharmacological treatment appears to be more efficacious in improving self-report of FMS symptoms than pharmacological treatment alone. A similar trend was suggested for functional measures. Conclusion: The optimal intervention for FMS would include nonpharmacological treatments, specifically exercise and cognitive-behavioral therapy, in addition to appropriate medication management as needed for sleep and pain symptoms.