Dissociable Neural Mechanisms Underlying the Modulation of Pain and Anxiety? An fMRI Pilot Study

The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a “behavioral control” paradigm, which involves the ability to terminate a noxious stimulus, and a “safety signaling” paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.     

Increased Neural Habituation in the Amygdala and Orbitofrontal Cortex in Social Anxiety Disorder Revealed by fMRI

A characterizing symptom of social anxiety disorder (SAD) is increased emotional reactivity towards potential social threat in combination with impaired emotion and stress regulation. While several neuroimaging studies have linked SAD with hyperreactivity in limbic brain regions when exposed to emotional faces, little is known about habituation in both the amygdala and neocortical regulation areas. 15 untreated SAD patients and 15 age- and gender-matched healthy controls underwent functional magnetic resonance imaging during repeated blocks of facial emotion () and object discrimination tasks (). Emotion processing networks were defined by a task-related contrast (). Linear regression was employed for assessing habituation effects in these regions. In both groups, the employed paradigm robustly activated the emotion processing and regulation network, including the amygdalae and orbitofrontal cortex (OFC). Statistically significant habituation effects were found in the amygdalae, OFC, and pulvinar thalamus of SAD patients. No such habituation was found in healthy controls. Concurrent habituation in the medial OFC and the amygdalae of SAD patients as shown in this study suggests intact functional integrity and successful short-term down-regulation of neural activation in brain areas responsible for emotion processing. Initial hyperactivation may be explained by an insufficient habituation to new stimuli during the first seconds of exposure. In addition, our results highlight the relevance of the orbitofrontal cortex in social anxiety disorders.     

Perceived Social Support Moderates the Link between Attachment Anxiety and Health Outcomes

Two literatures have explored some of the effects intimate relationships can have on physical and mental health outcomes. Research investigating health through the lens of attachment theory has demonstrated that more anxiously attached individuals in particular consistently report poorer health. Separate research on perceived social support (e.g., partner or spousal support) suggests that higher support has salutary influences on various health outcomes. Little to no research, however, has explored the interaction of attachment anxiety and perceived social support on health outcomes. The present study examined the attachment-health link and the moderating role of perceived social support in a community sample of married couples. Results revealed that more anxious persons reported poorer overall physical and mental health, more bodily pain, more medical symptoms, and impaired daily functioning, even after controlling for age, relationship length, neuroticism, and marital quality. Additionally, perceived social support interacted with attachment anxiety to influence health; more anxious individuals'' health was poorer even when perceived social support was high, whereas less anxious individuals'' health benefited from high support. Possible mechanisms underlying these findings and the importance of considering attachment anxiety in future studies of poor health in adulthood are discussed.     

Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces

Responses to threat-related stimuli are influenced by conscious and unconscious processes, but the neural systems underlying these processes and their relationship to anxiety have not been clearly delineated. Using fMRI, we investigated the neural responses associated with the conscious and unconscious (backwardly masked) perception of fearful faces in healthy volunteers who varied in threat sensitivity (Spielberger trait anxiety scale). Unconscious processing modulated activity only in the basolateral subregion of the amygdala, while conscious processing modulated activity only in the dorsal amygdala (containing the central nucleus). Whereas activation of the dorsal amygdala by conscious stimuli was consistent across subjects and independent of trait anxiety, activity in the basolateral amygdala to unconscious stimuli, and subjects' reaction times, were predicted by individual differences in trait anxiety. These findings provide a biological basis for the unconscious emotional vigilance characteristic of anxiety and a means for investigating the mechanisms and efficacy of treatments for anxiety.     

Spatial Attention Effects of Disgusted and Fearful Faces

Effective processing of threat-related stimuli is of significant evolutionary advantage. Given the intricate relationship between attention and the neural processing of threat-related emotions, this study manipulated attention allocation and emotional categories of threat-related stimuli as independent factors and investigated the time course of spatial-attention-modulated processing of disgusting and fearful stimuli. The participants were instructed to direct their attention either to the two vertical or to the two horizontal locations, where two faces and two houses would be presented. The task was to respond regarding the physical identity of the two stimuli at cued locations. Event-related potentials (ERP) evidences were found to support a two-stage model of attention-modulated processing of threat-related emotions. In the early processing stage, disgusted faces evoked larger P1 component at right occipital region despite the attention allocation while larger N170 component was elicited by fearful faces at right occipito-temporal region only when participants attended to houses. In the late processing stage, the amplitudes of the parietal P3 component enhanced for both disgusted and fearful facial expressions only when the attention was focused on faces. According to the results, we propose that the temporal dynamics of the emotion-by-attention interaction consist of two stages. The early stage is characterized by quick and specialized neural encoding of disgusting and fearful stimuli irrespective of voluntary attention allocation, indicating an automatic detection and perception of threat-related emotions. The late stage is represented by attention-gated separation between threat-related stimuli and neutral stimuli; the similar ERP pattern evoked by disgusted and fearful faces suggests a more generalized processing of threat-related emotions via top-down attentional modulation, based on which the defensive behavior in response to threat events is largely facilitated.     

前额叶皮层在社交行为中的作用

社交行为对于个体身心健康和社会发展都极其重要。社交行为障碍已成为多种精神类疾病的典型临床表征,对个体的发展有严重不良影响。前额叶皮层作为调节社交行为的关键脑区之一,参与了社交、情绪、决策等高级功能,其内部神经元、神经胶质细胞的活动变化及相互作用对调节社交行为有着重要影响,而且前额叶皮层与其他脑区之间的协作也会影响不同的社会行为。本文回顾了前额叶皮层中神经元、神经胶质细胞以及脑区投射与社交行为关系的最新研究,系统综述了前额叶皮层在社交行为调节中的作用,以期为社交障碍的神经机制和有效诊疗提供参考。     

Manipulation of the oxytocin system alters social behavior and attraction in pair-bonding primates, Callithrix penicillata

The establishment and maintenance of stable, long-term male-female relationships, or pair-bonds, are marked by high levels of mutual attraction, selective preference for the partner, and high rates of sociosexual behavior. Central oxytocin (OT) affects social preference and partner-directed social behavior in rodents, but the role of this neuropeptide has yet to be studied in heterosexual primate relationships. The present study evaluated whether the OT system plays a role in the dynamics of social behavior and partner preference during the first 3 weeks of cohabitation in male and female marmosets, Callithrix penicillata. OT activity was stimulated by intranasal administration of OT, and inhibited by oral administration of a non-peptide OT-receptor antagonist (L-368,899; Merck). Social behavior throughout the pairing varied as a function of OT treatment. Compared to controls, marmosets initiated huddling with their social partner more often after OT treatments but reduced proximity and huddling after OT antagonist treatments. OT antagonist treatment also eliminated food sharing between partners. During the 24-h preference test, all marmosets interacted more with an opposite-sex stranger than with the partner. By the third-week preference test, marmosets interacted with the partner and stranger equally with the exception that intranasal-OT treatments facilitated initial partner-seeking behavior over initial contact with the stranger. Our findings demonstrate that pharmacological manipulations of OT activity alter partner-directed social behavior during pair interactions, suggesting that central OT may facilitate the process of pair-bond formation and social relationships in marmoset monkeys.     

Personality influences the neural responses to viewing facial expressions of emotion

Cognitive research has long been aware of the relationship between individual differences in personality and performance on behavioural tasks. However, within the field of cognitive neuroscience, the way in which such differences manifest at a neural level has received relatively little attention. We review recent research addressing the relationship between personality traits and the neural response to viewing facial signals of emotion. In one section, we discuss work demonstrating the relationship between anxiety and the amygdala response to facial signals of threat. A second section considers research showing that individual differences in reward drive (behavioural activation system), a trait linked to aggression, influence the neural responsivity and connectivity between brain regions implicated in aggression when viewing facial signals of anger. Finally, we address recent criticisms of the correlational approach to fMRI analyses and conclude that when used appropriately, analyses examining the relationship between personality and brain activity provide a useful tool for understanding the neural basis of facial expression processing and emotion processing in general.     

Differential Brain Activation to Angry Faces by Elite Warfighters: Neural Processing Evidence for Enhanced Threat Detection

Background

Little is known about the neural basis of elite performers and their optimal performance in extreme environments. The purpose of this study was to examine brain processing differences between elite warfighters and comparison subjects in brain structures that are important for emotion processing and interoception.

Methodology/Principal Findings

Navy Sea, Air, and Land Forces (SEALs) while off duty (n = 11) were compared with n = 23 healthy male volunteers while performing a simple emotion face-processing task during functional magnetic resonance imaging. Irrespective of the target emotion, elite warfighters relative to comparison subjects showed relatively greater right-sided insula, but attenuated left-sided insula, activation. Navy SEALs showed selectively greater activation to angry target faces relative to fearful or happy target faces bilaterally in the insula. This was not accounted for by contrasting positive versus negative emotions. Finally, these individuals also showed slower response latencies to fearful and happy target faces than did comparison subjects.

Conclusions/Significance

These findings support the hypothesis that elite warfighters deploy greater processing resources toward potential threat-related facial expressions and reduced processing resources to non-threat-related facial expressions. Moreover, rather than expending more effort in general, elite warfighters show more focused neural and performance tuning. In other words, greater neural processing resources are directed toward threat stimuli and processing resources are conserved when facing a nonthreat stimulus situation.     

Oxytocin and vulnerable romantic relationships

Oxytocin (OT) has been implicated in the formation and maintenance of various social relationships, including human romantic relationships. Competing models predict, alternatively, positive or negative associations between naturally-occurring OT levels and romantic relationship quality. Empirical tests of these models have been equivocal. We propose a novel hypothesis (‘Identify and Invest’) that frames OT as an allocator of psychological investment toward valued, vulnerable relationships, and test this proposal in two studies. In one sample of 75 couples, and a second sample of 148 romantically involved individuals, we assess facets of relationships predicting changes in OT across a thought-writing task regarding one's partner. In both studies, participants' OT change across the task corresponded positively with multiple dimensions of high relationship involvement. However, increases in participants' OT also corresponded to their partners reporting lower relationship involvement. OT increases, then, reflected discrepancies between assessments of self and partner relationship involvement. These findings are robust in a combined analysis of both studies, and do not significantly differ between samples. Collectively, our findings support the ‘Identify and Invest’ hypothesis in romantic couples, and we argue for its relevance across other types of social bonds.     

Dogs' Social Referencing towards Owners and Strangers

Social referencing is a process whereby an individual uses the emotional information provided by an informant about a novel object/stimulus to guide his/her own future behaviour towards it. In this study adult dogs were tested in a social referencing paradigm involving a potentially scary object with either their owner or a stranger acting as the informant and delivering either a positive or negative emotional message. The aim was to evaluate the influence of the informant''s identity on the dogs'' referential looking behaviour and behavioural regulation when the message was delivered using only vocal and facial emotional expressions. Results show that most dogs looked referentially at the informant, regardless of his/her identity. Furthermore, when the owner acted as the informant dogs that received a positive emotional message changed their behaviour, looking at him/her more often and spending more time approaching the object and close to it; conversely, dogs that were given a negative message took longer to approach the object and to interact with it. Fewer differences in the dog''s behaviour emerged when the informant was the stranger, suggesting that the dog-informant relationship may influence the dog''s behavioural regulation. Results are discussed in relation to studies on human-dog communication, attachment, mood modification and joint attention.     

Interaction between valence of empathy and familiarity: is it difficult to empathize with the positive events of a stranger?

Background

Empathy in humans is thought to have evolved via social interactions caused by the formation of social groups. Considering the role of empathy within a social group, there might be a difference between emotional empathy for strangers and familiar others belonging to the same social group. In this study, we used the global field power (GFP) index to investigate empathic brain activity during observation of a cue indicating either a negative or positive image viewed by a stranger or close friend.

Methods

Sixteen healthy participants observed a partner performing an emotional gambling task displayed on a monitor. After the partner''s choice-response, a frowning or smiling face symbol was simultaneously presented to the participant’s monitor while a negative or positive emotional image was presented to the partner’s monitor. All participants observed a control condition (CT) showing a computer trial, a stranger-observation condition (SO) showing the trial of a stranger, and a friend-observation condition (FO) to observe the trial of a close friend. During these observations, participants’ event-related potentials (ERPs) were recorded to calculate GFP, and after the task, a subjective assessment of their feelings was measured.

Results

Positive emotion was significantly larger under the FO compared to the CT and the SO. Significantly larger negative emotion was found under the SO and FO compared to the CT. In response to a positive cue, significantly larger GFP during 300 to 600 ms was observed under the FO compared to the CT and SO. In response to a negative cue, significantly larger GFP was observed under the FO and SO compared to the CT. A significantly larger GFP under the SO was found in response to only a negative cue. Topographic map analysis suggested that these differences were related to frontal-occipital dynamics. GFP was significantly correlated with empathic trait.

Conclusion

These results revealed that familiarity with another person has different effects depending on the valence of empathy. Negative empathy, including the danger perception function, might easily occur even among strangers, whereas positive empathy related to nursing and supporting an inner group does not happen easily with strangers.     

Implicitly Priming the Social Brain: Failure to Find Neural Effects

Humans have a fundamental need for social relationships. Rejection from social groups is especially detrimental, rendering the ability to detect threats to social relationships and respond in adaptive ways critical. Indeed, previous research has shown that experiencing social rejection alters the processing of subsequent social cues in a variety of socially affiliative and avoidant ways. Because social perception and cognition occurs spontaneously and automatically, detecting threats to social relationships may occur without conscious awareness or control. Here, we investigated the automaticity of social threat detection by examining how implicit primes affect neural responses to social stimuli. However, despite using a well-established implicit priming paradigm and large sample size, we failed to find any evidence that implicit primes induced changes at the neural level. That implicit primes influence behavior has been demonstrated repeatedly and across a variety of domains, and our goal is not to question these effects. Rather, we offer the present study as cautionary evidence that such a paradigm may not be amenable to scanning in an fMRI environment.     

Dyadic associations between testosterone and relationship quality in couples

Testosterone is thought to be positively associated with “mating effort”, or the initiation and establishment of sexual relationships (Wingfield et al., 1990). Yet, because testosterone is negatively associated with nurturance (van Anders et al., 2011), high levels of testosterone may be incompatible with relationship maintenance. For instance, partnered men with high testosterone report lower relationship quality compared to partnered men with low testosterone (e.g., Booth and Dabbs, 1993). Findings for women are inconsistent, however, and even less is known about potential dyadic associations between testosterone and relationship quality in couples. In the current report, we assessed relationship satisfaction, commitment, and investment in heterosexual couples and tested the hypothesis that these aspects of relationship quality would be negatively associated with an individual's own and his/her partner's testosterone levels. We found that testosterone was in fact negatively associated with relationship satisfaction and commitment in both men and women. There was also evidence for dyadic associations: Participants' satisfaction and commitment were negatively related to their partners' levels of testosterone, and these associations were larger for women's than men's testosterone. Our findings are consistent with the idea that high testosterone may be incompatible with the maintenance of nurturant relationships. The current findings also provide some of the first evidence for dyadic associations between testosterone and relationship quality in couples, highlighting the interdependent nature of close relationship processes and the importance of considering this interdependence in social neuroendocrine research.     

Sex-Related Neuroanatomical Basis of Emotion Regulation Ability

Behavioral research has demonstrated that males have a higher capability of regulating their own and others'' emotions than females; however, little is known about the sex-specific brain mechanisms involved in emotion regulation ability. In the present study, we used voxel-based morphometry to investigate the neural basis underlying emotion regulation ability in a large sample of young adults. Assessment of emotion regulation ability was performed using the Wong and Law Emotional Intelligence Scale. As expected, males significantly scored higher in emotion regulation ability than females did. More importantly, we found the sex differences in the neuroanatomical basis of emotion regulation ability. Males showed a stronger positive relation between emotion regulation ability and regional gray matter volume (rGMV) in the right dorsolateral prefrontal cortex. In contrast, females demonstrated a stronger positive relation between emotion regulation ability and rGMV in an anatomical cluster that extends from the left brainstem to the left hippocampus, the left amygdala and the insular cortex. The present study provides the first empirical evidence regarding the sex-linked neuroanatomical correlates of emotion regulation ability. These findings may help understand why there is a higher prevalence of affective disorders in females and maladaptive behaviors in males.     

An evolutionary perspective on the association between grandmother-mother relationships and maternal mental health among a cohort of pregnant Latina women

Grandmothers are often critical helpers during a mother's reproductive career. Studies on the developmental origins of health and disease demonstrate how maternal psychological distress can negatively influence fetal development and birth outcomes, highlighting an area in which soon-to-be grandmothers (henceforth “grandmothers”) can invest to improve both mother and offspring well-being. Here, we examine if and how a pregnant woman's mental health– specifically, depression, state-anxiety, and pregnancy-related anxiety– is influenced by her relationship with her fetus' maternal and paternal grandmother, controlling for relationship characteristics with her fetus' father. In a cohort of pregnant Latina women in Southern California (N = 216), we assessed social support, geographic proximity, and communication between the fetus' grandmothers and pregnant mother. We assessed maternal mental health with validated questionnaire-based instruments. We find that both social support from and communication with the maternal grandmother were statistically associated with less depression, while no paternal grandmother relationship characteristics were statistically significant in association with any mental health variable. These results align with the idea that maternal grandmothers are more adaptively incentivized to invest in their daughters' well-being during pregnancy than paternal grandmothers are for their daughters-in-law. Results suggest that the positive association of maternal grandmothers with mothers' mental health may not hinge on geographic proximity, but rather, potentially function through emotional support. This work represents a novel perspective describing a psychological and prenatal grandmaternal effect.     

The temporal dynamics of voluntary emotion regulation

Background

Neuroimaging has demonstrated that voluntary emotion regulation is effective in reducing amygdala activation to aversive stimuli during regulation. However, to date little is known about the sustainability of these neural effects once active emotion regulation has been terminated.

Methodology/Principal Findings

We addressed this issue by means of functional magnetic resonance imaging (fMRI) in healthy female subjects. We performed an active emotion regulation task using aversive visual scenes (task 1) and a subsequent passive viewing task using the same stimuli (task 2). Here we demonstrate not only a significantly reduced amygdala activation during active regulation but also a sustained regulation effect on the amygdala in the subsequent passive viewing task. This effect was related to an immediate increase of amygdala signal in task 1 once active emotion regulation has been terminated: The larger this peak postregulation signal in the amygdala in task 1, the smaller the sustained regulation effect in task 2.

Conclusions/Significance

In summary, we found clear evidence that effects of voluntary emotion regulation extend beyond the period of active regulation. These findings are of importance for the understanding of emotion regulation in general, for disorders of emotion regulation and for psychotherapeutic interventions.     

Representation of Cognitive Reappraisal Goals in Frontal Gamma Oscillations

Recently, numerous efforts have been made to understand the neural mechanisms underlying cognitive regulation of emotion, such as cognitive reappraisal. Many studies have reported that cognitive control of emotion induces increases in neural activity of the control system, including the prefrontal cortex and the dorsal anterior cingulate cortex, and increases or decreases (depending upon the regulation goal) in neural activity of the appraisal system, including the amygdala and the insula. It has been hypothesized that information about regulation goals needs to be processed through interactions between the control and appraisal systems in order to support cognitive reappraisal. However, how this information is represented in the dynamics of cortical activity remains largely unknown. To address this, we investigated temporal changes in gamma band activity (35–55 Hz) in human electroencephalograms during a cognitive reappraisal task that was comprised of three reappraisal goals: to decease, maintain, or increase emotional responses modulated by affect-laden pictures. We examined how the characteristics of gamma oscillations, such as spectral power and large-scale phase synchronization, represented cognitive reappraisal goals. We found that left frontal gamma power decreased, was sustained, or increased when the participants suppressed, maintained, or amplified their emotions, respectively. This change in left frontal gamma power appeared during an interval of 1926 to 2453 ms after stimulus onset. We also found that the number of phase-synchronized pairs of gamma oscillations over the entire brain increased when participants regulated their emotions compared to when they maintained their emotions. These results suggest that left frontal gamma power may reflect cortical representation of emotional states modulated by cognitive reappraisal goals and gamma phase synchronization across whole brain regions may reflect emotional regulatory efforts to achieve these goals. Our study may provide the basis for an electroencephalogram-based neurofeedback system for the cognitive regulation of emotion.     

Male song sparrows have elevated testosterone in response to neighbors versus strangers

Upon hearing a conspecific signal, animals must assess their relationship with the signaller and respond appropriately. Territorial animals usually respond more aggressively to strangers than neighbors in a phenomenon known as the “dear enemy effect”. This phenomenon likely evolved because strangers represent a threat to an animal's territory tenure and parentage, whereas neighbors only represent a threat to an animal's parentage because they already possess a territory (providing territory boundaries are established and stable). Although the dear enemy effect has been widely documented using behavioral response variables, little research has been conducted on the physiological responses of animals to neighbors versus strangers. We sought to investigate whether the dear enemy effect is observed physiologically by exposing territorial male song sparrows (Melospiza melodia) to playback simulating a neighbor or a stranger, and then collecting blood samples to measure plasma testosterone levels. We predicted that song sparrows would exhibit increased testosterone levels after exposure to stranger playback compared to neighbor playback, due to the role testosterone plays in regulating aggression. Contrary to our prediction, we found that song sparrows had higher testosterone levels after exposure to neighbor playback compared to stranger playback. We discuss several explanations for our result, notably that corticosterone may regulate the dear enemy effect in male song sparrows and this may inhibit plasma testosterone. Future studies will benefit from examining corticosterone in addition to testosterone, to better understand the hormonal underpinnings of the dear enemy effect.     

On the relationship of emotional abilities and prosocial behavior

The ability to perceive and infer the meaning of facial expressions has been considered a critical component of emotional intelligence being essential for successful social functioning: Longitudinal findings suggest that the ability to recognize emotion cues is related to positive social interactions. Moreover, pronounced recognition abilities for at least some emotions facilitate prosocial behavior in everyday situations. Integrating paradigms from behavioral economics and psychometrics, we used an interdisciplinary approach to study the relationship between prosociality as trait cooperativeness and the ability to recognize emotions in others. We measured emotion recognition accuracy (ERA) using a multivariate test battery. We captured prosocial behavior in standard socio-economic games, along with spontaneous emotion expressions. Structural equation modeling revealed no significant relationship between overall ERA and prosocial behavior. However, modeling emotion-specific factors suggested that more prosocial individuals are better in recognizing fear and tend to express more spontaneous emotions during the prisoner's dilemma. In all, cooperative individuals seem to be more sensitive to the distress of others and more expressive, possibly fostering reciprocal interactions with like-minded others.