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Experientially opening oneself to pain rather than avoiding it is said to reduce the mind's tendency toward avoidance or anxiety which can further exacerbate the experience of pain. This is a central feature of mindfulness-based therapies. Little is known about the neural mechanisms of mindfulness on pain. During a meditation practice similar to mindfulness, functional magnetic resonance imaging was used in expert meditators (>10,000 h of practice) to dissociate neural activation patterns associated with pain, its anticipation, and habituation. Compared to novices, expert meditators reported equal pain intensity, but less unpleasantness. This difference was associated with enhanced activity in the dorsal anterior insula (aI), and the anterior mid-cingulate (aMCC) the so-called 'salience network', for experts during pain. This enhanced activity during pain was associated with reduced baseline activity before pain in these regions and the amygdala for experts only. The reduced baseline activation in left aI correlated with lifetime meditation experience. This pattern of low baseline activity coupled with high response in aIns and aMCC was associated with enhanced neural habituation in amygdala and pain-related regions before painful stimulation and in the pain-related regions during painful stimulation. These findings suggest that cultivating experiential openness down-regulates anticipatory representation of aversive events, and increases the recruitment of attentional resources during pain, which is associated with faster neural habituation.
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Meditation can be conceptualized as a family of complex emotional and attentional regulatory training regimes developed for various ends, including the cultivation of well-being and emotional balance. Among these various practices, there are two styles that are commonly studied. One style, focused attention meditation, entails the voluntary focusing of attention on a chosen object. The other style, open monitoring meditation, involves nonreactive monitoring of the content of experience from moment to moment. The potential regulatory functions of these practices on attention and emotion processes could have a long-term impact on the brain and behavior.

The brain and the cardiovascular system influence each other during the processing of emotion. The study of the interactions of these systems during emotion regulation has been limited in human functional neuroimaging, despite its potential importance for physical health. We have previously reported that mental expertise in cultivation of compassion alters the activation of circuits linked with empathy and theory of mind in response to emotional stimuli. Guided by the finding that heart rate increases more during blocks of compassion meditation than neutral states, especially for experts, we examined the interaction between state (compassion vs. neutral) and group (novice, expert) on the relation between heart rate and BOLD signal during presentation of emotional sounds presented during each state. Our findings revealed that BOLD signal in the right middle insula showed a significant association with heart rate (HR) across state and group. This association was stronger in the left middle/posterior insula when experts were compared to novices. The positive coupling of HR and BOLD was higher within the compassion state than within the neutral state in the dorsal anterior cingulate cortex for both groups, underlining the role of this region in the modulation of bodily arousal states. This state effect was stronger for experts than novices in somatosensory cortices and the right inferior parietal lobule (group by state interaction). These data confirm that compassion enhances the emotional and somatosensory brain representations of others' emotions, and that this effect is modulated by expertise. Future studies are needed to further investigate the impact of compassion training on these circuits.
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Mindfulness meditation is a set of attention-based, regulatory, and self-inquiry training regimes. Although the impact of mindfulness training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures renders difficult distinguishing their respective roles. To resolve this question we conducted a fully randomized 6 week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active-control group. We measured behavioral metacognition and whole-brain blood oxygenation level-dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention in healthy human subjects. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group-by-time interactions on negative affect-related reaction times or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response inhibition and increased recruitment of dorsal anterior cingulate cortex, medial prefrontal cortex, and right anterior insula during negative valence processing. Our findings highlight the importance of active control in MT research, indicate unique neural mechanisms for progressive stages of mindfulness training, and suggest that optimal application of MT may differ depending on context, contrary to a one-size-fits-all approach.

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.

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.

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.
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Pain is an unpleasant sensory and emotional experience, which can be regulated by many different cognitive mechanisms. We compared the regulatory qualities of two different meditation practices during noxious thermal stimuli: Focused Attention, directed at a fixation cross away from the stimulation, which could regulate negative affect through a sensory gating mechanism; and Open Monitoring, which could regulate negative affect through a mechanism of non-judgmental, non-reactive awareness of sensory experience. Here we report behavioral data from a comparison between novice and long-term meditation practitioners (long-term meditators, LTMs) using these techniques. LTMs, compared to novices, had a significant reduction of self-reported unpleasantness, but not intensity, of painful stimuli, while practicing Open Monitoring. No significant effects were found for FA. This finding illuminates the possible regulatory mechanism of meditation-based clinical interventions such as Mindfulness-Based Stress Reduction (MBSR). Implications are discussed in the broader context of training-induced changes in trait emotion regulation.
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Over the past several years meditation practice has gained increasing attention as a non-pharmacological intervention to provide health related benefits, from promoting general wellness to alleviating the symptoms of a variety of medical conditions. However, the effects of meditation training on brain activity still need to be fully characterized. Sleep provides a unique approach to explore the meditation-related plastic changes in brain function. In this study we performed sleep high-density electroencephalographic (hdEEG) recordings in long-term meditators (LTM) of Buddhist meditation practices (approximately 8700 mean hours of life practice) and meditation naive individuals. We found that LTM had increased parietal-occipital EEG gamma power during NREM sleep. This increase was specific for the gamma range (25–40 Hz), was not related to the level of spontaneous arousal during NREM and was positively correlated with the length of lifetime daily meditation practice. Altogether, these findings indicate that meditation practice produces measurable changes in spontaneous brain activity, and suggest that EEG gamma activity during sleep represents a sensitive measure of the long-lasting, plastic effects of meditative training on brain function.
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Attention to internal body sensations is practiced in most meditation traditions. Many traditions state that this practice results in increased awareness of internal body sensations, but scientific studies evaluating this claim are lacking. We predicted that experienced meditators would display performance superior to that of nonmeditators on heartbeat detection, a standard noninvasive measure of resting interoceptive awareness. We compared two groups of meditators (Tibetan Buddhist and Kundalini) to an age- and body mass index-matched group of nonmeditators. Contrary to our prediction, we found no evidence that meditators were superior to nonmeditators in the heartbeat detection task, across several sessions and respiratory modulation conditions. Compared to nonmeditators, however, meditators consistently rated their interoceptive performance as superior and the difficulty of the task as easier. These results provide evidence against the notion that practicing attention to internal body sensations, a core feature of meditation, enhances the ability to sense the heartbeat at rest.
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Practitioners understand "meditation," or mental training, to be a process of familiarization with one's own mental life leading to long-lasting changes in cognition and emotion. Little is known about this process and its impact on the brain. Here we find that long-term Buddhist practitioners self-induce sustained electroencephalographic high-amplitude gamma-band oscillations and phase-synchrony during meditation. These electroencephalogram patterns differ from those of controls, in particular over lateral frontoparietal electrodes. In addition, the ratio of gamma-band activity (25-42 Hz) to slow oscillatory activity (4-13 Hz) is initially higher in the resting baseline before meditation for the practitioners than the controls over medial frontoparietal electrodes. This difference increases sharply during meditation over most of the scalp electrodes and remains higher than the initial baseline in the postmeditation baseline. These data suggest that mental training involves temporal integrative mechanisms and may induce short-term and long-term neural changes.

Practitioners understand “meditation,” or mental training, to be a process of familiarization with one's own mental life leading to long-lasting changes in cognition and emotion. Little is known about this process and its impact on the brain. Here we find that long-term Buddhist practitioners self-induce sustained electroencephalographic high-amplitude gamma-band oscillations and phase-synchrony during meditation. These electroencephalogram patterns differ from those of controls, in particular over lateral frontoparietal electrodes. In addition, the ratio of gamma-band activity (25-42 Hz) to slow oscillatory activity (4-13 Hz) is initially higher in the resting baseline before meditation for the practitioners than the controls over medial frontoparietal electrodes. This difference increases sharply during meditation over most of the scalp electrodes and remains higher than the initial baseline in the postmeditation baseline. These data suggest that mental training involves temporal integrative mechanisms and may induce short-term and long-term neural changes.
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Intensive training in Vipassana meditation enhances one's ability to allocate attention efficiently in order to detect visual targets accurately. Behavioral and event-related potential evidence for a causal link between behavioral training and brain plasticity in adults is shown.
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The capacity to stabilize the content of attention over time varies among individuals, and its impairment is a hallmark of several mental illnesses. Impairments in sustained attention in patients with attention disorders have been associated with increased trial-to-trial variability in reaction time and event-related potential deficits during attention tasks. At present, it is unclear whether the ability to sustain attention and its underlying brain circuitry are transformable through training. Here, we show, with dichotic listening task performance and electroencephalography, that training attention, as cultivated by meditation, can improve the ability to sustain attention. Three months of intensive meditation training reduced variability in attentional processing of target tones, as indicated by both enhanced theta-band phase consistency of oscillatory neural responses over anterior brain areas and reduced reaction time variability. Furthermore, those individuals who showed the greatest increase in neural response consistency showed the largest decrease in behavioral response variability. Notably, we also observed reduced variability in neural processing, in particular in low-frequency bands, regardless of whether the deviant tone was attended or unattended. Focused attention meditation may thus affect both distracter and target processing, perhaps by enhancing entrainment of neuronal oscillations to sensory input rhythms, a mechanism important for controlling the content of attention. These novel findings highlight the mechanisms underlying focused attention meditation and support the notion that mental training can significantly affect attention and brain function.

The capacity to stabilize the content of attention over time varies among individuals, and its impairment is a hallmark of several mental illnesses. Impairments in sustained attention in patients with attention disorders have been associated with increased trial-to-trial variability in reaction time and event-related potential deficits during attention tasks. At present, it is unclear whether the ability to sustain attention and its underlying brain circuitry are transformable through training. Here, we show, with dichotic listening task performance and electroencephalography, that training attention, as cultivated by meditation, can improve the ability to sustain attention. Three months of intensive meditation training reduced variability in attentional processing of target tones, as indicated by both enhanced theta-band phase consistency of oscillatory neural responses over anterior brain areas and reduced reaction time variability. Furthermore, those individuals who showed the greatest increase in neural response consistency showed the largest decrease in behavioral response variability. Notably, we also observed reduced variability in neural processing, in particular in low-frequency bands, regardless of whether the deviant tone was attended or unattended. Focused attention meditation may thus affect both distracter and target processing, perhaps by enhancing entrainment of neuronal oscillations to sensory input rhythms, a mechanism important for controlling the content of attention. These novel findings highlight the mechanisms underlying focused attention meditation and support the notion that mental training can significantly affect attention and brain function.
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Although the adult brain was once seen as a rather static organ, it is now clear that the organization of brain circuitry is constantly changing as a function of experience or learning. Yet, research also shows that learning is often specific to the trained stimuli and task, and does not improve performance on novel tasks, even very similar ones. This perspective examines the idea that systematic mental training, as cultivated by meditation, can induce learning that is not stimulus or task specific, but process specific. Many meditation practices are explicitly designed to enhance specific, well-defined core cognitive processes. We will argue that this focus on enhancing core cognitive processes, as well as several general characteristics of meditation regimens, may specifically foster process-specific learning. To this end, we first define meditation and discuss key findings from recent neuroimaging studies of meditation. We then identify several characteristics of specific meditation training regimes that may determine process-specific learning. These characteristics include ongoing variability in stimulus input, the meta-cognitive nature of the processes trained, task difficulty, the focus on maintaining an optimal level of arousal, and the duration of training. Lastly, we discuss the methodological challenges that researchers face when attempting to control or characterize the multiple factors that may underlie meditation training effects.

Although the adult brain was once seen as a rather static organ, it is now clear that the organization of brain circuitry is constantly changing as a function of experience or learning. Yet, research also shows that learning is often specific to the trained stimuli and task, and does not improve performance on novel tasks, even very similar ones. This perspective examines the idea that systematic mental training, as cultivated by meditation, can induce learning that is not stimulus or task specific, but process specific. Many meditation practices are explicitly designed to enhance specific, well-defined core cognitive processes. We will argue that this focus on enhancing core cognitive processes, as well as several general characteristics of meditation regimens, may specifically foster process-specific learning. To this end, we first define meditation and discuss key findings from recent neuroimaging studies of meditation. We then identify several characteristics of specific meditation training regimes that may determine process-specific learning. These characteristics include ongoing variability in stimulus input, the meta-cognitive nature of the processes trained, task difficulty, the focus on maintaining an optimal level of arousal, and the duration of training. Lastly, we discuss the methodological challenges that researchers face when attempting to control or characterize the multiple factors that may underlie meditation training effects.
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Neuroimage phenotyping for psychiatric and neurological disorders is performed using voxelwise analyses also known as voxel based analyses or morphometry (VBM). A typical voxelwise analysis treats measurements at each voxel (e.g., fractional anisotropy, gray matter probability) as outcome measures to study the effects of possible explanatory variables (e.g., age, group) in a linear regression setting. Furthermore, each voxel is treated independently until the stage of correction for multiple comparisons. Recently, multi-voxel pattern analyses (MVPA), such as classification, have arisen as an alternative to VBM. The main advantage of MVPA over VBM is that the former employ multivariate methods which can account for interactions among voxels in identifying significant patterns. They also provide ways for computer-aided diagnosis and prognosis at individual subject level. However, compared to VBM, the results of MVPA are often more difficult to interpret and prone to arbitrary conclusions. In this paper, first we use penalized likelihood modeling to provide a unified framework for understanding both VBM and MVPA. We then utilize statistical learning theory to provide practical methods for interpreting the results of MVPA beyond commonly used performance metrics, such as leave-one-out-cross validation accuracy and area under the receiver operating characteristic (ROC) curve. Additionally, we demonstrate that there are challenges in MVPA when trying to obtain image phenotyping information in the form of statistical parametric maps (SPMs), which are commonly obtained from VBM, and provide a bootstrap strategy as a potential solution for generating SPMs using MVPA. This technique also allows us to maximize the use of available training data. We illustrate the empirical performance of the proposed framework using two different neuroimaging studies that pose different levels of challenge for classification using MVPA.
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SummaryBackground 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 = 8 h) 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.
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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.
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Recent brain imaging studies using functional magnetic resonance imaging (fMRI) have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices) during meditation (versus rest). During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ), and right posterior superior temporal sulcus (pSTS) in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in response to emotional stimuli.
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