Neuroanatomical correlates of individual differences in social anxiety in a non-clinical population

Socially anxious individuals are characterized as those with distorted negative self-beliefs (NSBs), which are thought to enhance reactions of social distress (emotional reactivity) and social avoidance (social functioning). However, it remains unclear whether individual differences in social distress and social avoidance are represented by differences in brain morphometry. To probe into these neural correlates, we analyzed magnetic resonance images of a sample of 130 healthy subjects and used the Connectome Computation System (CCS) to evaluate these factors. The results showed that social distress was correlated with the cortical volume of the right orbitofrontal cortex (OFC) and the subcortical volume of the left amygdala, while social avoidance was correlated with the cortical volume of the right dorsolateral prefrontal cortex (DLPFC). Additionally, loneliness might mediate the relationship between the amygdala volume and the social distress score. Our results demonstrated that social distress and social avoidance were represented by segregated cortical regions in the healthy individuals. These findings might provide a valuable basis for understanding the stable brain structures underlying individual differences in social anxiety.     

Neural correlates of self-focused attention in social anxiety

Socially anxious individuals tend to shift their attention away from external socially threatening cues and instead become highly self-focused. Such heightened self-focused attention has been suggested to be involved in the development and maintenance of social anxiety disorder. This study used functional magnetic resonance imaging to investigate the neural correlates of self-focused attention in 16 high socially anxious (HSA) and 16 low socially anxious (LSA) individuals. Participants were instructed to focus their attention either inwardly or outwardly during a simulated social situation. Results indicate hyperactivation of medial prefrontal cortex (mPFC), temporo-parietal junction (TPJ) and temporal pole during inward vs outward attention in HSA compared with LSA participants. Furthermore, activation of mPFC, right anterior insula, TPJ and posterior cingulate cortex was positively correlated with the trait of self-focused attention in HSA subjects. Results highlight the prominent role of the mPFC and other cortical structures in abnormal self-focused attention in social anxiety. Finally, findings for the insula suggest increased processing of bodily states that is related to the amount of habitual self-focused attention in social anxiety.     

Common and distinct neural features of social and non-social reward processing in autism and social anxiety disorder

Autism spectrum disorders (ASDs) and social anxiety disorder (SAD) are both characterized by social dysfunction, but no study to date has compared neural responses to social rewards in ASDs and SAD. Neural responses during social and non-social reward anticipation and outcomes were examined in individuals with ASD (n = 16), SAD (n = 15) and a control group (n = 19) via functional magnetic resonance imaging. Analyses modeling all three groups revealed increased nucleus accumbens (NAc) activation in SAD relative to ASD during monetary reward anticipation, whereas both the SAD and ASD group demonstrated decreased bilateral NAc activation relative to the control group during social reward anticipation. During reward outcomes, the SAD group did not differ significantly from the other two groups in ventromedial prefrontal cortex activation to either reward type. Analyses comparing only the ASD and SAD groups revealed greater bilateral amygdala activation to social rewards in SAD relative to ASD during both anticipation and outcome phases, and the magnitude of left amygdala hyperactivation in the SAD group during social reward anticipation was significantly correlated with the severity of trait anxiety symptoms. Results suggest reward network dysfunction to both monetary and social rewards in SAD and ASD during reward anticipation and outcomes, but that NAc hypoactivation during monetary reward anticipation differentiates ASD from SAD.     

Neural response to monetary and social feedback demonstrates differential associations with depression and social anxiety

An aberrant neural response to rewards has been linked to both depression and social anxiety. Most studies have focused on the neural response to monetary rewards, and few have tested different modalities of reward (e.g. social) that are more salient to particular forms of psychopathology. In addition, most studies contain critical confounds, including contrasting positive and negative feedback and failing to disentangle being correct from obtaining positive feedback. In the present study, 204 participants underwent electroencephalography during monetary and social feedback tasks that were matched in trial structure, timing and feedback stimuli. The reward positivity (RewP) was measured in response to correctly identifying stimuli that resulted in monetary win, monetary loss, social like or social dislike feedback. All monetary and social tasks elicited a RewP, which were positively correlated. Across all tasks, the RewP was negatively associated with depression and positively associated with social anxiety. The RewP to social dislike feedback, independent of monetary and social like feedback, was also associated with social anxiety. The present study suggests that a domain-general neural response to correct feedback demonstrates a differential association with depression and social anxiety, but a domain-specific neural response to social dislike feedback is uniquely associated with social anxiety.     

Mind the social feedback: effects of tDCS applied to the left DLPFC on psychophysiological responses during the anticipation and reception of social evaluations

The left dorsolateral prefrontal cortex (lDLPFC) is implicated in anticipatory (i.e. during anticipation of emotional stimuli) and online (i.e. during confrontation with emotional stimuli) emotion regulatory processes. However, research that investigates the causal role of the lDLPFC in these processes is lacking. In this study, 74 participants received active or sham transcranial direct current stimulation (tDCS) over the lDLPFC. Participants were told strangers evaluated them. These (rigged) social evaluations were presented, and in 50% of the trials, participants could anticipate the valence (positive or negative) of the upcoming social feedback. Pupil dilation (a marker of cognitive resource allocation) and skin conductance responses (a marker of arousal) were measured. The results indicate that active (compared to sham) tDCS reduced arousal during the confrontation with anticipated feedback but only marginally during the confrontation with unanticipated feedback. When participants were given the opportunity to anticipate the social feedback, tDCS reduced arousal, irrespective of whether one was anticipating or being confronted with the anticipated feedback. Moreover, tDCS reduced cognitive resource allocation during anticipation, which was associated with resource allocation increases during the subsequent confrontation. Altogether, results suggest that the lDLPFC is causally implicated in the interplay between anticipatory and online emotion regulatory processes.     

Looking at the self in front of others: Neural correlates of attentional bias in social anxiety

In social anxiety disorder (SAD), anxiety reactions are triggered by attentional bias to social threats that automatically appear in social situations. The present study aimed to investigate the neural basis and underlying resting-state pathology of attentional bias toward internal and external social threats as a core element of SAD. Twenty-two patients with SAD and 20 control subjects scanned functional magnetic resonance imaging during resting-state and while performing the visual search task. During the task, participants were exposed to internal threat (hearing participants’ own pulse-sounds) and external threat (crowds in facial matrices). Patients showed activations in the lateral orbitofrontal cortex, rostral anterior cingulate cortex and insula in response to internal threat and activations in the posterior cingulate cortex and middle temporal gyrus in response to external threat. In patients, neural activity related to combined internal and external threats in the posterior cingulate cortex was inversely correlated with the functional connectivity strengths with the default mode network during resting-state. These findings suggest that attentional bias may stem from limbic and paralimbic pathology, and the interactive process of internally- and externally-focused attentional bias in SAD is associated with the self-referential function of resting-state.     

Storm in a coffee cup: caffeine modifies brain activation to social signals of threat

Caffeine, an adenosine A₁ and A_2A receptor antagonist, is the most popular psychostimulant drug in the world, but it is also anxiogenic. The neural correlates of caffeine-induced anxiety are currently unknown. This study investigated the effects of caffeine on brain regions implicated in social threat processing and anxiety. Participants were 14 healthy male non/infrequent caffeine consumers. In a double-blind placebo-controlled crossover design, they underwent blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) while performing an emotional face processing task 1 h after receiving caffeine (250 mg) or placebo in two fMRI sessions (counterbalanced, 1-week washout). They rated anxiety and mental alertness, and their blood pressure was measured, before and 2 h after treatment. Results showed that caffeine induced threat-related (angry/fearful faces > happy faces) midbrain-periaqueductal gray activation and abolished threat-related medial prefrontal cortex wall activation. Effects of caffeine on extent of threat-related amygdala activation correlated negatively with level of dietary caffeine intake. In concurrence with these changes in threat-related brain activation, caffeine increased self-rated anxiety and diastolic blood pressure. Caffeine did not affect primary visual cortex activation. These results are the first to demonstrate potential neural correlates of the anxiogenic effect of caffeine, and they implicate the amygdala as a key site for caffeine tolerance.     

Cognitive modulation of emotion anticipation

Anticipating salient emotions is a vital function related to attention, self control and other cognitive mechanisms. Expecting affective events can trigger regulatory processes that prepare an organism, for example, to cope with possible threat. However, there are situations, like waiting at the dentist's or preparing for a public appearance, in which down-regulation of especially negative emotions linked with the upcoming event is necessary or favorable. A strategy to achieve this is cognitive distraction, a process with up to now barely known neural mechanisms. We used graded cognitive distraction during the anticipation of subsequent negative emotions in order to induce down-regulation of the emotional response in an event-related fMRI design. Accordingly, we found down-regulation of anterior rostral medial prefrontal cortex and amygdala activation during anticipatory cognitive distraction with the anterior medial prefrontal cortex being negatively correlated with the lateral prefrontal cortex. Furthermore, we demonstrated that anticipatory distraction does not influence subsequent emotion processing, i.e. does not reduce subsequent activation in emotion-processing brain areas. We conclude that effortful anticipatory cognitive distraction effectively down-regulates emotion processing during anticipation but not subsequent emotion information processing. These results help in the understanding of general mechanisms of emotion regulation and have implications for applied fields like cognitive behavioral therapy.     

Neural correlates of self-reflection in post-traumatic stress disorder

Bluhm RL, Frewen PA, Coupland NC, Densmore M, Schore AN, Lanius RA. Neural correlates of self‐reflection in post‐traumatic stress disorder. Objective: Disturbances in self‐referential processing (SRP) are increasingly recognized in post‐traumatic stress disorder (PTSD). In healthy adults, SRP tasks engage the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) brain regions that have shown altered function in PTSD. We hypothesized that individuals with PTSD would differ from controls in functional activation of the MPFC and PCC during SRP. Method: We compared neural activation in healthy controls (n = 15) and participants with PTSD (n = 20) during a SRP task, using fMRI at 4.0T. Results: Controls made faster responses to the self‐relevance of personal characteristics than to the accuracy of general facts, whereas response times did not differ between these conditions in PTSD. Controls also demonstrated greater MPFC (dorsal and ventral) and PCC response when considering the self‐relevance of personal characteristics in comparison with the accuracy of general facts. Individuals with PTSD demonstrated less MPFC response than did healthy controls for the contrast of self‐relevance of personal characteristics relative to general facts. Conclusions: These results implicate MPFC in SRP disturbances associated with PTSD. These findings are relevant to current proposals for including symptoms of negative self‐referential cognition and identity‐existential disturbance as diagnostically relevant to PTSD.     

Linear association between social anxiety symptoms and neural activations to angry faces: from subclinical to clinical levels

Social anxiety disorder (SAD), which is characterized by the fear of being rejected and negatively evaluated, involves altered brain activation during the processing of negative emotions in a social context. Although associated temperament traits, such as shyness or behavioral inhibition, have been studied, there is still insufficient knowledge to support the dimensional approach, which assumes a continuum from subclinical to clinical levels of social anxiety symptoms. This study used functional magnetic resonance imaging (fMRI) to examine the neural bases of individual differences in social anxiety. Our sample included participants with both healthy/subclinical as well as clinical levels of social anxiety. Forty-six participants with a wide range of social anxiety levels performed a gender decision task with emotional facial expressions during fMRI scanning. Activation in the left anterior insula and right lateral prefrontal cortex in response to angry faces was positively correlated with the level of social anxiety in a regression analysis. The results substantiate, with a dimensional approach, those obtained in previous studies that involved SAD patients or healthy and subclinical participants. It may help to refine further therapeutic strategies based on markers of social anxiety.     

The causal role of the bilateral ventrolateral prefrontal cortices on emotion regulation of social feedback

The ventrolateral prefrontal cortices (VLPFC) are crucial regions involved in voluntary emotion regulation. However, the lateralization of the VLPFC in downregulating negative emotions remains unclear; and whether the causal role of the VLPFC is generalizable to upregulating positive emotions is unexplored. This study used transcranial magnetic stimulation (TMS) to examine the causal relationship between the left/right VLPFC and social emotion reappraisal. One hundred and twenty participants were randomly assigned to either active (left and right VLPFC groups, n = 40/40) or sham (vertex, n = 40) TMS groups. Participants were instructed to passively receive social feedback or use reappraisal strategies to positively regulate their emotions. While the subjective emotional rating showed that the bilateral VLPFC facilitated the reappraisal success, the electrophysiological measure of the late positive potential (LPP) demonstrated a more critical role of the right VLPFC on social pain relief (decreased LPP amplitudes) and social reward magnification (enhanced LPP amplitudes). In addition, the influence of emotion regulation on social evaluation was found to be mediated by the memory of social feedback, indicating the importance of memory in social behavioral shaping. These findings suggest clinical protocols for the rehabilitation of emotion‐regulatory function in patients with affective and social disorders.     

Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuli

Prior neuroimaging studies support the hypothesis that anticipation, an important component of anxiety, may be mediated by activation within the insular and medial prefrontal cortices including the anterior cingulate cortex. However, there is an insufficient understanding of how affective anticipation differs across anxiety groups in emotional brain loci and networks. We examined 14 anxiety positive (AP) and 14 anxiety normative (AN) individuals completing an affective picture anticipation task during functional magnetic resonance imaging (fMRI). Brain activation was examined across groups for cued anticipation (to aversive or pleasant stimuli). Both groups showed greater activation in the bilateral anterior insula during cued differential anticipation (i.e., aversive vs. pleasant), and activation on the right was significantly higher in AP compared to AN subjects. Functional connectivity showed that the left anterior insula was involved in a similar network during pleasant anticipation in both groups. The left anterior insula during aversive and the right anterior insula during all anticipation conditions coactivated with a cortical network consisting of frontal and parietal lobes in the AP group to a greater degree. These results are consistent with the hypothesis that anxiety is related to greater anticipatory reactivity in the brain and that there may be functional asymmetries in the brain that interact with psychiatric traits.     

Neural correlates of observing pretend play in which one object is represented as another

Observers were scanned while they watched a video of an actor using an object. Three conditions were contrasted in which the same object was used: (i) normally (e.g. using a tennis racket to hit a ball), (ii) in an unusual way (e.g. using a tennis racket to strain spaghetti), (iii) in a pretend play (e.g. playing a tennis racket like a banjo). Observing real and unusual uses of objects activated areas previously seen in studies of tool use including areas associated with a mirror system for action. Observing pretend play activated additional areas previously associated with theory of mind tasks and listening to narrative, including medial prefrontal cortex, posterior superior temporal sulcus and temporal poles. After presentation of each video, observers were asked to name the object as used in the preceding action video (e.g. racket, sieve or banjo). Naming the pretend object elicited activity in medial prefrontal cortex. These results are consistent with proposals that pretend play is a form of communicative narrative, associated with the ability to mentalize. However, this leaves open the question as to whether pretence or mentalizing is the more basic process.     

Altered executive control network resting-state connectivity in social anxiety disorder

Objectives: Research into the neural basis of social anxiety disorder (SAD) suggests alterations in prefrontal networks, which may in turn disrupt regulation of the limbic system. Better understanding of the disturbed interface between these networks may improve current pathogenic models of this disorder. Methods: Applying group independent component analysis (ICA) to recordings of fMRI resting-state, connectivity in the executive control network was studied in 18 patients with SAD and 15 age- and sex-matched healthy controls. Results: Results revealed a dissociation within the left executive control network, with SAD patients showing decreased connectivity of the orbitofrontal gyrus and increased connectivity of the middle frontal gyrus compared to healthy controls. In a subsequent seed-based functional connectivity analysis, patients with SAD displayed increased connectivity between the left orbitofrontal gyrus and the left amygdala. Conclusions: Findings suggest that hypo-connectivity in the executive control network and hyper-connectivity between the orbitofrontal cortex and the amygdala may reflect a disturbance in the balance between top-down and bottom-up control processes, potentially contributing to the development of SAD.     

Socially excluded individuals fail to recruit medial prefrontal cortex for negative social scenes

Converging behavioral evidence suggests that people respond to experiences of social exclusion with both defensive and affiliative strategies, allowing them to avoid further distress while also encouraging re-establishment of positive social connections. However, there are unresolved questions regarding the cognitive mechanisms underlying people''s responses to social exclusion. Here, we sought to gain insight into these behavioral tendencies by using functional magnetic resonance imaging (fMRI) to examine the impact of social exclusion on neural responses to visual scenes that varied on dimensions of sociality and emotional valence. Compared to socially included participants, socially excluded participants failed to recruit dorsomedial prefrontal cortex (dmPFC), a brain region involved in mentalizing, for negative social scenes. Moreover, following social exclusion, dmPFC demonstrated a linear effect of valence, with greater activity to positive social scenes compared to negative social scenes. These results suggest that, following social exclusion, people display a preference for mentalizing about positive social information and tend to avoid negative aspects of their social world.     

Parsing neural mechanisms of social and physical risk identifications

Psychometric studies of risk perception have categorized personal risks into social and physical domains. To investigate whether and how the human brain differentiates social and physical risks, we scanned human adults using functional magnetic resonance imaging when they identified potential risks involved in social and physical behaviors. We found that the identification of risky behaviors in both domains induced increased activations in the anterior medial prefrontal cortex (MPFC, BA9/10)/ventral anterior cingulate (ACC) and posterior cingulate (PCC) relative to identification of safe behaviors. However, social risks induced stronger anterior MPFC activation whereas physical risks were associated with stronger ventral ACC activity. In addition, anterior MPFC activity was negatively correlated with the rating scores of the degree of social risk whereas PCC activity was positively correlated with the rating scores of the degree of physical risk. Relative to an autobiographical control task, the social risk identification task induced stronger sustained activity in the left supplementary motor area/dorsal ACC and increased transient activity in bilateral posterior insula. The physical risk identification task, however, resulted in stronger sustained activity in the right cuneus/precuneus and increased transient activation in bilateral amygdala. Our results indicate the existence of distinct neural mechanisms underlying social and physical risk identifications and provide neural bases for the psychometric categorization of risks into different domains.     

Neural correlates of verbal feedback processing: an fMRI study employing overt speech

Speakers use external auditory feedback to monitor their own speech. Feedback distortion has been found to increase activity in the superior temporal areas. Using fMRI, the present study investigates the neural correlates of processing verbal feedback without distortion. In a blocked design, the following conditions were presented: (1) overt picture-naming, (2) overt picture-naming while pink noise was presented to mask external feedback, (3) covert picture-naming, (4) listening to the picture names (previously recorded from participants' own voices), and (5) listening to pink noise. The results show that auditory feedback processing involves a network of different areas related to general performance monitoring and speech-motor control. These include the cingulate cortex and the bilateral insula, supplementary motor area, bilateral motor areas, cerebellum, thalamus and basal ganglia. Our findings suggest that the anterior cingulate cortex, which is often implicated in error-processing and conflict-monitoring, is also engaged in ongoing speech monitoring. Furthermore, in the superior temporal gyrus, we found a reduced response to speaking under normal feedback conditions. This finding is interpreted in the framework of a forward model according to which, during speech production, the sensory consequence of the speech-motor act is predicted to attenuate the sensitivity of the auditory cortex.     

Perception of arousal in social anxiety: effects of false feedback during a social interaction

Cognitive models suggest that during social interactions, socially anxious individuals direct their attention to internal cues of arousal and use this information to erroneously infer how they appear to others. High (N=36) and low (N=36) socially anxious adults had a conversation with a stooge, and were led to believe by false feedback that they were experiencing either an increase or decrease in arousal, or evaluating the comfort level of the feedback equipment. Compared to the other groups, participants who believed their arousal had increased, reported greater anxiety, poorer perceived performance, more physical cues of anxiety, and greater underestimation of their performance and overestimation of the visibility of their anxiety. The effects were not specific to participants with high social anxiety. Observers rated the behaviour of participants who believed that their arousal had decreased most favourably. The results have implications for the treatment of social phobia.     

Neural correlates of pre‐attentive processing of pattern deviance in professional musicians

Pre‐attentive registration of aberrations in predictable sound patterns is attributed to the temporal cortex. However, electrophysiology suggests that frontal areas become more important when deviance complexity increases. To play an instrument in an ensemble, professional musicians have to rely on the ability to detect even slight deviances from expected musical patterns and therefore have highly trained aural skills. Here, we aimed to identify the neural correlates of experience‐driven plasticity related to the processing of complex sound features. We used functional magnetic resonance imaging in combination with an event‐related oddball paradigm and compared brain activity in professional musicians and non‐musicians during pre‐attentive processing of melodic contour variations. The melodic pattern consisted of a sequence of five tones each lasting 50 ms interrupted by silent interstimulus intervals of 50 ms. Compared to non‐musicians, the professional musicians showed enhanced activity in the left middle and superior temporal gyri, the left inferior frontal gyrus and in the right ventromedial prefrontal cortex in response to pattern deviation. This differential brain activity pattern was correlated with behaviorally tested musical aptitude. Our results thus support an experience‐related role of the left temporal cortex in fast melodic contour processing and suggest involvement of the prefrontal cortex. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.