Alterations in Resting-State Functional Connectivity Link Mindfulness Meditation With Reduced Interleukin-6: A Randomized Controlled Trial

Abstract

Background: Mindfulness meditation training interventions have been shown to improve markers of health, but the underlying neurobiological mechanisms are not known. Building on initial cross-sectional research showing that mindfulness meditation may increase default mode network (DMN) resting state functional connectivity (rsFC) with regions important in top-down executive control (dorsolateral prefrontal cortex, dlPFC), here we test whether mindfulness meditation training increases DMN-dlPFC rsFC, and whether these rsFC alterations prospectively explain improvements in interleukin-6 (IL-6) in a randomized controlled trial.

Mindfulness Interventions

“…We have provided some initial supportive evidence for this neural mechanistic account with a RCT of mindfulness vs relaxation training in stressed unemployed adults (Creswell et al 2016, Taren et al 2015. Specifically, we showed that a mindfulness meditation retreat (relative to a well-matched relaxation retreat without a mindfulness component), increased resting state functional connectivity of the default mode network with stress regulatory areas of prefrontal cortex (dorsolateral prefrontal cortex), while also decreasing stress-related resting state functional connectivity of the amygdala with subgenual anterior cingulate cortex.…”

“…The scientific community has often assumed MBSR (and other 8-12 week mindfulness-based programs) are the exclusive way to deliver mindfulness training, but there are other evidence-based forms of mindfulness intervention available to researchers and practitioners. Mindfulness meditation residential retreat programs, ranging from 3 days to 3 months in scientific studies, are a powerful way to deliver intensive and well-controlled doses of mindfulness intervention (Creswell et al 2016, Rosenberg et al 2015. Brief mindfulness meditation interventions have also been developed, ranging from 2-3 week programs (Lim et al 2015, Mrazek et al 2013) to lab-based 3-4 day mindfulness interventions , Zeidan et al 2011.…”

“…The Health Enhancement Program (HEP) is an 8-week health education and relaxation program that was developed to match MBSR on program components, including group-support and education, home practice, and a day long retreat (MacCoon et al 2012). Other active group-based interventions have been effectively implemented, ranging from relaxation interventions (Creswell et al 2016) to targeted health education programs (Morone et al 2016). The brief mindfulness intervention literature (consisting of interventions that last two weeks or less) also offers a number of well-matched active control interventions, ranging from attention control training programs (e.g., listening to the same guided mindfulness exercise with the instruction to count the number of verbs) (Koole et al 2009, Schofield et al 2015, to placebo conditioning (Zeidan et al 2015), and health education interventions (Mrazek et al 2013).…”

“…Mindfulness interventions have the potential to modulate these stress-related immune outcomes, with initial RCTs demonstrating promising effects on some immune markers (for a review, see Black & Slavich 2016). For example, several initial well-controlled studies show that mindfulness interventions may reduce markers of pro-inflammation, including circulating blood markers of C Reactive Protein (Malarkey et al 2013), Interleukin-6 (Creswell et al 2016), and one's stress-induced inflammatory skin flare response (Garland et al 2014a) (although MBSR failed to affect stimulated Interleukin-6 responses in rheumatoid arthritis patients, see Zautra et al 2008). In contrast to inflammatory effects, there is currently mixed evidence on whether mindfulness interventions can boost antibody levels or one's antibody response to vaccination (Hayney et al 2014, Moynihan et al 2013.…”

Therapeutic Implications of Brain–Immune Interactions: Treatment in Translation

“…Moreover, many of these interventions have been shown to induce a variety of immune changes including a reduction in inflammation (Bower and Irwin, 2016). For example, mindfulness meditation has been shown to increase functional connectivity between the posterior cingulate cortex and the left dorsolateral prefrontal cortex that in turn was associated with decreases in IL-6 over a 4-month period (Creswell et al, 2016). In addition, both cognitive behavioral therapy and tai chi were associated with reduced levels of CRP, monocyte production of inflammatory cytokines, and inflammatory gene expression in elderly patients with insomnia (Irwin et al, 2015).…”