Mindfulness training and exercise differentially impact fear extinction neurocircuitry.

BACKGROUND: The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program. METHODS: We investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27). RESULTS: The groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement. CONCLUSIONS: Our results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.

Pain attenuation through mindfulness is associated with decreased cognitive control and increased sensory processing in the brain.

Pain can be modulated by several cognitive techniques, typically involving increased cognitive control and decreased sensory processing. Recently, it has been demonstrated that pain can also be attenuated by mindfulness. Here, we investigate the underlying brain mechanisms by which the state of mindfulness reduces pain. Mindfulness practitioners and controls received unpleasant electric stimuli in the functional magnetic resonance imaging scanner during a mindfulness and a control condition. Mindfulness practitioners, but not controls, were able to reduce pain unpleasantness by 22% and anticipatory anxiety by 29% during a mindful state. In the brain, this reduction was associated with decreased activation in the lateral prefrontal cortex and increased activation in the right posterior insula during stimulation and increased rostral anterior cingulate cortex activation during the anticipation of pain. These findings reveal a unique mechanism of pain modulation, comprising increased sensory processing and decreased cognitive control, and are in sharp contrast to established pain modulation mechanisms.

Mindfulness practice leads to increases in regional brain gray matter density.

Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular, but to date little is known about neural mechanisms associated with these interventions. Mindfulness-Based Stress Reduction (MBSR), one of the most widely used mindfulness training programs, has been reported to produce positive effects on psychological well-being and to ameliorate symptoms of a number of disorders. Here, we report a controlled longitudinal study to investigate pre-post changes in brain gray matter concentration attributable to participation in an MBSR program. Anatomical magnetic resonance (MR) images from 16 healthy, meditation-naïve participants were obtained before and after they underwent the 8-week program. Changes in gray matter concentration were investigated using voxel-based morphometry, and compared with a waiting list control group of 17 individuals. Analyses in a priori regions of interest confirmed increases in gray matter concentration within the left hippocampus. Whole brain analyses identified increases in the posterior cingulate cortex, the temporo-parietal junction, and the cerebellum in the MBSR group compared with the controls. The results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes, emotion regulation, self-referential processing, and perspective taking.

Hippocampal circuits underlie improvements in self-reported anxiety following mindfulness training.

INTRODUCTION: Mindfulness meditation has successfully been applied to cultivate skills in self-regulation of emotion, as it employs the unbiased present moment awareness of experience. This heightened attention to and awareness of sensory experience has been postulated to create an optimal therapeutic exposure condition and thereby improve extinction learning. We recently demonstrated increased connectivity in hippocampal circuits during the contextual retrieval of extinction memory following mindfulness training. METHODS: Here, we examine the role of structural changes in hippocampal subfields following mindfulness training in a randomized controlled longitudinal study using a two-day fear-conditioning and extinction protocol. RESULTS: We demonstrate an association between mindfulness training-related increases in subiculum and decreased hippocampal connectivity to lateral occipital regions during contextual retrieval of extinguished fear. Further, we demonstrate an association between decreased connectivity and decreases in self-reported anxiety following mindfulness training. CONCLUSIONS: The results highlight the role of the subiculum in gating interactions with contextual stimuli during memory retrieval and, also, the mechanisms through which mindfulness training may foster resilience.

Strengthened Hippocampal Circuits Underlie Enhanced Retrieval of Extinguished Fear Memories Following Mindfulness Training.

BACKGROUND: The role of hippocampus in context-dependent recall of extinction is well recognized. However, little is known about how intervention-induced changes in hippocampal networks relate to improvements in extinction learning. In this study, we hypothesized that mindfulness training creates an optimal exposure condition by heightening attention and awareness of present moment sensory experience, leading to enhanced extinction learning, improved emotion regulation, and reduced anxiety symptoms. METHODS: We tested this hypothesis in a randomized controlled longitudinal study design using a 2-day fear conditioning and extinction protocol. The mindfulness training group included 42 participants (28 women) and the control group included 25 participants (15 women). RESULTS: We show that mindfulness training is associated with differential engagement of the right supramarginal gyrus as well as hippocampal-cortical reorganization. We also report enhanced hippocampal connectivity to the primary sensory cortex during retrieval of extinguished stimuli following mindfulness training. CONCLUSIONS: These findings suggest hippocampal-dependent changes in contextual retrieval as one plausible neural mechanism through which mindfulness-based interventions enhance fear extinction and foster stress resilience.

Metabolic Syndrome in Dutch Patients With Bipolar Disorder: A Cross-Sectional Study.

OBJECTIVE: To characterize the prevalence of metabolic syndrome (MetS) among Dutch patients with bipolar disorder (BD), identify factors associated with MetS, and estimate the rate of pharmacologic treatment of MetS in this population. METHODS: A cross-sectional analysis of medical records of adult patients (≥ 18 years) with BD receiving psychotropic drug treatment was performed in a Dutch psychiatric outpatient setting. MetS was determined according to National Cholesterol Education Program Adult Treatment Panel III-Adapted (NCEP ATP III-A) criteria. Data collection via review of medical records from 2015 was conducted in 2016. RESULTS: The prevalence of MetS in the sample (N = 71) was 42.3%. Multivariate analysis showed sex and body mass index were independently associated with MetS. Males had an almost 8-fold higher risk of MetS than females (OR = 7.7, 95% CI, 1.5-39.6), and with every point of increase on BMI, the risk of MetS increased by 40% (OR = 1.4, 95% CI, 1.2-1.8). Of the patients with hyperglycemia, hypercholesterolemia, and hypertension, 81%, 72.4%, and 65.0%, respectively, did not receive drug treatment for these conditions. CONCLUSIONS: The study found a high prevalence rate of MetS and substantial undertreatment of the components of MetS in patients with BD in a Dutch outpatient clinic. Follow-up investigation in larger samples is warranted.

A Randomized Controlled Pilot Study on Mindfulness-Based Cognitive Therapy for Unipolar Depression in Patients With Chronic Pain.

OBJECTIVE: Chronic pain is a disabling illness, often comorbid with depression. We performed a randomized controlled pilot study on mindfulness-based cognitive therapy (MBCT) targeting depression in a chronic pain population. METHOD: Participants with chronic pain lasting ≥ 3 months; DSM-IV major depressive disorder (MDD), dysthymic disorder, or depressive disorder not otherwise specified; and a 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) score ≥ 6 were randomly assigned to MBCT (n = 26) or waitlist (n = 14). We adapted the original MBCT intervention for depression relapse prevention by modifying the psychoeducation and cognitive-behavioral therapy elements to an actively depressed chronic pain population. We analyzed an intent-to-treat (ITT) and a per-protocol sample; the per-protocol sample included participants in the MBCT group who completed at least 4 of 8 sessions. Changes in scores on the QIDS-C16 and 17-item Hamilton Depression Rating Sale (HDRS17) were the primary outcome measures. Pain, quality of life, and anxiety were secondary outcome measures. Data collection took place between January 2012 and July 2013. RESULTS: Nineteen participants (73%) completed the MBCT program. No significant adverse events were reported in either treatment group. ITT analysis (n = 40) revealed no significant differences. Repeated-measures analyses of variance for the per-protocol sample (n = 33) revealed a significant treatment × time interaction (F1,31 = 4.67, P = .039, η²p = 0.13) for QIDS-C16 score, driven by a significant decrease in the MBCT group (t18 = 5.15, P < .001, d = >1.6), but not in the control group (t13 = 2.01, P = .066). The HDRS17 scores did not differ significantly between groups. The study ended before the projected sample size was obtained, which might have prevented effect detection in some outcome measures. CONCLUSIONS: MBCT shows potential as a treatment for depression in individuals with chronic pain, but larger controlled trials are needed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01473615.

Computational Psychosomatics and Computational Psychiatry: Toward a Joint Framework for Differential Diagnosis.

This article outlines how a core concept from theories of homeostasis and cybernetics, the inference-control loop, may be used to guide differential diagnosis in computational psychiatry and computational psychosomatics. In particular, we discuss 1) how conceptualizing perception and action as inference-control loops yields a joint computational perspective on brain-world and brain-body interactions and 2) how the concrete formulation of this loop as a hierarchical Bayesian model points to key computational quantities that inform a taxonomy of potential disease mechanisms. We consider the utility of this perspective for differential diagnosis in concrete clinical applications.

Effects of Mindfulness-Based Cognitive Therapy on Body Awareness in Patients with Chronic Pain and Comorbid Depression.

Body awareness has been proposed as one of the major mechanisms of mindfulness interventions, and it has been shown that chronic pain and depression are associated with decreased levels of body awareness. We investigated the effect of Mindfulness-Based Cognitive Therapy (MBCT) on body awareness in patients with chronic pain and comorbid active depression compared to treatment as usual (TAU; N = 31). Body awareness was measured by a subset of the Multidimensional Assessment of Interoceptive Awareness (MAIA) scales deemed most relevant for the population. These included: Noticing, Not-Distracting, Attention Regulation, Emotional Awareness, and Self-Regulation. In addition, pain catastrophizing was measured by the Pain Catastrophizing Scale (PCS). These scales had adequate to high internal consistency in the current sample. Depression severity was measured by the Quick Inventory of Depressive Symptomatology-Clinician rated (QIDS-C16). Increases in the MBCT group were significantly greater than in the TAU group on the "Self-Regulation" and "Not Distracting" scales. Furthermore, the positive effect of MBCT on depression severity was mediated by "Not Distracting." These findings provide preliminary evidence that a mindfulness-based intervention may increase facets of body awareness as assessed with the MAIA in a population of pain patients with depression. Furthermore, they are consistent with a long hypothesized mechanism for mindfulness and emphasize the clinical relevance of body awareness.

Mindfulness-Based Stress Reduction, Fear Conditioning, and The Uncinate Fasciculus: A Pilot Study.

Mindfulness has been suggested to impact emotional learning, but research on these processes is scarce. The classical fear conditioning/extinction/extinction retention paradigm is a well-known method for assessing emotional learning. The present study tested the impact of mindfulness training on fear conditioning and extinction memory and further investigated whether changes in white matter fiber tracts might support such changes. The uncinate fasciculus (UNC) was of particular interest in the context of emotional learning. In this pilot study, 46 healthy participants were quasi-randomized to a Mindfulness-Based Stress Reduction (MBSR, N = 23) or waitlist control (N = 23) group and underwent a two-day fear conditioning, extinction learning, and extinction memory protocol before and after the course or control period. Skin conductance response (SCR) data served to measure the physiological response during conditioning and extinction memory phases. Diffusion tensor imaging (DTI) data were analyzed with probabilistic tractography and analyzed for changes of fractional anisotropy in the UNC. During conditioning, participants were able to maintain a differential response to conditioned vs. not conditioned stimuli following the MBSR course (i.e., higher sensitivity to the conditioned stimuli), while controls dropped the response. Extinction memory results were not interpretable due to baseline differences. MBSR participants showed a significant increase in fractional anisotropy in the UNC, while controls did not (group by time interaction missed significance). Pre-post changes in UNC were correlated with changes in the response to the conditioned stimuli. The findings suggest effects of mindfulness practice on the maintenance of sensitivity of emotional responses and suggest underlying neural plasticity. (ClinicalTrials.gov, Identifier NCT01320969, https://clinicaltrials.gov/ct2/show/NCT01320969).

Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression.

This paper outlines a hierarchical Bayesian framework for interoception, homeostatic/allostatic control, and meta-cognition that connects fatigue and depression to the experience of chronic dyshomeostasis. Specifically, viewing interoception as the inversion of a generative model of viscerosensory inputs allows for a formal definition of dyshomeostasis (as chronically enhanced surprise about bodily signals, or, equivalently, low evidence for the brain's model of bodily states) and allostasis (as a change in prior beliefs or predictions which define setpoints for homeostatic reflex arcs). Critically, we propose that the performance of interoceptive-allostatic circuitry is monitored by a metacognitive layer that updates beliefs about the brain's capacity to successfully regulate bodily states (allostatic self-efficacy). In this framework, fatigue and depression can be understood as sequential responses to the interoceptive experience of dyshomeostasis and the ensuing metacognitive diagnosis of low allostatic self-efficacy. While fatigue might represent an early response with adaptive value (cf. sickness behavior), the experience of chronic dyshomeostasis may trigger a generalized belief of low self-efficacy and lack of control (cf. learned helplessness), resulting in depression. This perspective implies alternative pathophysiological mechanisms that are reflected by differential abnormalities in the effective connectivity of circuits for interoception and allostasis. We discuss suitably extended models of effective connectivity that could distinguish these connectivity patterns in individual patients and may help inform differential diagnosis of fatigue and depression in the future.

Greater widespread functional connectivity of the caudate in older adults who practice kripalu yoga and vipassana meditation than in controls.

There has been a growing interest in understanding how contemplative practices affect brain functional organization. However, most studies have restricted their exploration to predefined networks. Furthermore, scientific comparisons of different contemplative traditions are largely lacking. Here we explored differences in whole brain resting state functional connectivity between experienced yoga practitioners, experienced meditators, and matched controls. Analyses were repeated in an independent sample of experienced meditators and matched controls. Analyses utilizing Network-Based Statistics (Zalesky et al., 2010) revealed difference components for yoga practitioners > controls and meditators > controls in which the right caudate was a central node. Follow up analyses revealed that yoga practitioners and meditators had significantly greater degree centrality in the caudate than controls. This greater degree centrality was not driven by single connections but by greater connectivity between the caudate and numerous brain regions. Findings of greater caudate connectivity in meditators than in controls was replicated in an independent dataset. These findings suggest that yoga and meditation practitioners have stronger functional connectivity within basal ganglia cortico-thalamic feedback loops than non-practitioners. Although we could not provide evidence for its mechanistic role, this greater connectivity might be related to the often reported effects of meditation and yoga on behavioral flexibility, mental health, and well-being.

Interoception, contemplative practice, and health.

Interoception can be broadly defined as the sense of signals originating within the body. As such, interoception is critical for our sense of embodiment, motivation, and well-being. And yet, despite its importance, interoception remains poorly understood within modern science. This paper reviews interdisciplinary perspectives on interoception, with the goal of presenting a unified perspective from diverse fields such as neuroscience, clinical practice, and contemplative studies. It is hoped that this integrative effort will advance our understanding of how interoception determines well-being, and identify the central challenges to such understanding. To this end, we introduce an expanded taxonomy of interoceptive processes, arguing that many of these processes can be understood through an emerging predictive coding model for mind-body integration. The model, which describes the tension between expected and felt body sensation, parallels contemplative theories, and implicates interoception in a variety of affective and psychosomatic disorders. We conclude that maladaptive construal of bodily sensations may lie at the heart of many contemporary maladies, and that contemplative practices may attenuate these interpretative biases, restoring a person's sense of presence and agency in the world.

The potential effects of meditation on age-related cognitive decline: a systematic review.

With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

Potential self-regulatory mechanisms of yoga for psychological health.

Research suggesting the beneficial effects of yoga on myriad aspects of psychological health has proliferated in recent years, yet there is currently no overarching framework by which to understand yoga's potential beneficial effects. Here we provide a theoretical framework and systems-based network model of yoga that focuses on integration of top-down and bottom-up forms of self-regulation. We begin by contextualizing yoga in historical and contemporary settings, and then detail how specific components of yoga practice may affect cognitive, emotional, behavioral, and autonomic output under stress through an emphasis on interoception and bottom-up input, resulting in physical and psychological health. The model describes yoga practice as a comprehensive skillset of synergistic process tools that facilitate bidirectional feedback and integration between high- and low-level brain networks, and afferent and re-afferent input from interoceptive processes (somatosensory, viscerosensory, chemosensory). From a predictive coding perspective we propose a shift to perceptual inference for stress modulation and optimal self-regulation. We describe how the processes that sub-serve self-regulation become more automatized and efficient over time and practice, requiring less effort to initiate when necessary and terminate more rapidly when no longer needed. To support our proposed model, we present the available evidence for yoga affecting self-regulatory pathways, integrating existing constructs from behavior theory and cognitive neuroscience with emerging yoga and meditation research. This paper is intended to guide future basic and clinical research, specifically targeting areas of development in the treatment of stress-mediated psychological disorders.

Moving beyond Mindfulness: Defining Equanimity as an Outcome Measure in Meditation and Contemplative Research.

In light of a growing interest in contemplative practices such as meditation, the emerging field of contemplative science has been challenged to describe and objectively measure how these practices affect health and well-being. While "mindfulness" itself has been proposed as a measurable outcome of contemplative practices, this concept encompasses multiple components, some of which, as we review here, may be better characterized as equanimity. Equanimity can be defined as an even-minded mental state or dispositional tendency toward all experiences or objects, regardless of their origin or their affective valence (pleasant, unpleasant, or neutral). In this article we propose that equanimity be used as an outcome measure in contemplative research. We first define and discuss the inter-relationship between mindfulness and equanimity from the perspectives of both classical Buddhism and modern psychology and present existing meditation techniques for cultivating equanimity. We then review psychological, physiological, and neuroimaging methods that have been used to assess equanimity, either directly or indirectly. In conclusion, we propose that equanimity captures potentially the most important psychological element in the improvement of well-being, and therefore should be a focus in future research studies.

Fluid intelligence and brain functional organization in aging yoga and meditation practitioners.

Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation.

Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training.

Mindfulness training aims to impact emotion regulation. Generalized anxiety disorder (GAD) symptoms can be successfully addressed through mindfulness-based interventions. This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training. Furthermore, we compared brain activation between GAD patients and healthy participants at baseline. 26 patients with a current DSM-IV GAD diagnosis were randomized to an 8-week Mindfulness Based Stress Reduction (MBSR, N = 15) or a stress management education (SME, N = 11) active control program. 26 healthy participants were included for baseline comparisons. BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions. At baseline, GAD patients showed higher amygdala activation than healthy participants in response to neutral, but not angry faces, suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients. In patients, amygdala activation in response to neutral faces decreased following both interventions. BOLD response in ventrolateral prefrontal regions (VLPFC) showed greater increase in MBSR than SME participants. Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR, but not SME group. Both, change in VLPFC activation and amygdala-prefrontal connectivity were correlated with change in Beck Anxiety Inventory (BAI) scores, suggesting clinical relevance of these changes. Amygdala-prefrontal connectivity turned from negative coupling (typically seen in down-regulation of emotions), to positive coupling; potentially suggesting a unique mechanism of mindfulness. Findings suggest that in GAD, mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion; these changes correspond with reported symptom improvements.

How Does Mindfulness Meditation Work? Proposing Mechanisms of Action From a Conceptual and Neural Perspective.

Cultivation of mindfulness, the nonjudgmental awareness of experiences in the present moment, produces beneficial effects on well-being and ameliorates psychiatric and stress-related symptoms. Mindfulness meditation has therefore increasingly been incorporated into psychotherapeutic interventions. Although the number of publications in the field has sharply increased over the last two decades, there is a paucity of theoretical reviews that integrate the existing literature into a comprehensive theoretical framework. In this article, we explore several components through which mindfulness meditation exerts its effects: (a) attention regulation, (b) body awareness, (c) emotion regulation (including reappraisal and exposure, extinction, and reconsolidation), and (d) change in perspective on the self. Recent empirical research, including practitioners' self-reports and experimental data, provides evidence supporting these mechanisms. Functional and structural neuroimaging studies have begun to explore the neuroscientific processes underlying these components. Evidence suggests that mindfulness practice is associated with neuroplastic changes in the anterior cingulate cortex, insula, temporo-parietal junction, fronto-limbic network, and default mode network structures. The authors suggest that the mechanisms described here work synergistically, establishing a process of enhanced self-regulation. Differentiating between these components seems useful to guide future basic research and to specifically target areas of development in the treatment of psychological disorders.