Personal insult disrupts regulatory brain networks in violent offenders.

The failure to adequately regulate negative emotions represents a prominent characteristic of violent offenders. In this functional magnetic resonance imaging study, we used technical, nonsocial frustration to elicit anger in violent offenders (n = 19) and then increased the provocation by adding personal insults (social provocation). The aim was to investigate neural connectivity patterns involved in anger processing, to detect the effect of increasing provocation by personal insult, and to compare anger-related connectivity patterns between offenders and noncriminal controls (n = 12). During technical frustration, the offenders showed increased neural connectivity between the amygdala and prefrontal cortex compared to the controls. Conversely, personal insults, and thus increased levels of provocation, resulted in a significant reduction of neural connectivity between regions involved in cognitive control in the offenders but not controls. We conclude that, when (nonsocially) frustrated, offenders were able to employ regulatory brain networks by displaying stronger connectivity between regulatory prefrontal and limbic regions than noncriminal controls. In addition, offenders seemed particularly sensitive to personal insults, which led to increased implicit aggression (by means of motoric responses) and reduced connectivity in networks involved in cognitive control (including dorsomedial prefrontal cortex, precuneus, middle/superior temporal regions).

Accurate machine learning prediction of sexual orientation based on brain morphology and intrinsic functional connectivity.

BACKGROUND: Sexual orientation in humans represents a multilevel construct that is grounded in both neurobiological and environmental factors. OBJECTIVE: Here, we bring to bear a machine learning approach to predict sexual orientation from gray matter volumes (GMVs) or resting-state functional connectivity (RSFC) in a cohort of 45 heterosexual and 41 homosexual participants. METHODS: In both brain assessments, we used penalized logistic regression models and nonparametric permutation. RESULTS: We found an average accuracy of 62% (±6.72) for predicting sexual orientation based on GMV and an average predictive accuracy of 92% (±9.89) using RSFC. Regions in the precentral gyrus, precuneus and the prefrontal cortex were significantly informative for distinguishing heterosexual from homosexual participants in both the GMV and RSFC settings. CONCLUSIONS: These results indicate that, aside from self-reports, RSFC offers neurobiological information valuable for highly accurate prediction of sexual orientation. We demonstrate for the first time that sexual orientation is reflected in specific patterns of RSFC, which enable personalized, brain-based predictions of this highly complex human trait. While these results are preliminary, our neurobiologically based prediction framework illustrates the great value and potential of RSFC for revealing biologically meaningful and generalizable predictive patterns in the human brain.

Predictive Pattern Classification Can Distinguish Gender Identity Subtypes from Behavior and Brain Imaging.

The exact neurobiological underpinnings of gender identity (i.e., the subjective perception of oneself belonging to a certain gender) still remain unknown. Combining both resting-state functional connectivity and behavioral data, we examined gender identity in cisgender and transgender persons using a data-driven machine learning strategy. Intrinsic functional connectivity and questionnaire data were obtained from cisgender (men/women) and transgender (trans men/trans women) individuals. Machine learning algorithms reliably detected gender identity with high prediction accuracy in each of the four groups based on connectivity signatures alone. The four normative gender groups were classified with accuracies ranging from 48% to 62% (exceeding chance level at 25%). These connectivity-based classification accuracies exceeded those obtained from a widely established behavioral instrument for gender identity. Using canonical correlation analyses, functional brain measurements and questionnaire data were then integrated to delineate nine canonical vectors (i.e., brain-gender axes), providing a multilevel window into the conventional sex dichotomy. Our dimensional gender perspective captures four distinguishable brain phenotypes for gender identity, advocating a biologically grounded reconceptualization of gender dimorphism. We hope to pave the way towards objective, data-driven diagnostic markers for gender identity and transgender, taking into account neurobiological and behavioral differences in an integrative modeling approach.

Externalization Errors of Olfactory Source Monitoring in Healthy Controls-An fMRI Study.

Using a combined approach of functional magnetic resonance imaging (fMRI) and noninvasive brain stimulation (transcranial direct current stimulation [tDCS]), the present study investigated source memory and its link to mental imagery in the olfactory domain, as well as in the auditory domain. Source memory refers to the knowledge of the origin of mental experiences, differentiating events that have occurred and memories of imagined events. Because of a confusion between internally generated and externally perceived information, patients that are prone to hallucinations show decreased source memory accuracy; also, vivid mental imagery can lead to similar results in healthy controls. We tested source memory following cathodal tDCS stimulation using a mental imagery task, which required participants to perceive or imagine a set of the same olfactory and auditory stimuli during fMRI. The supplementary motor area (SMA) is involved in mental imagery across different modalities and potentially linked to source memory. Therefore, we attempted to modulate participants' SMA activation before entering the scanner using tDCS to influence source memory accuracy in healthy participants. Our results showed the same source memory accuracy between the olfactory and auditory modalities with no effects of stimulation. Finally, we found SMA's subregions differentially involved in olfactory and auditory imagery, with activation of dorsal SMA correlated with auditory source memory.

Blunted insula activation reflects increased risk and reward seeking as an interaction of testosterone administration and the MAOA polymorphism.

Testosterone, a male sex hormone, has been suggested to partly explain mixed findings in males and females when investigating behavioral tendencies associated with the MAOA polymorphism. Prior studies indicated that the MAOA polymorphism represents a vulnerability factor for financial risk-taking and harm avoidance and that testosterone increases human risk-taking. We therefore assumed an interactive influence of the MAOA polymorphism and testosterone application on decision making and corresponding neural correlates in a risk and reward context. Stratified for the MAOA polymorphism (S =short, L =long), 103 healthy males were assigned to a placebo or testosterone group (double blind, randomized) receiving a topical gel containing 50 mg testosterone. During a functional MRI scan, the participants performed a sequential decision making task. Our results indicate that testosterone and the MAOA polymorphism jointly influence sequential decision making. The MAOA-S variant was associated with less automatic harm avoidance as reflected in response times on safe decisions. Moreover, after testosterone administration, MAOA-S carriers were more risk-taking. Overall activity in the anterior cingulate cortex, anterior insula and inferior frontal gyrus increased with growing risk for losses. In the anterior insula, testosterone administration mitigated this effect solely in MAOA-S carriers. This might be a reflection of an improved coping during risk-reward conflicts subsequently modulating risky decision making. While the molecular basis is not well defined so far, our results support the assumption of testosterone as a modulatory factor for previously reported sex differences of behavioral associations with the MAOA-S variant. Hum Brain Mapp 38:4574-4593, 2017. © 2017 Wiley Periodicals, Inc.

Effect of MAOA Genotype on Resting-State Networks in Healthy Participants.

Up to now, it remains unclear how monoamine oxidase A (MAOA), which has been repeatedly linked to aggression, affects brain activity within resting-state networks (RSN). Here, we used functional magnetic resonance imaging (fMRI) to test whether the MAOA genotype might influence activity within the common RSN. Our results demonstrate that during rest, participants with the low-activity genotype (MAOA-L) exhibit more activity within frontoparietal and temporal parts of the default mode network (DMN) and the cerebellum. The executive control and salience RSN revealed reduced activity for the MAOA-L group in several areas related to executive control, namely the right middle frontal gyrus (BA 6 and BA 9), and the dorsal part of the anterior cingulate cortex. Participants with the high-activity genotype (MAOA-H) showed increased activity in the posterior cingulate part of the DMN. Taken together, we found widespread hyperactivity within the DMN and reduced activity in brain areas related to executive and inhibitory control for the MAOA-L group. We discuss how these first results examining the influence of MAOA on the resting brain might be related to previous findings regarding the genetics of aggression, while acknowledging that this is an exploratory study which needs further confirmation.

[Violence and health. Symptoms, consequences and treatment of victimized patients]. / Gewalt und Gesundheit. Symptome, Folgen und Behandlung betroffener Patientinnen und Patienten.

BACKGROUND: Violence has many faces and often results in a variety of consequences. Some studies indicated different types of violence and health consequences in men and women. However, it is still unclear whether this is reflected in clinical context, for example in a patient sample of a German university hospital. OBJECTIVES: The primary goal of the present study was to analyze associations of violence with health, gender and social, economic, job-related, psychological and physical consequences. In addition, the effects of psychological treatment were examined. MATERIALS AND METHODS: One line of research refers to the survey of more than 5000 patients of the university hospital Aachen, evaluating violence experience and several health complaints anonymously. Another line of research deals with detailed interviews with victims of violence and their experienced consequences. A final data source stems from the evaluation of psychological counseling of patients with prior experience of violence. Changes in subjectively perceived depressive symptoms and acceptance of the treatment are evaluated. RESULTS AND CONCLUSIONS: Experience of violence increases the risk for several health problems, especially the experience of multiple types of violence. The interviews showed that more than 60% of the victims had a clinical diagnosis--independent of sex. The risk for a clinical diagnosis increased with multiple violence experiences during childhood. Patients with a clinical diagnosis indicated more subjective consequences of violence, and consequences of violence were more pronounced in patients that experienced multiple types of violence. The good acceptance as well as the effects on symptomatology and other relevant therapeutic variables provides a first indication for a successful treatment of victims of violence in a clinical context.

Increased anger and stress and heightened connectivity between IFG and vmPFC in victims during social interaction.

Self-identification as a victim of violence may lead to increased negative emotions and stress and thus, may change both structure and function of the underlying neural network(s). In a trans-diagnostic sample of individuals who identified themselves as victims of violence and a matched control group with no prior exposure to violence, we employed a social exclusion paradigm, the Cyberball task, to stimulate the re-experience of stress. Participants were partially excluded in the ball-tossing game without prior knowledge. We analyzed group differences in brain activity and functional connectivity during exclusion versus inclusion in exclusion-related regions. The victim group showed increased anger and stress levels during all conditions. Activation patterns during the task did not differ between groups but an enhanced functional connectivity between the IFG and the right vmPFC distinguished victims from controls during exclusion. This effect was driven by aberrant connectivity in victims during inclusion rather than exclusion, indicating that victimization affects emotional responses and inclusion-related brain connectivity rather than exclusion-related brain activity or connectivity. Victims may respond differently to the social context itself. Enhanced negative emotions and connectivity deviations during social inclusion may depict altered social processing and may thus affect social interactions.

The influence of the COMT Val158Met polymorphism on prefrontal TDCS effects on aggression.

Increasing dorsolateral prefrontal cortex (DLPFC) activity by anodal transcranial direct current stimulation (tDCS) enhances cognitive control and might reduce aggression. The Val158Met polymorphism within the catechol-O-methyltransferase gene (rs4680) plays a pivotal role in prefrontal dopamine signaling, displaying associations with aggressive behavior, and potentially influencing the effects of tDCS. In a double-blind, sham-controlled study, we investigated the influence of rs4680 on tDCS effects on aggression. While undergoing functional magnetic resonance imaging, 89 healthy male participants performed the Taylor aggression paradigm before and immediately after tDCS. Actively stimulated participants (n = 45) received anodal tDCS (1.5 mA) for 20 min targeting the right DLPFC. Carriers of the val-allele (val+; n = 46; active tDCS n = 23) were compared to met-allele homozygotes (val-; n = 43; active tDCS n = 22). Analysis revealed decreased aggressive behavior in the val- group following active tDCS (p < 0.001). The val+ group showed increased aggression during the second session (p < 0.001) with an even higher increase following active as compared to sham tDCS (p < 0.001). No effects of stimulation or rs4680 on brain activation were found. Our study provides evidence for opposite tDCS effects on aggressive behavior in val-carriers and val-noncarriers. By shedding light on genetic factors predicting tDCS responsivity, the study will help to pave the way toward individualized-and thus more effective-tDCS treatment options.

Brain networks underlying mental imagery of auditory and visual information.

Mental imagery is a complex cognitive process that resembles the experience of perceiving an object when this object is not physically present to the senses. It has been shown that, depending on the sensory nature of the object, mental imagery also involves correspondent sensory neural mechanisms. However, it remains unclear which areas of the brain subserve supramodal imagery processes that are independent of the object modality, and which brain areas are involved in modality-specific imagery processes. Here, we conducted a functional magnetic resonance imaging study to reveal supramodal and modality-specific networks of mental imagery for auditory and visual information. A common supramodal brain network independent of imagery modality, two separate modality-specific networks for imagery of auditory and visual information, and a common deactivation network were identified. The supramodal network included brain areas related to attention, memory retrieval, motor preparation and semantic processing, as well as areas considered to be part of the default-mode network and multisensory integration areas. The modality-specific networks comprised brain areas involved in processing of respective modality-specific sensory information. Interestingly, we found that imagery of auditory information led to a relative deactivation within the modality-specific areas for visual imagery, and vice versa. In addition, mental imagery of both auditory and visual information widely suppressed the activity of primary sensory and motor areas, for example deactivation network. These findings have important implications for understanding the mechanisms that are involved in generation of mental imagery.

HD-tDCS induced changes in resting-state functional connectivity: Insights from EF modeling.

BACKGROUND: High-definition transcranial direct current stimulation (HD-tDCS) holds promise for therapeutic use in psychiatric disorders. One obstacle for the implementation into clinical practice is response variability. One way to tackle this obstacle is the use of Individualized head models. OBJECTIVE: This study investigated the variability of HD-tDCS induced electric fields (EFs) and its impact on resting-state functional connectivity (rsFC) during different time windows. METHODS: In this randomized, double-blind, and sham controlled study, seventy healthy males underwent 20 min of 1.5 mA HD-tDCS on the right inferior frontal gyrus (rIFG) while undergoing resting-state functional magnetic resonance imaging (rs-fMRI). Individual head models and EF simulations were created from anatomical images. The effects of HD-tDCS on rsFC were assessed using a seed-to-voxel analysis. A subgroup analysis explored the relationship between EF magnitude and rsFC during different stimulation time windows. RESULTS: Results highlighted significant variability in HD-tDCS-induced EFs. Compared to the sham group, the active group showed increased rsFC between the rIFG and the left prefrontal cortex, during and after stimulation. During active stimulation, EF magnitude correlated positively with rsFC between the rIFG and the left hippocampus initially, and negatively during the subsequent period. CONCLUSION: This study indicated an HD-tDCS induced increase of rsFC between left and right prefrontal areas. Furthermore, an interaction between the magnitude and the duration of HD-tDCS on rsFC was observed. Due to the high EF variability that was apparent, these findings highlight the need for individualized HD-tDCS protocols and the creation of head models to optimize effects and reduce response heterogeneity.

Accurate sex prediction of cisgender and transgender individuals without brain size bias.

The increasing use of machine learning approaches on neuroimaging data comes with the important concern of confounding variables which might lead to biased predictions and in turn spurious conclusions about the relationship between the features and the target. A prominent example is the brain size difference between women and men. This difference in total intracranial volume (TIV) can cause bias when employing machine learning approaches for the investigation of sex differences in brain morphology. A TIV-biased model will not capture qualitative sex differences in brain organization but rather learn to classify an individual's sex based on brain size differences, thus leading to spurious and misleading conclusions, for example when comparing brain morphology between cisgender- and transgender individuals. In this study, TIV bias in sex classification models applied to cis- and transgender individuals was systematically investigated by controlling for TIV either through featurewise confound removal or by matching the training samples for TIV. Our results provide strong evidence that models not biased by TIV can classify the sex of both cis- and transgender individuals with high accuracy, highlighting the importance of appropriate modeling to avoid bias in automated decision making.

Consequences of prefrontal tDCS on inhibitory control and reactive aggression.

Increased aggression and impulsivity represent a key component of several psychiatric disorders, including substance use disorder, which is often associated with deficient prefrontal brain activation. Thus, innovative tools to increase cognitive control are highly warranted. The current study investigates the potential of transcranial direct current stimulation (tDCS), a tool to modulate cortical activation and to increase cognitive control in individuals with a high potential for impulsive and aggressive behavior. In a double-blind, sham-controlled study, we applied anodal tDCS over the right dorsolateral prefrontal cortex in an all-male sample of alcohol-dependent patients (AD), tobacco users (TU) and healthy controls (HC), who completed the Taylor Aggression Paradigm and Stop Signal Reaction Time Task twice. While there were no observable effects of tDCS in controls, the results revealed altered aggressive behavior in AD following active stimulation. Specifically, these individuals did not show the standard increase in aggression over time seen in the other groups. Furthermore, improved response inhibition was found in AD and TU following active but not sham stimulation. Our study demonstrates that prefrontal tDCS improves our laboratory measure of impulse control in at-risk groups, illustrating the importance of sample characteristics such as nicotine intake and personality traits for understanding the effects of brain stimulation.

Survival of migrating salmon smolts in large rivers with and without dams.

The mortality of salmon smolts during their migration out of freshwater and into the ocean has been difficult to measure. In the Columbia River, which has an extensive network of hydroelectric dams, the decline in abundance of adult salmon returning from the ocean since the late 1970s has been ascribed in large measure to the presence of the dams, although the completion of the hydropower system occurred at the same time as large-scale shifts in ocean climate, as measured by climate indices such as the Pacific Decadal Oscillation. We measured the survival of salmon smolts during their migration to sea using elements of the large-scale acoustic telemetry system, the Pacific Ocean Shelf Tracking (POST) array. Survival measurements using acoustic tags were comparable to those obtained independently using the Passive Integrated Transponder (PIT) tag system, which is operational at Columbia and Snake River dams. Because the technology underlying the POST array works in both freshwater and the ocean, it is therefore possible to extend the measurement of survival to large rivers lacking dams, such as the Fraser, and to also extend the measurement of survival to the lower Columbia River and estuary, where there are no dams. Of particular note, survival during the downstream migration of at least some endangered Columbia and Snake River Chinook and steelhead stocks appears to be as high or higher than that of the same species migrating out of the Fraser River in Canada, which lacks dams. Equally surprising, smolt survival during migration through the hydrosystem, when scaled by either the time or distance migrated, is higher than in the lower Columbia River and estuary where dams are absent. Our results raise important questions regarding the factors that are preventing the recovery of salmon stocks in the Columbia and the future health of stocks in the Fraser River.

An assessment of terminology for intraspecific diversity in fishes, with a focus on "ecotypes" and "life histories".

Understanding and preserving intraspecific diversity (ISD) is important for species conservation. However, ISD units do not have taxonomic standards and are not universally recognized. The terminology used to describe ISD is varied and often used ambiguously. We compared definitions of terms used to describe ISD with use in recent studies of three fish taxa: sticklebacks (Gasterosteidae), Pacific salmon and trout (Oncorhynchus spp., "PST"), and lampreys (Petromyzontiformes). Life history describes the phenotypic responses of organisms to environments and includes biological parameters that affect population growth or decline. Life-history pathway(s) are the result of different organismal routes of development that can result in different life histories. These terms can be used to describe recognizable life-history traits. Life history is generally used in organismal- and ecology-based journals. The terms paired species/species pairs have been used to describe two different phenotypes, whereas in some species and situations a continuum of phenotypes may be expressed. Our review revealed overlapping definitions for race and subspecies, and subspecies and ecotypes. Ecotypes are genotypic adaptations to particular environments, and this term is often used in genetic- and evolution-based journals. "Satellite species" is used for situations in which a parasitic lamprey yields two or more derived, nonparasitic lamprey species. Designatable Units, Evolutionary Significant Units (ESUs), and Distinct Population Segments (DPS) are used by some governments to classify ISD of vertebrate species within distinct and evolutionary significant criteria. In situations where the genetic or life-history components of ISD are not well understood, a conservative approach would be to call them phenotypes.

Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals.

The brain structural changes related to gender incongruence (GI) are still poorly understood. Previous studies comparing gray matter volumes (GMV) between cisgender and transgender individuals with GI revealed conflicting results. Leveraging a comprehensive sample of transmen (n = 33), transwomen (n = 33), cismen (n = 24), and ciswomen (n = 25), we employ a region-of-interest (ROI) approach to examine the most frequently reported brain regions showing GMV differences between trans- and cisgender individuals. The primary aim is to replicate previous findings and identify anatomical regions which differ between transgender individuals with GI and cisgender individuals. On the basis of a comprehensive literature search, we selected a set of ROIs (thalamus, putamen, cerebellum, angular gyrus, precentral gyrus) for which differences between cis- and transgender groups have been previously observed. The putamen was the only region showing significant GMV differences between cis- and transgender, across previous studies and the present study. We observed increased GMV in the putamen for transwomen compared to both transmen and ciswomen and for all transgender participants compared to all cisgender participants. Such a pattern of neuroanatomical differences corroborates the large majority of previous studies. This potential replication of previous findings and the known involvement of the putamen in cognitive processes related to body representations and the creation of the own body image indicate the relevance of this region for GI and its potential as a structural biomarker for GI.

Morphology of the criminal brain: gray matter reductions are linked to antisocial behavior in offenders.

Aggression and psychopathy are multifaceted conditions determined interpersonal and antisocial factors. Only a few studies analyze the link between these separate factors and specific brain morphology distinctively. A voxel-based morphometry (VBM) analysis was performed on 27 violent offenders and 27 controls aiming to associate sub-features of aggressive and psychopathic behavior with specific gray matter volumes. Trait aggression was assessed using two self-report tests (Aggression Questionnaire, AQ, and Reactive-Proactive-Aggression Questionnaire, RPQ) and psychopathy with the Psychopathy Checklist-Revised (PCL-R). Total and sub-scale scores of these tests were correlated to the brain morphometry of the offenders group in separate analyses. It was found that psychopathic behavior was negatively correlated with prefrontal gray matter volume and that this result was primarily driven by the antisocial behavior sub-scale of the PCL-R. Furthermore, less gray matter in right superior frontal and left inferior parietal regions with increasing antisocial behavior could be observed. One cluster comprising the right middle and superior temporal gyrus was negatively correlated with both, reactive aggression and antisocial behavior. These results outline (1) the importance of distinctively analyzing sub-features that contribute to aggressive and psychopathic behavior, given that the negative correlation of psychopathy global scores with prefrontal volume was driven by one single facet of the PCL-R scale (antisocial behavior). Moreover, these results indicate (2) fronto-temporo-parietal network deficits in antisocial, criminal offenders, with a particular strong effect in the temporal lobe.

The influence of the OPRM1 (A118G) polymorphism on behavioral and neural correlates of aggression in healthy males.

Current models of aggression suggest that in addition to personality traits and environmental factors, biological vulnerability associated with genetics substantially impacts aggressive behavior. In a functional imaging study, we investigated the influence of the single nucleotide polymorphism of the mu 1 subtype opioid receptor gene (OPRM1), implicated in sociability, on correlates of trait and state aggression to delineate the function of these influences in aggression. A key aim was further to differentiate different aspects of aggressive reactions - namely, the reaction to provocation and the decision to punish an opponent. 59 healthy males performed a modified Taylor Aggression Paradigm during functional magnetic resonance imaging. The implementation of the paradigm allowed for individual assessments of the decision to behave aggressively, the experience of provocation and the ramification of punishment for the participant or the opponent. The influence of variation in the OPRM1 gene was measured by the functional A118G polymorphism. G allele carriers showed lower levels of general aggression and self-reported physical aggression. Additionally, these participants exhibited increased activation in dorsolateral prefrontal, orbitofrontal, anterior cingulate and insular cortices when choosing higher punishments for the opponent. The OPRM1 polymorphism did not influence aggression in reaction to social provocation. Thus, we suggest that this genetic variant affects one's trait aggressiveness rather than actual behavioral reactivity to provocation. Investigating brain regions that are specifically linked to provocation yielded activation in cortico-limbic circuits which might mediate the evaluation of provocation and the experience of anger and thus shed light on neural processes underlying the risk for aggressive behavior. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

Alerted default mode: functional connectivity changes in the aftermath of social stress.

Stress affects the brain at a network level: the salience network is supposedly upregulated, while at the same time the executive control network is downregulated. While theoretically described, the effects in the aftermath of stress have thus far not been tested empirically. Here, we compared for the first time resting-state functional connectivity in a large sample of healthy volunteers before and after a mild social stressor. Following the theoretical prediction, we focused on connectivity of the salience network (SN), the executive control network (ECN) and the default mode network (DMN). The DMN exhibited increased resting-state functional connectivity following the cyberball task to the key nodes of the SN, namely the dorsal anterior cingulate cortex (dACC) and the anterior insula, as well as sensorimotor regions and higher-order visual areas. We conclude that this increased connectivity of the DMN with key nodes of the SN and regions responsible for preparatory motor activity and visual motion processing indicates a shift towards an 'alerted default mode' in the aftermath of stress. This brain response may be triggered or aggravated by (social) stress induced by the cyberball task, enabling individuals to better reorient attention, detect salient external stimuli, and deal with the emotional and affective consequences of stress.

Contextual exclusion processing: an fMRI study of rejection in a performance-related context.

Social stress has a major detrimental impact on subjective well-being. Previous research mainly focused on two methods to induce and measure social stress: social exclusion and performance evaluation. For social exclusion researchers frequently focused on the Cyberball task, which in contrast to many psychosocial stress paradigms does not include a performance component. The aim of the current study was to establish an optimized psychosocial stress paradigm by combining both, social exclusion as well as performance evaluation within a single fMRI paradigm. We implemented a modification of the Cyberball task including a performance game (with exclusion and inclusion periods) in addition to the already established exclusion and inclusion periods. This indeed resulted in increased subjective stress in the performance game. Hence, the modified Cyberball version seems to be superior in mapping relevant neural social stress correlates more pronounced and reliably. Exclusion within the performance-related context contrasted to the unmodified exclusion was associated with higher activation in the dorsal anterior cingulate cortex and the anterior insula. Moreover, the modified exclusion reflected greater social processing in the precuneus, several temporo-parietal and medial prefrontal areas, as suggested by the additional task aspects of social evaluation and social perspective taking. The findings emphasize that public negative evaluation is effective in substantially enlarging and potentiating the distressing effect of exclusion on a subjective as well as on a neural level. This may have a great potential for further experimental research on social stress.