Resting state functional connectivity changes following mindfulness-based stress reduction predict improvements in disease control for patients with asthma.

BACKGROUND: The staggering morbidity associated with chronic inflammatory diseases can be reduced by psychological interventions, including Mindfulness-Based Stress Reduction (MBSR). Proposed mechanisms for MBSR's beneficial effects include changes in salience network function. Salience network perturbations are also associated with chronic inflammation, including airway inflammation in asthma, a chronic inflammatory disease affecting approximately 10% of the population. However, no studies have examined whether MBSR-related improvements in disease control are related to changes in salience network function. METHODS: Adults with asthma were randomized to 8 weeks of MBSR or a waitlist control group. Resting state functional connectivity was measured using fMRI before randomization, immediately post-intervention, and 4 months post-intervention. Using key salience network regions as seeds, we calculated group differences in change in functional connectivity over time and examined whether functional connectivity changes were associated with increased mindfulness, improved asthma control, and decreased inflammatory biomarkers. RESULTS: The MBSR group showed greater increases in functional connectivity between salience network regions relative to the waitlist group. Improvements in asthma control correlated with increased functional connectivity between the salience network and regions important for attention control and emotion regulation. Improvements in inflammatory biomarkers were related to decreased functional connectivity between the salience network and other networks. CONCLUSIONS: Increased resting salience network coherence and connectivity with networks that subserve attention and emotion regulation may contribute to the benefits of MBSR for patients with asthma. Understanding the neural underpinnings of MBSR-related benefits in patients is a critical step towards optimizing brain-targeted interventions for chronic inflammatory disease management.

Slower respiration rate is associated with higher self-reported well-being after wellness training.

Mind-body interventions such as mindfulness-based stress reduction (MBSR) may improve well-being by increasing awareness and regulation of physiological and cognitive states. However, it is unclear how practice may alter long-term, baseline physiological processes, and whether these changes reflect improved well-being. Using respiration rate (RR), which can be sensitive to effects of meditation, and 3 aspects of self-reported well-being (psychological well-being [PWB], distress, and medical symptoms), we tested pre-registered hypotheses that: (1) Lower baseline RR (in a resting, non-meditative state) would be a physiological marker associated with well-being, (2) MBSR would decrease RR, and (3) Training-related decreases in RR would be associated with improved well-being. We recruited 245 adults (age range = 18-65, M = 42.4): experienced meditators (n = 42), and meditation-naïve participants randomized to MBSR (n = 72), active control (n = 41), or waitlist control (n = 66). Data were collected at pre-randomization, post-intervention (or waiting), and long-term follow-up. Lower baseline RR was associated with lower psychological distress among long-term meditators (p* = 0.03, b = 0.02, 95% CI [0.01, 0.03]), though not in non-meditators prior to training. MBSR decreased RR compared to waitlist (p = 0.02, Cohen's d = - 0.41, 95% CI [- 0.78, - 0.06]), but not the active control. Decreased RR related to decreased medical symptoms, across all participants (p* = 0.02, b = 0.57, 95% CI [0.15, 0.98]). Post-training, lower RR was associated with higher PWB across training groups compared to waitlist (p* = 0.01, b = 0.06, 95% CI [0.02, 0.10]), though there were no significant differences in change in PWB between groups. This physiological marker may indicate higher physical and/or psychological well-being in those who engage in wellness practices.

Clinically relevant effects of Mindfulness-Based Stress Reduction in individuals with asthma.

Background: Psychological distress and comorbid psychopathology contribute to exacerbation risk in patients with asthma. Thus, interventions designed to reduce stress and improve emotion regulation, such as Mindfulness-Based Stress Reduction (MBSR), may augment standard care. Few studies have addressed this question and a paucity of data exists to determine the ability of MBSR to impact clinical outcomes in asthma. Methods: This randomized controlled trial investigated effects of MBSR training on asthma control and airway inflammation, in relation to psychological symptoms, in adults with asthma. Participants were randomized to an 8-week MBSR training (n = 35) or wait-list control group (n = 34). Clinically relevant asthma assessments, including Asthma Control Questionnaire and inflammatory biomarkers, were collected at baseline and six approximately-monthly follow-ups. Self-reported mindfulness, distress, depression, and anxiety symptoms were assessed at baseline, post-intervention, and study completion. Chronic stress level was determined at baseline only. Results: Asthma control improved significantly in individuals randomized to MBSR, relative to wait-list controls (p = .01; effect size d = 0.76), which was maintained at 4mo post-intervention. 32% of MBSR participants achieved a clinically significant improvement, based on the ACQ6 Minimally Important Difference, relative to 12% of wait-list participants. Moreover, MBSR-related improvement in asthma control was associated with a reduction in distress (p = .043) and the intervention was most efficacious for those with the highest baseline depressive symptoms (p = .023). Importantly, MBSR also reduced levels of exhaled nitric oxide, a biomarker of airway inflammation, relative to wait-list controls (p < .05). Conclusion: Supporting and extending extant evidence of mind-body relationships in asthma and the benefits of stress reduction for these patients, this is, to the best of our knowledge, the first RCT to demonstrate that training in MBSR improves clinically relevant asthma outcomes. MBSR may thus be a valuable addition to optimal asthma management, particularly for those with comorbid psychopathology. Clinical trial registration: NCT02157766.

Long-term Meditation Training Is Associated with Enhanced Subjective Attention and Stronger Posterior Cingulate-Rostrolateral Prefrontal Cortex Resting Connectivity.

Mindfulness meditation has been shown to increase resting-state functional connectivity (rsFC) between the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC), which is thought to reflect improvements in shifting attention to the present moment. However, prior research in long-term meditation practitioners lacked quantitative measures of attention that would provide a more direct behavioral correlate and interpretational anchor for PCC-DLPFC connectivity and was inherently limited by small sample sizes. Moreover, whether mindfulness meditation primarily impacts brain function locally, or impacts the dynamics of large-scale brain networks, remained unclear. Here, we sought to replicate and extend prior findings of increased PCC-DLPFC rsFC in a sample of 40 long-term meditators (average practice = 3759 hr) who also completed a behavioral assay of attention. In addition, we tested a network-based framework of changes in interregional connectivity by examining network-level connectivity. We found that meditators had stronger PCC-rostrolateral prefrontal cortex (RLPFC) rsFC, lower connector hub strength across the default mode network, and better subjective attention, compared with 124 meditation-naive controls. Orienting attention positively correlated with PCC-RLPFC connectivity and negatively correlated with default mode network connector hub strength. These findings provide novel evidence that PCC-RLPFC rsFC may support attention orienting, consistent with a role for RLPFC in the attention shifting component of metacognitive awareness that is a core component of mindfulness meditation training. Our results further demonstrate that long-term mindfulness meditation may improve attention and strengthen the underlying brain networks.

Absence of structural brain changes from mindfulness-based stress reduction: Two combined randomized controlled trials.

Studies purporting to show changes in brain structure following the popular, 8-week mindfulness-based stress reduction (MBSR) course are widely referenced despite major methodological limitations. Here, we present findings from a large, combined dataset of two, three-arm randomized controlled trials with active and waitlist (WL) control groups. Meditation-naïve participants (n = 218) completed structural magnetic resonance imaging scans during two visits: baseline and postintervention period. After baseline, participants were randomly assigned to WL (n = 70), an 8-week MBSR program (n = 75), or a validated, matched active control (n = 73). We assessed changes in gray matter volume, gray matter density, and cortical thickness. In the largest and most rigorously controlled study to date, we failed to replicate prior findings and found no evidence that MBSR produced neuroplastic changes compared to either control group, either at the whole-brain level or in regions of interest drawn from prior MBSR studies.

Does meditation training promote pro-environmental behavior? A cross-sectional comparison and a randomized controlled trial.

Meditation training may promote pro-environmental behavior and related variables, though limited research has tested this experimentally. We investigated whether short- or long-term meditation training were associated with pro-environmental behavior, environmental attitudes, and sustainable well-being (i.e., well-being per unit consumption). In a cross-sectional comparison, long-term meditators (n=31; mean=9,154 meditation hours) displayed greater environmental attitudes (d=0.63) but not pro-environmental behavior or sustainable well-being compared to meditation-naïve participants (ds=-0.14-0.27). In a randomized controlled trial (n=125), eight-week training in Mindfulness-Based Stress Reduction did not significantly improve target variables relative to waitlist or structurally-matched active control (ds=-0.38-0.43). However, relative to waitlist, randomization to either meditation or active control predicted increases in pro-environmental behavior (d=-0.40) and sustainable well-being (d=0.42), although the latter finding was not robust to multiple imputation. While meditation training may promote pro-environmental behavior and its antecedents, the training investigated here does not appear to be uniquely effective.

The Impact of Mindfulness Training on Police Officer Stress, Mental Health, and Salivary Cortisol Levels.

Unaddressed occupational stress and trauma contribute to elevated rates of mental illness and suicide in policing, and to violent and aggressive behavior that disproportionately impacts communities of color. Emerging evidence suggests mindfulness training with police may reduce stress and aggression and improve mental health, but there is limited evidence for changes in biological outcomes or the lasting benefits of mindfulness training. We conducted a randomized controlled trial (RCT) of 114 police officers from three Midwestern U.S. law enforcement agencies. We assessed stress-related physical and mental health symptoms, blood-based inflammatory markers, and hair and salivary cortisol. Participants were then randomized to an 8-week mindfulness intervention or waitlist control (WLC), and the same assessments were repeated post-intervention and at 3-month follow-up. Relative to waitlist control, the mindfulness group had greater improvements in psychological distress, mental health symptoms, and sleep quality post-training, gains that were maintained at 3-month follow-up. Intervention participants also had a significantly lower cortisol awakening response (CAR) at 3-month follow-up relative to waitlist control. Contrary to hypotheses, there were no intervention effects on hair cortisol, diurnal cortisol slope, or inflammatory markers. In summary, an 8-week mindfulness intervention for police officers led to self-reported improvements in distress, mental health, and sleep, and a lower CAR. These benefits persisted (or emerged) at 3-month follow-up, suggesting that this training may buffer against the long-term consequences of chronic stress. Future research should assess the persistence of these benefits over a longer period while expanding the scope of outcomes to consider the broader community of mindfulness training for police. Clinical Trial Registration: ClinicalTrials.gov#NCT03488875.

Harnessing Life's Slings and Arrows: The Science and Opportunities for Mindfulness Meditation During a Global Pandemic and Beyond.

ABSTRACT: We are at a difficult time in history with societal increases in stress, loneliness, and psychopathology, along with high rates of obesity, sedentary lifestyles, and chronic pain. Mindfulness interventions offer promise to address these societal issues. However, in order to make best use of the opportunities revealed by our current challenges, we must: (1) tackle these issues head-on with inclusive, innovative, and creative experimental designs and interventions, and (2) collectively adhere to rigorous, high quality methods so as to provide an evidence-based integration of mindfulness interventions into mainstream medicine and public health.We find there are several areas for which important advances are happening, including sampling socially diverse populations, examining mechanisms of action, pain management, and health behaviors. Furthermore, rigorous methods, including measurement, causal inference from control groups, delivery and scalability of mindfulness interventions, and effect modifiers to determine who mindfulness programs work best for are also gaining traction. This special issue on Mindfulness: Biobehavioral Mechanisms and Health Outcomes attends to many of these issues, several of which are highlighted in this editorial perspective.

Testing the Efficacy of a Multicomponent, Self-Guided, Smartphone-Based Meditation App: Three-Armed Randomized Controlled Trial.

BACKGROUND: A growing number of randomized controlled trials (RCTs) suggest psychological benefits associated with meditation training delivered via mobile health. However, research in this area has primarily focused on mindfulness, only one of many meditative techniques. OBJECTIVE: This study aims to evaluate the efficacy of 2 versions of a self-guided, smartphone-based meditation app-the Healthy Minds Program (HMP)-which includes training in mindfulness (Awareness), along with practices designed to cultivate positive relationships (Connection) or insight into the nature of the self (Insight). METHODS: A three-arm, fully remote RCT compared 8 weeks of one of 2 HMP conditions (Awareness+Connection and Awareness+Insight) with a waitlist control. Adults (≥18 years) without extensive previous meditation experience were eligible. The primary outcome was psychological distress (depression, anxiety, and stress). Secondary outcomes were social connection, empathy, compassion, self-reflection, insight, rumination, defusion, and mindfulness. Measures were completed at pretest, midtreatment, and posttest between October 2019 and April 2020. Longitudinal data were analyzed using intention-to-treat principles with maximum likelihood. RESULTS: A total of 343 participants were randomized and 186 (54.2%) completed at least one posttest assessment. The majority (166/228, 72.8%) of those assigned to HMP conditions downloaded the app. The 2 HMP conditions did not differ from one another in terms of changes in any outcome. Relative to the waitlist control, the HMP conditions showed larger improvements in distress, social connectedness, mindfulness, and measures theoretically linked to insight training (d=-0.28 to 0.41; Ps≤.02), despite modest exposure to connection- and insight-related practice. The results were robust to some assumptions about nonrandom patterns of missing data. Improvements in distress were associated with days of use. Candidate mediators (social connection, insight, rumination, defusion, and mindfulness) and moderators (baseline rumination, defusion, and empathy) of changes in distress were identified. CONCLUSIONS: This study provides initial evidence of efficacy for the HMP app in reducing distress and improving outcomes related to well-being, including social connectedness. Future studies should attempt to increase study retention and user engagement. TRIAL REGISTRATION: ClinicalTrials.gov NCT04139005; https://clinicaltrials.gov/ct2/show/NCT04139005.

Mindfulness-Based Stress Reduction-related changes in posterior cingulate resting brain connectivity.

Mindfulness meditation training has been shown to increase resting-state functional connectivity between nodes of the frontoparietal executive control network (dorsolateral prefrontal cortex [DLPFC]) and the default mode network (posterior cingulate cortex [PCC]). We investigated whether these effects generalized to a Mindfulness-Based Stress Reduction (MBSR) course and tested for structural and behaviorally relevant consequences of change in connectivity. Healthy, meditation-naïve adults were randomized to either MBSR (N = 48), an active (N = 47) or waitlist (N = 45) control group. Participants completed behavioral testing, resting-state fMRI scans and diffusion tensor scans at pre-randomization (T1), post-intervention (T2) and ~5.5 months later (T3). We found increased T2-T1 PCC-DLPFC resting connectivity for MBSR relative to control groups. Although these effects did not persist through long-term follow-up (T3-T1), MBSR participants showed a significantly stronger relationship between days of practice (T1 to T3) and increased PCC-DLPFC resting connectivity than participants in the active control group. Increased PCC-DLPFC resting connectivity in MBSR participants was associated with increased microstructural connectivity of a white matter tract connecting these regions and increased self-reported attention. These data show that MBSR increases PCC-DLPFC resting connectivity, which is related to increased practice time, attention and structural connectivity.

The next generation of mindfulness-based intervention research: what have we learned and where are we headed?

The previous two decades have seen an exponential increase in the number of published scientific investigations on the efficacy of mindfulness-based stress reduction (MBSR) training to improve function in a wide range of physical and psychological processes. The resulting body of work provides strong evidence that MBSR has salubrious effects. Yet, when compared directly to groups with training that matches MBSR in factors common to most legitimate interventions, such as learning new skills, expectation of benefit, social engagement and support, and attention from expert instructors, both groups tend to improve to a similar extent. This raises the question of whether there are benefits that are specific to training in mindfulness and if so, why are we not detecting them? Here, we discuss the factors that contribute to the general lack of differentiation between MBSR and active control groups, including the specificity of outcome measures and experimental design, random assignment, inclusion/exclusion criteria, and the time course and trajectory of change. In addition, we offer recommendations to address these factors in future research.

Impact of short- and long-term mindfulness meditation training on amygdala reactivity to emotional stimuli.

Meditation training can improve mood and emotion regulation, yet the neural mechanisms of these affective changes have yet to be fully elucidated. We evaluated the impact of long- and short-term mindfulness meditation training on the amygdala response to emotional pictures in a healthy, non-clinical population of adults using blood-oxygen level dependent functional magnetic resonance imaging. Long-term meditators (N = 30, 16 female) had 9081 h of lifetime practice on average, primarily in mindfulness meditation. Short-term training consisted of an 8-week Mindfulness- Based Stress Reduction course (N = 32, 22 female), which was compared to an active control condition (N = 35, 19 female) in a randomized controlled trial. Meditation training was associated with less amygdala reactivity to positive pictures relative to controls, but there were no group differences in response to negative pictures. Reductions in reactivity to negative stimuli may require more practice experience or concentrated practice, as hours of retreat practice in long-term meditators was associated with lower amygdala reactivity to negative pictures - yet we did not see this relationship for practice time with MBSR. Short-term training, compared to the control intervention, also led to increased functional connectivity between the amygdala and a region implicated in emotion regulation - ventromedial prefrontal cortex (VMPFC) - during affective pictures. Thus, meditation training may improve affective responding through reduced amygdala reactivity, and heightened amygdala-VMPFC connectivity during affective stimuli may reflect a potential mechanism by which MBSR exerts salutary effects on emotion regulation ability.

Reduced stress and inflammatory responsiveness in experienced meditators compared to a matched healthy control group.

Psychological stress is a major contributor to symptom exacerbation across many chronic inflammatory conditions and can acutely provoke increases in inflammation in healthy individuals. With the rise in rates of inflammation-related medical conditions, evidence for behavioral approaches that reduce stress reactivity is of value. Here, we compare 31 experienced meditators, with an average of approximately 9000 lifetime hours of meditation practice (M age=51years) to an age- and sex-matched control group (n=37; M age=48years) on measures of stress- and inflammatory responsivity, and measures of psychological health. The Trier Social Stress Test (TSST) was used to induce psychological stress and a neurogenic inflammatory response was produced using topical application of capsaicin cream to forearm skin. Size of the capsaicin-induced flare response and increase in salivary cortisol and alpha amylase were used to quantify the magnitude of inflammatory and stress responses, respectively. Results show that experienced meditators have lower TSST-evoked cortisol (62.62±2.52 vs. 70.38±2.33; p<.05) and perceived stress (4.18±.41 vs. 5.56±.30; p<.01), as well as a smaller neurogenic inflammatory response (81.55±4.6 vs. 96.76±4.26; p<.05), compared to the control group. Moreover, experienced meditators reported higher levels of psychological factors associated with wellbeing and resilience. These results suggest that the long-term practice of meditation may reduce stress reactivity and could be of therapeutic benefit in chronic inflammatory conditions characterized by neurogenic inflammation.

Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators.

BACKGROUND: A growing body of research shows that mindfulness meditation can alter neural, behavioral and biochemical processes. However, the mechanisms responsible for such clinically relevant effects remain elusive. METHODS: Here we explored the impact of a day of intensive practice of mindfulness meditation in experienced subjects (n=19) on the expression of circadian, chromatin modulatory and inflammatory genes in peripheral blood mononuclear cells (PBMC). In parallel, we analyzed a control group of subjects with no meditation experience who engaged in leisure activities in the same environment (n=21). PBMC from all participants were obtained before (t1) and after (t2) the intervention (t2-t1=8h) and gene expression was analyzed using custom pathway focused quantitative-real time PCR assays. Both groups were also presented with the Trier Social Stress Test (TSST). RESULTS: Core clock gene expression at baseline (t1) was similar between groups and their rhythmicity was not influenced in meditators by the intensive day of practice. Similarly, we found that all the epigenetic regulatory enzymes and inflammatory genes analyzed exhibited similar basal expression levels in the two groups. In contrast, after the brief intervention we detected reduced expression of histone deacetylase genes (HDAC 2, 3 and 9), alterations in global modification of histones (H4ac; H3K4me3) and decreased expression of pro-inflammatory genes (RIPK2 and COX2) in meditators compared with controls. We found that the expression of RIPK2 and HDAC2 genes was associated with a faster cortisol recovery to the TSST in both groups. CONCLUSIONS: The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions. Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions.

A comparison of mindfulness-based stress reduction and an active control in modulation of neurogenic inflammation.

Psychological stress is a major provocative factor of symptoms in chronic inflammatory conditions. In recent years, interest in addressing stress responsivity through meditation training in health-related domains has increased astoundingly, despite a paucity of evidence that reported benefits are specific to meditation practice. We designed the present study to rigorously compare an 8-week Mindfulness-Based Stress Reduction (MBSR) intervention to a well-matched active control intervention, the Health Enhancement Program (HEP) in ability to reduce psychological stress and experimentally-induced inflammation. The Trier Social Stress Test (TSST) was used to induce psychological stress and inflammation was produced using topical application of capsaicin cream to forearm skin. Immune and endocrine measures of inflammation and stress were collected both before and after MBSR training. Results show those randomized to MBSR and HEP training had comparable post-training stress-evoked cortisol responses, as well as equivalent reductions in self-reported psychological distress and physical symptoms. However, MBSR training resulted in a significantly smaller post-stress inflammatory response compared to HEP, despite equivalent levels of stress hormones. These results suggest behavioral interventions designed to reduce emotional reactivity may be of therapeutic benefit in chronic inflammatory conditions. Moreover, mindfulness practice, in particular, may be more efficacious in symptom relief than the well-being promoting activities cultivated in the HEP program.

The validation of an active control intervention for Mindfulness Based Stress Reduction (MBSR).

Most of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons. The current article specifies and validates an active control condition, the Health Enhancement Program (HEP), thus providing the foundation necessary for rigorous investigations of the relative efficacy of Mindfulness Based Stress Reduction (MBSR) and for testing mindfulness as an active ingredient. 63 participants were randomized to either MBSR (n = 31) or HEP (n = 32). Compared to HEP, MBSR led to reductions in thermal pain ratings in the mindfulness- but not the HEP-related instruction condition (η(2) = .18). There were significant improvements over time for general distress (η(2) = .09), anxiety (η(2) = .08), hostility (η(2) = .07), and medical symptoms (η(2) = .14), but no effects of intervention. Practice was not related to change. HEP is an active control condition for MBSR while remaining inert to mindfulness. These claims are supported by results from a pain task. Participant-reported outcomes (PROs) replicate previous improvements to well-being in MBSR, but indicate that MBSR is no more effective than a rigorous active control in improving these indices. These results emphasize the importance of using an active control condition like HEP in studies evaluating the effectiveness of MBSR.