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.
This article reviews the modern literature on two key aspects of the central circuitry of emotion: the prefrontal cortex (PFC) and the amygdala. There are several different functional divisions of the PFC, including the dorsolateral, ventromedial, and orbital sectors. Each of these regions plays some role in affective processing that shares the feature of representing affect in the absence of immediate rewards and punishments as well as in different aspects of emotional regulation. The amygdala appears to be crucial for the learning of new stimulus-threat contingencies and also appears to be important in the expression of cue-specific fear. Individual differences in both tonic activation and phasic reactivity in this circuit play an important role in governing different aspects of anxiety. Emphasis is placed on affective chronometry, or the time course of emotional responding, as a key attribute of individual differences in propensity for anxiety that is regulated by this circuitry.
On the basis of a review of the extant literature describing emotion-cognition interactions, the authors propose 4 methodological desiderata for studying how task-irrelevant affect modulates cognition and present data from an experiment satisfying them. Consistent with accounts of the hemispheric asymmetries characterizing withdrawal-related negative affect and visuospatial working memory (WM) in prefrontal and parietal cortices, threat-induced anxiety selectively disrupted accuracy of spatial but not verbal WM performance. Furthermore, individual differences in physiological measures of anxiety statistically mediated the degree of disruption. A second experiment revealed that individuals characterized by high levels of behavioral inhibition exhibited more intense anxiety and relatively worse spatial WM performance in the absence of threat, solidifying the authors' inference that anxiety causally mediates disruption. These observations suggest a revision of extant models of how anxiety sculpts cognition and underscore the utility of the desiderata.
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.
<p>A model of asymmetric contributions to the control of different subcomponents of approach- and withdrawal-related emotion and psychopathology is presented. Two major forms of positive affect are distinguished. An approach-related form arises prior to goal attainment, and another form follows goal attainment. The former is hypothesized to be associated with activation of the left prefrontal cortex. Individual differences in patterns of prefrontal activation are stable over time. Hypoactivation in this region is proposed to result in approach-related deficits and increase an individual's vulnerability to depression. Data in support of these proposals are presented. The issue of plasticity is then considered from several perspectives. Contextual factors are superimposed upon tonic individual differences and modulate the magnitude of asymmetry. Pharmacological challenges also alter patterns of frontal asymmetry. A diverse array of evidence was then reviewed that lends support to the notion that these patterns of asymmetry may be importantly influenced by early environmental factors that result in enduring changes in brain function and structure.</p>
Research on the neural substrates of emotion has found evidence for cortical asymmetries for aspects of emotion. A recent article by Nicholls et al. has used a new imaging method to interrogate facial movement in 3D to assess possible asymmetrical action during expressions of happiness and sadness. Greater left-sided movement, particularly during expressions of sadness was observed. These findings have implications for understanding hemispheric differences in emotion and lend support to the notion that aspects of emotion processing might be differentially localized in the two hemispheres.
<p>Assessed the cortical concomitants of selective mode-specific attention in Ss differing in the capacity for sustained attentional involvement. 10 high- and 10 low-scoring Ss on the Tellegen Absorption Scale were required to (a) simply attend to either a randomly flashing light or a randomly produced tapping sensation on the forearm during one block of trials and to (b) count the flashes and the taps during another trial block. The EEG was recorded from the left occipital and left sensorimotor regions and was filtered for alpha activity and quantified on line. Selective mode-specific attention produced reliable shifts in cortical patterning between kinesthetic and visual attention trials. During the counting condition, high-scoring Ss showed significantly greater specificity in cortical patterning than did low-scoring Ss. This difference was primarily a function of high-scoring Ss' ability to inhibit activation in the occipital region while counting taps. Findings suggest that high scores on the Absorption scale are associated with a flexible attentional style and that, given the requisite task demands, attentionally absorbed Ss show greater mode-specific cortical patterning during selective attention than do low scorers. (36 ref)</p>
Meditation can be conceptualized as a family of complex emotional and attentional regulatory training regimes developed for various ends, including the cultivation of well-being and emotional balance. Among these various practices, there are two styles that are commonly studied. One style, focused attention meditation, entails the voluntary focusing of attention on a chosen object. The other style, open monitoring meditation, involves nonreactive monitoring of the content of experience from moment to moment. The potential regulatory functions of these practices on attention and emotion processes could have a long-term impact on the brain and behavior.
Functional MRI resting state and connectivity studies of brain focus on neural fluctuations at low frequencies which share power with physiological fluctuations originating from lung and heart. Due to the lack of automated software to process physiological signals collected at high magnetic fields, a gap exists in the processing pathway between the acquisition of physiological data and its use in fMRI software for both physiological noise correction and functional analyses of brain activation and connectivity. To fill this gap, we developed an open source, physiological signal processing program, called PhysioNoise, in the python language. We tested its automated processing algorithms and dynamic signal visualization on resting monkey cardiac and respiratory waveforms. PhysioNoise consistently identifies physiological fluctuations for fMRI noise correction and also generates covariates for subsequent analyses of brain activation and connectivity.
<p>Forty-four right-handed participants were assessed on 2 occasions 6 weeks apart on electrophysiological measures of activation asymmetry derived from spectral estimates of electroencephalogram (EEG) alpha power in homologous scalp electrodes. Approximately 4 months following the final EEG assessment. participants were administered a dichotic listening CV-syllables task. Overall, participants exhibited a highly significant right-ear advantage. Differences among individuals in ear asymmetry were predicted by the earlier recorded electrophysiological data. Participants with greater activation in left-sided posterior temporal and parietal regions showed a larger right-ear advantage. In addition, a larger right-ear advantage was predicted by right-sided prefrontal activation. These data indicate that some of the variance in dichotic listening performance can be explained by dispositional activation asymmetries and is associated with a complex pattern of posterior and anterior activation asymmetries.</p>
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.
Despite decades of research on the etiology and treatment of depression, a significant proportion of the population is affected by the disorder, fails to respond to treatment and is plagued by relapse. Six prominent scientists, Aaron Beck, Richard Davidson, Fritz Henn, Steven Maier, Helen Mayberg, and Martin Seligman, gathered to discuss the current state of scientific knowledge on depression, and in particular on the basic neurobiological and psychopathological processes at play in the disorder. These general themes were addressed: 1) the relevance of learned helplessness as a basic process involved in the development of depression; 2) the limitations of our current taxonomy of psychological disorders; 3) the need to work towards a psychobiological process-based taxonomy; and 4) the clinical implications of implementing such a process-based taxonomy.
The brain and the cardiovascular system influence each other during the processing of emotion. The study of the interactions of these systems during emotion regulation has been limited in human functional neuroimaging, despite its potential importance for physical health. We have previously reported that mental expertise in cultivation of compassion alters the activation of circuits linked with empathy and theory of mind in response to emotional stimuli. Guided by the finding that heart rate increases more during blocks of compassion meditation than neutral states, especially for experts, we examined the interaction between state (compassion vs. neutral) and group (novice, expert) on the relation between heart rate and BOLD signal during presentation of emotional sounds presented during each state. Our findings revealed that BOLD signal in the right middle insula showed a significant association with heart rate (HR) across state and group. This association was stronger in the left middle/posterior insula when experts were compared to novices. The positive coupling of HR and BOLD was higher within the compassion state than within the neutral state in the dorsal anterior cingulate cortex for both groups, underlining the role of this region in the modulation of bodily arousal states. This state effect was stronger for experts than novices in somatosensory cortices and the right inferior parietal lobule (group by state interaction). These data confirm that compassion enhances the emotional and somatosensory brain representations of others' emotions, and that this effect is modulated by expertise. Future studies are needed to further investigate the impact of compassion training on these circuits.
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: The frontal lobe has been crucially involved in the neurobiology of major depression, but inconsistencies among studies exist, in part due to a failure of considering modulatory variables such as symptom severity, comorbidity with anxiety, and distinct subtypes, as codeterminants for patterns of brain activation in depression. METHODS: Resting electroencephalogram was recorded in 38 unmedicated subjects with major depressive disorder and 18 normal comparison subjects, and analyzed with a tomographic source localization method that computes the cortical three-dimensional distribution of current density for standard electroencephalogram frequency bands. Symptom severity and anxiety were measured via self-report and melancholic features via clinical interview. RESULTS: Depressed subjects showed more excitatory (beta3, 21.5-30.0 Hz) activity in the right superior and inferior frontal lobe (Brodmann's area 9/10/11) than comparison subjects. In melancholic subjects, this effect was particularly pronounced for severe depression, and right frontal activity correlated positively with anxiety. Depressed subjects showed posterior cingulate and precuneus hypoactivity. CONCLUSIONS: While confirming prior results implicating right frontal and posterior cingulate regions, this study highlights the importance of depression severity, anxiety, and melancholic features in patterns of brain activity accompanying depression.
Fragile X syndrome (FXS) is the most commonly known genetic disorder associated with autism spectrum disorder (ASD). Overlapping features in these populations include gaze aversion, communication deficits, and social withdrawal. Although the association between FXS and ASD has been well documented at the behavioral level, the underlying neural mechanisms associated with the social/emotional deficits in these groups remain unclear. We collected functional brain images and eye-gaze fixations from 9 individuals with FXS and 14 individuals with idiopathic ASD, as well as 15 typically developing (TD) individuals, while they performed a facial-emotion discrimination task. The FXS group showed a similar yet less aberrant pattern of gaze fixations compared with the ASD group. The FXS group also showed fusiform gyrus (FG) hypoactivation compared with the TD control group. Activation in FG was strongly and positively associated with average eye fixation and negatively associated with ASD characteristics in the FXS group. The FXS group displayed significantly greater activation than both the TD control and ASD groups in the left hippocampus (HIPP), left superior temporal gyrus (STG), right insula (INS), and left postcentral gyrus (PCG). These group differences in brain activation are important as they suggest unique underlying face-processing neural circuitry in FXS versus idiopathic ASD, largely supporting the hypothesis that ASD characteristics in FXS and idiopathic ASD reflect partially divergent impairments at the neural level, at least in FXS individuals without a co-morbid diagnosis of ASD.
The experience of aversion is shaped by multiple physiological and psychological factors including one's expectations. Recent work has shown that expectancy manipulation can alter perceptions of aversive events and concomitant brain activation. Accruing evidence indicates a primary role of altered expectancies in the placebo effect. Here, we probed the mechanism by which expectation attenuates sensory taste transmission by examining how brain areas activated by misleading information during an expectancy period modulate insula and amygdala activation to a highly aversive bitter taste. In a rapid event-related fMRI design, we showed that activations in the rostral anterior cingulate cortex (rACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex to a misleading cue that the taste would be mildly aversive predicted decreases in insula and amygdala activation to the highly aversive taste. OFC and rACC activation to the misleading cue were also associated with less aversive ratings of that taste. Additional analyses revealed consistent results demonstrating functional connectivity among the OFC, rACC, and insula. Altering expectancies of upcoming aversive events are shown here to depend on robust functional associations among brain regions implicated in prior work on the placebo effect.
Background A key to successful adaptation is the ability to regulate emotional responses in relation to changing environmental demands or contexts. Methods High-resolution PET 18fluoro-deoxyglucose (FDG) scanning in rhesus monkeys was performed during two contexts (alone, and human intruder with no eye contact) during which the duration of anxiety related freezing behavior was assessed. Correlations between individual differences in freezing duration and brain activity were performed for each of the two conditions, as well as for the contextual regulation between the two conditions. Results In both conditions, activity in the basal forebrain, including the bed nucleus of the stria terminalis and the nucleus accumbens were correlated with individual differences in freezing duration. In contrast, individual differences in the ability to regulate freezing behavior between contexts were correlated with activity in the dorsal anterior cingulate cortex, the thalamus and the dorsal raphe nucleus. Conclusions These findings demonstrate differences in the neural circuitry mediating the expression compared to the contextual regulation of freezing behavior. These findings are relevant since altered regulatory processes may underlie anxiety disorders.
Neuroscientists should help to develop compelling video games that boost brain function and improve well-being, say Daphne Bavelier and Richard J. Davidson.
Biological systems are particularly prone to variation, and the authors argue that such variation must be regarded as important data in its own right. The authors describe a method in which individual differences are studied within the framework of a general theory of the population as a whole and illustrate how this method can be used to address three types of issues: the nature of the mechanisms that give rise to a specific ability, such as mental imagery; the role of psychological or biological mediators of environmental challenges, such as the biological bases for differences in dispositional mood; and the existence of processes that have nonadditive effects with behavioral and physiological variables, such as factors that modulate the response to stress and its effects on the immune response.
Stimulated by a recent meeting between Western psychologists and the Dalai Lama on the topic of destructive emotions, we report on two issues: the achievement of enduring happiness, what Tibetan Buddhists call sukha, and the nature of afflictive and nonafflictive emotional states and traits. A Buddhist perspective on these issues is presented, along with discussion of the challenges the Buddhist view raises for empirical research and theory.