Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution (18)F-labelled deoxyglucose positron-emission tomography (FDG-PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament-associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression.
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.
The amygdalae are important, if not critical, brain regions for many affective, attentional and memorial processes, and dysfunction of the amygdalae has been a consistent finding in the study of clinical depression. Theoretical models of the functional neuroanatomy of both normal and psychopathological affective processes which posit cortical hemispheric specialization of functions have been supported by both lesion and functional neuroimaging studies in humans. Results from human neuroimaging studies in support of amygdalar hemispheric specialization are inconsistent. However, recent results from human lesion studies are consistent with hemispheric specialization. An important, yet largely ignored, feature of the amygdalae in the primate brain--derived from both neuroanatomical and electrophysiological data--is that there are virtually no direct interhemispheric connections via the anterior commissure (AC). This feature stands in stark contrast to that of the rodent brain wherein virtually all amygdalar nuclei have direct interhemispheric connections. We propose this feature of the primate brain, in particular the human brain, is a result of influences from frontocortical hemispheric specialization which have developed over the course of primate brain evolution. Results consistent with this notion were obtained by examining the nature of human amygdalar interhemispheric connectivity using both functional magnetic resonance imaging (FMRI) and positron emission tomography (PET). We found modest evidence of amygdalar interhemispheric functional connectivity in the non-depressed brain, whereas there was strong evidence of functional connectivity in the depressed brain. We interpret and discuss the nature of this connectivity in the depressed brain in the context of dysfunctional frontocortical-amygdalar interactions which accompany clinical depression.
BACKGROUND: Autism is a syndrome of unknown cause, marked by abnormal development of social behavior. Attempts to link pathological features of the amygdala, which plays a key role in emotional processing, to autism have shown little consensus. OBJECTIVE: To evaluate amygdala volume in individuals with autism spectrum disorders and its relationship to laboratory measures of social behavior to examine whether variations in amygdala structure relate to symptom severity. DESIGN: We conducted 2 cross-sectional studies of amygdala volume, measured blind to diagnosis on high-resolution, anatomical magnetic resonance images. Participants were 54 males aged 8 to 25 years, including 23 with autism and 5 with Asperger syndrome or pervasive developmental disorder not otherwise specified, recruited and evaluated at an academic center for developmental disabilities and 26 age- and sex-matched community volunteers. The Autism Diagnostic Interview-Revised was used to confirm diagnoses and to validate relationships with laboratory measures of social function. MAIN OUTCOME MEASURES: Amygdala volume, judgment of facial expressions, and eye tracking. RESULTS: In study 1, individuals with autism who had small amygdalae were slowest to distinguish emotional from neutral expressions (P=.02) and showed least fixation of eye regions (P=.04). These same individuals were most socially impaired in early childhood, as reported on the Autism Diagnostic Interview-Revised (P<.04). Study 2 showed smaller amygdalae in individuals with autism than in control subjects (P=.03) and group differences in the relation between amygdala volume and age. Study 2 also replicated findings of more gaze avoidance and childhood impairment in participants with autism with the smallest amygdalae. Across the combined sample, severity of social deficits interacted with age to predict different patterns of amygdala development in autism (P=.047). CONCLUSIONS: These findings best support a model of amygdala hyperactivity that could explain most volumetric findings in autism. Further psychophysiological and histopathological studies are indicated to confirm these findings.
<p>Previous research on anger and childhood sexual abuse (CSA) is largely cross-sectional and retrospective. In this study, we prospectively examined the consequences of expressing anger among sexually abused women in contexts of either voluntarily disclosing or not disclosing a previous abuse episode. All CSA survivors in the study had documented histories of CSA. These participants and a matched, nonabused sample were asked to describe their most distressing experience while being videotaped to allow coding of anger expression. Approximately two thirds of the CSA survivors voluntarily disclosed a previous abuse experience. Participants completed measures of internalizing symptoms and externalizing symptoms at the time of disclosure and again two years later. The expression of anger was associated with better long-term adjustment (decreased internalizing and externalizing symptoms) but only among CSA survivors who had expressed anger while not disclosing an abuse experience. For CSA survivors who disclosed an abuse experience, anger expression was unrelated to long-term outcome. These findings suggest that the benefits of anger expression for CSA survivors may be context specific.</p>
Extensive animal and recent human research have helped inform neuroendocrinological models of social cognition, motivation and behavior. In this review, we first summarize important findings regarding oxytocin, arginine vasopressin and testosterone in the domains of affiliation, social cognition, aggression and stress/anxiety. We then suggest ways in which human research can continue to profit from animal research, particularly by exploring the interactive nature of neuromodulatory effects at neurochemical, organismic and contextual levels. We further propose methods inspired by the animal literature for the ecologically valid assessment of affiliative behavior in humans. We conclude with suggestions for how human research could advance by directly assessing specific social cognitive and motivational mechanisms as intermediate variables. We advocate a more comprehensive look at the distinct networks identified by social neuroscience and the importance of a motivational state, in addition to approach and avoidance, associated with quiescence and homeostatic regulation.
A variety of recent research indicates that when subjects are induced to experience certain negative emotions, there is greater suppression of alpha power in the right than left frontal region, while during the experience of positive emotion, alpha power asymmetry in this region shows the opposite pattern. We have conceptualized this assymetry as reflecting specialization for approach and withdrawal processes in the left and right frontal regions, respectively. In this experiment, reward and punishment contingencies were directly manipulated to produce approach and withdrawal response motional states. In addition, subjects responded to imperative stimuli using either an approach response (finger press) or a withdrawal response (finger lift). EEG was recorded from multiple scalp locations. During the foreperiod prior to the response to the imperative stimuli, the EEG was extracted, Fourier-transformed and power computed in the theta, alpha and beta frequency bands. In addition, the contingent negative variation (CNV) was derived from the identical epoch. Reward trials were associated with greater left frontal alpha power suppression than punishment trials, while during the latter trials, there was greater right-sided frontal alpha power suppression than during reward trials. There was also some evidence to indicate that withdrawal responses were associated with greater right-sided alpha power suppression in the temporo-parietal region compared with approach responses. Power in the theta and beta bands did not systematically vary with condition. The CNV was larger during trials on which subjects responded quickly compared with slow trials, but did not differentiate between reward and punishment contingencies. The findings support the hypothesis that approach-related processes can be differentiated from withdrawal-related processes on the basis of asymmetrical shifts in alpha power in the frontal region. They also indicate that the CNV and spectral power estimates from the identical epochs reflect different neural processes.
This article presents an overview of the author's recent electrophysiological studies of anterior cerebral asymmetries related to emotion and affective style. A theoretical account is provided of the role of the two hemispheres in emotional processing. This account assigns a major role in approach- and withdrawal-related behavior to the left and right frontal and anterior temporal regions of two hemispheres, respectively. Individual differences in approach- and withdrawal-related emotional reactivity and temperament are associated with stable differences in baseline measures of activation asymmetry in these anterior regions. Phasic state changes in emotion result in shifts in anterior activation asymmetry which are superimposed upon these stable baseline differences. Future directions for research in this area are discussed.
OBJECTIVE: The anterior cingulate cortex has been implicated in depression. Results are best interpreted by considering anatomic and cytoarchitectonic subdivisions. Evidence suggests depression is characterized by hypoactivity in the dorsal anterior cingulate, whereas hyperactivity in the rostral anterior cingulate is associated with good response to treatment. The authors tested the hypothesis that activity in the rostral anterior cingulate during the depressed state has prognostic value for the degree of eventual response to treatment. Whereas prior studies used hemodynamic imaging, this investigation used EEG. METHOD: The authors recorded 28-channel EEG data for 18 unmedicated patients with major depression and 18 matched comparison subjects. Clinical outcome was assessed after nortriptyline treatment. Of the 18 depressed patients, 16 were considered responders 4-6 months after initial assessment. A median split was used to classify response, and the pretreatment EEG data of patients showing better (N=9) and worse (N=9) responses were analyzed with low-resolution electromagnetic tomography, a new method to compute three-dimensional cortical current density for given EEG frequency bands according to a Talairach brain atlas. RESULTS: The patients with better responses showed hyperactivity (higher theta activity) in the rostral anterior cingulate (Brodmann's area 24/32). Follow-up analyses demonstrated the specificity of this finding, which was not confounded by age or pretreatment depression severity. CONCLUSIONS: These results, based on electrophysiological imaging, not only support hemodynamic findings implicating activation of the anterior cingulate as a predictor of response in depression, but they also suggest that differential activity in the rostral anterior cingulate is associated with gradations of response.
Two reports in the last issue of this journal attempted to replicate aspects of our previous studies on anterior electroencephalogram (EEG) asymmetry, affective style, and depression. In this commentary, an overview is provided of our model of anterior asymmetries, affective style, and psychopathology. Emphasis is placed on conceptualizing the prefrontal and anterior temporal activation patterns within a circuit that includes cortical and subcortical structures. The causal status of individual differences in asymmetric activation in the production of affective style and psychopathology is considered. Major emphasis is placed on EEG methods, particularly the need for multiple assessments to obtain estimates of asymmetric activation that better reflect an individual's true score. Issues specific to each of the two articles are also considered. Each of the articles has more consistency with our previously published data than the authors themselves suggest. Recommendations are made for future research to resolve some of the outstanding issues.
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.
In this article we examine the role of appeasement in human emotion, social practice, and personality. We first present an analysis of human appeasement. Appeasement begins when the conditions of social relations lead one individual to anticipate aggression from others, is expressed in submissive, inhibited behavior, which in turn evokes inferences and emotions in others that bring about social reconciliation. Our empirical review focuses on two classes of human appeasement: reactive forms of appeasement, including embarrassment and shame, which placate others after social transgressions; and anticipatory forms of appeasement, including polite modesty and shyness, which reduce the likelihood of social conflict and aggression. Our review of the empirical evidence indicates that embarrassment, shame, modesty, and shyness share the eliciting conditions, submissive behavior, and social consequences of appeasement. We conclude by discussing social processes that allow humans to appease one another, such as teasing, and those that prevent appeasement, such as legal and negotiation practices, to the benefit and detriment of human relations. Aggr. Behav. 23:359–374, 1997. © 1997 Wiley-Liss, Inc.
In this experiment, we combined the measurement of observable facial behavior with simultaneous measures of brain electrical activity to assess patterns of hemispheric activation in different regions during the experience of happiness and disgust. Disgust was found to be associated with right-sided activation in the frontal and anterior temporal regions compared with the happy condition. Happiness was accompanied by left-sided activation in the anterior temporal region compared with disgust. No differences in asymmetry were found between emotions in the central and parietal regions. When data aggregated across positive films were compared to aggregate negative film data, no reliable differences in brain activity were found. These findings illustrate the utility of using facial behavior to verify the presence of emotion, are consistent with the notion of emotion-specific physiological patterning, and underscore the importance of anterior cerebral asymmetries for emotions associated with approach and withdrawal.
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.
Theories typically emphasize affordances or intentions as the primary determinant of an object's perceived function. The HIPE theory assumes that people integrate both into causal models that produce functional attributions. In these models, an object's physical structure and an agent's action specify an affordance jointly, constituting the immediate causes of a perceived function. The object's design history and an agent's goal in using it constitute distant causes. When specified fully, the immediate causes are sufficient for determining the perceived function--distant causes have no effect (the causal proximity principle). When the immediate causes are ambiguous or unknown, distant causes produce inferences about the immediate causes, thereby affecting functional attributions indirectly (the causal updating principle). Seven experiments supported HIPE's predictions.
Ten-month-old infants viewed videotape segments of an actress spontaneously generating a happy or sad facial expression. Brain activity was recorded from the left and right frontal and parietal scalp regions. In two studies, infants showed greater activation of the left frontal than of the right frontal area in response to the happy segments. Parietal asymmetry failed to discriminate between the conditions. Differential lateralization of the hemispheres for affective processes seems to be established by 10 months of age.
This study compared the asymmetry of different features of brain electrical activity during the performance of a verbal task (word finding) and a spatial task (dot localization) that had been carefully matched on psychometric properties and accompanying motor activity. Nineteen right-handed subjects were tested. EEG was recorded from F3, F4, C3, C4, P3, and P4, referred to both CZ and computer-derived averaged-ears references, and Fourier transformed. Power in the delta, theta, alpha, and beta bands was computed. There were significant Task X Hemisphere effects in all bands for CZ-referenced data and for the alpha and beta bands for ears-referenced data. The effects were always either greater power suppression in the hemisphere putatively most engaged in task processing or greater power in the opposite hemisphere. Correlations between EEG and task performance indicated that CZ-referenced parietal alpha asymmetry accounted for the most variance in verbal task performance. Power within individual hemispheres or across hemispheres was unrelated to task performance. The findings indicate robust differences in asymmetrical brain physiology that are produced by well-matched verbal and spatial cognitive tasks.
<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>