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BackgroundAsthma is a chronic inflammatory disease noteworthy for its vulnerability to stress and emotion-induced symptom intensification. The fact that psychological stress and mood and anxiety disorders appear to increase expression of asthma symptoms suggests that neural signaling between the brain and lung at least partially modulates the inflammatory response and lung function. However, the precise nature of the neural pathways implicated in modulating asthma symptoms is unknown. Moreover, the extent to which variations in neural signaling predict different phenotypes of disease expression has not been studied.Methods and ResultsWe used functional magnetic resonance imaging to measure neural signals in response to asthma-specific emotional cues, following allergen exposure, in asthmatics with a dual response to allergen challenge (significant inflammation), asthmatics with only an immediate response (minimal inflammation), and healthy controls. The anterior insular cortex was differentially activated by asthma-relevant cues, compared to general negative cues, during the development of the late phase of the dual response in asthmatics. Moreover, the degree of this differential activation predicted changes in airway inflammation.ConclusionsThese findings indicate that neurophenotypes for asthma may be identifiable by neural reactivity of brain circuits known to be involved in processing emotional information. Those with greater activation in the anterior insula, in response to asthma-relevant psychological stimuli, exhibit greater inflammatory signals in the lung and increased severity of disease and may reflect a subset of asthmatics most vulnerable to the development of psychopathology. This approach offers an entirely new target for potential therapeutic intervention in asthma.

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.

Given the central role of the amygdala in fear perception and expression and its likely abnormality in affective disorders and autism, there is great demand for a technique to measure differences in neurochemistry of the human amygdala. Unfortunately, it is also a technically complex target for magnetic resonance spectroscopy (MRS) due to a small volume, high field inhomogeneity and a shared boundary with hippocampus, which can undergo opposite changes in response to stress. We attempted to achieve reliable PRESS-localized single-voxel MRS at 3T of the isolated human amygdala by using anatomy to guide voxel size and location. We present data from 106 amygdala-MRS sessions from 58 volunteers aged 10 to 52 years, including two tests of one-week stability and a feasibility study in an adolescent sample. Our main outcomes were indices of spectral quality, repeated measurement variability (within- and between-subject standard deviations), and sensitivity to stable individual differences measured by intra-class correlation (ICC). We present metrics of amygdala-MRS reliability for n-acetyl-aspartate, creatine, choline, myo-Inositol, and glutamate+glutamine (Glx). We found that scan quality suffers an age-related difference in field homogeneity and modified our protocol to compensate. We further identified an effect of anatomical inclusion near the endorhinal sulcus, a region of high synaptic density, that contributes up to 29% of within-subject variability across 4 sessions (n=14). Remaining variability in line width but not signal-to-noise also detracts from reliability. Statistical correction for partial inclusion of these strong neurochemical gradients decreases n-acetyl-aspartate reliability from an intraclass correlation of 0.84 to 0.56 for 7-minute acquisitions. This suggests that systematic differences in anatomical inclusion can contribute greatly to apparent neurochemical concentrations and could produce false group differences in experimental studies. Precise, anatomically-based prescriptions that avoid age-related sources of inhomogeneity and use longer scan times may permit study of individual differences in neurochemistry throughout development in this late-maturing structure.

Most of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons. The current article specifies and validates an active control condition, the Health Enhancement Program (HEP), thus providing the foundation necessary for rigorous investigations of the relative efficacy of Mindfulness Based Stress Reduction (MBSR) and for testing mindfulness as an active ingredient. 63 participants were randomized to either MBSR (n = 31) or HEP (n = 32). Compared to HEP, MBSR led to reductions in thermal pain ratings in the mindfulness- but not the HEP-related instruction condition (η(2) = .18). There were significant improvements over time for general distress (η(2) = .09), anxiety (η(2) = .08), hostility (η(2) = .07), and medical symptoms (η(2) = .14), but no effects of intervention. Practice was not related to change. HEP is an active control condition for MBSR while remaining inert to mindfulness. These claims are supported by results from a pain task. Participant-reported outcomes (PROs) replicate previous improvements to well-being in MBSR, but indicate that MBSR is no more effective than a rigorous active control in improving these indices. These results emphasize the importance of using an active control condition like HEP in studies evaluating the effectiveness of MBSR.

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.

Tasks that tax working memory (WM) have consistently been found to decrease mind wandering. These findings may indicate that maintenance of mind wandering requires WM resources, such that mind wandering cannot persist when WM resources are being consumed by a task. An alternative explanation for these findings, however, is that mind wandering persists without the support of WM but is nonetheless decreased during any demanding task because good task performance requires that attention be restricted from task-unrelated thought (TUT). The present study tested these two competing theories by investigating whether individuals with greater WM resources mind-wander more during an undemanding task, as would be predicted only by the theory that WM supports TUT. We found that individuals with higher WM capacity reported more TUT in undemanding tasks, which suggests that WM enables the maintenance of mind wandering.

Despite growing evidence on the neural bases of emotion regulation, little is known about the mechanisms underlying individual differences in cognitive regulation of negative emotion, and few studies have used objective measures to quantify regulatory success. Using a trait-like psychophysiological measure of emotion regulation, corrugator electromyography, we obtained an objective index of the ability to cognitively reappraise negative emotion in 56 healthy men (Session 1), who returned 1.3 years later to perform the same regulation task using fMRI (Session 2). Results indicated that the corrugator measure of regulatory skill predicted amygdala-prefrontal functional connectivity. Individuals with greater ability to down-regulate negative emotion as indexed by corrugator at Session 1 showed not only greater amygdala attenuation but also greater inverse connectivity between the amygdala and several sectors of the prefrontal cortex while down-regulating negative emotion at Session 2. Our results demonstrate that individual differences in emotion regulation are stable over time and underscore the important role of amygdala-prefrontal coupling for successful regulation of negative emotion.

Although the co-occurrence of negative affect and pain is well recognized, the mechanism underlying their association is unclear. To examine whether a common self-regulatory ability impacts the experience of both emotion and pain, we integrated neuroimaging, behavioral, and physiological measures obtained from three assessments separated by substantial temporal intervals. Our results demonstrated that individual differences in emotion regulation ability, as indexed by an objective measure of emotional state, corrugator electromyography, predicted self-reported success while regulating pain. In both emotion and pain paradigms, the amygdala reflected regulatory success. Notably, we found that greater emotion regulation success was associated with greater change of amygdalar activity following pain regulation. Furthermore, individual differences in degree of amygdalar change following emotion regulation were a strong predictor of pain regulation success, as well as of the degree of amygdalar engagement following pain regulation. These findings suggest that common individual differences in emotion and pain regulatory success are reflected in a neural structure known to contribute to appraisal processes.

We present a new sparse shape modeling framework on the Laplace-Beltrami (LB) eigenfunctions. Traditionally, the LB-eigenfunctions are used as a basis for intrinsically representing surface shapes by forming a Fourier series expansion. To reduce high frequency noise, only the first few terms are used in the expansion and higher frequency terms are simply thrown away. However, some lower frequency terms may not necessarily contribute significantly in reconstructing the surfaces. Motivated by this idea, we propose to filter out only the significant eigenfunctions by imposing l1-penalty. The new sparse framework can further avoid additional surface-based smoothing often used in the field. The proposed approach is applied in investigating the influence of age (38-79 years) and gender on amygdala and hippocampus shapes in the normal population. In addition, we show how the emotional response is related to the anatomy of the subcortical structures.

We present a new subcortical structure shape modeling framework using heat kernel smoothing constructed with the Laplace-Beltrami eigenfunctions. The cotan discretization is used to numerically obtain the eigenfunctions of the Laplace-Beltrami operator along the surface of subcortical structures of the brain. The eigenfunctions are then used to construct the heat kernel and used in smoothing out measurements noise along the surface. The proposed framework is applied in investigating the influence of age (38-79 years) and gender on amygdala and hippocampus shape. We detected a significant age effect on hippocampus in accordance with the previous studies. In addition, we also detected a significant gender effect on amygdala. Since we did not find any such differences in the traditional volumetric methods, our results demonstrate the benefit of the current framework over traditional volumetric methods.

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum.

Greater levels of conscientiousness have been associated with lower levels of negative affect. We focus on one mechanism through which conscientiousness may decrease negative affect: effective emotion regulation, as reflected by greater recovery from negative stimuli. In 273 adults who were 35-85 years old, we collected self-report measures of personality including conscientiousness and its self-control facet, followed on average 2 years later by psychophysiological measures of emotional reactivity and recovery. Among middle-aged adults (35-65 years old), the measures of conscientiousness and self-control predicted greater recovery from, but not reactivity to, negative emotional stimuli. The effect of conscientiousness and self-control on recovery was not driven by other personality variables or by greater task adherence on the part of high conscientiousness individuals. In addition, the effect was specific to negative emotional stimuli and did not hold for neutral or positive emotional stimuli.

A large corpus of research indicates exposure to stress impairs cognitive abilities, specifically executive functioning dependent on the prefrontal cortex (PFC). We collected structural MRI scans (n=61), well-validated assessments of executive functioning, and detailed interviews assessing stress exposure in humans, to examine whether cumulative life stress affected brain morphometry and one type of executive functioning, spatial working memory, during adolescence—a critical time of brain development and reorganization. Analysis of variations in brain structure revealed that cumulative life stress and spatial working memory were related to smaller volumes in the PFC, specifically prefrontal gray and white matter between the anterior cingulate and the frontal poles. Mediation analyses revealed that individual differences in prefrontal volumes accounted for the association between cumulative life stress and spatial working memory. These results suggest that structural changes in the PFC may serve as a mediating mechanism through which greater cumulative life stress engenders decrements in cognitive functioning.

Children with anxious temperament (AT) are particularly sensitive to new social experiences and have increased risk for developing anxiety and depression. The young rhesus monkey is optimal for studying the origin of human AT because it shares with humans the genetic, neural, and phenotypic underpinnings of complex social and emotional functioning. In vivo imaging in young monkeys demonstrated that central nucleus of the amygdala (Ce) metabolism is relatively stable across development and predicts AT. Transcriptome-wide gene expression, which reflects combined genetic and environmental influences, was assessed within the Ce. Results support a maladaptive neurodevelopmental hypothesis linking decreased amygdala neuroplasticity to early-life dispositional anxiety. For example, high AT individuals had decreased mRNA expression of neurotrophic tyrosine kinase, receptor, type 3 (NTRK3). Moreover, variation in Ce NTRK3 expression was inversely correlated with Ce metabolism and other AT-substrates. These data suggest that altered amygdala neuroplasticity may play a role the early dispositional risk to develop anxiety and depression.

This article draws on research in neuroscience, cognitive science, developmental psychology, and education, as well as scholarship from contemplative traditions concerning the cultivation of positive development, to highlight a set of mental skills and socioemotional dispositions that are central to the aims of education in the 21st century. These include self-regulatory skills associated with emotion and attention, self-representations, and prosocial dispositions such as empathy and compassion. It should be possible to strengthen these positive qualities and dispositions through systematic contemplative practices, which induce plastic changes in brain function and structure, supporting prosocial behavior and academic success in young people. These putative beneficial consequences call for focused programmatic research to better characterize which forms and frequencies of practice are most effective for which types of children and adolescents. Results from such research may help refine training programs to maximize their effectiveness at different ages and to document the changes in neural function and structure that might be induced.

Experiential factors shape the neural circuits underlying social and emotional behavior from the prenatal period to the end of life. These factors include both incidental influences, such as early adversity, and intentional influences that can be produced in humans through specific interventions designed to promote prosocial behavior and well-being. Here we review important extant evidence in animal models and humans. Although the precise mechanisms of plasticity are still not fully understood, moderate to severe stress appears to increase the growth of several sectors of the amygdala, whereas the effects in the hippocampus and prefrontal cortex tend to be opposite. Structural and functional changes in the brain have been observed with cognitive therapy and certain forms of meditation and lead to the suggestion that well-being and other prosocial characteristics might be enhanced through training.

Early life stress (ELS) and function of the hypothalamic-pituitary-adrenal axis predict later psychopathology. Animal studies and cross-sectional human studies suggest that this process might operate through amygdala-ventromedial prefrontal cortex (vmPFC) circuitry implicated in the regulation of emotion. Here we prospectively investigated the roles of ELS and childhood basal cortisol amounts in the development of adolescent resting-state functional connectivity (rs-FC), assessed by functional connectivity magnetic resonance imaging (fcMRI), in the amygdala-PFC circuit. In females only, greater ELS predicted increased childhood cortisol levels, which predicted decreased amygdala-vmPFC rs-FC 14 years later. For females, adolescent amygdala-vmPFC functional connectivity was inversely correlated with concurrent anxiety symptoms but positively associated with depressive symptoms, suggesting differing pathways from childhood cortisol levels function through adolescent amygdala-vmPFC functional connectivity to anxiety and depression. These data highlight that, for females, the effects of ELS and early HPA-axis function may be detected much later in the intrinsic processing of emotion-related brain circuits.

General linear modeling (GLM) is one of the most commonly used approaches to perform voxel based analyses (VBA) for hypotheses testing in neuroimaging. In this paper we tie support vector machine based regression (SVR) and classical significance testing to provide the benefits of max margin estimation in the GLM setting. Using Welch-Satterthwaite approximations, we compute degrees of freedom (df) of error (also known as residual df) for ε-SVR. We demonstrate that ε-SVR can result not only in robustness of estimation but also improved residual df compared to the very commonly used ordinary least squares (OLS) estimation. This can result in higher sensitivity to signal in neuroimaging studies and also allow for better control of confounding effects of nuisance covariates. We demonstrate the application of our approach in white matter analyses using diffusion tensor imaging (DTI) data from autism and emotion-regulation studies.

Diffusion tensor imaging (DTI) plays a key role in analyzing the physical structures of biological tissues, particularly in reconstructing fiber tracts of the human brain in vivo. On the one hand, eigenvalues of diffusion tensors (DTs) estimated from diffusion weighted imaging (DWI) data usually contain systematic bias, which subsequently biases the diffusivity measurements popularly adopted in fiber tracking algorithms. On the other hand, correctly accounting for the spatial information is important in the construction of these diffusivity measurements since the fiber tracts are typically spatially structured. This paper aims to establish test-based approaches to identify anisotropic water diffusion areas in the human brain. These areas in turn indicate the areas passed by fiber tracts. Our proposed test statistic not only takes into account the bias components in eigenvalue estimates, but also incorporates the spatial information of neighboring voxels. Under mild regularity conditions, we demonstrate that the proposed test statistic asymptotically follows a $\chi^2$ distribution under the null hypothesis. Simulation and real DTI data examples are provided to illustrate the efficacy of our proposed methods.

Compassion is a key motivator of altruistic behavior, but little is known about individuals’ capacity to cultivate compassion through training. We examined whether compassion may be systematically trained by testing whether (i) short-term compassion training increases altruistic behavior, and (ii) individual differences in altruism are associated with training-induced changes in neural responses to suffering. In healthy young adults, we found that compassion training increased altruistic redistribution of funds to a victim encountered outside of the training context. Furthermore, greater altruistic behavior after compassion training was associated with altered activation in regions implicated in social cognition and emotion regulation, including the inferior parietal cortex, dorsolateral prefrontal cortex (DLPFC), and DLPFC connectivity with the nucleus accumbens. These results suggest that compassion can be cultivated with training, where greater altruistic behavior may emerge from increased engagement in neural systems implicated in understanding the suffering of others, executive and emotional control, and reward processing.

Children with an anxious temperament (AT) are at risk for developing psychiatric disorders along the internalizing spectrum, including anxiety and depression. Like these disorders, AT is a multidimensional phenotype and children with extreme anxiety show varying mixtures of physiological, behavioral, and other symptoms. Using a well-validated juvenile monkey model of AT, we addressed the degree to which this phenotypic heterogeneity reflects fundamental differences or similarities in the underlying neurobiology. The rhesus macaque is optimal for studying AT because children and young monkeys express the anxious phenotype in similar ways and have similar neurobiology. Fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET) in 238 freely behaving monkeys identified brain regions where metabolism predicted variation in three dimensions of the AT phenotype: hypothalamic-pituitary-adrenal (HPA) activity, freezing behavior, and expressive vocalizations. We distinguished brain regions that predicted all three dimensions of the phenotype from those that selectively predicted a single dimension. Elevated activity in the central nucleus of the amygdala and the anterior hippocampus was consistently found across individuals with different presentations of AT. In contrast, elevated activity in the lateral anterior hippocampus was selective to individuals with high levels of HPA activity, and decreased activity in the motor cortex (M1) was selective to those with high levels of freezing behavior. Furthermore, activity in these phenotype-selective regions mediated relations between amygdala metabolism and different expressions of anxiety. These findings provide a framework for understanding the mechanisms that lead to heterogeneity in the clinical presentation of internalizing disorders and set the stage for developing improved interventions.

Purpose in life predicts both health and longevity suggesting that the ability to find meaning from life’s experiences, especially when confronting life’s challenges, may be a mechanism underlying resilience. Having purpose in life may motivate reframing stressful situations to deal with them more productively, thereby facilitating recovery from stress and trauma. In turn, enhanced ability to recover from negative events may allow a person to achieve or maintain a feeling of greater purpose in life over time. In a large sample of adults (aged 36-84 years) from the MIDUS study (Midlife in the U.S., http://www.midus.wisc.edu/), we tested whether purpose in life was associated with better emotional recovery following exposure to negative picture stimuli indexed by the magnitude of the eyeblink startle reflex (EBR), a measure sensitive to emotional state. We differentiated between initial emotional reactivity (during stimulus presentation) and emotional recovery (occurring after stimulus offset). Greater purpose in life, assessed over two years prior, predicted better recovery from negative stimuli indexed by a smaller eyeblink after negative pictures offset, even after controlling for initial reactivity to the stimuli during the picture presentation, gender, age, trait affect, and other well-being dimensions. These data suggest a proximal mechanism by which purpose in life may afford protection from negative events and confer resilience is through enhanced automatic emotion regulation after negative emotional provocation.
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.
The corticotrophin-releasing hormone (CRH) system integrates the stress response and is associated with stress-related psychopathology. Previous reports have identified interactions between childhood trauma and sequence variation in the CRH receptor 1 gene (CRHR1) that increase risk for affective disorders. However, the underlying mechanisms that connect variation in CRHR1 to psychopathology are unknown. To explore potential mechanisms, we used a validated rhesus macaque model to investigate association between genetic variation in CRHR1, anxious temperament (AT) and brain metabolic activity. In young rhesus monkeys, AT is analogous to the childhood risk phenotype that predicts the development of human anxiety and depressive disorders. Regional brain metabolism was assessed with (18)F-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography in 236 young, normally reared macaques that were also characterized for AT. We show that single nucleotide polymorphisms (SNPs) affecting exon 6 of CRHR1 influence both AT and metabolic activity in the anterior hippocampus and amygdala, components of the neural circuit underlying AT. We also find evidence for association between SNPs in CRHR1 and metabolism in the intraparietal sulcus and precuneus. These translational data suggest that genetic variation in CRHR1 affects the risk for affective disorders by influencing the function of the neural circuit underlying AT and that differences in gene expression or the protein sequence involving exon 6 may be important. These results suggest that variation in CRHR1 may influence brain function before any childhood adversity and may be a diathesis for the interaction between CRHR1 genotypes and childhood trauma reported to affect human psychopathology.
Many of us go through our daily lives on autopilot, not fully aware of our conscious experiences. In a discussion moderated by Steve Paulson, executive producer and host of To the Best of Our Knowledge, neuroscientists Richard Davidson and Amishi Jha and clinical mindfulness expert Jon Kabat-Zinn explore the role of consciousness in mental and physical health, how we can train our minds to be more flexible and adaptable, and cutting-edge neuroscience findings about the transformation of consciousness through mindfulness and contemplative practice. The following is an edited transcript of the discussion that occurred February 6, 2013, 7:00-8:15 PM, at the New York Academy of Sciences in New York City.
Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus–subgenual cingulate rs-FC in both adolescent females and males and lower amygdala–subgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain’s fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto–hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto–amygdala and –hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.
Eudaimonic well-being—a sense of purpose, meaning, and engagement with life—is protective against psychopathology and predicts physical health, including lower levels of the stress hormone cortisol. Although it has been suggested that the ability to engage the neural circuitry of reward may promote well-being and mediate the relationship between well-being and health, this hypothesis has remained untested. To test this hypothesis, we had participants view positive, neutral, and negative images while fMRI data were collected. Individuals with sustained activity in the striatum and dorsolateral prefrontal cortex to positive stimuli over the course of the scan session reported greater well-being and had lower cortisol output. This suggests that sustained engagement of reward circuitry in response to positive events underlies well-being and adaptive regulation of the hypothalamic-pituitary-adrenal axis.
Context: Emotion regulation is critically disrupted in depression and use of paradigms tapping these processes may uncover essential changes in neurobiology during treatment. In addition, as neuroimaging outcome studies of depression commonly utilize solely baseline and endpoint data – which is more prone to week-to week noise in symptomatology – we sought to use all data points over the course of a six month trial. Objective: To examine changes in neurobiology resulting from successful treatment. Design: Double-blind trial examining changes in the neural circuits involved in emotion regulation resulting from one of two antidepressant treatments over a six month trial. Participants were scanned pretreatment, at 2 months and 6 months posttreatment. Setting: University functional magnetic resonance imaging facility. Participants: 21 patients with Major Depressive Disorder and without other Axis I or Axis II diagnoses and 14 healthy controls. Interventions: Venlafaxine XR (doses up to 300mg) or Fluoxetine (doses up to 80mg). Main Outcome Measure: Neural activity, as measured using functional magnetic resonance imaging during performance of an emotion regulation paradigm as well as regular assessments of symptom severity by the Hamilton Rating Scale for Depression. To utilize all data points, slope trajectories were calculated for rate of change in depression severity as well as rate of change of neural engagement. Results: Those depressed individuals showing the steepest decrease in depression severity over the six months were those individuals showing the most rapid increases in BA10 and right DLPFC activity when regulating negative affect over the same time frame. This relationship was more robust than when using solely the baseline and endpoint data. Conclusions: Changes in PFC engagement when regulating negative affect correlate with changes in depression severity over six months. These results are buttressed by calculating these statistics which are more reliable and robust to week-to-week variation than difference scores.
OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.
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.
Despite the crucial role of teachers in fostering children's academic learning and social-emotional well-being, addressing teacher stress in the classroom remains a significant challenge in education. The present study reports results from a randomized controlled pilot trial of a modified Mindfulness-Based Stress Reduction course (mMBSR) adapted specifically for teachers. Results suggest the course may be a promising intervention, with participants showing significant reductions in psychological symptoms and burnout, improvements in observer-rated classroom organization and performance on a computer task of affective attentional bias, and increases in self-compassion. In contrast, control group participants showed declines in cortisol functioning over time and marginally significant increases in burnout. Furthermore, changes in mindfulness were correlated in the expected direction with changes across several outcomes (psychological symptoms, burnout, sustained attention) in the intervention group. Implications of these findings for the training and support of teachers are discussed.
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.
Despite implications that stranger fear is an important aspect of developing behavioral inhibition, a known risk factor for anxiety, normative and atypical developmental trajectories of stranger fear across infancy and toddlerhood remain understudied. We used a large, longitudinal data set (N = 1285) including multi-trait, multi-method assessments of temperament to examine the normative course of development for stranger fear and to explore the possibility that individual differences exist in trajectories of stranger fear development between 6 and 36 months of age. A latent class growth analysis suggested four different trajectories of stranger fear during this period. Stable, high levels of stranger fear over time were associated with poorer RSA suppression at 6 months of age. Rates of concordance in trajectory-based class membership for identical (monozygotic) and fraternal (dizygotic) twins, along with associations between atypical stranger fear development and greater anxiety-related maternal characteristics, suggested that individual differences in developmental trajectories of stranger fear may be heritable. Importantly, trajectories of stranger fear during infancy and toddlerhood were linked to individual differences in behavioral inhibition, with chronically high levels of stranger fear and sharp increases in stranger fear over time related to greater levels of inhibition than other developmental trajectories.
Brain training: Games to do you good (n.d., Journal Article)
Neuroscientists should help to develop compelling video games that boost brain function and improve well-being, say Daphne Bavelier and Richard J. Davidson.
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.
Background Comorbidity among childhood mental health symptoms is common in clinical and community samples and should be accounted for when investigating etiology. We therefore aimed to uncover latent classes of mental health symptoms in middle childhood in a community sample, and to determine the latent genetic and environmental influences on those classes. Methods The sample comprised representative cohorts of twins. A questionnaire-based assessment of mental health symptoms was used in latent class analyses. Data on 3223 twins (1578 boys and 1645 girls) with a mean age of 7.5 years were analyzed. The sample was predominantly non-Hispanic Caucasian (92.1%). Results Latent class models delineated groups of children according to symptom profiles–not necessarily clinical groups but groups representing the general population, most with scores in the normative range. The best-fitting models suggested 9 classes for both girls and boys. Eight of the classes were very similar across sexes; these classes ranged from a “Low Symptom” class to a “Moderately Internalizing & Severely Externalizing” class. In addition, a “Moderately Anxious” class was identified for girls but not boys, and a “Severely Impulsive & Inattentive” class was identified for boys but not girls. Sex-combined analyses implicated moderate genetic influences for all classes. Shared environmental influences were moderate for the “Low Symptom” and “Moderately Internalizing & Severely Externalizing” classes, and small to zero for other classes. Conclusions We conclude that symptom classes are largely similar across sexes in middle childhood. Heritability was moderate for all classes, but shared environment played a greater role for classes in which no one type of symptom predominated.
Humans show consistent differences in the extent to which their behavior reflects a bias toward appetitive approach-related behavior or avoidance of aversive stimuli [Elliot, A. J. Approach and avoidance motivation. In A. J. Elliot (Ed.), Handbook of approach and avoidance motivation (pp. 3-14). New York: Psychology Press, 2008]. We examined the hypothesis that in healthy participants this motivational bias (assessed by self-report and by a probabilistic learning task that allows direct comparison of the relative sensitivity to reward and punishment) reflects lateralization of dopamine signaling. Using [F-18]fallypride to measure D2/D3 binding, we found that self-reported motivational bias was predicted by the asymmetry of frontal D2 binding. Similarly, striatal and frontal asymmetries in D2 dopamine receptor binding, rather than absolute binding levels, predicted individual differences in learning from reward versus punishment. These results suggest that normal variation in asymmetry of dopamine signaling may, in part, underlie human personality and cognition.
The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction.
Background Mindfulness Based Stress Reduction (MBSR) is a secular form of meditation training. The vast majority of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons. Previous studies have found that meditation training over several months is associated with improvements in cognitive control and attention. Methodology/Principal Findings We used a visual continuous performance task (CPT) to test the effects of eight weeks of mindfulness training on sustained attention by comparing MBSR to the Health Enhancement Program (HEP), a structurally equivalent, active control condition in a randomized, longitudinal design (ClinicalTrials.gov, NCT01301105) focusing on a non-clinical population typical of MBSR participants. Researchers were blind to group assignment. 63 community participants were randomized to either MBSR (n = 31) or HEP (n = 32). CPT analyses were conducted on 29 MBSR participants and 25 HEP participants. We predicted that MBSR would improve visual discrimination ability and sustained attention over time on the CPT compared to HEP, with more home practice associated with greater improvements. Our hypotheses were not confirmed but we did find some evidence for improved visual discrimination similar to effects in partial replication of other research. Our study had sufficient power to demonstrate that intervention groups do not differ in their improvement over time in sustained attention performance. One of our primary predictions concerning the effects of intervention on attentional fatigue was significant but not interpretable. Conclusions Attentional sensitivity is not affected by mindfulness practice as taught in MBSR, but it is unclear whether mindfulness might positively affect another aspect of attention, vigilance. These results also highlight the relevant procedural modifications required by future research to correctly investigate the role of sustained attention in similar samples. Trial Registration ClinicalTrials.gov, NCT01301105
Marital stress is associated with a higher incidence of psychiatric disorders, in particular major depression. One pathway through which marital stress may impact emotional health is by compromising emotion-responding processes. We examined a longitudinal sample of adults (N = 116; 59 males; 39-84 years) to verify how marital stress predicts reactivity to, and recovery from, emotional provocation. Individuals watched positive, neutral, and negative pictures while an objective measure of affective state, corrugator supercilii muscle activity, was recorded continuously. Our results indicate that marital stress is associated with short-lived responses to positive pictures, indexed by a less persistent decrease in corrugator activity after picture offset. Extending beyond the prior focus on negative emotional processes, these results suggest that social stress may impact health by influencing the time course of responding to positive events.
Emotions can color people’s attitudes toward unrelated objects in the environment. Existing evidence suggests that such emotional coloring is particularly strong when emotion-triggering information escapes conscious awareness. But is emotional reactivity stronger after nonconscious emotional provocation than after conscious emotional provocation, or does conscious processing specifically change the association between emotional reactivity and evaluations of unrelated objects? In this study, we independently indexed emotional reactivity and coloring as a function of emotional-stimulus awareness to disentangle these accounts. Specifically, we recorded skin-conductance responses to spiders and fearful faces, along with subsequent preferences for novel neutral faces during visually aware and unaware states. Fearful faces increased skin-conductance responses comparably in both stimulus-aware and stimulus-unaware conditions. Yet only when visual awareness was precluded did skin-conductance responses to fearful faces predict decreased likability of neutral faces. These findings suggest a regulatory role for conscious awareness in breaking otherwise automatic associations between physiological reactivity and evaluative emotional responses.
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.
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with significant alterations in neuronal integrity resulting from either hypoxemia and/or sleep loss. A large body of imaging research supports reductions in gray matter volume, alterations in white matter integrity and resting state activity, and functional abnormalities in response to cognitive challenge in various brain regions in patients with OSA. In this study, we used high-density electroencephalography (hdEEG), a functional imaging tool that could potentially be used during routine clinical care, to examine the regional distribution of neural activity in a non-clinical sample of untreated men and women with moderate/severe OSA. DESIGN: Sleep was recorded with 256-channel EEG in relatively healthy subjects with apnea-hypopnea index (AHI) > 10, as well as age-, sex-, and body mass index-matched controls selected from a research population initially recruited for a study on sleep and meditation. SETTING: Sleep laboratory. PATIENTS OR PARTICIPANTS: Nine subjects with AHI > 10 and nine matched controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Topographic analysis of hdEEG data revealed a broadband reduction in EEG power in a circumscribed region overlying the parietal cortex in OSA subjects. This parietal reduction in neural activity was present, to some extent, across all frequency bands in all stages and episodes of nonrapid eye movement sleep. CONCLUSION: This investigation suggests that regional deficits in electroencephalography (EEG) power generation may be a useful clinical marker for neural disruption in obstructive sleep apnea, and that high-density EEG may have the sensitivity to detect pathological cortical changes early in the disease process.
The ability to simultaneously acquire objective physiological measures of emotion concurrent with fMRI holds the promise to enhance our understanding of the biological bases of affect and thus improve our knowledge of the neural circuitry underlying psychiatric disorders. However, the vast majority of neuroimaging studies to date examining emotion have not anchored the examination of emotion-responding circuitry to objective measures of emotional processing. To that end, we acquired EMG activity of a valence-sensitive facial muscle involved in the frowning response (corrugator muscle) concurrent with fMRI while twenty-six human participants viewed negative and neutral images. Trial-by-trial increases in corrugator EMG activity to negative pictures were associated with greater amygdala activity and a concurrent decrease in ventromedial PFC activity. Thus, this study highlights the reciprocal relation between amygdalar and ventromedial PFC in the encoding of emotional valence as reflected by facial expression.
Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance abuse. These disorders are highly prevalent, debilitating and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and young monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the amygdala is an important substrate. Although it is widely believed that the flow of information across the structural network connecting the Ce nucleus to other brain regions underlies primates' capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting children with anxiety disorders to identify an evolutionarily conserved pattern of functional connectivity relevant to early-life anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex, a region thought to play a central role in the control of cognition and emotion, and the Ce nucleus was associated with increased anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography imaging provided evidence that elevated Ce nucleus metabolism statistically mediates the association between prefrontal-amygdalar connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.
BACKGROUND: Anxious temperament (AT) is identifiable early in life and predicts the later development of anxiety disorders and depression. Neuropeptide Y (NPY) is a putative endogenous anxiolytic neurotransmitter that adaptively regulates responses to stress and might confer resilience to stress-related psychopathology. With a well-validated nonhuman primate model of AT, we examined expression of the NPY system in the central nucleus (Ce) of the amygdala, a critical neural substrate for extreme anxiety. METHODS: In 24 young rhesus monkeys, we measured Ce messenger RNA (mRNA) levels of all members of the NPY system that are detectable in the Ce with quantitative real time polymerase chain reaction. We then examined the relationship between these mRNA levels and both AT expression and brain metabolism. RESULTS: Lower mRNA levels of neuropeptide Y receptor 1 (NPY1R) and NPY5R but not NPY or NPY2R in the Ce predicted elevated AT; mRNA levels for NPY1R and NPY5R in the motor cortex were not related to AT. In situ hybridization analysis provided for the first time a detailed description of NPY1R and NPY5R mRNA distribution in the rhesus amygdala and associated regions. Lastly, mRNA levels for these two receptors in the Ce predicted metabolic activity in several regions that have the capacity to regulate the Ce. CONCLUSIONS: Decreased NPY signaling in the Ce might contribute to the altered metabolic activity that is a component of the neural substrate underlying AT. This suggests that enhancement of NPY signaling might reduce the risk to develop psychopathology.
Background Early life stress (ELS) can compromise development, with higher amounts of adversity linked to behavioral problems. To understand this linkage, a growing body of research has examined two brain regions involved with socioemotional functioning—amygdala and hippocampus. Yet empirical studies have reported increases, decreases, and no differences within human and nonhuman animal samples exposed to different forms of ELS. This divergence in findings may stem from methodological factors, nonlinear effects of ELS, or both. Methods We completed rigorous hand-tracing of the amygdala and hippocampus in three samples of children who experienced different forms of ELS (i.e., physical abuse, early neglect, or low socioeconomic status). Interviews were also conducted with children and their parents or guardians to collect data about cumulative life stress. The same data were also collected in a fourth sample of comparison children who had not experienced any of these forms of ELS. Results Smaller amygdala volumes were found for children exposed to these different forms of ELS. Smaller hippocampal volumes were also noted for children who were physically abused or from low socioeconomic status households. Smaller amygdala and hippocampal volumes were also associated with greater cumulative stress exposure and behavioral problems. Hippocampal volumes partially mediated the relationship between ELS and greater behavioral problems. Conclusions This study suggests ELS may shape the development of brain areas involved with emotion processing and regulation in similar ways. Differences in the amygdala and hippocampus may be a shared diathesis for later negative outcomes related to ELS.
Being in the Now (n.d., Journal Article)
A focus on the present, dubbed mindfulness, can make you happier and healthier. Training to deepen your immersion in the moment works by improving attention
Many of us go through our daily lives on autopilot, not fully aware of our conscious experiences. In a discussion moderated by Steve Paulson, executive producer and host of To the Best of Our Knowledge, neuroscientists Richard Davidson and Amishi Jha and clinical mindfulness expert Jon Kabat-Zinn explore the role of consciousness in mental and physical health, how we can train our minds to be more flexible and adaptable, and cutting-edge neuroscience findings about the transformation of consciousness through mindfulness and contemplative practice. The following is an edited transcript of the discussion that occurred February 6, 2013, 7:00-8:15 PM, at the New York Academy of Sciences in New York City.
Eastern spiritual traditions have long maintained that mindfulness meditation can improve well-being. More recently, mindfulness-based treatment approaches have been successfully utilized to treat anxiety, depressive relapse, eating disorders, psychosis, and borderline personality disorder. This book discusses the conceptual foundation, implementation, and evidence base for the four best-researched mindfulness treatments: mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy (MBCT), dialectical behavior therapy (DBT) and acceptance and commitment therapy (ACT). All chapters were written by researchers with extensive clinical experience. Each chapter includes the conceptual rationale for using a mindfulness-based treatment and a review of the relevant evidence base. A detailed case study illustrates how the intervention is implemented in "real life," exploring the clinical and practical issues that may arise and how they can be managed. This book will be of use to clinicians and researchers interested in understanding and implementing mindfulness based treatments. * Comprehensive introduction to the best-researched mindfulness-based treatments* Covers wide range of problems & disorders (anxiety, depression, eating, psychosis, personality disorders, stress, pain, relationship problems, etc)* Discusses a wide range of populations (children, adolescents, older adults, couples)* Includes wide range of settings (outpatient, inpatient, medical, mental health, workplace)* Clinically rich, illustrative case study in every chapter* International perspectives represented (authors from US, Canada, Britain, Sweden)
Research on temporal-order judgments, reference frames, discrimination tasks, and links to oculomotor control suggest important differences between inhibition of return (IOR) and attentional costs and benefits. Yet, it is generally assumed that IOR is an attentional effect even though there is little supporting evidence. The authors evaluated this assumption by examining how several factors that are known to influence attentional costs and benefits affect the magnitude of IOR: target modality, target intensity, and response mode. Results similar to those previously reported for attention were observed: IOR was greater for visual than for auditory targets, showed an inverse relationship with target intensity, and was equivalent for manual and saccadic responses. Important parallels between IOR and attentional costs and benefits are indicated, suggesting that, like attention, IOR may in part affect sensory-perceptual processes.
Three patients with complete resection of the corpus callosum were tested in a series of memory tasks to determine the effects of callosotomy on the encoding and retrieval of information in memory. Verbal and pictorial conjunction tests were administered to measure patients' ability to consolidate the elements of a stimulus into an accurate composite memory. Patients were also tested in a paired-associate learning task to determine the consequences of callosotomy on the encoding and retrieval of associations between stimuli. Although callosotomy patients were unimpaired in the verbal conjunction task, results from both the pictorial conjunction task and the paired-associate learning task suggest that the absence of callosal cross-talk impairs encoding in these patients. In addition, the pattern of results in the paired-associate learning task suggests that callosotomy impairs retrieval processes. The role of the callosum in the formation of memory traces for nonverbal material and associations between verbal stimuli is discussed.
To facilitate visual search of complex scenes, information arising from recently attended locations is subject to a selective inhibition in processing known as inhibition of return (IOR). Although the mechanisms of IOR remain unresolved, both motor and perceptual influences have been proposed based on reaction time (RT) studies. Here we report the results of two reflexive cuing studies in which signal detection methodology was employed to directly examine the effects of IOR on perception. IOR was found to be associated with a significant reduction in the accuracy of target discriminations at recently attended locations. Further, these effects of IOR on response accuracy were independent of whether emphasis was placed on the speed of responding. These results provide the first direct evidence that IOR can affect the perceptual quality of visual processing.
Noninvasive recordings of electrical and magnetic fields generated by neuronal activity have helped to characterize the temporal sequencing and mechanisms underlying human cognition. Progress is being made toward the goal of localizing the intracranial loci at which many important electromagnetic signals are generated through the use of new analytic techniques and of scalp recordings of electromagnetic activity in neurological patients and through related work in animals. Such methods alone, however, do not yet have the three-dimensional spatial resolution that is necessary in order to identify the intracranial anatomical structures that are involved in the generation of externally recorded activity and, thus, cannot yet inform us with precision about the anatomical substrates of neural events. In comparison, neuroimaging methods, such as positron emission tomography and functional magnetic resonance imaging, can provide higher spatial resolution information about which brain structures are involved in perceptual, motor, and cognitive processes. However, these imaging methods do not yield much information about the time course of brain activity. One promising approach is to combine electromagnetic recordings and functional neuroimaging in order to gain knowledge about the spatiotemporal organization of human cognition. Here we review how electrophysiology and functional neuroimaging can be combined in the study of attention in normal humans.
Spatial working memory is a cognitive brain mechanism that enables the temporary maintenance and manipulation of spatial information. Recent neuroimaging and behavioral studies have led to the proposal that directed spatial attention is the mechanism by which location information is maintained in spatial working memory. Yet it is unclear whether attentional involvement is required throughout the period of active maintenance or is only invoked during discrete task-phases such as mnemonic encoding. In the current study, we aimed to track the time-course of attentional involvement during spatial working memory by recording event-related brain potentials (ERPs) from healthy volunteers. In Experiment 1, subjects performed a delayed-recognition task. Each trial began with the presentation of a brief stimulus (S1) that indicated the relevant location that subjects were to maintain in working memory. A 4.8-5.3 sec delay interval followed during which a single task-irrelevant probe was presented. The delay interval concluded with a test item (S2) to which subjects made a response indicating whether the S2-location was the same as the S1-memory location. To determine if attention was differentially engaged during discrete phases of the trial, task-irrelevant probes were presented early (400-800 msec following S1-offset) or late (2600-3000 msec following S1-offset) during the delay interval. Sensory-evoked ERPs (P1 and N1) elicited by these irrelevant probes showed attention-like modulations with greater amplitude responses for probes occurring at the S1-memory locations in comparison to probes presented at other locations. This pattern was obtained for both early- and late-delay probes. Probe-evoked activity during delayed-recognition trials was similar to activity observed when spatial attention was explicitly focused on a location in visual space (Experiment 2). These results are consistent with a model of spatial working memory in which perceptual level selective attention is utilized throughout the entire period of active maintenance to keep relevant spatial information in mind.
We investigate the hypothesis that those subregions of the prefrontal cortex (PFC) found to support proactive interference resolution may also support delay-spanning distractor interference resolution. Ten subjects performed delayed-recognition tasks requiring working memory for faces or shoes during functional MRI scanning. During the 15-sec delay interval, task-irrelevant distractors were presented. These distractors were either all faces or all shoes and were thus either congruent or incongruent with the domain of items in the working memory task. Delayed-recognition performance was slower and less accurate during congruent than during incongruent trials. Our fMRI analyses revealed significant delay interval activity for face and shoe working memory tasks within both dorsal and ventral PFC. However, only ventral PFC activity was modulated by distractor category, with greater activity for congruent than for incongruent trials. Importantly, this congruency effect was only present for correct trials. In addition to PFC, activity within the fusiform face area was investigated. During face distraction, activity was greater for face relative to shoe working memory. As in ventrolateral PFC, this congruency effect was only present for correct trials. These results suggest that the ventrolateral PFC and fusiform face area may work together to support delay-spanning interference resolution.
Recent neuroimaging and neuropsychological work has begun to shed light on how the brain responds to the viewing of facial expressions of emotion. However, one important category of facial expression that has not been studied on this level is the facial expression of pain. We investigated the neural response to pain expressions by performing functional magnetic resonance imaging (fMRI) as subjects viewed short video sequences showing faces expressing either moderate pain or, for comparison, no pain. In alternate blocks, the same subjects received both painful and non-painful thermal stimulation. Facial expressions of pain were found to engage cortical areas also engaged by the first-hand experience of pain, including anterior cingulate cortex and insula. The reported findings corroborate other work in which the neural response to witnessed pain has been examined from other perspectives. In addition, they lend support to the idea that common neural substrates are involved in representing one's own and others' affective states.
There is mounting evidence that prefrontal cortex (PFC) is activated during mnemonic operations such as working memory maintenance and also during response-related operations. In the current study, we examine the neural organization of mnemonic and response operations with respect to each other within PFC. Stimulus-evoked and sustained functional MRI activity was recorded during performance of a mental calculation task. The presence or absence of mnemonic and response demands was manipulated in a 2 x 2 factorial design with conditions requiring: (1) memory encoding and maintenance (M+); (2) response selection and execution (R+); (3) encoding, maintenance, and response execution (M+R+); (4) neither mnemonic nor response-related processes (M-R-). The first step of the analyses identified PFC voxels exhibiting differential activity during (M+) vs. (R+) trials. Within these voxels, we then examined activity during multiple phases of (M+R+) trials. Greater stimulus-evoked and sustained activity was observed within the anterior extent of dorsolateral prefrontal cortex (BA 46) during R+ vs. M+ trials. In contrast, greater activity was observed in the posterior extent of dorsolateral PFC during M+ vs. R+ trials. Importantly, both regions were activated during (M+R+) trials. Activity levels during all of these conditions exceeded levels observed during (M-R-) control trials. These results suggest that integrative functions of PFC that allow past information to guide future actions may emerge from communication between discrete subregions supporting mnemonic and response operations.
Selective attention has been shown to bias sensory processing in favor of relevant stimuli and against irrelevant or distracting stimuli in perceptual tasks. Increasing evidence suggests that selective attention plays an important role during working memory maintenance, possibly by biasing sensory processing in favor of to-be-remembered items. In the current study, we investigated whether selective attention may also support working memory by biasing processing against irrelevant and potentially distracting information. Event-related potentials (ERPs) were recorded while subjects (n = 22) performed a delayed-recognition task for faces and shoes. The delay period was filled with face or shoe distractors. Behavioral performance was impaired when distractors were congruent with the working memory domain (e.g., face distractor during working memory for faces) relative to when distractors were incongruent with the working memory domain (e.g., face distractor during shoe working memory). If attentional biasing against distractor processing is indeed functionally relevant in supporting working memory maintenance, perceptual processing of distractors is predicted to be attenuated when distractors are more behaviorally intrusive relative to when they are nonintrusive. As such, we predicted that perceptual processing of distracting faces, as measured by the face-sensitive N170 ERP component, would be reduced in the context of congruent (face) working memory relative to incongruent (shoe) working memory. The N170 elicited by distracting faces demonstrated reduced amplitude during congruent versus incongruent working memory. These results suggest that perceptual processing of distracting faces may be attenuated due to attentional biasing against sensory processing of distractors that are most behaviorally intrusive during working memory maintenance.

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