Individuals with asthma have twice the risk of developing mood and anxiety disorders as individuals without asthma and these psychological factors are associated with worse outcomes and greater need for medical intervention. Similarly, asthma symptom onset and exacerbation often occur during times of increased psychological stress. Remission from depression, on the other hand, is associated with improvement in asthma symptoms and decreased usage of asthma medication. Yet research aimed at understanding the biological underpinnings of asthma has focused almost exclusively on the periphery. An extensive literature documents the relationship between emotion and asthma, but little work has explored the function of affective neural circuitry in asthma symptom expression. Therefore, the following review integrates neuroimaging research related to factors that may impact symptom expression in asthma, such as individual differences in sensitivity to visceral signals, the influence of expectation and emotion on symptom perception, and changes related to disease chronicity, such as conditioning and plasticity. The synthesis of these literatures suggests that the insular and anterior cingulate cortices, in addition to other brain regions previously implicated in the regulation of emotion, may be both responsive to asthma-related bodily changes and important in influencing the appearance and persistence of symptom expression in asthma.

OBJECTIVE: The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response.
METHOD: Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine.
RESULTS: Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms.
CONCLUSIONS: These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.

The capacity to stabilize the content of attention over time varies among individuals, and its impairment is a hallmark of several mental illnesses. Impairments in sustained attention in patients with attention disorders have been associated with increased trial-to-trial variability in reaction time and event-related potential deficits during attention tasks. At present, it is unclear whether the ability to sustain attention and its underlying brain circuitry are transformable through training. Here, we show, with dichotic listening task performance and electroencephalography, that training attention, as cultivated by meditation, can improve the ability to sustain attention. Three months of intensive meditation training reduced variability in attentional processing of target tones, as indicated by both enhanced theta-band phase consistency of oscillatory neural responses over anterior brain areas and reduced reaction time variability. Furthermore, those individuals who showed the greatest increase in neural response consistency showed the largest decrease in behavioral response variability. Notably, we also observed reduced variability in neural processing, in particular in low-frequency bands, regardless of whether the deviant tone was attended or unattended. Focused attention meditation may thus affect both distracter and target processing, perhaps by enhancing entrainment of neuronal oscillations to sensory input rhythms, a mechanism important for controlling the content of attention. These novel findings highlight the mechanisms underlying focused attention meditation and support the notion that mental training can significantly affect attention and brain function.

Some children show emotion that is not consistent with normative appraisal of the context and can therefore be defined as context inappropriate (CI). The authors used individual growth curve modeling and hierarchical multiple regression analyses to examine whether CI anger predicts differences in hypothalamic-pituitary-adrenal axis activity, as manifest in salivary cortisol measures. About 23% of the 360 children (ages 6-10 years, primarily 7-8) showed at least 1 expression of CI anger in situations designed to elicit positive affect. Expression of anger across 2 positive assessments was less common (around 4%). CI anger predicted the hypothesized lower levels of cortisol beyond that attributed to context appropriate anger. Boys' CI anger predicted lower morning cortisol and flatter slopes. Results suggest that this novel approach to studying children's emotion across varying contexts can provide insight into affective style.

Despite growing interest in emotion regulation, the degree to which psychophysiological measures of emotion regulation are stable over time remains unknown. We examined four-week test-retest reliability of corrugator electromyographic and eyeblink startle measures of negative emotion and its regulation. Both measures demonstrated similar sensitivity to the emotion manipulation, but only individual differences in corrugator modulation and regulation showed adequate reliability. Startle demonstrated diminished sensitivity to the regulation instructions across assessments and poor reliability. This suggests that corrugator represents a trait-like measure of voluntary emotion regulation, whereas startle should be used with caution for assessing individual differences. The data also suggest that corrugator and startle might index partially dissociable constructs and underscore the need to collect multiple measures of emotion.

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.

The length polymorphism of the serotonin (5-HT) transporter gene promoter region has been implicated in altered 5-HT function and, in turn, neuropsychiatric illnesses, such as anxiety and depression. The nonhuman primate has been used as a model to study anxiety-related mechanisms in humans based upon similarities in behavior and the presence of a similar 5-HT transporter gene polymorphism. Stressful and threatening contexts in the nonhuman primate model have revealed 5-HT transporter genotype dependent differences in regional glucose metabolism. Using the rhesus monkey, we examined the extent to which serotonin transporter genotype is associated with 5-HT transporter binding in brain regions implicated in emotion-related pathology.
METHODS: Genotype data and high resolution PET scans were acquired in 29 rhesus (Macaca mulatta) monkeys. [C-11]DASB dynamic PET scans were acquired for 90 min in the anesthetized animals and images of distribution volume ratio (DVR) were created to serve as a metric of 5-HT transporter binding for group comparison based on a reference region method of analysis. Regional and voxelwise statistical analysis were performed with corrections for anatomical differences in gray matter probability, sex, age and radioligand mass.
RESULTS: There were no significant differences when comparing l/l homozygotes with s-carriers in the regions of the brain implicated in anxiety and mood related illnesses (amygdala, striatum, thalamus, raphe nuclei, temporal and prefrontal cortex). There was a significant sex difference in 5-HT transporter binding in all regions with females having 18%-28% higher DVR than males.
CONCLUSIONS: Because these findings are consistent with similar genotype findings in humans, this further strengthens the use of the rhesus model for studying anxiety-related neuropathologies.

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36-84 years). We recorded eye-blink startle magnitudes and corrugator activity during and after the presentation of positive, neutral and negative pictures. The most robust age effect was found in response to neutral stimuli, where increasing age is associated with a decreased corrugator and eyeblink startle response to neutral stimuli. These data suggest that an age-related positivity effect does not essentially alter the response to emotion-laden information, but is reflected in a more positive interpretation of affectively ambiguous information. Furthermore, older women showed reduced corrugator recovery from negative pictures relative to the younger women and men, suggesting that an age-related prioritization of well-being is not necessarily reflected in adaptive regulation of negative affect.

Background
The information processing capacity of the human mind is limited, as is evidenced by the attentional blink (AB) - a deficit in identifying the second of two temporally-close targets (T1 and T2) embedded in a rapid stream of distracters. Theories of the AB generally agree that it results from competition between stimuli for conscious representation. However, they disagree in the specific mechanisms, in particular about how attentional processing of T1 determines the AB to T2.

Methodology/Principal Findings
The present study used the high spatial resolution of functional magnetic resonance imaging (fMRI) to examine the neural mechanisms underlying the AB. Our research approach was to design T1 and T2 stimuli that activate distinguishable brain areas involved in visual categorization and representation. ROI and functional connectivity analyses were then used to examine how attentional processing of T1, as indexed by activity in the T1 representation area, affected T2 processing. Our main finding was that attentional processing of T1 at the level of the visual cortex predicted T2 detection rates Those individuals who activated the T1 encoding area more strongly in blink versus no-blink trials generally detected T2 on a lower percentage of trials. The coupling of activity between T1 and T2 representation areas did not vary as a function of conscious T2 perception.

Conclusions/Significance
These data are consistent with the notion that the AB is related to attentional demands of T1 for selection, and indicate that these demands are reflected at the level of visual cortex. They also highlight the importance of individual differences in attentional settings in explaining AB task performance.

Recent years have seen an explosion of interest in using neural oscillations to characterize the mechanisms supporting cognition and emotion. Oftentimes, oscillatory activity is indexed by mean power density in predefined frequency bands. Some investigators use broad bands originally defined by prominent surface features of the spectrum. Others rely on narrower bands originally defined by spectral factor analysis (SFA). Presently, the robustness and sensitivity of these competing band definitions remains unclear. Here, a Monte Carlo-based SFA strategy was used to decompose the tonic ("resting" or "spontaneous") electroencephalogram (EEG) into five bands: delta (1-5Hz), alpha-low (6-9Hz), alpha-high (10-11Hz), beta (12-19Hz), and gamma (>21Hz). This pattern was consistent across SFA methods, artifact correction/rejection procedures, scalp regions, and samples. Subsequent analyses revealed that SFA failed to deliver enhanced sensitivity; narrow alpha sub-bands proved no more sensitive than the classical broadband to individual differences in temperament or mean differences in task-induced activation. Other analyses suggested that residual ocular and muscular artifact was the dominant source of activity during quiescence in the delta and gamma bands. This was observed following threshold-based artifact rejection or independent component analysis (ICA)-based artifact correction, indicating that such procedures do not necessarily confer adequate protection. Collectively, these findings highlight the limitations of several commonly used EEG procedures and underscore the necessity of routinely performing exploratory data analyses, particularly data visualization, prior to hypothesis testing. They also suggest the potential benefits of using techniques other than SFA for interrogating high-dimensional EEG datasets in the frequency or time-frequency (event-related spectral perturbation, event-related synchronization/desynchronization) domains.

Pain is an unpleasant sensory and emotional experience, which can be regulated by many different cognitive mechanisms. We compared the regulatory qualities of two different meditation practices during noxious thermal stimuli: Focused Attention, directed at a fixation cross away from the stimulation, which could regulate negative affect through a sensory gating mechanism; and Open Monitoring, which could regulate negative affect through a mechanism of non-judgmental, non-reactive awareness of sensory experience. Here we report behavioral data from a comparison between novice and long-term meditation practitioners (long-term meditators, LTMs) using these techniques. LTMs, compared to novices, had a significant reduction of self-reported unpleasantness, but not intensity, of painful stimuli, while practicing Open Monitoring. No significant effects were found for FA. This finding illuminates the possible regulatory mechanism of meditation-based clinical interventions such as Mindfulness-Based Stress Reduction (MBSR). Implications are discussed in the broader context of training-induced changes in trait emotion regulation.

Muscle electrical activity, or "electromyogenic" (EMG) artifact, poses a serious threat to the validity of electroencephalography (EEG) investigations in the frequency domain. EMG is sensitive to a variety of psychological processes and can mask genuine effects or masquerade as legitimate neurogenic effects across the scalp in frequencies at least as low as the alpha band (8-13 Hz). Although several techniques for correcting myogenic activity have been described, most are subjected to only limited validation attempts. Attempts to gauge the impact of EMG correction on intracerebral source models (source "localization" analyses) are rarer still. Accordingly, we assessed the sensitivity and specificity of one prominent correction tool, independent component analysis (ICA), on the scalp and in the source-space using high-resolution EEG. Data were collected from 17 participants while neurogenic and myogenic activity was independently varied. Several protocols for classifying and discarding components classified as myogenic and non-myogenic artifact (e.g., ocular) were systematically assessed, leading to the exclusion of one-third to as much as three-quarters of the variance in the EEG. Some, but not all, of these protocols showed adequate performance on the scalp. Indeed, performance was superior to previously validated regression-based techniques. Nevertheless, ICA-based EMG correction exhibited low validity in the intracerebral source-space, likely owing to incomplete separation of neurogenic from myogenic sources. Taken with prior work, this indicates that EMG artifact can substantially distort estimates of intracerebral spectral activity. Neither regression- nor ICA-based EMG correction techniques provide complete safeguards against such distortions. In light of these results, several practical suggestions and recommendations are made for intelligently using ICA to minimize EMG and other common artifacts.

How does language reliably evoke emotion, as it does when people read a favorite novel or listen to a skilled orator? Recent evidence suggests that comprehension involves a mental simulation of sentence content that calls on the same neural systems used in literal action, perception, and emotion. In this study, we demonstrated that involuntary facial expression plays a causal role in the processing of emotional language. Subcutaneous injections of botulinum toxin-A (BTX) were used to temporarily paralyze the facial muscle used in frowning. We found that BTX selectively slowed the reading of sentences that described situations that normally require the paralyzed muscle for expressing the emotions evoked by the sentences. This finding demonstrates that peripheral feedback plays a role in language processing, supports facial-feedback theories of emotional cognition, and raises questions about the effects of BTX on cognition and emotional reactivity. We account for the role of facial feedback in language processing by considering neurophysiological mechanisms and reinforcement-learning theory.

In children, behavioral inhibition (BI) in response to potential threat predicts the development of anxiety and affective disorders, and primate lesion studies suggest involvement of the orbitofrontal cortex (OFC) in mediating BI. Lesion studies are essential for establishing causality in brain-behavior relationships, but should be interpreted cautiously because the impact of a discrete lesion on a complex neural circuit extends beyond the lesion location. Complementary functional imaging methods assessing how lesions influence other parts of the circuit can aid in precisely understanding how lesions affect behavior. Using this combination of approaches in monkeys, we found that OFC lesions concomitantly alter BI and metabolism in the bed nucleus of stria terminalis (BNST) region and that individual differences in BNST activity predict BI. Thus it appears that an important function of the OFC in response to threat is to modulate the BNST, which may more directly influence the expression of BI.

Although there are many imaging studies on traditional ROI-based amygdala volumetry, there are very few studies on modeling amygdala shape variations. This paper presents a unified computational and statistical framework for modeling amygdala shape variations in a clinical population. The weighted spherical harmonic representation is used to parameterize, smooth out, and normalize amygdala surfaces. The representation is subsequently used as an input for multivariate linear models accounting for nuisance covariates such as age and brain size difference using the SurfStat package that completely avoids the complexity of specifying design matrices. The methodology has been applied for quantifying abnormal local amygdala shape variations in 22 high functioning autistic subjects.

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36-84 years). We recorded eye-blink startle magnitudes and corrugator activity during and after the presentation of positive, neutral and negative pictures. The most robust age effect was found in response to neutral stimuli, where increasing age is associated with a decreased corrugator and eyeblink startle response to neutral stimuli. These data suggest that an age-related positivity effect does not essentially alter the response to emotion-laden information, but is reflected in a more positive interpretation of affectively ambiguous information. Furthermore, older women showed reduced corrugator recovery from negative pictures relative to the younger women and men, suggesting that an age-related prioritization of well-being is not necessarily reflected in adaptive regulation of negative affect.

Stress can fundamentally alter neural responses to incoming information. Recent research suggests that stress and anxiety shift the balance of attention away from a task-directed mode, governed by prefrontal cortex (PFC), to a sensory-vigilance mode, governed by the amygdala and other threat-sensitive regions. A key untested prediction of this framework is that stress exerts dissociable effects on different stages of information processing. This study exploited the temporal resolution afforded by event-related potentials to disentangle the impact of stress on vigilance, indexed by early perceptual activity, from its impact on task-directed cognition, indexed by later post-perceptual activity in humans. Results indicated that threat-of-shock amplified stress, measured using retrospective ratings and concurrent facial electromyography (EMG). Stress also double-dissociated early sensory-specific from the later task-directed processing of emotionally-neutral stimuli: stress amplified N1 (184-236 ms) and attenuated P3 (316-488 ms) activity. This demonstrates that stress can have strikingly different consequences at different processing stages. Consistent with recent suggestions, stress amplified earlier extrastriate activity in a manner consistent with vigilance for threat (N1), but disrupted later activity associated with the evaluation of task-relevant information (P3). These results provide a novel basis for understanding how stress can modulate information processing in everyday life and stress-sensitive disorders.

BACKGROUND: Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity.
METHODS: Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task. Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task. Anhedonia scores were collected at three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and 6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time. Analyses were conducted utilizing hierarchical linear modeling software.
RESULTS: Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication (p < .05). Control subjects showed a similar trend between baseline and time 3.
CONCLUSIONS: To reduce anhedonia, it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system.

The development of functional neuroimaging of emotion holds the promise to enhance our understanding of the biological bases of affect and improve our knowledge of psychiatric diseases. However, up to this point, researchers have been unable to objectively, continuously and unobtrusively measure the intensity and dynamics of affect concurrently with functional magnetic resonance imaging (fMRI). This has hindered the development and generalizability of our field. Facial electromyography (EMG) is an objective, reliable, valid, sensitive, and unobtrusive measure of emotion. Here, we report the successful development of a method for simultaneously acquiring fMRI and facial EMG. The ability to simultaneously acquire brain activity and facial physiology will allow affective neuroscientists to address theoretical, psychiatric, and individual difference questions in a more rigorous and generalizable way.

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.

Our outside world changes continuously, for example, when driving through traffic. An important question is how our brain deals with this constant barrage of rapidly changing sensory input and flexibly selects only newly goal-relevant information for further capacity-limited processing in working memory. The challenge our brain faces is experimentally captured by the attentional blink (AB): an impairment in detecting the second of two target stimuli presented in close temporal proximity among distracters. Many theories have been proposed to explain this deficit in processing goal-relevant information, with some attributing the AB to capacity limitations related to encoding of the first target and others assigning a critical role to on-line selection mechanisms that control access to working memory. The current study examined the role of striatal dopamine in the AB, given its known role in regulating the contents of working memory. Specifically, participants performed an AB task and their basal level of dopamine D2-like receptor binding was measured using PET and [F-18]fallypride. As predicted, individual differences analyses showed that greater D2-like receptor binding in the striatum was associated with a larger AB, implicating striatal dopamine and mechanisms that control access to working memory in the AB. Specifically, we propose that striatal dopamine may determine the AB by regulating the threshold for working memory updating, providing a testable physiological basis for this deficit in gating rapidly changing visual information. A challenge for current models of the AB lies in connecting more directly to these neurobiological data.

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.

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.

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.

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.

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.

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.

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.

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.