Brain-Body Pathways Linking Psychological Stress and Physical Health

Abstract

Psychological stress is thought to arise from appraisal processes that ascribe threat-related meaning to experiences that tax or exceed our coping ability. Neuroimaging research indicates that these appraisal processes originate in brain systems that also control physiological stress reactions in the body. Separate lines of research in health psychology and behavioral medicine indicate that these physiological stress reactions confer risk for physical disease. Accordingly, integrative research that cuts across historically separated disciplines may help to define the brain-body pathways linking psychological stress to physical health. We describe recent studies aimed at this goal, focusing on studies of the brain bases of stressor-evoked cardiovascular system reactions and heart disease risk. We also outline an interpretive framework for these studies, as well as needs for next-generation models and metrics to better understand how the brain encodes and embodies stress in relation to health.

Keywords: appraisal; health; neuroimaging; stress.

Figure 1

Four core elements comprise at least one kind of brain-body pathway linking psychological stress and physiological stress reactions to physical health. The first encompasses networked brain systems that appraise internal and external sources of information as threats that tax or exceed coping resources and translate these appraisals into visceromotor commands. These systems likely include the anterior mid-cingulate cortex (aMCC), pregenual anterior cingulate cortex (pgACC), subgenual anterior cingulate cortex (sgACC), and ventromedial prefrontal cortex (vmPFC). The second encompasses visceromotor (e.g., autonomic nervous system) channels that translate appraisal-based neural commands into a change in an end organ state in the body (e.g., a rise in blood pressure and heart rate). A corollary of this third component is that the patterning of the end-organ state change (e.g., a sizeable and sustained rise in blood pressure or heart rate) should plausibly relate to disease progression or risk. For example, chronically large or prolonged rises in blood pressure may exert shear or tensile stress on blood vessel walls over time, possibly accelerating atherosclerosis and influencing risk for later heart disease. The fourth component encompasses viscerosensory (e.g., autonomic nervous system) channels that relay feedback signals from the body, enabling the representation of end organ state changes in the brain. The interaction between appraisal systems and visceromotor and viscerosensory channels may thus represent part of the possible basis for stress-health relationships.

Figure 2

Brain regions where neural activity has been associated with cardiovascular and cardiac autonomic physiology in neuroimaging studies. A) Areas of the mPFC coded in yellow indicate where activity was associated with heart rate reactivity to social stressor involving evaluative threat (Wager et al., 2009, Neuroimage, 47, 821–835; Wager et al., 2009, Neuroimage, 47, 836–851); areas of the mPFC coded in red indicate where activity was associated with blood pressure reactivity to a cognitive stressor (Gianaros et al., 2005, Psychophysiology, 42, 627–635). B) An illustrative summary of brain regions where changes in cardiovascular and cardiac autonomic activity have been associated with neural activity in existing neuroimaging studies (a complete reference list of the studies contributing to this summary is available on request). Areas in warmer colors (red and yellow) correspond to brain coordinates where increases in neural activity have been associated with ‘pro-sympathetic’ or ‘anti-parasympathetic’ autonomic responding, as reflected by increases in heart rate and blood pressure and decreases in high-frequency heart rate variability (HRV). Areas in cooler colors (blue and light blue) correspond to brain coordinates where increases in neural activity have been associated with ‘anti-sympathetic’ or ‘pro-parasympathetic’ responding, as reflected by decreases in heart rate and blood pressure and increases in high-frequency heart rate variability (HRV). mACC, mid-anterior cingulate cortex; pgACC, pregenual anterior cingulate cortex.

Figure 3

Illustration of selected brain areas engaged by psychological stressors and related to the expression of stressor-evoked cardiovascular (blood pressure and heart rate) responses, presumably via interactions with the baroreflex. On the left side of the figure are brain areas where stressor-evoked neural activity has been related to simultaneous changes in blood pressure, heart rate, and baroreflex measures (see text). Key areas include those presumably involved in mediating stressor appraisals and coordinating these appraisals with behavioral and physiological responding, including the dorsal anterior mid-cingulate cortex (aMCC), pregenual and subgenual areas of the anterior cingulate cortex (pgACC, sgACC), the ventromedial and ventrolateral prefrontal cortex (vmPFC, vlOFC), insula, and amygdala. These areas are networked with one another and with subcortical areas that play more proximal roles in the visceral regulation of cardiovascular function, including areas in the thalamus, periaqueductal gray, and pons. We note that this is not an exhaustive illustration of all brain areas involved in cardiovascular regulation. On the right side of the figure is a simplified illustration of the major motor and sensory limbs of the baroreflex, a homeostatic visceral control loop that regulates blood pressure. For clarity, not all components and connections are shown. Pressure sensitive cells (baroreceptors) that encode changes in blood pressure are concentrated in the major arteries (e.g., aorta, carotid artery). Their sensory signals (baroafferent traffic) are relayed via the vagal and glossopharyngeal nerves to a cell group in the medulla of the brainstem that influences both sympathetic and parasympathetic nervous system outflow: the NTS (nucleus of the solitary tract). The NTS not only projects to higher subcortical and cortical regions, but also to the dorsal vagal nucleus (DVN) and nucleus ambiguous (NA), which regulate parasympathetic outflow to the sinoatrial (SA) node of the heart to affect heart rate. The NTS also influences the rostral ventrolateral medulla (RVLM) indirectly via the caudal ventrolateral medulla (CVLM). The RVLM is a major source of excitatory drive to the sympathetic nervous system. Accordingly, indirect inputs from the NTS to the RVLM have the net effects of influencing sympathetic nervous system outflow to heart muscle (myocardium) to influence its contractility and the blood vessels (vascular tissue) to influence their level of dilation and resistance to blood flow in the periphery. These influences occur via RVLM projections to preganglionic cells of the sympathetic nervous system in the intermediolateral cell column (IML) of the spinal cord. Blood pressure itself is the product of the level of resistance to blood flow in the periphery and the volume of blood being pumped by the heart (cardiac output), which is determined by heart rate and myocardial contractility. Blocked endpoints denote inhibitory influences; arrowed endpoints denote excitatory influences. Broken lines correspond to ascending (afferent) visceral input, particularly from peripheral baroreceptors. The baroreflex is one example of a visceral control loop by which appraisal systems of the brain may link states of psychological stress and physiological responding to influence health.