An Inflammatory Pathway Links Atherosclerotic Cardiovascular Disease Risk to Neural Activity Evoked by the Cognitive Regulation of Emotion

Abstract

Background Cognitive reappraisal is a form of emotion regulation that alters emotional responding by changing the meaning of emotional stimuli. Reappraisal engages regions of the prefrontal cortex that support multiple functions, including visceral control functions implicated in regulating the immune system. Immune activity plays a role in the preclinical pathophysiology of atherosclerotic cardiovascular disease (CVD), an inflammatory condition that is highly comorbid with affective disorders characterized by problems with emotion regulation. Here, we tested whether prefrontal engagement by reappraisal would be associated with atherosclerotic CVD risk and whether this association would be mediated by inflammatory activity. Methods Community volunteers (n=157; aged 30–54; 80 women) without DSM-IV Axis-1 psychiatric diagnoses or cardiovascular or immune disorders performed a functional neuroimaging task involving the reappraisal of negative emotional stimuli. Carotid artery intima-media thickness and inter-adventitial diameter were measured by ultrasonography and used as markers of preclinical atherosclerosis. Also measured were circulating levels of interleukin-6 (IL-6), an inflammatory cytokine linked to CVD risk and prefrontal neural activity. Results Greater reappraisal-related engagement of the dorsal anterior cingulate cortex (dACC) was associated with greater preclinical atherosclerosis and IL-6. Moreover, IL-6 mediated the association of dACC engagement with preclinical atherosclerosis. These results were independent of age, sex, race, smoking status, and other known CVD risk factors. Conclusions The cognitive regulation of emotion may relate to CVD risk through a pathway involving the functional interplay between the anterior cingulate region of the prefrontal cortex and inflammatory activity.

Systemic inflammation and resting state connectivity of the default mode network

“…Indeed, we have previously shown an association of circulating IL-6 with engagement of ACC and mPFC during effortful emotion regulation among a sample of 183 participants that partly overlaps with the current sample (Gianaros et al, 2014). Similarly, increased activity of the dACC in response to a social rejection task has been shown to associate positively with stress-induced increases in peripheral inflammation (Slavich, Way, Eisenberger, & Taylor, 2010).…”

“…One participant was missing depressive symptom scores. Although we have published neuroimaging findings from AHAB-II (Allen, Jennings, Gianaros, Thayer, & Manuck, 2015; Gianaros et al, 2014; Jennings, Allen, Gianaros, Thayer, & Manuck, 2015; Jennings et al, 2016; Marsland et al, 2015), the current findings are the first bearing on resting-state connectivity and inflammation in this sample.…”

Trajectories of peripheral interleukin-6, structure of the hippocampus, and cognitive impairment over 14 years in older adults

“…(Frodl & Amico, 2014; Savitz, et al, 2013) There have been additional functional MRI studies showing cross-sectional associations between peripheral IL-6, and the levels of activation in the hippocampus and medial temporal lobe. (Gianaros, et al, 2014; Harrison, Cercignani, Voon, & Critchley, 2014; Harrison, Doeller, Voon, Burgess, & Critchley, 2014) Collectively, prior studies strongly indicate a link between circulating IL-6 levels, and cognitive decline, likely through changes in the hippocampus, an area known to regulate memory formation. However, longitudinal studies are needed to investigate whether changes in IL-6 levels over time are associated with micro- or macro- structural brain changes and subsequent cognitive outcomes.…”

Recent advances in laboratory assessment of emotion regulation

“…For example, in a recent study, cues which signaled participants to get ready to switch from rest to executing a task were associated with activation in the right anterior insula, an area involved in regulating autonomic activity and supporting externally-oriented attention and behavior [53]. Examining anticipation and other forms of ‘mental time travel’ may provide insight into how cognitive emotion regulation, including internally-mediated efforts, might influence physical [54] as well as psychological [51] health.. Similarly, despite a wealth of evidence implicating emotion regulation in health-related decision-making, outcomes and behaviors [2], the vast majority of these studies have been correlational or cross-sectional in nature.…”