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

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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.

Section snippets

Cortical control of cardiac activity

Heart rate is determined by intrinsic cardiac mechanisms and the joint activity of the sympathetic nerves and parasympathetic (vagus) nerves at the sinoatrial node. In healthy systems both branches of the autonomic nervous system are tonically active with sympathetic activity associated with heart rate acceleration and parasympathetic activity associated with heart rate deceleration (Jose and Collison, 1970, Levy, 1990). Importantly, heart rate in many species including humans is under tonic

The importance of inhibition

Sympathoexcitatory, cardioacceleratory subcortical threat circuits are under tonic inhibitory control by the prefrontal cortex (Amat et al., 2005, Thayer, 2006). As outlined above, the amygdala, which has outputs to autonomic, endocrine, and other physiological regulation systems, and becomes active during threat and uncertainty, is under tonic inhibitory control via GABAergic mediated projections from the prefrontal cortex (Thayer, 2006, Davidson, 2000). Importantly, we have proposed that the

Inhibition and the right prefrontal cortex

One of the primary functions associated with the prefrontal cortex is that of inhibition. Inhibitory processes are a component of many tasks associated with so-called executive functions including working memory, attentional set-shifting, and response inhibition. The prefrontal cortex has also been implicated in affective processes including emotional regulation, affective set-shifting, and extinction, all of which also rely heavily on inhibitory processes. It has been suggested that there is a

Physiological regulation

The regulation of physiological systems that are important for health and disease has been linked to vagal function and HRV. Thayer and Sternberg (2006) have recently summarized data linking HRV to glucose regulation, hypothalamic–pituitary–adrenal axis function, and inflammation. In addition, Thayer and Lane (2007) have recently reviewed the literature on the relationship between vagal function and the risk for cardiovascular disease (CVD) and stroke. The National Heart, Lung, and Blood

Emotional regulation

We and others have recently reviewed the literature on the relationship between HRV and emotional regulation (Thayer and Brosschot, 2005, Appelhans and Luecken, 2006). Emotional regulation is a valuable skill that has clear implications for health. Emotions represent a distillation of an individual's perception of personally relevant environmental interactions, including not only challenges and threats but also the ability to respond to them (Frijda, 1988). Viewed as such, emotions reflect the

Cognitive regulation

We have also recently reviewed our research on the relationship between HRV and cognitive regulation (Thayer and Johnsen, 2004, Thayer et al., 2005). Attentional regulation and the ability to inhibit prepotent but inappropriate responses are important for health in a complex environment. Many tasks important for survival in today's world involve cognitive functions such as working memory, sustained attention, behavioral inhibition, and general mental flexibility. These tasks are all associated

The genetics of HRV

The investigation of the genetics of HRV is currently an area of very active exploration both by our group and by others. Both behavioral and molecular genetic studies suggest that there is a significant genetic component to the individual differences in HRV including stress induced HRV changes (Boomsma et al., 1990, Wang et al., in press). Kupper et al. (2004) reported heritabilities for the time domain indices of SDNN (35–47%) and RMSSD (40–48%) in a large twin study of 772 participants

HRV as an endophenotype

It is possible that low vagally mediated HRV, as an index of activity in a set of neural structures involved in physiologic, affective, and cognitive regulation, may serve as a useful endophenotype for a range of physical and psychological disorders including psychopathology. For example in the context of psychopathology, the endophenotype concept represents an alternative to the traditional nosological categorization of disease as exemplified by the Diagnostic and Statistical Manual (Gottesman

Summary and conclusions

In 1865 Claude Bernard delivered a lecture at the Sorbonne on the physiology of the heart and its connections with the brain (Bernard, 1867). Therefore, we suspect that he would not be surprised to see the extensive evidence for the connections between the heart and the brain that we have reviewed here. In the neurovisceral integration model we have proposed that the relationship between HRV and important physiological, cognitive, and emotional regulation functions is due to the ability of HRV

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