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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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<p>Contemplative practices, from meditation to Zen, are growing in popularity as methods to inspire physical and mental health. "Contemplative Practices in Action: Spirituality, Meditation, and Health" offers readers an introduction to these practices and the ways they can be used in the service of well being, wisdom, healing, and stress reduction. Bringing together various traditions from the East and West, this thought-provoking work summarizes the history of each practice, highlights classic and emerging research proving its power, and details how each practice is performed. Expert authors offer step-by-step approaches to practice methods including the 8-Point Program of Passage Meditation, Centering Prayer, mindful stress management, mantram meditation, energizing meditation, yoga, and Zen. Beneficial practices from Christian, Buddhist, Jewish, Hindu, and Islamic religions are also featured. Vignettes illustrate each of the practices, while the contributors explain how and why they are effective in facing challenges as varied as the loss of a partner or child, job loss, chronic pain or disease, or psychological disorders.</p>

This article examines the lay meditation movement occurring in contemporary Buddhism in Sri Lanka. The lay meditation movement represents a different perspective from the nationalistic Sinhala Buddhism that has dominated the discourse in the wake of the intractable ethnic conflict in the country. The lay meditation movement reflects the contemporary ferment in Buddhist discourse among the laity. One of the key themes in this movement is the privileging of experience because it gives the lay groups authority to challenge contemporary orthodoxy and it has empowered a new class of spiritual leaders, the lay gurus. Paraphrasing Stirrat, we can say that these lay gurus are leading the lay meditation movement towards ‘a series of different interpretations of what it means’ to be a Buddhist today. In its overall effect the lay meditation movement not only reconstructs what it means to be a Buddhist today but also points in the direction of establishing new forms of sectarianism that could be considered to be ‘new religious movements’ under the umbrella of Buddhism.

Concepts develop for many aspects of experience, including abstract internal states and abstract social activities that do not refer to concrete entities in the world. The current study assessed the hypothesis that, like concrete concepts, distributed neural patterns of relevant nonlinguistic semantic content represent the meanings of abstract concepts. In a novel neuroimaging paradigm, participants processed two abstract concepts (convince, arithmetic) and two concrete concepts (rolling, red) deeply and repeatedly during a concept-scene matching task that grounded each concept in typical contexts. Using a catch trial design, neural activity associated with each concept word was separated from neural activity associated with subsequent visual scenes to assess activations underlying the detailed semantics of each concept. We predicted that brain regions underlying mentalizing and social cognition (e.g., medial prefrontal cortex, superior temporal sulcus) would become active to represent semantic content central to convince, whereas brain regions underlying numerical cognition (e.g., bilateral intraparietal sulcus) would become active to represent semantic content central to arithmetic. The results supported these predictions, suggesting that the meanings of abstract concepts arise from distributed neural systems that represent concept-specific content.
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In a recent neuroimaging study of macaque monkeys, Gil-da-Costa and colleagues reported that a distributed circuit of modality-specific properties represents macaques' conceptual knowledge of social situations. The circuit identified shows striking similarities to analogous circuits in humans that represent conceptual knowledge. This parallel suggests that a common architecture underlies the conceptual systems of different species, although with additional systems extending human conceptual abilities significantly.
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We present a novel data smoothing and analysis framework for cortical thickness data defined on the brain cortical manifold. Gaussian kernel smoothing, which weights neighboring observations according to their 3D Euclidean distance, has been widely used in 3D brain images to increase the signal-to-noise ratio. When the observations lie on a convoluted brain surface, however, it is more natural to assign the weights based on the geodesic distance along the surface. We therefore develop a framework for geodesic distance-based kernel smoothing and statistical analysis on the cortical manifolds. As an illustration, we apply our methods in detecting the regions of abnormal cortical thickness in 16 high functioning autistic children via random field based multiple comparison correction that utilizes the new smoothing technique.
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Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered 1 h prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol's effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol's effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol's effects on emotional memory formation and hippocampal function are related.
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In rodents, theta rhythm has been linked to the hippocampal formation, as well as other regions, including the anterior cingulate cortex (ACC). To test the role of the ACC in theta rhythm, concurrent measurements of brain electrical activity (EEG) and glucose metabolism (PET) were performed in 29 subjects at baseline. EEG data were analyzed with a source localization technique that enabled voxelwise correlations of EEG and PET data. For theta, but not other bands, the rostral ACC (Brodmann areas 24/32) was the largest cluster with positive correlations between current density and glucose metabolism. Positive correlations were also found in right fronto-temporal regions. In control but not depressed subjects, theta within ACC and prefrontal/orbitofrontal regions was positively correlated. The results reveal a link between theta and cerebral metabolism in the ACC as well as disruption of functional connectivity within frontocingulate pathways in depression.
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Sensitivity, specificity, and reproducibility are vital to interpret neuroscientific results from functional magnetic resonance imaging (fMRI) experiments. Here we examine the scan-rescan reliability of the percent signal change (PSC) and parameters estimated using Dynamic Causal Modeling (DCM) in scans taken in the same scan session, less than 5 min apart. We find fair to good reliability of PSC in regions that are involved with the task, and fair to excellent reliability with DCM. Also, the DCM analysis uncovers group differences that were not present in the analysis of PSC, which implies that DCM may be more sensitive to the nuances of signal changes in fMRI data.
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Cognitive deficits have been reported in children who experienced early neglect, especially children raised in institutionalized settings. Previous research suggests that early neglect may differentially affect the directional organization of white matter in the prefrontal cortex (PFC). This may be one mechanism to explain cognitive deficits associated with neglect. To test this idea, properties of white matter and neurocognitive performance were assessed in children who suffered early neglect and those raised in typical environments (n = 63, Mage  = 11.75 years). As predicted, prefrontal white matter microstructure was affected, consistent with more diffuse organization, in children that suffered early neglect and this was related to neurocognitive deficits. Such findings underscore how early adversity may affect the PFC and explain cognitive deficits associated with neglect.
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Individuals who experience early adversity, such as child maltreatment, are at heightened risk for a broad array of social and health difficulties. However, little is known about how this behavioral risk is instantiated in the brain. Here we examine a neurobiological contribution to individual differences in human behavior using methodology appropriate for use with pediatric populations paired with an in-depth measure of social behavior. We show that alterations in the orbitofrontal cortex among individuals who experienced physical abuse are related to social difficulties. These data suggest a biological mechanism linking early social learning to later behavioral outcomes.
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OBJECTIVE: This study was undertaken to identify brain structures associated with emotion in normal elderly subjects. METHOD: Eight normal subjects aged 55-78 years were shown film clips intended to provoke the emotions of happiness, fear, or disgust as well as a neutral state. During emotional activation, regional cerebral blood flow was measured with the use of [15O]H2O positron emission tomography imaging, and subjective emotional responses were recorded. Data were analyzed by subtracting the values during the neutral condition from the values in the various emotional activations. RESULTS: The stimuli produced a general activation in visual pathways that included the primary and secondary visual cortex, involving regions associated with object and spatial recognition. In addition, the specific emotions produced different regional limbic activations, which suggests that different pathways may be used for different types of emotional stimuli. CONCLUSIONS: Emotional activation in normal elderly subjects was associated with increases in blood flow in limbic and paralimbic brain structures. Brain activation may be specific to the emotion being elicited but probably involves complex sensory, association, and memory circuitry. Further studies are needed to identify activations that are specific for emotion.
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<p>In two prior studies, we investigated the neural mechanisms of spatial attention using a combined event-related potential (ERP) and positron emission tomography (PET) approach (Heinze et al. [1994]: Nature 392:543-546; Mangun et al. [1997]: Hum Brain Mapp 5:273-279). Neural activations in extrastriate cortex were observed in the PET measures for attended stimuli, and these effects were related to attentional modulations in the ERPs at specific latencies. The present study used functional magnetic resonance imaging (fMRI) and ERPs in single subjects to investigate the intersubject variability in extrastriate spatial attention effects, and to qualitatively compare this to variations in ERP attention effects. Activations in single subjects replicated our prior group-averaged PET findings, showing attention-related increases in blood flow in the posterior fusiform and middle occipital gyri in the hemisphere contralateral to attended visual stimuli. All subjects showed attentional modulations of the occipital P1 component of the ERPs. These findings in single subjects demonstrate the consistency of extrastriate attention effects, and provide information about the feasibility of this approach for integration of electrical and functional imaging data.</p>
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BACKGROUND: Relationships between aberrant social functioning and depression have been explored via behavioral, clinical, and survey methodologies, highlighting their importance in the etiology of depression. The neural underpinnings of these relationships, however, have not been explored. METHODS: Nine depressed participants and 14 never-depressed control subjects viewed emotional and neutral pictures at two functional magnetic resonance imaging (fMRI) scanning sessions approximately 22 weeks apart. In the interim, depressed patients received the antidepressant Venlafaxine. Positively rated images were parsed into three separate comparisons: social interaction, human faces, and sexual images; across scanning session, activation to these images was compared with other positively rated images. RESULTS: For each of the three social stimulus types (social interaction, faces, sexual images), a distinguishable circuitry was activated equally in non-depressed control subjects and post-treatment depressed subjects but showed a hypo-response in the depressed group pre-treatment. These structures include regions of prefrontal, temporal, and parietal cortices, insula, basal ganglia, and the hippocampus. CONCLUSIONS: The neural hypo-response to positively valenced social stimuli that is observed in depression remits as response to antidepressant medication occurs, suggesting a state-dependent deficiency in response to positive social incentives. These findings underscore the importance of addressing social dysfunction in research and treatment of depression.
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Neuroanatomists posit that the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST) comprise two major nodes of a macrostructural forebrain entity termed the extended amygdala. The extended amygdala is thought to play a critical role in adaptive motivational behavior and is implicated in the pathophysiology of maladaptive fear and anxiety. Resting functional connectivity of the Ce was examined in 107 young anesthetized rhesus monkeys and 105 young humans using standard resting-state functional magnetic resonance imaging (fMRI) methods to assess temporal correlations across the brain. The data expand the neuroanatomical concept of the extended amygdala by finding, in both species, highly significant functional coupling between the Ce and the BST. These results support the use of in vivo functional imaging methods in nonhuman and human primates to probe the functional anatomy of major brain networks such as the extended amygdala.
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The LASS theory proposes that Language and Situated Simulation both play central roles in conceptual processing. Depending on stimuli and task conditions, different mixtures of language and simulation occur. When a word is processed in a conceptual task, it first activates other linguistic forms, such as word associates. More slowly, the word activates a situated simulation to represent its meaning in neural systems for perception, action, and mental states. An fMRI experiment tested the LASS account. In a first scanning session, participants performed the property generation task to provide a measure of conceptual processing. In a second scanning session a week later, participants performed two localizer tasks measuring word association and situated simulation. Conjunction analyses supported predictions of the LASS theory. Activations early in conceptual processing overlapped with activations for word association. Activations late in conceptual processing overlapped with activations for situation generation. These results, along with others in the literature, indicate that conceptual processing uses multiple representations, not one. Furthermore, researchers must be careful drawing conclusions about conceptual processing, given that different paradigms are likely to produce different mixtures of language and simulation. Whereas some paradigms produce high levels of linguistic processing and low levels of simulation, other paradigms produce the opposite pattern.
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Previous research indicates that drug motivational systems are instantiated in structures that process information related to incentive, motivational drive, memorial, motor/habit, craving, and cognitive control processing. The present research tests the hypothesis that activity in such systems will be powerfully affected by the combination of drug anticipation and drug withdrawal. Event-related fMRI was used to examine activation in response to a preinfusion warning cue in two experimental sessions that manipulated withdrawal status. Significant cue-induced effects were seen in the caudate, ventral anterior nucleus of the thalamus, the insula, subcallosal gyrus, nucleus accumbens, and anterior cingulate. These results suggest that withdrawal and nicotine anticipation produce (1) different motor preparatory and inhibitory response processing and (2) different craving related processing.
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Major depression is a heterogeneous condition, and the search for neural correlates specific to clinically defined subtypes has been inconclusive. Theoretical considerations implicate frontostriatal, particularly subgenual prefrontal cortex (PFC), dysfunction in the pathophysiology of melancholia--a subtype of depression characterized by anhedonia--but no empirical evidence has been found yet for such a link. To test the hypothesis that melancholic, but not nonmelancholic depression, is associated with the subgenual PFC impairment, concurrent measurement of brain electrical (electroencephalogram, EEG) and metabolic (positron emission tomography, PET) activity were obtained in 38 unmedicated subjects with DSM-IV major depressive disorder (20 melancholic, 18 nonmelancholic subjects), and 18 comparison subjects. EEG data were analyzed with a tomographic source localization method that computed the cortical three-dimensional distribution of current density for standard frequency bands, allowing voxelwise correlations between the EEG and PET data. Voxel-based morphometry analyses of structural magnetic resonance imaging (MRI) data were performed to assess potential structural abnormalities in melancholia. Melancholia was associated with reduced activity in the subgenual PFC (Brodmann area 25), manifested by increased inhibitory delta activity (1.5-6.0 Hz) and decreased glucose metabolism, which themselves were inversely correlated. Following antidepressant treatment, depressed subjects with the largest reductions in depression severity showed the lowest post-treatment subgenual PFC delta activity. Analyses of structural MRI revealed no group differences in the subgenual PFC, but in melancholic subjects, a negative correlation between gray matter density and age emerged. Based on preclinical evidence, we suggest that subgenual PFC dysfunction in melancholia may be associated with blunted hedonic response and exaggerated stress responsiveness.
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