A review of neuroimaging studies of stressor-evoked blood pressure reactivity: emerging evidence for a brain-body pathway to coronary heart disease risk

Abstract

An individual's tendency to show exaggerated or otherwise dysregulated cardiovascular reactions to acute stressors has long been associated with increased risk for clinical and preclinical endpoints of coronary heart disease (CHD). However, the 'brain-body' pathways that link stressor-evoked cardiovascular reactions to CHD risk remain uncertain. This review summarizes emerging neuroimaging research indicating that individual differences in stressor-evoked blood pressure reactivity (a particular form of cardiovascular reactivity) are associated with activation patterns in corticolimbic brain areas that are jointly involved in processing stressors and regulating the cardiovascular system. As supported empirically by activation likelihood estimates derived from a meta-analysis, these corticolimbic areas include divisions of the cingulate cortex, insula, and amygdala--as well as networked cortical and subcortical areas involved in mobilizing hemodynamic and metabolic support for stress-related behavioral responding. Contextually, the research reviewed here illustrates how behavioral medicine and health neuroscience methods can be integrated to help characterize the 'brain-body' pathways that mechanistically link stressful experiences with CHD risk.

Figure 1

Conceptual diagram summarizing selected brain systems wherein the processing of stressor-related information may relate to the expression of stressor-evoked blood pressure reactivity. Although the model is anatomically incomplete, key areas implicated by animal and human evidence are included. PVN, paraventricular nucleus; LHA, lateral hypothalamic area; NTS, nucleus tractus solitarius; DVN, dorsal vagal nucleus; NA, nucleus ambiguous; CVLM, caudal ventrolateral medulla; RVL, rostral ventrolateral medullary; IML, intermediolateral cell column; HR, heart rate; BRS, baroreflex sensitivity; CO, cardiac output; TPR, total peripheral resistance. Blocked endpoints denote inhibitory influences; arrowed endpoints denote excitatory influences. Broken gray lines correspond to ascending (afferent) visceral input, particularly from peripheral baroreceptors. This model was derived explicitly from the work of Berntson et al. (1998), Dampney (1994), Saha (2005), Saper (2002) and Westerhaus and Loewy (2001).

Figure 2

Lateral and medial surface projections of foci where a significant positive correlation between stressor-evoked neural activation and blood pressure reactivity has been reported in neuroimaging studies reviewed in the text (see Tables 1-2). These foci (47 in total, not all visible in this figure) were submitted to a meta-analysis using the activation likelihood estimation method.

Figure 3

Meta-analytic activation likelihood estimation map thresholded at a corrected false discovery rate of q = 0.05 (or p-value of 0.0038). This map illustrates clusters wherein greater neural activation correlated with greater stressor-evoked blood pressure reactivity in the neuroimaging studies listed in Tables 1-2. Cluster numbering system corresponds to Table 2 labels.