Brain correlates of stress‐induced peripheral vasoconstriction in patients with cardiovascular disease

Abstract

The influence of acute psychological stress on cardiovascular disease is an emerging public health concern. Identification of brain mechanisms underlying this may aid in the discovery of possible treatments. Acute psychological stress may induce arteriolar vasoconstriction and reduce blood flow to vital organs. We hypothesized that functional changes in brain regions involved with memory and autonomic/emotional regulation are implicated in the vasoconstrictive stress response, including the medial prefrontal cortex (anterior cingulate), insula, and dorsolateral prefrontal cortex. Subjects with a history of coronary artery disease (N = 59) underwent measurement of microvascular vasomotor tone with the EndoPAT device and O–15 positron emission tomography (PET) imaging of the brain during exposure to mental stress and control conditions. The peripheral arterial tonometry (PAT) ratio was calculated as the mean peripheral vasomotor tone during stress divided by the mean tone during rest. Whole brain contrasts were performed between groups above and below the median PAT ratio, and significant contrasts were defined with cutoff p < 0.005. Stress‐induced peripheral vasoconstriction (below median PAT ratio) was associated with increased stress activation in insula and parietal cortex, and decreased activation in the medial prefrontal cortex with stress tasks compared to control tasks. These findings demonstrate that stress‐induced vasoreactivity is associated with changes in brain responses to stress in areas involved in emotion and autonomic regulation. These findings have important implications on possible treatments for mental stress‐induced vascular toxicity.

Early childhood trauma alters neurological responses to mental stress in patients with coronary artery disease

“…This study made the following novel observations: (1) within those with CAD, the presence of early childhood trauma is associated with altered brain activations, (2) altered neural activity with early childhood trauma involve areas known to be implicated in cognitive, sensory, and autonomic processing, (3) activity within some brain areas, specifically the hippocampus and prefrontal cortex, appear to be associated with early child trauma severity. These findings suggest that childhood trauma can exacerbate neural changes to mental stress in areas that, as shown in our previous studies (Bremner et al, 2018;Shah et al, 2018), may also be involved within adverse cardiovascular responses. Whether these findings are applicable to non-CAD populations merits further investigation.…”

“…Presence of early childhood trauma resulted in greater left insula deactivations and severity positively correlated with left hippocampus and ventromedial prefrontal cortex activity. Furthermore, within CAD patients, insula activity correlates positively with stress-induced peripheral vasoconstriction (Shah et al, 2018) which has been linked to mental stress ischemia (Hammadah et al, 2017b). During autonomic processing, the insula receives interoceptive information from a specialized spinothalamocortical tract which assists in the cortical representation of salient visceral and somatosensory information (Critchley, 2005).…”

Coronary Artery Spasm, Coronary Reactivity, and Their Psychological Context

“…Smooth muscle hyperactivity due to autonomic nervous system dysfunction with sympathetic predominance, inflammation and oxidative stress, have all been implicated (Figure). That these effects are mediated by the neuroendocrine and autonomic nervous system is suggested by emerging research linking psychological stress and myocardial ischemia to brain areas contributing to emotional regulation, autonomic outflow and vascular reactivity (6,7). On the other hand, traditional cardiovascular risk factors have been inconsistently associated with CAS (8).…”

Adverse cardiovascular outcomes in women: blame the amygdala?

“…2,8,9 As a consequence, that tonic amygdalar activation results in chronic sympathetic activation leading to immune activation with increased inflammation 13 and endothelial dysfunction. 14 Amygdala is also implicated in modulation of autonomic outflow in response to physiological stress. 15 As found in the present investigation, sex differences in amygdala (de)activation, and its role in autonomic cardiovascular control, have indeed previously been reported 16 ; however, how these sex differences change with age/ hormone status, or may be potentiated with disease, remains poorly understood and warrants future research.…”