Individual differences in resilience to stress are associated with affective flexibility.

Cognitive flexibility is frequently linked to resilience because of its important contribution to stress regulation. In this context, particularly affective flexibility, defined as the ability to flexibly attend and disengage from affective information, may play a significant role. In the present study, the relationship of cognitive and affective flexibility and resilience was examined in 100 healthy participants. Resilience was measured with three self-report questionnaires, two defining resilience as a personality trait and one focusing on resilience as an outcome in the sense of stress coping abilities. Cognitive and affective flexibility were assessed in two experimental task switching paradigms with non-affective and affective materials and tasks, respectively. The cognitive flexibility paradigm additionally included measures of cognitive stability and spontaneous switching in ambiguous situations. In the affective flexibility paradigm, we explicitly considered the affective valence of the stimuli. Response time switch costs in the affective flexibility paradigm were significantly correlated to all three measures of resilience. The correlation was not specific for particular valences of the stimuli before or during switching. For cognitive (non-affective) flexibility, a significant correlation of response time switch costs was found with only one resilience measure. A regression analysis including both affective and cognitive switch costs as predictors of resilience indicated that only affective, but not cognitive switch costs, explained unique variance components. Furthermore, the experimental measures of cognitive stability and the rate of spontaneous switching in ambiguous situations did not correlate with resilience scores. These findings suggest that specifically the efficiency of flexibly switching between affective and non-affective information is related to resilience.

Association of stress-related neural activity and baseline interleukin-6 plasma levels in healthy adults.

Several studies suggest a link between acute changes in inflammatory parameters due to an endotoxin or (psychological) stressor and the brain's stress response. The extent to which basal circulating levels of inflammatory markers are associated with the brain's stress response has been hardly investigated so far. In the present study, baseline plasma levels of the cytokine interleukin (IL)-6 were obtained and linked to neural markers of psychosocial stress using a modified version of the Montreal Imaging Stress Task in a sample of N = 65 healthy subjects (N = 39 female). Of three a-priori defined regions of interest - the amygdala, anterior insula, and anterior cingulate cortex - baseline IL-6 was significantly and negatively associated with stress-related neural activation in the right amygdala and left anterior insula. Our results suggest that baseline cytokines might be related to differences in the neural stress response and that this relationship could be inverse to that previously reported for induced acute changes in inflammation markers.

Peripheral Oxytocin Predicts Higher-Level Social Cognition in Men Regardless of Empathy Quotient.

INTRODUCTION: Pharmaceutical oxytocin (OT) administration is being tested as a novel treatment for social deficits in various psychiatric populations. However, little is known about how naturally occurring variation in peripheral OT relates to differences in social cognition. This study investigates whether healthy individuals with very high or very low levels of empathy differ in endogenous OT and whether OT plasma levels can predict performance in a mentalizing task. METHODS: 40 healthy men were included based upon their score above the 85th or below the 15th percentile of the empathy quotient inventory 1. Participants' abilities to interpret social information was assessed via the Social Detection Task 2. Plasma OT levels were analyzed using enzyme immunoassay. RESULTS: OT plasma levels predicted mentalizing performance for more ambiguous social scenes (i. e., difficult items) for all participants. We found no group differences in OT plasma levels between subjects with high and low empathy. DISCUSSION: These findings confirm a link between peripheral OT and the ability to read subtle nonverbal social cues in healthy individuals, which is independent of self-reported empathy.

Acute and sustained effects of methylphenidate on cognition and presynaptic dopamine metabolism: an [18F]FDOPA PET study.

Methylphenidate (MPH) inhibits the reuptake of dopamine and noradrenaline. PET studies with MPH challenge show increased competition at postsynaptic D2/3-receptors, thus indirectly revealing presynaptic dopamine release. We used [(18)F]fluorodopamine ([(18)F]FDOPA)-PET in conjunction with the inlet-outlet model (IOM) of Kumakura et al. (2007) to investigate acute and long-term changes in dopamine synthesis capacity and turnover in nigrostriatal fibers of healthy subjects with MPH challenge. Twenty healthy human females underwent two dynamic [(18)F]FDOPA PET scans (124 min; slow bolus-injection; arterial blood sampling), with one scan in untreated baseline condition and the other after MPH administration (0.5 mg/kg, p.o.), in randomized order. Subjects underwent cognitive testing at each PET session. Time activity curves were obtained for ventral putamen and caudate and were analyzed according to the IOM to obtain the regional net-uptake of [(18)F]FDOPA (K; dopamine synthesis capacity) as well as the [(18)F]fluorodopamine washout rate (kloss, index of dopamine turnover). MPH substantially decreased kloss in putamen (-22%; p = 0.003). In the reversed treatment order group (MPH/no drug), K was increased by 18% at no drug follow-up. The magnitude of K at the no drug baseline correlated with cognitive parameters. Furthermore, individual kloss changes correlated with altered cognitive performance under MPH. [(18)F]FDOPA PET in combination with the IOM detects an MPH-evoked decrease in striatal dopamine turnover, in accordance with the known acute pharmacodynamics of MPH. Furthermore, the scan-ordering effect on K suggested that a single MPH challenge persistently increased striatal dopamine synthesis capacity. Attenuation of dopamine turnover by MPH is linked to enhanced cognitive performance in healthy females.

Evidence from pupillometry and fMRI indicates reduced neural response during vicarious social pain but not physical pain in autism.

Autism spectrum disorder (ASD) is characterized by substantial social deficits. The notion that dysfunctions in neural circuits involved in sharing another's affect explain these deficits is appealing, but has received only modest experimental support. Here we evaluated a complex paradigm on the vicarious social pain of embarrassment to probe social deficits in ASD as to whether it is more potent than paradigms currently in use. To do so we acquired pupillometry and fMRI in young adults with ASD and matched healthy controls. During a simple vicarious physical pain task no differences emerged between groups in behavior, pupillometry, and neural activation of the anterior insula (AIC) and anterior cingulate cortex (ACC). In contrast, processing complex vicarious social pain yielded reduced responses in ASD on all physiological measures of sharing another's affect. The reduced activity within the AIC was thereby explained by the severity of autistic symptoms in the social and affective domain. Additionally, behavioral responses lacked correspondence with the anterior cingulate and anterior insula cortex activity found in controls. Instead, behavioral responses in ASD were associated with hippocampal activity. The observed dissociation echoes the clinical observations that deficits in ASD are most pronounced in complex social situations and simple tasks may not probe the dysfunctions in neural pathways involved in sharing affect. Our results are highly relevant because individuals with ASD may have preserved abilities to share another's physical pain but still have problems with the vicarious representation of more complex emotions that matter in life.

The impact of dopamine on aggression: an [18F]-FDOPA PET Study in healthy males.

Cerebral dopamine (DA) transmission is thought to be an important modulator for the development and occurrence of aggressive behavior. However, the link between aggression and DA transmission in humans has not been investigated using molecular imaging and standardized behavioral tasks. We investigated aggression as a function of DA transmission in a group of (N = 21) healthy male volunteers undergoing 6-[18F]-fluoro-L-DOPA (FDOPA)-positron emission tomography (PET) and a modified version of the Point Subtraction Aggression Paradigm (PSAP). This task measures aggressive behavior during a monetary reward-related paradigm, where a putative adversary habitually tries to cheat. The participant can react in three ways (i.e., money substraction of the putative opponent [aggressive punishment], pressing a defense button, or continuing his money-making behavior). FDOPA-PET was analyzed using a steady-state model yielding estimates of the DA-synthesis capacity (K), the turnover of tracer DA formed in living brain (kloss), and the tracer distribution volume (Vd), which is an index of DA storage capacity. Significant negative correlations between PSAP aggressive responses and the DA-synthesis capacity were present in several regions, most prominently in the midbrain (r = -0.640; p = 0.002). Lower degrees of aggressive responses were associated with higher DA storage capacity in the striatum and midbrain. Additionally, there was a significant positive correlation between the investment into monetary incentive responses on the PSAP and DA-synthesis capacity, notably in the midbrain (r = +0.618, p = 0.003). The results suggest that individuals with low DA transmission capacity are more vulnerable to reactive/impulsive aggression in response to provocation.

Neural activation during anticipation of opposite-sex and same-sex faces in heterosexual men and women.

Psychobiological accounts of face processing predict that greater salience is attributed to faces matching a viewer's sexual preference than to faces that do not. However, behaviorally, this effect could only be demonstrated in tasks assessing reward 'wanting' (e.g. work-per-view-tasks) but not in tasks assessing 'liking' (e.g. facial attractiveness ratings), and has been found to be more pronounced in heterosexual men than women, especially with regard to very attractive faces. Here, we addressed the question if sex differences at the level of 'wanting' persist if participants are uninformed about the attractiveness of an anticipated male or female face. Seventeen heterosexual men and 13 heterosexual women (all single) participated in a social incentive delay task (SID). Participants were required to react on simple graphical cues in order to view a smiling face. Cues provided a priori information on the level of smile intensity (low/medium/high) as well as sex of the face (male/ female). A significant interaction of sex-of-face and sex-of-participant was observed in a priori defined regions of interest in the brain reward system (including ventral tegmental area, nucleus accumbens and ventromedial prefrontal cortex), reflecting enhanced activation to cues signaling opposite-sex faces relative to same-sex faces in both, men and women. Women additionally recruited the temporo-parietal junction (TPJ) during processing of opposite- vs. same-sex cues, suggesting stronger incorporation of social cognition processes in women than men. The findings speak against a general male bias for opposite-sex faces. Instead they provide preliminary evidence that men and women recruit different brain circuits during reward value assessment of facial stimuli.

Lack of association of a functional catechol-O-methyltransferase gene polymorphism with risk of tobacco smoking: results from a multicenter case-control study.

BACKGROUND: The catechol-O-methyltransferase (COMT) modulates dopaminergic neurotransmission in the prefrontal cortex as well as in the mesolimbic reward system. Since the reward system mediates addictive behavior, the COMT gene is a strong candidate gene regarding the pathophysiology of tobacco dependence and smoking behavior. Because of rather conflicting results in previous studies, the purpose of the present study was to test for association between a functional genetic variant in the COMT gene (single nucleotide polymorphism [SNP] rs4680) and tobacco smoking behavior. METHODS: In a population-based case-control multicenter study designed for tobacco addiction research, a total of 551 current smokers of European ancestry and 548 age-matched healthy volunteers (never-smokers) were genotyped for SNP rs4680 and extensively characterized concerning their smoking behavior. RESULTS: We found no association between smoking status and SNP rs4680 genotype nor did we find a significant association to the degree of tobacco dependence. CONCLUSIONS: Although prefrontal cortical and ventral striatal activity are highly relevant for addictive behavior, and under partial control of COMT rs4680 genotype, no association between COMT and smoking behavior was observed. Other genetic variants may account for the high heritability of behavioral smoking phenotypes.

Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women.

OBJECTIVE: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. METHOD: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). RESULTS: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. CONCLUSION: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity.

Neural correlates of affective task switching and asymmetric affective task switching costs.

The control of emotions is of potentially great clinical relevance. Accordingly, there has been increasing interest in understanding the cognitive mechanisms underlying the ability to switch efficiently between the processing of affective and non-affective information. Reports of asymmetrically increased switch costs when switching toward the more salient emotion task indicate specific demands in the flexible control of emotion. The neural mechanisms underlying affective task switching, however, are so far not fully understood. Using functional Magnetic Resonance Imaging (MRI) (N = 57), we observed that affective task switching was accompanied by increased activity in domain-general fronto-parietal control systems. Blood-oxygen-level-dependent (BOLD) activity in the posterior medial frontal and anterolateral prefrontal cortex was directly related to affective switch costs, indicating that these regions play a particular role in individual differences in (affective) task-switching ability. Asymmetric switch costs were associated with increased activity in the right inferior frontal and dorsal anterior medial prefrontal cortex, two brain regions critical for response inhibition. This suggests that asymmetric switch costs might-to a great extent-reflect higher demands on inhibitory control of the dominant emotion task. These results contribute to a refined understanding of brain systems for the flexible control of emotions and thereby identify valuable target systems for future clinical research.

Your smile won't affect me: Association between childhood maternal antipathy and adult neural reward function in a transdiagnostic sample.

Aberrant activation in the ventral striatum (VS) during reward anticipation may be a key mechanism linking adverse childhood experiences (ACE) to transdiagnostic psychopathology. This study aimed to elucidate whether retrospectively reported ACE, specifically maternal antipathy, relate to monetary and social reward anticipation in a transdiagnostic adult sample. A cross-sectional neuroimaging study was conducted in 118 participants with varying levels of ACE, including 25 participants with posttraumatic stress disorder (PTSD), 32 with major depressive disorder (MDD), 29 with somatic symptom disorder (SSD), and 32 healthy volunteers (HVs). Participants underwent functional magnetic resonance imaging during a monetary and social incentive delay task, and completed a self-report measure of ACE, including maternal antipathy. Neural correlates of monetary and social reward anticipation and their association with ACE, particularly maternal antipathy, were analyzed. Participants showed elevated activation in brain regions underlying reward processing, including the VS, only while anticipating social, but not monetary rewards. Participants reporting higher levels of maternal antipathy exhibited reduced activation in the brain reward network, including the VS, only during social, but not monetary reward anticipation. Group affiliation moderated the association between maternal antipathy and VS activation to social reward anticipation, with significant associations found in participants with PTSD and HVs, but not in those with MDD and SSD. Results were not associated with general psychopathology or psychotropic medication use. Childhood maternal antipathy may confer risk for aberrant social reward anticipation in adulthood, and may thus be considered in interventions targeting reward expectations from social interactions.

Assessment of Reward-Related Brain Function After a Single Dose of Oxytocin in Autism: A Randomized Controlled Trial.

Background: Autism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, which have been related to atypical neural processing of rewards, especially in the social domain. As intranasal oxytocin has been shown to modulate activation of the brain's reward circuit, oxytocin might ameliorate the processing of social rewards in ASD and thus improve social difficulties. Methods: In this randomized, double-blind, placebo-controlled, crossover functional magnetic resonance imaging study, we examined effects of a 24-IU dose of intranasal oxytocin on reward-related brain function in 37 men with ASD without intellectual impairment and 37 age- and IQ-matched control participants. Participants performed an incentive delay task that allows the investigation of neural activity associated with the anticipation and receipt of monetary and social rewards. Results: Nonsignificant tests suggested that oxytocin did not influence neural processes related to the anticipation of social or monetary rewards in either group. Complementary Bayesian analyses indicated moderate evidence for a null model, relative to an alternative model. Our results were inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. There were no significant differences in reward-related brain function between the two groups under placebo. Conclusions: Our results do not support the hypothesis that intranasal oxytocin generally enhances activation of reward-related neural circuits in men with and without ASD.

Perceived Risk of Infection Linked to Changes in Comfort in Social Situations From Before to During the COVID-19 Pandemic.

Background: Social lives have significantly changed since social distancing measures have been implemented to prevent the spread of the coronavirus disease 2019 (COVID-19). This study aimed to investigate how our appraisal of social situations changed during the pandemic. Methods: In two online surveys, conducted in October 2019 and April 2020, 58 participants rated their personal level of comfort for sketches depicting social situations. Situations were separately categorized according to the risk of a possible COVID-19 infection and changes in ratings were analyzed by using a repeated measures ANOVA. Moreover, potential influencing factors on the change in ratings such as perceived infection risk and social factors like regular frequency and liking of social interactions were examined. Results: There was a significant interaction (p < 0.001) between time of measurement and risk category. Comfort ratings of depicted situations with low and medium infection risk were higher during the second compared to the first survey period. Ratings of high-risk situations did not change significantly, although there was a tendency toward lower ratings during the pandemic. Multiple regression analyses showed that perceived probability of short-term infection could explain variance in the change of ratings of social situations with low- and medium risk, but not perceived probability of long-term infection or social factors. Conclusion: The results suggest that the change of participant's appraisal of the social situations during the COVID-19 pandemic relates to perceived infection risk. Both, the risk associated with the specific scenario as well as the general belief of short-term infection risk were associated with change. This change predominantly manifested in greater thought of comfort during low and medium risk situations, which might give a sense of safety during the pandemic. The finding that high-risk social situations were not rated as uncomfortable as expected must be considered with regard to the young sample and may not be generalizable to other individuals. Further research is necessary to evaluate long-term effects on social interactions caused by global pandemics such as the COVID-19 pandemic.

Self-beneficial belief updating as a coping mechanism for stress-induced negative affect.

Being confronted with social-evaluative stress elicits a physiological and a psychological stress response. This calls for regulatory processes to manage negative affect and maintain self-related optimistic beliefs. The aim of the current study was to investigate the affect-regulating potential of self-related updating of ability beliefs after exposure to social-evaluative stress, in comparison to non-social physical stress or no stress. We assessed self-related belief updating using trial-by-trial performance feedback and described the updating behavior in a mechanistic way using computational modeling. We found that social-evaluative stress was accompanied by an increase in cortisol and negative affect which was related to a positive shift in self-related belief updating. This self-beneficial belief updating, which was absent after physical stress or control, was associated with a better recovery from stress-induced negative affect. This indicates that enhanced integration of positive self-related feedback can act as a coping strategy to deal with social-evaluative stress.

Dissociation of neural networks for anticipation and consumption of monetary and social rewards.

Human behaviour is generally guided by the anticipation of potential outcomes that are considered to be rewarding. Reward processing can thus be dissected into a phase of reward anticipation and a phase of reward consumption. A number of brain structures have been suggested to be involved in reward processing. However, it is unclear whether anticipation and consumption are mediated by the same or different neural networks. We examined the neural basis of these processes using functional magnetic resonance imaging (fMRI) in an incentive delay task offering either money or social approval. In both conditions participants (N=28) were given a cue indicating potential reward. In order to receive reward a target button had to be pushed within a certain time window (adapted for individual reaction time). Cues triggering either monetary or social reward anticipation were presented sessionwise. Imaging was performed on a 1.5-Tesla Philips scanner in an event-related design. Anticipation of both reward types activated brain structures constituting the brain reward system including the ventral striatum. In contrast to the task independent activity in the anticipation phase, reward consumption evoked different patterns of activation for money and social approval, respectively. While social stimuli were mainly associated with amygdala activation, the thalamus was more strongly activated by the presentation of monetary rewards. Our results identify dissociable neural networks for the anticipation and consumption of reward. The findings implicate that the neural mechanisms underlying reward consumption are more modality-specific than those for reward anticipation, and that they are mediated by subjective reward value.

Cognitive, Affective, and Feedback-Based Flexibility - Disentangling Shared and Different Aspects of Three Facets of Psychological Flexibility.

Cognitive flexibility - the ability to adjust one ´s behavior to changing environmental demands - is crucial for controlled behavior. However, the term 'cognitive flexibility' is used heterogeneously, and associations between cognitive flexibility and other facets of flexible behavior have only rarely been studied systematically. To resolve some of these conceptual uncertainties, we directly compared cognitive flexibility (cue-instructed switching between two affectively neutral tasks), affective flexibility (switching between a neutral and an affective task using emotional stimuli), and feedback-based flexibility (non-cued, feedback-dependent switching between two neutral tasks). Three experimental paradigms were established that share as many procedural features (in terms of stimuli and/or task rules) as possible and administered in a pre-registered study plan (N = 100). Correlation analyses revealed significant associations between the efficiency of cognitive and affective task switching (response time switch costs). Feedback-based flexibility (measured as mean number of errors after rule reversals) did not correlate with task switching efficiency in the other paradigms, but selectively with the effectiveness of affective switching (error rate costs when switching from neutral to emotion task). While preregistered confirmatory factor analysis (CFA) provided no clear evidence for a shared factor underlying the efficiency of switching in all three domains of flexibility, an exploratory CFA suggested commonalities regarding switching effectiveness (accuracy-based switch costs). We propose shared mechanisms controlling the efficiency of cue-dependent task switching across domains, while the relationship to feedback-based flexibility may depend on mechanisms controlling switching effectiveness. Our results call for a more stringent conceptual differentiation between different variants of psychological flexibility.

Laugh or cringe? Common and distinct processes of reward-based schadenfreude and empathy-based fremdscham.

Witnessing others' plights can be funny for observers, but may also trigger one to empathically cringe with the victim of the predicament. In the present study, we examined the common and distinct neural networks involved in schadenfreude (i.e. pleasure derived from another's misfortune) and fremdscham (i.e. empathically sharing the embarrassment about another's misfortune). Using functional magnetic resonance imaging we examined a total of N = 34 participants while they observed social integrity threats of a misfortunate other and either reported on their schadenfreude or fremdscham. In this between-subject design, we found that despite a broad overlap in brain regions involved in social cognition, the left anterior insula (AI) was activated less if observers were asked to focus on their schadenfreude. Further, the nucleus accumben's activity exclusively covaried with the intensity of the schadenfreude experience and had a higher functional connectivity with the left AI in the context of schadenfreude than during fremdscham. With the present findings, we demonstrate that the valence and intensity of interpersonal emotions strongly depend on the experimental context and that empathy and reward circuits are involved in shaping the subjective experience.

Reward: From Basic Reinforcers to Anticipation of Social Cues.

Reward processing plays a major role in goal-directed behavior and motivation. On the neural level, it is mediated by a complex network of brain structures called the dopaminergic reward system. In the last decade, neuroscientific researchers have become increasingly interested in aspects of social interaction that are experienced as rewarding. Recent neuroimaging studies have provided evidence that the reward system mediates the processing of social stimuli in a manner analogous to nonsocial rewards and thus motivates social behavior. In this context, the neuropeptide oxytocin is assumed to play a key role by activating dopaminergic reward pathways in response to social cues, inducing the rewarding quality of social interactions. Alterations in the dopaminergic reward system have been found in several psychiatric disorders that are accompanied by social interaction and motivation problems, for example autism, attention deficit/hyperactivity disorder, addiction disorders, and schizophrenia.

When your friends make you cringe: social closeness modulates vicarious embarrassment-related neural activity.

Social closeness is a potent moderator of vicarious affect and specifically vicarious embarrassment. The neural pathways of how social closeness to another person affects our experience of vicarious embarrassment for the other's public flaws, failures and norm violations are yet unknown. To bridge this gap, we examined the neural response of participants while witnessing threats to either a friend's or a stranger's social integrity. The results show consistent responses of the anterior insula (AI) and anterior cingulate cortex (ACC), shared circuits of the aversive quality of affect, as well as the medial prefrontal cortex and temporal pole, central structures of the mentalizing network. However, the ACC/AI network activation was increased during vicarious embarrassment in response to a friend's failures. At the same time, the precuneus, a brain region associated with self-related thoughts, showed a specific activation and an increase in functional connectivity with the shared circuits in the frontal lobe while observing friends. This might indicate a neural systems mechanism for greater affective sharing and self-involvement while people interact with close others that are relevant to oneself.