Judson A. Brewer

Meditation experience is associated with differences in default mode network activity and connectivity

Many philosophical and contemplative traditions teach that “living in the moment” increases happiness. However, the default mode of humans appears to be that of mind-wandering, which correlates with unhappiness, and with activation in a network of brain areas associated with self-referential processing. We investigated brain activity in experienced meditators and matched meditation-naive controls as they performed several different meditations (Concentration, Loving-Kindness, Choiceless Awareness). We found that the main nodes of the default-mode network (medial prefrontal and posterior cingulate cortices) were relatively deactivated in experienced meditators across all meditation types. Furthermore, functional connectivity analysis revealed stronger coupling in experienced meditators between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices (regions previously implicated in self-monitoring and cognitive control), both at baseline and during meditation. Our findings demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. As such, these provide a unique understanding of possible neural mechanisms of meditation.

Glucocorticoids suppress bone formation via the osteoclast.

The pathogenesis of glucocorticoid-induced (GC-induced) bone loss is unclear. For example, osteoblast apoptosis is enhanced by GCs in vivo, but they stimulate bone formation in vitro. This conundrum suggests that an intermediary cell transmits a component of the bone-suppressive effects of GCs to osteoblasts in the intact animal. Bone remodeling is characterized by tethering of the activities of osteoclasts and osteoblasts. Hence, the osteoclast is a potential modulator of the effect of GCs on osteoblasts. To define the direct impact of GCs on bone-resorptive cells, we compared the effects of dexamethasone (DEX) on WT osteoclasts with those derived from mice with disruption of the GC receptor in osteoclast lineage cells (GRoc-/- mice). While the steroid prolonged longevity of osteoclasts, their bone-degrading capacity was suppressed. The inhibitory effect of DEX on bone resorption reflects failure of osteoclasts to organize their cytoskeleton in response to M-CSF. DEX specifically arrested M-CSF activation of RhoA, Rac, and Vav3, each of which regulate the osteoclast cytoskeleton. In all circumstances GRoc-/- mice were spared the impact of DEX on osteoclasts and their precursors. Consistent with osteoclasts modulating the osteoblast-suppressive effect of DEX, GRoc-/- mice are protected from the steroids inhibition of bone formation.

The neurobiology of substance and behavioral addictions.

Behavioral addictions, such as pathological gambling, kleptomania, pyromania, compulsive buying, and compulsive sexual behavior, represent significant public health concerns and are associated with high rates of psychiatric comorbidity and mortality. Although research into the biology of these behaviors is still in the early stages, recent advances in the understanding of motivation, reward, and addiction have provided insight into the possible pathophysiology of these disorders. Biochemical, functional neuroimaging, genetic studies, and treatment research have suggested a strong neurobiological link between behavioral addictions and substance use disorders. Given the substantial co-occurrence of these groups of disorders, improved understanding of their relationship has important implications not only for further understanding the neurobiology of both categories of disorders but also for improving prevention and treatment strategies.

Pretreatment Brain Activation During Stroop Task Is Associated with Outcomes in Cocaine-Dependent Patients

BACKGROUND Cognitive behavioral and related therapies for cocaine dependence may exert their effects, in part, by enhancing cognitive control over drug use behavior. No prior studies have systematically examined the neural correlates of cognitive control as related to treatment outcomes for cocaine dependence. METHODS Twenty treatment-seeking cocaine-dependent individuals performed a Stroop color-word interference task while undergoing functional magnetic resonance imaging (fMRI) prior to initiating treatment. The primary outcome measures were percent of urine drug screens negative for cocaine, percent days abstinent, and treatment retention. Correlations between regional brain activation during Stroop task performance and treatment outcome measures were analyzed. RESULTS During Stroop performance, individuals activated brain regions similar to those reported in nonaddicted individuals, including the anterior cingulate cortex, dorsolateral prefrontal cortex, parietal lobule, insula, and striatum. Activations at treatment onset correlated differentially with specific outcomes: longer duration of self-reported abstinence correlated with activation of ventromedial prefrontal cortex, left posterior cingulate cortex, and right striatum; percent drug-free urine screens correlated with striatal activation; and treatment retention correlated with diminished activation of dorsolateral prefrontal cortex. A modest correlation between Stroop effect and treatment retention was found. CONCLUSIONS The functions of specific brain regions underlying cognitive control relate differentially to discrete outcomes for the treatment of cocaine dependence. These findings implicate neurocircuitry underlying cognitive control in behavioral treatment outcome and provide insight into the mechanisms of behavioral therapies for cocaine dependence. They also suggest neural activation patterns during cognitive control tasks are more sensitive predictors of treatment response than behavioral measures.

Mindfulness training for smoking cessation: Results from a randomized controlled trial

BACKGROUND Cigarette smoking is the leading cause of preventable death in the world, and long-term abstinence rates remain modest. Mindfulness training (MT) has begun to show benefits in a number of psychiatric disorders, including depression, anxiety and more recently, in addictions. However, MT has not been evaluated for smoking cessation through randomized clinical trials. METHODS 88 treatment-seeking, nicotine-dependent adults who were smoking an average of 20cigarettes/day were randomly assigned to receive MT or the American Lung Associations freedom from smoking (FFS) treatment. Both treatments were delivered twice weekly over 4 weeks (eight sessions total) in a group format. The primary outcomes were expired-air carbon monoxide-confirmed 7-day point prevalence abstinence and number of cigarettes/day at the end of the 4-week treatment and at a follow-up interview at week 17. RESULTS 88% of individuals received MT and 84% of individuals received FFS completed treatment. Compared to those randomized to the FFS intervention, individuals who received MT showed a greater rate of reduction in cigarette use during treatment and maintained these gains during follow-up (F=11.11, p=.001). They also exhibited a trend toward greater point prevalence abstinence rate at the end of treatment (36% vs. 15%, p=.063), which was significant at the 17-week follow-up (31% vs. 6%, p=.012). CONCLUSIONS This initial trial of mindfulness training may confer benefits greater than those associated with current standard treatments for smoking cessation.

Mindfulness Training and Stress Reactivity in Substance Abuse: Results from a Randomized, Controlled Stage I Pilot Study

ABSTRACT Stress is important in substance use disorders (SUDs). Mindfulness training (MT) has shown promise for stress-related maladies. No studies have compared MT to empirically validated treatments for SUDs. The goals of this study were to assess MT compared to cognitive behavioral therapy (CBT) in substance use and treatment acceptability, and specificity of MT compared to CBT in targeting stress reactivity. Thirty-six individuals with alcohol and/or cocaine use disorders were randomly assigned to receive group MT or CBT in an outpatient setting. Drug use was assessed weekly. After treatment, responses to personalized stress provocation were measured. Fourteen individuals completed treatment. There were no differences in treatment satisfaction or drug use between groups. The laboratory paradigm suggested reduced psychological and physiological indices of stress during provocation in MT compared to CBT. This pilot study provides evidence of the feasibility of MT in treating SUDs and suggests that MT may be efficacious in targeting stress.

Thymocyte Apoptosis Induced by T Cell Activation Is Mediated by Glucocorticoids In Vivo

Glucocorticoids, administered in pharmacological doses, potently modulate immune system function and are a mainstay therapy for many common human diseases. Physiologic production of glucocorticoids may play a role in optimization of the immune repertoire both centrally and peripherally. Possible effects include alteration of lymphocyte development and down-regulation of cytokine responses, but essential roles remain unclear. To determine the part that endogenous glucocorticoids play in thymocyte development, we used fetal liver from mice lacking the glucocorticoid receptor GRko for immunological reconstitution of lethally irradiated wild-type (WT) mice. We find normal numbers and subset distribution of GRko thymocytes. GRko thymocytes also exhibit similar sensitivity to apoptosis induced by activating anti-CD3ε Ab as WT thymocytes in vitro. Surprisingly, GRko thymocytes are significantly more resistant than WT thymocytes to anti-CD3ε-mediated thymocyte apoptosis in vivo. Consistent with this finding, in vivo TCR complex activation induces sustained high levels of glucocorticoids that correlate strongly with thymocyte apoptosis in WT mice. We find that while direct engagement of the TCR complex may cause death of a subset of thymocytes, glucocorticoids are required for deletion of the majority of thymocytes. Thus, TCR stimulation by Ab administration may more accurately reflect polyclonal T cell activation than negative selection in vivo.

T-cell glucocorticoid receptor is required to suppress COX-2-mediated lethal immune activation

Glucocorticoids, acting through the glucocorticoid receptor, potently modulate immune function and are a mainstay of therapy for treatment of inflammatory conditions, autoimmune diseases, leukemias and lymphomas. Moreover, removal of systemic glucocorticoids, by adrenalectomy in animal models or adrenal insufficiency in humans, has shown that endogenous glucocorticoid production is required for regulation of physiologic immune responses. These effects have been attributed to suppression of cytokines, although the crucial cellular and molecular targets remain unknown. In addition, considerable controversy remains as to whether glucocorticoids are required for thymocyte development. To assess the role of the glucocorticoid receptor in immune system development and function, we generated T-cell-specific glucocorticoid receptor knockout mice. Here we show that the T-cell is a critical cellular target of glucocorticoid receptor signaling, as immune activation in these mice resulted in significant mortality. This lethal activation is rescued by cyclooxygenase-2 (COX-2) inhibition but not steroid administration or cytokine neutralization. These studies indicate that glucocorticoid receptor suppression of COX-2 is crucial for curtailing lethal immune activation, and suggest new therapeutic approaches for regulation of T-cell-mediated inflammatory diseases.

Contemplating Mindfulness at Work: An Integrative Review

Mindfulness research activity is surging within organizational science. Emerging evidence across multiple fields suggests that mindfulness is fundamentally connected to many aspects of workplace functioning, but this knowledge base has not been systematically integrated to date. This review coalesces the burgeoning body of mindfulness scholarship into a framework to guide mainstream management research investigating a broad range of constructs. The framework identifies how mindfulness influences attention, with downstream effects on functional domains of cognition, emotion, behavior, and physiology. Ultimately, these domains impact key workplace outcomes, including performance, relationships, and well-being. Consideration of the evidence on mindfulness at work stimulates important questions and challenges key assumptions within management science, generating an agenda for future research.

Craving to quit: psychological models and neurobiological mechanisms of mindfulness training as treatment for addictions.

Humans suffer heavily from substance use disorders and other addictions. Despite much effort that has been put into understanding the mechanisms of the addictive process, treatment strategies have remained suboptimal over the past several decades. Mindfulness training, which is based on ancient Buddhist models of human suffering, has recently shown preliminary efficacy in treating addictions. These early models show remarkable similarity to current models of the addictive process, especially in their overlap with operant conditioning (positive and negative reinforcement). Further, they may provide explanatory power for the mechanisms of mindfulness training, including its effects on core addictive elements, such as craving, and the underlying neurobiological processes that may be active therein. In this review, using smoking as an example, we will highlight similarities between ancient and modern views of the addictive process, review studies of mindfulness training for addictions and their effects on craving and other components of this process, and discuss recent neuroimaging findings that may inform our understanding of the neural mechanisms of mindfulness training.