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OBJECTIVE: In this case study, we describe the effects of a particular individual's concentration/meditation technique on autonomic nervous system activity and the innate immune response. The study participant holds several world records with regard to tolerating extreme cold and claims that he can influence his autonomic nervous system and thereby his innate immune response. METHODS: The individual's ex vivo cytokine response (stimulation of peripheral blood mononuclear cells with lipopolysaccharide [LPS]) was determined before and after an 80-minute full-body ice immersion during which the individual practiced his concentration/meditation technique. Furthermore, the individual's in vivo innate immune response was studied while practicing his concentration/mediation technique during human endotoxemia (intravenous administration of 2 ng/kg LPS). The results from the endotoxemia experiment were compared with a historical cohort of 112 individuals who participated in endotoxemia experiments in our institution. RESULTS: The ex vivo proinflammatory and anti-inflammatory cytokine response was greatly attenuated by concentration/meditation during ice immersion, accompanied by high levels of cortisol. In the endotoxemia experiment, concentration/meditation resulted in increased circulating concentrations of catecholamines, and plasma cortisol concentrations were higher than in any of the previously studied participants. The individual's in vivo cytokine response and clinical symptoms after LPS administration were remarkably low compared with previously studied participants. CONCLUSIONS: The concentration/meditation technique used by this particular individual seems to evoke a controlled stress response. This response is characterized by sympathetic nervous system activation and subsequent catecholamine/cortisol release, which seems to attenuate the innate immune response.
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A growing body of literature has documented the differential role of the frontal regions of the two cerebral hemispheres in certain positive and negative affective processes. This corpus of evidence has led to the hypothesis of a possible differential effect of diazepam on asymmetry of frontal activation. To examine this question, nine infant rhesus monkeys were tested on two occasions during which brain electrical activity was recorded from left and right frontal and parietal scalp regions. During one session, recordings were obtained under a baseline restraint condition and then after an injection of diazepam (1 mg/kg). In the other session, following the same baseline restraint condition, a vehicle injection was given. In response to diazepam, the animals showed an asymmetrical decrease in power in the 4-8 Hz frequency band, which was most pronounced in the left frontal region. No change in electroencephalogram (EEG) activity was observed in response to vehicle. Asymmetry in parietal EEG activity was also unchanged by diazepam. Diazepam also produced overall reductions in power across different frequency bands in both frontal and parietal regions. Good test-retest stability of EEG measures of activation asymmetry was also found between the two testing sessions separated by three months. The possible proximal cause of the asymmetrical change in frontal brain electrical activity in response to diazepam, as well as the implications of these findings for understanding the mechanism of action of benzodiazepines are discussed.
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Meditation is a mental training, which involves attention and the ability to maintain focus on a particular object. In this study we have applied a specific attentional task to simply measure the performance of the participants with different levels of meditation experience, rather than evaluating meditation practice per se or task performance during meditation. Our objective was to evaluate the performance of regular meditators and non-meditators during an fMRI adapted Stroop Word-Colour Task (SWCT), which requires attention and impulse control, using a block design paradigm. We selected 20 right-handed regular meditators and 19 non-meditators matched for age, years of education and gender. Participants had to choose the colour (red, blue or green) of single words presented visually in three conditions: congruent, neutral and incongruent. Non-meditators showed greater activity than meditators in the right medial frontal, middle temporal, precentral and postcentral gyri and the lentiform nucleus during the incongruent conditions. No regions were more activated in meditators relative to non-meditators in the same comparison. Non-meditators showed an increased pattern of brain activation relative to regular meditators under the same behavioural performance level. This suggests that meditation training improves efficiency, possibly via improved sustained attention and impulse control.

A growing body of evidence suggests that empathy for pain is underpinned by neural structures that are also involved in the direct experience of pain. In order to assess the consistency of this finding, an image-based meta-analysis of nine independent functional magnetic resonance imaging (fMRI) investigations and a coordinate-based meta-analysis of 32 studies that had investigated empathy for pain using fMRI were conducted. The results indicate that a core network consisting of bilateral anterior insular cortex and medial/anterior cingulate cortex is associated with empathy for pain. Activation in these areas overlaps with activation during directly experienced pain, and we link their involvement to representing global feeling states and the guidance of adaptive behavior for both self- and other-related experiences. Moreover, the image-based analysis demonstrates that depending on the type of experimental paradigm this core network was co-activated with distinct brain regions: While viewing pictures of body parts in painful situations recruited areas underpinning action understanding (inferior parietal/ventral premotor cortices) to a stronger extent, eliciting empathy by means of abstract visual information about the other's affective state more strongly engaged areas associated with inferring and representing mental states of self and other (precuneus, ventral medial prefrontal cortex, superior temporal cortex, and temporo-parietal junction). In addition, only the picture-based paradigms activated somatosensory areas, indicating that previous discrepancies concerning somatosensory activity during empathy for pain might have resulted from differences in experimental paradigms. We conclude that social neuroscience paradigms provide reliable and accurate insights into complex social phenomena such as empathy and that meta-analyses of previous studies are a valuable tool in this endeavor.
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An emerging body of research suggests that mindfulness-based interventions may be beneficial for smoking cessation and the treatment of other addictive disorders. One way that mindfulness may facilitate smoking cessation is through the reduction of craving to smoking cues. The present work considers whether mindful attention can reduce self-reported and neural markers of cue-induced craving in treatment seeking smokers. Forty-seven (n = 47) meditation-naïve treatment-seeking smokers (12-h abstinent from smoking) viewed and made ratings of smoking and neutral images while undergoing functional magnetic resonance imaging (fMRI). Participants were trained and instructed to view these images passively or with mindful attention. Results indicated that mindful attention reduced self-reported craving to smoking images, and reduced neural activity in a craving-related region of subgenual anterior cingulate cortex (sgACC). Moreover, a psychophysiological interaction analysis revealed that mindful attention reduced functional connectivity between sgACC and other craving-related regions compared to passively viewing smoking images, suggesting that mindfulness may decouple craving neurocircuitry when viewing smoking cues. These results provide an initial indication that mindful attention may describe a ‘bottom-up’ attention to one’s present moment experience in ways that can help reduce subjective and neural reactivity to smoking cues in smokers.

Studies have suggested that the default mode network is active during mind wandering, which is often experienced intermittently during sustained attention tasks. Conversely, an anticorrelated task-positive network is thought to subserve various forms of attentional processing. Understanding how these two systems work together is central for understanding many forms of optimal and sub-optimal task performance. Here we present a basic model of naturalistic cognitive fluctuations between mind wandering and attentional states derived from the practice of focused attention meditation. This model proposes four intervals in a cognitive cycle: mind wandering, awareness of mind wandering, shifting of attention, and sustained attention. People who train in this style of meditation cultivate their abilities to monitor cognitive processes related to attention and distraction, making them well suited to report on these mental events. Fourteen meditation practitioners performed breath-focused meditation while undergoing fMRI scanning. When participants realized their mind had wandered, they pressed a button and returned their focus to the breath. The four intervals above were then constructed around these button presses. We hypothesized that periods of mind wandering would be associated with default mode activity, whereas cognitive processes engaged during awareness of mind wandering, shifting of attention and sustained attention would engage attentional subnetworks. Analyses revealed activity in brain regions associated with the default mode during mind wandering, and in salience network regions during awareness of mind wandering. Elements of the executive network were active during shifting and sustained attention. Furthermore, activations during these cognitive phases were modulated by lifetime meditation experience. These findings support and extend theories about cognitive correlates of distributed brain networks.

Many studies in humans suggest that altered temporal lobe functioning, especially functioning in the right temporal lobe, is involved in mystical and religious experiences. We investigated temporal lobe functioning in individuals who reported having transcendental "near-death experiences" during life-threatening events. These individuals were found to have more temporal lobe epileptiform electroencephalographic activity than control subjects and also reported significantly more temporal lobe epileptic symptoms. Contrary to predictions, epileptiform activity was nearly completely lateralized to the left hemisphere. The near-death experience was not associated with dysfunctional stress reactions such as dissociation, posttraumatic stress disorder, and substance abuse, but rather was associated with positive coping styles. Additional analyses revealed that near-death experiencers had altered sleep patterns, specifically, a shorter duration of sleep and delayed REM sleep relative to the control group. These results suggest that altered temporal lobe functioning may be involved in the near-death experience and that individuals who have had such experiences are physiologically distinct from the general population.
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SummaryObjectives To investigate neural representation evoked by acupuncture from human somatosensory cortices, especially from primary (SI) and secondary (SII) somatosensory areas. Design and setting Neuroimaging study – Blood-oxygenation-level-dependent (BOLD) functional MRI was performed during acupuncture on LI4 (n = 12 healthy participants). Sham acupuncture and innocuous tactile stimulation were also applied on the same acupuncture site as control comparisons. Outcome measures Responsive neural substrates were visualized and identified based on both individual and group-level surface activation maps. Results Discrete regions within the precentral gyrus (area 4) and the fundus of the central sulcus (area 3a) were selectively activated during the real acupuncture stimulation. In SII, the activation was extended in a postero-inferior direction to the fundus of the lateral sulcus. Conclusion This specific pattern of acupuncture-related activation indicates that deep tissue stimulation (as seen in area 3a activation) and concurrent processing of sensory stimulation (as seen in activation in SII) may mediate neural responses to manual acupuncture.
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Objective: Mindfulness is a process whereby one is aware and receptive to present moment experiences. Although mindfulness-enhancing interventions reduce pathological mental and physical health symptoms across a wide variety of conditions and diseases, the mechanisms underlying these effects remain unknown. Converging evidence from the mindfulness and neuroscience literature suggests that labeling affect may be one mechanism for these effects. Methods: Participants (n = 27) indicated trait levels of mindfulness and then completed an affect labeling task while undergoing functional magnetic resonance imaging. The labeling task consisted of matching facial expressions to appropriate affect words (affect labeling) or to gender-appropriate names (gender labeling control task). Results: After controlling for multiple individual difference measures, dispositional mindfulness was associated with greater widespread prefrontal cortical activation, and reduced bilateral amygdala activity during affect labeling, compared with the gender labeling control task. Further, strong negative associations were found between areas of prefrontal cortex and right amygdala responses in participants high in mindfulness but not in participants low in mindfulness. Conclusions: The present findings with a dispositional measure of mindfulness suggest one potential neurocognitive mechanism for understanding how mindfulness meditation interventions reduce negative affect and improve health outcomes, showing that mindfulness is associated with enhanced prefrontal cortical regulation of affect through labeling of negative affective stimuli.

'Mindfulness' is a capacity for heightened present-moment awareness that we all possess to a greater or lesser extent. Enhancing this capacity through training has been shown to alleviate stress and promote physical and mental well-being. As a consequence, interest in mindfulness is growing and so is the need to better understand it. This study employed functional magnetic resonance imaging (fMRI) to identify the brain regions involved in state mindfulness and to shed light on its mechanisms of action. Significant signal decreases were observed during mindfulness meditation in midline cortical structures associated with interoception, including bilateral anterior insula, left ventral anterior cingulate cortex, right medial prefrontal cortex, and bilateral precuneus. Significant signal increase was noted in the right posterior cingulate cortex. These findings lend support to the theory that mindfulness achieves its positive outcomes through a process of disidentification.

Meditation comprises a series of practices mainly developed in eastern cultures aiming at controlling emotions and enhancing attentional processes. Several authors proposed to divide meditation techniques in focused attention (FA) and open monitoring (OM) techniques. Previous studies have reported differences in brain networks underlying FA and OM. On the other hand common activations across different meditative practices have been reported. Despite differences between forms of meditation and their underlying cognitive processes, we propose that all meditative techniques could share a central process that would be supported by a core network for meditation since their general common goal is to induce relaxation, regulating attention and developing an attitude of detachment from one’s own thoughts. To test this hypothesis, we conducted a quantitative meta-analysis based on activation likelihood estimation (ALE) of 10 neuroimaging studies (91 subjects) on different meditative techniques to evidence the core cortical network subserving meditation. We showed activation of basal ganglia (caudate body), limbic system (enthorinal cortex) and medial prefrontal cortex (MPFC). We discuss the functional role of these structures in meditation and we tentatively propose a neurocognitive model of meditation that could guide future research.

Concepts originating from ancient Eastern texts are now being explored scientifically, leading to new insights into mind/brain function. Meditative practice, often viewed as an emotion regulation strategy, has been associated with pain reduction, low pain sensitivity, chronic pain improvement, and thickness of pain-related cortices. Zen meditation is unlike previously studied emotion regulation techniques; more akin to ‘no appraisal’ than ‘reappraisal’. This implies the cognitive evaluation of pain may be involved in the pain-related effects observed in meditators. Using functional magnetic resonance imaging and a thermal pain paradigm we show that practitioners of Zen, compared to controls, reduce activity in executive, evaluative and emotion areas during pain (prefrontal cortex, amygdala, hippocampus). Meditators with the most experience showed the largest activation reductions. Simultaneously, meditators more robustly activated primary pain processing regions (anterior cingulate cortex, thalamus, insula). Importantly, the lower pain sensitivity in meditators was strongly predicted by reductions in functional connectivity between executive and pain-related cortices. Results suggest a functional decoupling of the cognitive-evaluative and sensory-discriminative dimensions of pain, possibly allowing practitioners to view painful stimuli more neutrally. The activation pattern is remarkably consistent with the mindset described in Zen and the notion of mindfulness. Our findings contrast and challenge current concepts of pain and emotion regulation and cognitive control; commonly thought to manifest through increased activation of frontal executive areas. We suggest it is possible to self-regulate in a more ‘passive’ manner, by reducing higher-order evaluative processes, as demonstrated here by the disengagement of anterior brain systems in meditators.

Examined were electroencephalogram (EEG) asymmetries during the presence of discrete facial signs of emotion among 10-month-old infants who were tested in a standard stranger- and mother-approach paradigm that included a brief separation from mother. Data underscore the usefulness of EEG measures of hemispheric activation in differentiating among certain emotional states. (RH)
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<p>Early childhood is marked by substantial development in the self-regulatory skills supporting school readiness and socioemotional competence. Evidence from developmental social cognitive neuroscience suggests that these skills develop as a function of changes in a dynamic interaction between more top-down (controlled) regulatory processes and more bottom-up (automatic) influences on behavior. Mindfulness training—using age-appropriate activities to exercise children's reflection on their moment-to-moment experiences—may support the development of self-regulation by targeting top-down processes while lessening bottom-up influences (such as anxiety, stress, curiosity) to create conditions conducive to reflection, both during problem solving and in more playful, exploratory ways.</p>

Temperamentally anxious individuals can be identified in childhood and are at risk to develop anxiety and depressive disorders. In addition, these individuals tend to have extreme asymmetric right prefrontal brain activity. Although common and clinically important, little is known about the pathophysiology of anxious temperament. Regardless, indirect evidence from rodent studies and difficult to interpret primate studies is used to support the hypothesis that the amygdala plays a central role. In previous studies using rhesus monkeys, we characterized an anxious temperament endophenotype that is associated with excessive anxiety and fear-related responses and increased electrical activity in right frontal brain regions. To examine the role of the amygdala in mediating this endophenotype and other fearful responses, we prepared monkeys with selective fiber sparing ibotenic acid lesions of the amygdala. Unconditioned trait-like anxiety-fear responses remained intact in monkeys with >95% bilateral amygdala destruction. In addition, the lesions did not affect EEG frontal asymmetry. However, acute unconditioned fear responses, such as those elicited by exposure to a snake and to an unfamiliar threatening conspecific were blunted in monkeys with >70% lesions. These findings demonstrate that the primate amygdala is involved in mediating some acute unconditioned fear responses but challenge the notion that the amygdala is the key structure underlying the dispositional behavioral and physiological characteristics of anxious temperament.
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The Indo-Tibetan tradition claims that proficiency in the suggested longevity practices of meditation, diet, and physical exercise (yoga), will result in profound anti-aging, stress-mediating and health enhancing effects. Western biomedical research has begun to demonstrate that the psychobiological states induced and cultivated by cognitive behavioral practices which are emblematic of those contained within the Indo-Tibetan tradition (hypnosis, meditation, visualization, systematic relaxation), indeed do have a profound impact on the body's protective and regulatory systems. Although continued study is necessary, much of the early research illuminating the mechanisms responsible for the life-span extending and health-enhancing effects of these cognitive behavioral practices points to the importance of their anti-inflammatory, anti-stress, and antioxidant effects as well as their impact in enhancing the production of endogenous substances that possess general longevity-enhancing, regenerative properties.
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<p>Although mindfulness meditation traditionally is viewed as a lifelong practice, much current knowledge about its effects is based on short-term practitioners who have participated in mindfulness-based treatment. In the current study, long-term meditators and demographically similar nonmeditators completed self-report measures of constructs expected to be related to the practice of mindfulness meditation. Extent of meditation experience was correlated in the expected directions with levels of mindfulness and with many other variables. Mean differences between meditators and nonmeditators were significant in most cases. Mediation analyses were consistent with the hypothesis that practicing meditation is associated with increased mindfulness in daily life, which is related to decreased rumination, decreased fear of emotion, and increased behavioral self-regulation. These mechanisms appear partially responsible for the relationships between mindfulness skills and psychological adjustment. Overall, the current study suggests that the long-term practice of mindfulness meditation may cultivate mindfulness skills and promote adaptive functioning.</p>

BACKGROUND: Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity. METHODS: Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task. Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task. Anhedonia scores were collected at three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and 6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time. Analyses were conducted utilizing hierarchical linear modeling software. RESULTS: Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication (p < .05). Control subjects showed a similar trend between baseline and time 3. CONCLUSIONS: To reduce anhedonia, it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system.
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Baseline resting electroencephalogram (EEG) activity was recorded from 6 normothymic depressives and 8 controls using three different reference montages. Power in all frequency bands was extracted by Fourier transformation. Significant Group X Region X Hemisphere interactions were found consistently for alpha band power only. Previously depressed subjects had less left-sided anterior and less right-sided posterior activation (i.e., more alpha activity) than did never depressed subjects. Previously depressed subjects had no history of pharmacological treatment and did not differ from controls in emotional state at the time of testing. The pattern of anterior and posterior asymmetry in the previously depressed subjects is similar to that found in acutely depressed subjects and suggests that this may be a state-independent marker for depression.
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Electroencephalogram (EEG) alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The thalamus has been proposed as an important site for modulation of rhythmic alpha activity. Studies in animals have suggested that cortical alpha rhythms are correlated with alpha rhythms in the thalamus. However, little empirical evidence exists for this relation in humans. In the current study, resting EEG and a fluorodeoxyglucose positron emission tomography scan were measured during the same experimental session. Over a 30-min period, average EEG alpha power across 28 electrodes from 27 participants was robustly inversely correlated with glucose metabolic activity in the thalamus. These data provide the first evidence for a relation between alpha EEG power and thalamic activity in humans.
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<p>The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.</p>
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Although several studies have examined anterior asymmetric brain electrical activity and cortisol in infants, children, and adults, the direct association between asymmetry and cortisol has not systematically been reported. In nonhuman primates, greater relative right anterior activation has been associated with higher cortisol levels. The current study examines the relation between frontal electroencephalographic (EEG) asymmetry and cortisol (basal and reactive) and withdrawal-related behaviors (fear and sadness) in 6-month-old infants. As predicted, the authors found that higher basal and reactive cortisol levels were associated with extreme right EEG asymmetry. EEG during the withdrawal-negative affect task was associated with fear and sadness behaviors. Results are interpreted in the context of the previous primate work, and some putative mechanisms are discussed.
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Right-handed subjects tend to look to the left when answering affective questions. The relative shift in gaze from right to left is accentuated when the questions also involve spatial manipulation and attenuated when the questions require verbal manipulation. The data support the hypothesis that the right hemisphere has a special role in emotion in the intact brain, and that predictable patterning of hemispheric activity can occur when specific combinations of cognitive and affective processes interact.
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