Disrupted regulation of social exclusion in alcohol-dependence: an FMRI study

Alcohol-dependence is associated with cognitive and biological alterations, and also with interpersonal impairments. Although overwhelming in clinical settings and involved in relapse, these social impairments have received little attention from researchers. Particularly, brain alterations related to social exclusion have not been explored in alcohol-dependence. Our primary purpose was to determine the neural correlates of social exclusion feelings in this population. In all, 44 participants (22 abstinent alcohol-dependent patients and 22 paired controls) played a virtual game ('cyberball') during fMRI recording. They were first included by other players, then excluded, and finally re-included. Brain areas involved in social exclusion were identified and the functional connectivity between these areas was explored using psycho-physiological interactions (PPI). Results showed that while both groups presented dorsal anterior cingulate cortex (dACC) activations during social exclusion, alcohol-dependent participants exhibited increased insula and reduced frontal activations (in ventrolateral prefrontal cortex) as compared with controls. Alcohol-dependence was also associated with persistent dACC and parahippocampal gyrus activations in re-inclusion. PPI analyses showed reduced frontocingulate connectivity during social exclusion in alcohol-dependence. Alcohol-dependence is thus linked with increased activation in areas eliciting social exclusion feelings (dACC-insula), and with impaired ability to inhibit these feelings (indexed by reduced frontal activations). Altered frontal regulation thus appears implied in the interpersonal alterations observed in alcohol-dependence, which seem reinforced by impaired frontocingulate connectivity. This first exploration of the neural correlates of interpersonal problems in alcohol-dependence could initiate the development of a social neuroscience of addictive states.     

Heightened neural sensitivity to social exclusion in boys with a history of low peer preference during primary school

Peer preference among classmates is a highly influential factor in children’s social development and not being preferred by peers has long-term consequences for children’s developmental outcomes. However, little is known about how a history of low peer preference during primary school is associated with neural responses to a new social exclusion experience in childhood. In this functional magnetic resonance imaging (fMRI) study, we examined self-reported social distress and neural responses to social exclusion using the Cyberball paradigm in primary school boys (M_age = 10.40 years) with a history of low (n = 27) versus high peer preference (n = 28). Boys were selected from a longitudinal classroom-based study in which children’s peer social preferences were assessed in three consecutive years prior to this study. Neuroimaging results showed that low peer preferred boys exhibited increased activation in the bilateral dorsolateral prefrontal cortex and right supramarginal gyrus during social exclusion as compared to high peer preferred boys. Increased neural activity was not accompanied by higher self-reported levels of social distress during social exclusion in low versus high peer preferred boys. Findings of this study may provide insight into the neural processes associated with real-life peer experiences in children attending primary school.     

Changes in neural mechanisms of cognitive control during the transition from late adolescence to young adulthood

The transition from late adolescence to young adulthood is marked by anatomical maturation of various brain regions. In parallel, defining life changes take place, such as entrance into college. Up till now research has not focused on functional brain differences during this particular developmental stage. The current cross-sectional fMRI study investigates age differences in cognitive control by comparing late adolescents, 18–19 years old, with young adults, 23–25 years old. Seventy-four male and female medical students carried out a combined cognitive and emotional Stroop task. Overall, lateral frontoparietal and medial parietal activation was observed during cognitive interference resolution. Young adults showed stronger activation in the dorsomedial prefrontal cortex, left inferior frontal gyrus, left middle temporal gyrus and middle cingulate, compared to late adolescents. During emotional interference resolution, the left precentral and postcentral gyrus were involved across age and sex. The dorsomedial prefrontal cortex and precuneus were activated more in young adults than in late adolescents. No sex-related differences were found in this homogeneous sample. The results suggest that the neural bases of cognitive control continue to change between late adolescence and young adulthood.     

Social appraisal in chronic psychosis: Role of medial frontal and occipital networks

Persons with schizophrenia often appraise other individuals as threatening or persecutory. To evaluate social appraisal in schizophrenia, we probed brain networks with a task in which subjects judged whether or not they liked face stimuli with emotional expressions. We predicted that appraising negative expressions would engage patients, more than controls, and negative faces would be related to higher levels of negative affect and produce increased activity in the medial frontal cortex, an area involved in social appraisal. Twenty-one stable outpatients with chronic non-affective psychosis (16 schizophrenic, 5 schizoaffective) and 21 healthy subjects underwent functional magnetic resonance imaging. Compared with the control subjects, patients were slower to respond, but particularly slow when they judged negatively-valenced faces, a slowness correlated with negative affect in the psychosis patients. Appraisal activated the medial prefrontal cortex (mPFC) across all face valences. For negative expressions, patients exhibited greater activation of the dorsal anterior cingulate cortex (dACC). A psychophysiological interaction analysis of the dACC revealed co-modulation of the mPFC in controls, significantly less in patients, and a trend for co-modulation of occipital cortex in the patients. Activity in occipital cortex correlated with poor social adjustment and impaired social cognition, and co-modulation of the occipital gyrus by the dACC was correlated with poorer social cognition. The findings link appraisal of negative affect with aberrant activation of the medial frontal cortex, while early sensory processing of this social cognitive task was linked with poor social function, reflecting either top-down or bottom-up influences.     

How the brain reacts to social stress (exclusion) – A scoping review

ObjectivesThe Cyberball paradigm is often used to study social stress by exclusion/rejection. We aimed to review the existing neuroimaging literatures in order to provide an overview of the neurophysiological mechanisms of social exclusion.MethodLiterature search was conducted to identify neurophysiological studies that investigated effects of social exclusion on neural activity using the Cyberball game and the relevant influential factors on these effects.ResultsIn total, 42 studies using different neuroimaging methods were considered. Regions of the insula, anterior cingulate cortex, temporal and prefrontal cortex were activated to social exclusion. These neural activities were pronounced at latencies ranging from 200 to 400 ms, and between 400 and 900 ms. Influential factors were identified and categorized as intrinsic and extrinsic factors.ConclusionAn integrated framework describing neural activities under social exclusion in terms of both, temporal and spatial processes is provided. Furthermore, the summary of influential intrinsic and extrinsic factors may help us to understand the diversity of the processes and may guide clinical therapy of stress related disorders.     

Enhanced neural responses to rule violation in children with autism: a comparison to social exclusion

The present study aimed to explore the neural correlates of two characteristic deficits in autism spectrum disorders (ASD); social impairment and restricted, repetitive behavior patterns. To this end, we used comparable experiences of social exclusion and rule violation to probe potentially atypical neural networks in ASD. In children and adolescents with and without ASD, we used the interactive ball-toss game (Cyberball) to elicit social exclusion and a comparable game (Cybershape) to elicit a non-exclusive rule violation. Using functional magnetic resonance imaging (fMRI), we identified group differences in brain responses to social exclusion and rule violation. Though both groups reported equal distress following exclusion, the right insula and ventral anterior cingulate cortex were hypoactive during exclusion in children with ASD. In rule violation, right insula and dorsal prefrontal cortex were hyperactive in ASD. Right insula showed a dissociation in activation; it was hypoactive to social exclusion and hyperactive to rule violation in the ASD group. Further probed, different regions of right insula were modulated in each game, highlighting differences in regional specificity for which subsequent analyses revealed differences in patterns of functional connectivity. These results demonstrate neurobiological differences in processing social exclusion and rule violation in children with ASD.     

Neural processing of social rejection: the role of schizotypal personality traits

A fear of being rejected can cause perceptions of more insecurity and stress in close relationships. Healthy individuals activate the dorsal anterior cingulate cortex (dACC) when experiencing social rejection, while those who are vulnerable to depression deactivate the dACC presumably to downregulate salience of rejection cues and minimize distress. Schizotypal individuals, characterized by unusual perceptual experiences and/or odd beliefs, are more rejection sensitive than normal. We tested the hypothesis, for the first time, that individuals with high schizotypy also have an altered dACC response to rejection stimuli. Twenty-six healthy individuals, 14 with low schizotypy (LS) and 12 with high schizotypy (HS), viewed depictions of rejection and acceptance and neutral scenes while undergoing functional MRI. Activation maps in LS and HS groups during each image type were compared using SPM5, and their relation to participant mood and subjective ratings of the images was examined. During rejection relative to neutral scenes, LS activated and HS deactivated the bilateral dACC, right superior frontal gyrus, and left ventral prefrontal cortex. Across both groups, a temporo-occipito-parieto-cerebellar network was active during rejection, and a left fronto-parietal network during acceptance, relative to neutral scenes, and the bilateral lingual gyrus during rejection relative to acceptance scenes. Our finding of dACC-dorso-ventral PFC activation in LS, but deactivation in HS individuals when perceiving social rejection scenes suggests that HS individuals attach less salience to and distance themselves from such stimuli. This may enable them to cope with their higher-than-normal sensitivity to rejection.     

Acting on social exclusion: neural correlates of punishment and forgiveness of excluders

This functional magnetic resonance imaging study examined the neural correlates of punishment and forgiveness of initiators of social exclusion (i.e. ‘excluders’). Participants divided money in a modified Dictator Game between themselves and people who previously either included or excluded them during a virtual ball-tossing game (Cyberball). Participants selectively punished the excluders by decreasing their outcomes; even when this required participants to give up monetary rewards. Punishment of excluders was associated with increased activation in the pre-supplementary motor area (pre-SMA) and bilateral anterior insula. Costly punishment was accompanied by higher activity in the pre-SMA compared with punishment that resulted in gains or was non-costly. Refraining from punishment (i.e. forgiveness) was associated with self-reported perspective-taking and increased activation in the bilateral temporoparietal junction, dorsomedial prefrontal cortex, dorsal anterior cingulate cortex, and ventrolateral and dorsolateral prefrontal cortex. These findings show that social exclusion can result in punishment as well as forgiveness of excluders and that separable neural networks implicated in social cognition and cognitive control are recruited when people choose either to punish or to forgive those who excluded them.     

Narcissists’ social pain seen only in the brain

Narcissism is a complex phenomenon, involving a level of defensive self-enhancement. Narcissists have avoidant attachment styles, maintain distance in relationships and claim not to need others. However, they are especially sensitive to others’ evaluations, needing positive reflected appraisals to maintain their inflated self-views, and showing extreme responses (e.g. aggression) when rejected. The current study tested the hypothesis that narcissists also show hypersensitivity in brain systems associated with distress during exclusion. We measured individual differences in narcissism (Narcissistic Personality Inventory) and monitored neural responses to social exclusion (Cyberball). Narcissism was significantly associated with activity in an a priori anatomically defined social pain network (anterior insula, dorsal anterior cingulate cortex and subgenual anterior cingulate cortex) during social exclusion. Results suggest hypersensitivity to exclusion in narcissists may be a function of hypersensitivity in brain systems associated with distress, and suggests a potential pathway that connects narcissism to negative consequences for longer-term physical and mental health—findings not apparent with self-report alone.     

Alexithymia is associated with blunted anterior cingulate response to social rejection: implications for daily rejection

Social rejection elicits distress through the brain’s alarm system, the dorsal anterior cingulate cortex (dACC). The distress of rejection facilitates subsequent inclusion. As a result, traits that blunt this dACC response to social rejection might then threaten group membership, leading to further subsequent rejection. Alexithymia, the inability to identify and describe affective states, is associated with social impairment and reduced dACC activity under conditions of negative affect. Thus, we expected that alexithymia would relate to less dACC activation during rejection and that this blunted response would explain an association between alexithymia and greater rejection in everyday life. Using functional magnetic resonance imaging and daily diaries, we found that subclinical individual differences in the core feature of alexithymia, difficulty identifying affect, was associated with a blunted dACC response to social rejection. Deficits in affect identification were also associated with greater daily rejection and that this effect was mediated and suppressed by dACC activation to rejection. Our findings emphasize the crucial role of the dACC in response to social rejection and extend the literature on alexithymia’s ability to dampen neural responses and contribute to poor social functioning. The suppressing role of the dACC suggests future directions for clinical interventions on those with affective disorders.     

An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders

Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives.     

Neural correlates of social exclusion during adolescence: understanding the distress of peer rejection

Developmental research has demonstrated the harmful effects of peer rejection during adolescence; however, the neural mechanisms responsible for this salience remain unexplored. In this study, 23 adolescents were excluded during a ball-tossing game in which they believed they were playing with two other adolescents during an fMRI scan; in reality, participants played with a preset computer program. Afterwards, participants reported their exclusion-related distress and rejection sensitivity, and parents reported participants’ interpersonal competence. Similar to findings in adults, during social exclusion adolescents displayed insular activity that was positively related to self-reported distress, and right ventrolateral prefrontal activity that was negatively related to self-reported distress. Findings unique to adolescents indicated that activity in the subgenual anterior cingulate cortex (subACC) related to greater distress, and that activity in the ventral striatum related to less distress and appeared to play a role in regulating activity in the subACC and other regions involved in emotional distress. Finally, adolescents with higher rejection sensitivity and interpersonal competence scores displayed greater neural evidence of emotional distress, and adolescents with higher interpersonal competence scores also displayed greater neural evidence of regulation, perhaps suggesting that adolescents who are vigilant regarding peer acceptance may be most sensitive to rejection experiences.     

An fMRI study of attentional control in the context of emotional distracters in euthymic adults with bipolar disorder

Inability to modulate attention away from emotional stimuli may be a key component of dysregulated emotion in bipolar disorder (BD). Previous studies of BD indicate abnormalities in neural circuitry underlying attentional control, yet few studies examined attentional control in the context of emotional distracters. We compared activity and connectivity in neural circuitry supporting attentional control and emotion processing among 22 individuals with BD type 1, currently remitted and euthymic, and 19 healthy controls. Participants performed an emotional n-back paradigm, comprising high and low attentional demand conditions, each with either emotional (happy, fearful), neutral or no face flanker distracters. During the high attentional control demand conditions without emotional distracters, BD individuals showed reduced activity relative to controls in dorsolateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and inferior parietal cortex. During the high attentional control demand conditions with fearful-face distracters, BD individuals showed greater activity than controls in these regions and amygdala and striatum. Relative to controls, BD individuals also showed abnormal patterns of effective connectivity between dACC and amygdala during high attentional control demand with emotional face distracters. Inter-episode bipolar disorder is characterized by abnormal recruitment of attentional control neural circuitry, especially in the context of emotionally distracting information.     

Brain responses to success and failure: Direct recordings from human cerebral cortex

Evaluating the outcome of our own actions is a fundamental process by which we adapt our behavior in our interaction with the external world. fMRI and electrophysiological studies in monkeys have found feedback‐specific responses in several brain regions, unveiling facets of a large‐scale network predominantly distributed in the frontal lobes. However, a consensus has yet to be reached regarding the exact contribution of each region. The present study benefited from intracerebral EEG recordings in epileptic patients to record directly the neural activity in each of those frontal structures in response to positive and negative feedback. Both types of feedback induced a sequence of high‐frequency responses (>40 Hz) in a widespread network involving medial frontal cortex, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and insular cortex. The pre‐supplementary motor area (pre‐SMA), DLPFC, and lateral OFC showed higher activation in response to negative feedback, while medial OFC and dorsal anterior cingulate cortex (dACC) were more responsive to positive feedback. Responses in the medial prefrontal cortex (pre‐SMA and dACC) were sustained (lasting more than 1,000 ms), while responses in the DLPFC, insula, and the OFC were short lasting (less than 800 ms). Taken together, our findings show that evaluating the outcome of our actions triggers γ‐range activity modulations in several frontal and insular regions. Moreover, we found that the timing and amplitude of those γ‐band responses reveal fine‐scale dissociations between the neural dynamics of positive versus negative feedback processing. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Ventromedial prefrontal activity correlates with depressed mood in adolescent children

In adults, the medial prefrontal cortex and anterior cingulate gyrus are preferentially activated during emotion-related processes, including normal sadness and pathological depression. It is not clear, however, whether similar regional activity is also characteristic of depressed mood during adolescence. We correlated whole brain activity during a fear face perception task with scores on the Beck Depression Inventory in 16 adolescents undergoing functional magnetic resonance imaging. After controlling for age, depressed mood scores correlated with increased activity within the ventromedial prefrontal cortex and rostral anterior cingulate gyrus, consistent with findings previously reported for sadness and depression in adults, suggesting that the neural substrates of depressed mood are established early in life and remain relatively consistent across development into adulthood.     

The enduring effects of an adolescent social stressor on synaptic density, part II: Poststress reversal of synaptic loss in the cortex by adinazolam and MK-801

Experience programs synaptic development to match the needs of the environment. This process depends on the nature and timing of the experience. Exposure to stress during adolescence selectively reduces synaptic density in the prefrontal cortex (a later maturing region), while sparing hippocampal synapses (an earlier maturing region). To determine whether the anatomical effects of an adolescent social stressor in rats endures into adulthood and are reversible, male subjects were isolation or group housed between days 30 and 35 and then treated with vehicle, adinazolam, MK-801, or tianeptine between days 40 and 55. At day 60, immunohistochemistry revealed a 13.5% +/- 5.3% reduction in synaptophysin in the infralimbic cortex and cingulate gyrus in isolation-housed subjects. MK-801 and adinazolam restored cortical synaptic density to within 2% of group-housed values, suggesting that the synaptic loss induced by stress during adolescence is modulated through reduced glutamatergic activity directly by NMDA antagonism or indirectly by enhancing GABAergic activity. Tianeptine did not modulate adolescent stress effects in the prefrontal cortex. None of these drugs increased cortical synaptophysin in group-housed controls. Increased synaptophysin was observed in the group-housed condition in the hippocampus, striatum, and nucleus accumbens following drug exposure. Although stress did not decrease synaptic density in these regions, drug exposure failed to increase synaptic density when compared with the controls. Taken together, stress-induced changes in cortical, but not hippocampal, synaptic density initiated during adolescence endure into adulthood. These cortical changes can be reversed through a reduction of glutamatergic activity, but not serotonin augmentation.     

Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning.     

The roles of internal locus of control and neighborhood affluence in predicting the continuity of negative self-feelings from adolescence to young adulthood

The present study examines the moderating effect of locus of control on the continuity in negative self-feelings from adolescence to young adulthood. We use longitudinal data of 1296 respondents from adolescence (11–13 years old) to young adulthood (20–24 years old). Using interaction effects in linear regression with robust standard errors we find that those with an internal locus of control experience stronger continuity in negative self-feelings from adolescence to young adulthood. Furthermore, based on both self-reported and objective measures of neighborhood status, internal locus of control increases the continuity in negative self-feelings in the transition to adulthood in disadvantaged neighborhoods but not in advantaged neighborhoods. Thus, locus of control acts as a maladaptive mechanism in less affluent neighborhoods. This result demonstrates the importance of considering both the individual social psychological and the contextual sociological perspectives when investigating the role of internal locus of control on the perpetuation of negative self-feelings.     

Neurodevelopmental changes across adolescence in viewing and labeling dynamic peer emotions

Adolescence is a sensitive period of social-affective development, characterized by biological, neurological, and social changes. The field currently conceptualizes these changes in terms of an imbalance between systems supporting reactivity and regulation, specifically nonlinear changes in reactivity networks and linear changes in regulatory networks. Previous research suggests that the labeling or reappraisal of emotion increases activity in lateral prefrontal cortex (LPFC), and decreases activity in amygdala relative to passive viewing of affective stimuli. However, past work in this area has relied heavily on paradigms using static, adult faces, as well as explicit regulation. In the current study, we assessed cross-sectional trends in neural responses to viewing and labeling dynamic peer emotional expressions in adolescent girls 10–23 years old. Our dynamic adolescent stimuli set reliably and robustly recruited key brain regions involved in emotion reactivity (medial orbital frontal cortex/ventral medial prefrontal cortex; MOFC/vMPFC, bilateral amygdala) and regulation (bilateral dorsal and ventral LPFC). However, contrary to the age-trends predicted by the dominant models in studies of risk/reward, the LPFC showed a nonlinear age trend across adolescence to labeling dynamic peer faces, whereas the MOFC/vMPFC showed a linear decrease with age to viewing dynamic peer faces. There were no significant age trends observed in the amygdala.     

Neural correlates of using distancing to regulate emotional responses to social situations

Cognitive reappraisal is a commonly used and highly adaptive strategy for emotion regulation that has been studied in healthy volunteers. Most studies to date have focused on forms of reappraisal that involve reinterpreting the meaning of stimuli and have intermixed social and non-social emotional stimuli. Here we examined the neural correlates of the regulation of negative emotion elicited by social situations using a less studied form of reappraisal known as distancing. Whole brain fMRI data were obtained as participants viewed aversive and neutral social scenes with instructions to either simply look at and respond naturally to the images or to downregulate their emotional responses by distancing. Three key findings were obtained accompanied with the reduced aversive response behaviorally. First, across both instruction types, aversive social images activated the amygdala. Second, across both image types, distancing activated the precuneus and posterior cingulate cortex (PCC), intraparietal sulci (IPS), and middle/superior temporal gyrus (M/STG). Third, when distancing one's self from aversive images, activity increased in dorsal anterior cingulate (dACC), medial prefrontal cortex (mPFC), lateral prefrontal cortex, precuneus and PCC, IPS, and M/STG, meanwhile, and decreased in the amygdala. These findings demonstrate that distancing from aversive social cues modulates amygdala activity via engagement of networks implicated in social perception, perspective-taking, and attentional allocation.