Brain Correlates of Mental Stress-Induced Myocardial Ischemia

Abstract

Objective: Coronary artery disease (CAD) is a major cause of morbidity and mortality, and despite important advances in our understanding of this disorder, the underlying mechanisms remain under investigation. Recently, increased attention has been placed on the role of behavioral factors such as emotional stress on CAD risk. Brain areas involved in memory and the stress response, including medial prefrontal cortex, insula, and parietal cortex, also have outputs to the peripheral cardiovascular system. The purpose of this study was to assess the effects of mental stress on brain and cardiac function in patients with CAD.

Methods: CAD patients (N = 170) underwent cardiac imaging with [Tc-99m] sestamibi single-photon emission tomography at rest and during a public speaking mental stress task. On another day, they underwent imaging of the brain with [O-15] water positron emission tomography (PET) during mental stress (arithmetic and public speaking) and control conditions.

Results: Patients with mental stress-induced myocardial ischemia showed increased activation with stress in anterior cingulate, inferior frontal gyrus, and parietal cortex (p < .005). This was seen with both arithmetic stress and public speaking stress. Arithmetic stress was additionally associated with left insula activation, and public speaking with right pre/postcentral gyrus and middle temporal gyrus activation (p < .005).

Conclusions: These findings suggest that mental stress-induced myocardial ischemia is associated with activation in brain areas involved in the stress response and autonomic regulation of the cardiovascular system. Altered brain reactivity to stress could possibly represent a mechanism through which stress leads to increased risk of CAD-related morbidity and mortality.

Figure 1

Brain and cardiac imaging with mental stress protocol. Participants underwent eight brain scans following injection of radiolabeled water in conjunction with exposure to control and mental stress conditions. Control conditions involving counting out loud for two scans, then reading a neutral paragraph out loud for two scans. Mental stress conditions included performing a series of increasingly complicated mathematical calculations under time pressure for two scans, followed by a public speaking task in which patients were given two stressful situations and then asked to prepare and give a speech for each situation that was two minutes in duration.

Figure 2

Areas of increased activation with mental arithmetic stress in CAD patients with mental stress-induced myocardial ischemia (MSI) versus CAD patients without MSI. Increases are seen in anterior cingulate and inferior frontal gyrus (in addition to parietal cortex).

Figure 3

Areas of increased activation with public speaking stress in CAD patients with mental stress-induced myocardial ischemia (MSI) versus CAD patients without MSI. Increases are seen in in anterior cingulate and inferior frontal gyrus (and also parietal cortex).