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Evidence suggests that intranasal application of oxytocin facilitates empathy and modulates its underlying neural processes, which are often impaired in individuals with autism spectrum disorders (ASD). Oxytocin has therefore been considered a promising candidate for the treatment of social difficulties in ASD. However, evidence linking oxytocin treatment to social behavior and brain function in ASD is limited and heterogeneous effects might depend on variations in the oxytocin-receptor gene (OXTR). We examined 25 male ASD patients without intellectual disability in a double-blind, cross-over, placebo-controlled fMRI-protocol, in which a single dose of oxytocin or placebo was applied intranasally. Patients performed three experiments in the MRI examining empathy for other's physical pain, basic emotions, and social pain. All participants were genotyped for the rs53576 single-nucleotide polymorphism of the OXTR. Oxytocin increased bilateral amygdala responsiveness during the physical pain task for both painful and neutral stimuli. Other than that, there were no effects of oxytocin treatment. OXTR genotype did not significantly interact with oxytocin treatment. Our results contribute to the growing body of empirical literature suggesting heterogenous effects of oxytocin administration in ASD. To draw clinically relevant conclusions regarding the usefulness of oxytocin treatment, however, empirical studies need to consider methods of delivery, dose, and moderating individual factors more carefully in larger samples., (© 2021. The Author(s).)

Narcissistic Personality Disorder (NPD) entails severe impairments in interpersonal functioning that are likely driven by self-beneficial and exploitative behavior. Here, we investigate the underlying motivational and neural mechanisms of prosocial decision-making by experimentally manipulating motivational conflict between self-beneficial and prosocial incentives. One group of patients diagnosed with NPD and a group of healthy controls (CTL) were scanned using functional magnetic resonance imaging while performing a prosocial decision-making task. In this task, we systematically varied the level of conflict between self-beneficial and prosocial options on each trial. We analyzed choice behavior, response times, and neural activity in regions associated with conflict monitoring to test how motivational conflict drives prosocial choice behavior. Participants in the NPD group behaved less prosocially than the CTL group overall. Varying degrees of motivational conflict between self-beneficial and prosocial options induced response variability in both groups, but more so in the CTL group. The NPD group responded faster than the CTL group, unless choosing prosocially, which slowed response times to a level comparable to the CTL group. Additionally, neural activity tracking motivational conflict in dorsomedial prefrontal cortex was reduced in the NPD group. Collectively, low generosity in NPD appears to arise from reduced consideration of prosocial motives, which obviates motivational conflict with self-beneficial motives and entails reduced activity in neural conflict monitoring systems. Yet, our data also indicate that NPD is not marked by an absolute indifference to others' needs. This points to potentials for improving interpersonal relationships, effectively supporting the well-being of patients and their peers., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Humans experience vicarious embarrassment when they observe other's mishaps in public settings, even when the protagonist is not embarrassed at all. Though neural correlates of vicarious embarrassment have been studied before, it is yet poorly understood how they are influenced by egocentric or allocentric processes of perspective-taking. In the present study we examined the effects of deliberate allocentric and egocentric perspectives during the evaluation of others' public mishaps that pose a threat to the protagonist's reputation. Forty-three participants were shown sketches depicting a protagonist's mishaps and were asked to rate either their own vicarious embarrassment as observers (egocentric perspective) or the protagonist's embarrassment (allocentric perspective). Using functional magnetic resonance imaging, we found that observing others' mishaps engaged the anterior insula, anterior cingulate cortex and medial prefrontal cortex, irrespective of the adopted mental perspective. Further, as part of the mentalizing network, the right middle temporal gyrus and right temporo-parietal junction were exclusively engaged when participants adopted an allocentric perspective while observing others' mishaps. Activation within bilateral areas of the inferior parietal cortex extending to the somatosensory cortex varied as a function of the protagonist's awareness of the blunder and the adopted perspective. In this study, we for the first time dissociate regions within the mentalizing network that contribute to a rather spontaneous versus a rather deliberate and motivated act of understanding other's mental states in the context of vicarious embarrassment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Experiencing events as controllable is essential for human well-being. Based on classic psychological theory, we test how internal control beliefs impact the affective valuation of task outcomes, neural dynamics and ensuing behavioral preferences. In three consecutive studies we show that dynamics in positive affect increase, with a qualitative shift towards self-evaluative pride, when agents believe they caused a given outcome. We demonstrate that these outcomes engage brain networks processing self-referential information in the cortical midline. Here, activity in the ventromedial prefrontal cortex tracks outcome valence regarding both success as well as internal control, and covaries with positive affect in response to outcomes. These affective dynamics also relate to increased functional coupling between the ventral striatum and cortical midline structures. Finally, we show that pride predicts preferences for control, even at monetary costs. Our investigations extend recent models of positive affect and well-being, and emphasize that control beliefs drive intrinsic motivation.

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

It has been shown, using functional magnetic resonance imaging (fMRI), that hemispheric lateralization of brain activity depends on the requirements of the cognitive task performed during the processing of a sensory stimulus rather than on the intrinsic characteristics of that stimulus [Stephan et al., 2003, Science 301 (5631): 384-6]. Task-dependent increase in the coupling of the anterior cingulate cortex (ACC), a region involved in cognitive control, and brain areas in the left prefrontal and right parietal cortex, respectively, regions involved in task execution, was proposed as the mechanism underlying this task-dependency of hemispheric lateralization. The aim of the present study was two-fold: First, we aimed for a conceptual replication of these findings in an independent sample of subjects. Second, we investigated the test-retest reliability of the imaging paradigm to assess whether the task can be used to capture reliable measures of inter-individual differences in hemispheric lateralization. We were able to confirm previous findings showing that hemispheric lateralization depends on the nature of the cognitive task rather than on the nature of the processed stimuli. The task-related brain activation patterns were highly reliable across sessions (as indicated by intra-class correlation coefficients - ICCs, ≥.51). We could, however, not replicate previous results proposing task-dependent changes in the coupling between ACC and brain regions for task execution as the mechanism underlying hemispheric lateralization. This re-opens the question which mechanisms could determine the task-dependent functional asymmetries that were observed previously and replicated in this study., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In our daily lives, we constantly engage in reciprocal interactions with other individuals and represent ourselves in the context of our surrounding social world. Within social interactions, humans often experience interpersonal emotions such as embarrassment, shame, guilt, or pride. How interpersonal emotions are processed on the neural systems level is of major interest for social neuroscience research. While the configuration of laboratory settings in general is constraining for emotion research, recent neuroimaging investigations came up with new approaches to implement socially interactive and immersive scenarios for the real-life investigation of interpersonal emotions. These studies could show that among other brain regions the so-called mentalizing network, which is typically involved when we represent and make sense of others' states of mind, is associated with interpersonal emotions. The anterior insula/anterior cingulate cortex network at the same time processes one's own bodily arousal during such interpersonal emotional experiences. Current research aimed to explore how we make sense of others' emotional states during social interactions and investigates the modulating factors of our emotional experiences during social interactions. Understanding how interpersonal emotions are processed on the neural systems level may yield significant implications for neuropsychiatric disorders that affect social behavior such as social anxiety disorders or autism.

Computational approaches have great potential for moving neuroscience toward mechanistic models of the functional integration among brain regions. Dynamic causal modeling (DCM) offers a promising framework for inferring the effective connectivity among brain regions and thus unraveling the neural mechanisms of both normal cognitive function and psychiatric disorders. While the benefit of such approaches depends heavily on their reliability, systematic analyses of the within-subject stability are rare. Here, we present a thorough investigation of the test-retest reliability of an fMRI paradigm for DCM analysis dedicated to unraveling intra- and interhemispheric integration among the core regions of the face perception network. First, we examined the reliability of face-specific BOLD activity in 25 healthy volunteers, who performed a face perception paradigm in two separate sessions. We found good to excellent reliability of BOLD activity within the DCM-relevant regions. Second, we assessed the stability of effective connectivity among these regions by analyzing the reliability of Bayesian model selection and model parameter estimation in DCM. Reliability was excellent for the negative free energy and good for model parameter estimation, when restricting the analysis to parameters with substantial effect sizes. Third, even when the experiment was shortened, reliability of BOLD activity and DCM results dropped only slightly as a function of the length of the experiment. This suggests that the face perception paradigm presented here provides reliable estimates for both conventional activation and effective connectivity measures. We conclude this paper with an outlook on potential clinical applications of the paradigm for studying psychiatric disorders. Hum Brain Mapp 37:730-744, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Perceiving human faces constitutes a fundamental ability of the human mind, integrating a wealth of information essential for social interactions in everyday life. Neuroimaging studies have unveiled a distributed neural network consisting of multiple brain regions in both hemispheres. Whereas the individual regions in the face perception network and the right-hemispheric dominance for face processing have been subject to intensive research, the functional integration among these regions and hemispheres has received considerably less attention. Using dynamic causal modeling (DCM) for fMRI, we analyzed the effective connectivity between the core regions in the face perception network of healthy humans to unveil the mechanisms underlying both intra- and interhemispheric integration. Our results suggest that the right-hemispheric lateralization of the network is due to an asymmetric face-specific interhemispheric recruitment at an early processing stage - that is, at the level of the occipital face area (OFA) but not the fusiform face area (FFA). As a structural correlate, we found that OFA gray matter volume was correlated with this asymmetric interhemispheric recruitment. Furthermore, exploratory analyses revealed that interhemispheric connection asymmetries were correlated with the strength of pupil constriction in response to faces, a measure with potential sensitivity to holistic (as opposed to feature-based) processing of faces. Overall, our findings thus provide a mechanistic description for lateralized processes in the core face perception network, point to a decisive role of interhemispheric integration at an early stage of face processing among bilateral OFA, and tentatively indicate a relation to individual variability in processing strategies for faces. These findings provide a promising avenue for systematic investigations of the potential role of interhemispheric integration in future studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (© 2015 Wiley Periodicals, Inc.)

The experience of embarrassment provides a highly salient cue for the human moral apparatus. Interestingly, people also experience embarrassment on behalf of others' inappropriate conditions. The perceiver's embarrassment often lacks an equivalent expression of embarrassment in the social counterpart. The present study examines this phenomenon and distinguishes neural circuits involved in embarrassment with and embarrassment for another person's mishaps. Using functional magnetic resonance imaging, we show that the embarrassment on behalf of others engages the temporal pole and the medial prefrontal cortex, central structures of the mentalizing network, together with the anterior insula and anterior cingulate cortex. In contrast, sharing others' embarrassment additionally stimulated the posterior superior temporal sulcus (STS), which exhibited increased functional integration with inferior parietal and insular cortex areas. These findings characterize common neural circuits involved in the embodied representation of embarrassment and further unravel the unique role of the posterior STS in sharing others' affective state., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Emotional instability, difficulties in social adjustment, and disinhibited behavior are the most common symptoms of the psychiatric comorbidities in juvenile myoclonic epilepsy (JME). This psychopathology has been associated with dysfunctions of mesial-frontal brain circuits. The present work is a first direct test of this link and adapted a paradigm for probing frontal circuits during empathy for pain. Neural and psychophysiological parameters of pain empathy were assessed by combining functional magnetic resonance imaging (fMRI) with simultaneous pupillometry in 15 JME patients and 15 matched healthy controls. In JME patients, we observed reduced neural activation of the anterior cingulate cortex (ACC), the anterior insula (AI), and the ventrolateral prefrontal cortex (VLPFC). This modulation was paralleled by reduced pupil dilation during empathy for pain in patients. At the same time, pupil dilation was positively related to neural activity of the ACC, AI, and VLPFC. In JME patients, the ACC additionally showed reduced functional connectivity with the primary and secondary somatosensory cortex, areas fundamentally implicated in processing the somatic cause of another's pain. Our results provide first evidence that alterations of mesial-frontal circuits directly affect psychosocial functioning in JME patients and draw a link of pupil dynamics with brain activity during emotional processing. The findings of reduced pain empathy related activation of the ACC and AI and aberrant functional integration of the ACC with somatosensory cortex areas provide further evidence for this network's role in social behavior and helps explaining the JME psychopathology and patients' difficulties in social adjustment., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this Hypothesis and Theory is to question the recently increasing use of the "race" concept in contemporary genetic, psychiatric, neuroscience as well as social studies. We discuss "race" and related terms used to assign individuals to distinct groups and caution that also concepts such as "ethnicity" or "culture" unduly neglect diversity. We suggest that one factor contributing to the dangerous nature of the "race" concept is that it is based on a mixture of traditional stereotypes about "physiognomy", which are deeply imbued by colonial traditions. Furthermore, the social impact of "race classifications" will be critically reflected. We then examine current ways to apply the term "culture" and caution that while originally derived from a fundamentally different background, "culture" is all too often used as a proxy for "race", particularly when referring to the population of a certain national state or wider region. When used in such contexts, suggesting that all inhabitants of a geographical or political unit belong to a certain "culture" tends to ignore diversity and to suggest a homogeneity, which consciously or unconsciously appears to extend into the realm of biological similarities and differences. Finally, we discuss alternative approaches and their respective relevance to biological and cultural studies.

The affective responses to another person's condition depend on the ability to reflect about another's thoughts and intentions. This is relevant also for high-functioning individuals with ASD who have considerable difficulties in reading the intentions of others. With the present study we introduce a novel paradigm to induce vicarious embarrassment as a form of social pain. We predicted that the vicarious embarrassment experiences of high-functioning individuals with ASD should specifically decline in social contexts that require reflecting on another's intentions. Thirty-two young adults with high-functioning ASD were matched with regards to age, gender, and verbal IQ to a control group. Vicarious embarrassment was examined with previously validated stimuli describing 30 situations that elicit vicarious embarrassment in the observer. The situations manipulated whether the displayed protagonist either accidentally or intentionally transgressed a social norm in public and participants rated their vicarious embarrassment from the observer's perspective. The ASD group showed comparable vicarious embarrassment experience in response to observing another's accidental norm transgressions but significantly reduced vicarious embarrassment when observing another who intentionally violated socials norms. Vicarious embarrassment was significantly correlated with trait empathy in the ASD group. In complex social scenarios individuals with ASD are impaired in reporting experience of vicarious embarrassment, primarily when it is required to reflect on another's intentions. The present study thus contributes to a better understanding of how persons with ASD are affected in the diversity of empathic processes in the social, everyday life environment they are embedded in., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The glutamatergic N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Administered to healthy volunteers, a subanesthetic dose of the non-competitive NMDA receptor antagonist ketamine leads to psychopathological symptoms similar to those observed in schizophrenia. In patients with schizophrenia, ketamine exacerbates the core symptoms of illness, supporting the hypothesis of a glutamatergic dysfunction. In a counterbalanced, placebo-controlled, double-blind study design, healthy subjects were administered a continuous subanesthetic S-ketamine infusion while differences in BOLD responses measured with fMRI were detected. During the scanning period, subjects performed continuous overt verbal fluency tasks (phonological, lexical and semantic). Ketamine-induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Ketamine elicited psychosis like psychopathology. Post-hoc t-tests revealed significant differences between placebo and ketamine for the amounts of words generated during lexical and semantic verbal fluency, while the phonological domain remained unaffected. Ketamine led to enhanced cortical activations in supramarginal and frontal brain regions for phonological and lexical verbal fluency, but not for semantic verbal fluency. Ketamine induces activation changes in healthy subjects similar to those observed in patients with schizophrenia, particularly in frontal and temporal brain regions. Our results provide further support for the hypothesis of an NMDA receptor dysfunction in the pathophysiology of schizophrenia., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Memory dysfunction is a prominent feature in schizophrenia. Impairments of declarative memory have been consistently linked to alterations especially within hippocampal-prefrontal regions. Due to the high heritability of schizophrenia, susceptibility genes and their modulatory impact on the neural correlates on memory are of major relevance. In the present study the influence of the COMT val(158)met status on the neural correlates of declarative memory was investigated in healthy subjects., Methods: From an initial behavioural sample of 522 healthy individuals (Sheldrick et al., 2008), 84 subjects underwent fMRI scanning while performing a memory encoding and a retrieval task. The COMT val(158)met status was determined for the whole sample and correlated with cortical activation within the group of n=84 individuals., Results: There were no effects of COMT status on behavioural performance. For declarative memory processing the number of met alleles predicted circumscribed bilateral insula and anterior hippocampus activations during memory encoding as well as less deactivations within the bilateral posterior parahippocampal gyri during memory retrieval., Discussion: Although declarative memory performance was unaffected, the neural correlates within hippocampal-prefrontal regions demonstrate a link between COMT val(158)met carrier status and brain areas associated with declarative memory processing. The study contributes to a better understanding of the role that susceptibility genes might play in the aetiology of schizophrenia., (Copyright 2009 Elsevier Inc. All rights reserved.)

Neuregulin 1 (NRG1) has been found to be associated with schizophrenia. Impaired performance in episodic memory tasks is an often replicated finding in this disorder. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal and medial temporal areas. Therefore, it is of interest whether genes associated with the disorder, such as NRG1, modulate episodic memory performance and its neural correlates. Ninety-four healthy individuals performed an episodic memory encoding and a retrieval task while brain activation was measured with functional MRI. All subjects were genotyped for the single nucleotide polymorphism (SNP) rs35753505 in the NRG1 gene. The effect of genotype on brain activation was assessed with fMRI during the two tasks. While there were no differences in performance, brain activation in the cingulate gyrus (BA 24), the left middle frontal gyrus (BA 9), the bilateral fusiform gyrus and the left middle occipital gyrus (BA 19) was positively correlated with the number of risk alleles in NRG1 during encoding. During retrieval brain activation was positively correlated with the number of risk alleles in the left middle occipital gyrus (BA 19). NRG1 genotype does modulate brain activation during episodic memory processing in key areas for memory encoding and retrieval. The results suggest that subjects with risk alleles show hyperactivations in areas associated with elaborate encoding strategies., (Copyright 2009 Elsevier Inc. All rights reserved.)

Polymorphisms in the G72 (also named d-amino acid oxidase activator, DAOA) gene increase the vulnerability for schizophrenia and affective psychosis. Three recent genetic neuroimaging studies showed that variation in G72 influences the brain activity in the medial temporal lobe (MTL), supporting the hypothesis that G72 might play a modulatory role on brain activity in MTL structures. In the present study we therefore investigated the effect of G72 on the neural correlates of long-term memory encoding and retrieval in a large sample of healthy subjects (n=83) using functional magnetic resonance imaging. A face encoding and a face retrieval memory task were chosen because on the one hand they specifically activate MTL structures and on the other hand they tap into memory processes that are compromised in patients with schizophrenia and affective disorder. Despite a strong a-priori hypothesis of genotype group activation differences in the MTL along with a large sample size we did neither find an effect of G72 genotype status on brain activity in the MTL nor in any other brain regions. The present data therefore do not support the view of a general modulatory role of G72 on MTL brain activity, at least not in the domain of long-term memory encoding and retrieval. Our results highlight the importance of replication studies in genetic neuroimaging., (Copyright 2009 Elsevier Inc. All rights reserved.)

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., (Copyright 2009 Elsevier B.V. All rights reserved.)

Categorization is a basic principle of knowledge organization in the brain. The goal of the current fMRI study was to compare the neural correlates of thematic (e.g., car - garage) and taxonomic (e.g., couch - bed) categories under automatic processing conditions using auditory-to-visual semantic priming. Behavioral data revealed a priming effect for thematically but not for taxonomically related word pairs. On a neural level, thematically related words led to a left-lateralized temporal activation (superior temporal sulcus), whereas taxonomically related word pairs evoked a right-lateralized frontal activation and within the hippocampus. A direct comparison between both categories revealed enhanced activation for thematically related and response suppression for taxonomically related trials in the left superior temporal sulcus. These results suggest that processing of thematic and taxonomic categories leads to activation of distinct brain areas. The mainly right-lateralized fronto-temporal activation for taxonomic relations suggests increased attention and effort for processing this category. The interaction within the left superior temporal sulcus reflects the processing and retrieval of semantic relations whereby specific memory contents seem to influence the direction of activation.

G72 is a vulnerability gene for schizophrenia and affective psychosis, disorders that are characterized by deficits in working memory. In the present study we investigated whether the G72 genotype influences verbal and spatial working memory functions in healthy individuals. Working memory was assessed at the behavioural level in 423 subjects using the spatial span of the Wechsler Memory Scale (spatial working memory) and the letter-number-span test (verbal working memory). In a sub-sample of 83 subjects, we assessed working memory functions also at the neural level using functional magnetic resonance imaging during a classical letter variant of the n-back task. Unexpectedly the high risk allele carriers performed better in the verbal working memory task than the other subjects. These behavioural differences were accompanied by brain activation differences in the right parahippocampus, a brain region that plays a major role in schizophrenia and affective disorders. The high risk variant of a vulnerability gene therefore does not necessarily have to negatively affect cognitive abilities per se, but may even have beneficial effects on cognitive functions in the non-affected population.