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Variation in the val158met polymorphism of the COMT gene has been found to be associated with cognitive performance. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal areas. Given the complex modulation and functional heterogeneity of frontal lobe systems, further specification of COMT gene-related phenotypes differing in prefrontally mediated cognitive performance are of major interest. Eighty healthy individuals (54 men, 26 women; mean age 23.3 years) performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (fMRI). COMT val158met genotype was determined and correlated with brain activation measured with fMRI during the task. Although there were no differences in performance, brain activation in the left inferior frontal gyrus [Brodmann area 10] was positively correlated with the number of val alleles in the COMT gene. COMT val158met status modulates brain activation during the language production on a semantic level in an area related to executive functions. [ABSTRACT FROM AUTHOR]

How do we switch between "playing along" and treating robots as technical agents? We propose interaction breakdowns to help solve this "social artifact puzzle": Breaks cause changes from fluid interaction to explicit reasoning and interaction with the raw artifact. These changes are closely linked to understanding the technical architecture and could be used to design better human–robot interaction (HRI). [ABSTRACT FROM AUTHOR]

Healthy sleep, positive general affect, and the ability to regulate emotional experiences are fundamental for well-being. In contrast, various mental disorders are associated with altered rapid eye movement (REM) sleep, negative affect, and diminished emotion regulation abilities. However, the neural processes mediating the relationship between these different phenomena are still not fully understood. In the present study of 42 healthy volunteers, we investigated the effects of selective REM sleep suppression (REMS) on general affect, as well as on feelings of social exclusion, cognitive reappraisal (CRA) of emotions, and their neural underpinnings. Using functional magnetic resonance imaging we show that, on the morning following sleep suppression, REMS increases general negative affect, enhances amygdala responses and alters its functional connectivity with anterior cingulate cortex during passively experienced experimental social exclusion. However, we did not find effects of REMS on subjective emotional ratings in response to social exclusion, their regulation using CRA, nor on functional amygdala connectivity while participants employed CRA. Our study supports the notion that REM sleep is important for affective processes, but emphasizes the need for future research to systematically investigate how REMS impacts different domains of affective experience and their neural correlates, in both healthy and (sub-)clinical populations. [ABSTRACT FROM AUTHOR]

During everyday interactions people constantly receive feedback on their behavior, which shapes their beliefs about themselves. While classic studies in the field of social learning suggest that people have a tendency to learn better from good news (positivity bias) when they perceive little opportunities to immediately improve their own performance, we show updating is biased towards negative information when participants perceive the opportunity to adapt their performance during learning. In three consecutive experiments we applied a computational modeling approach on the subjects' learning behavior and reveal the negativity bias was specific for learning about own compared to others' performances and was modulated by prior beliefs about the self, i.e. stronger negativity bias in individuals lower in self-esteem. Social anxiety affected self-related negativity biases only when individuals were exposed to a judging audience thereby potentially explaining the persistence of negative self-images in socially anxious individuals which commonly surfaces in social settings. Self-related belief formation is therefore surprisingly negatively biased in situations suggesting opportunities to improve and this bias is shaped by trait differences in self-esteem and social anxiety. [ABSTRACT FROM AUTHOR]

The emotional matching paradigm, introduced by Hariri and colleagues in 2000, is a widely used neuroimaging experiment that reliably activates the amygdala. In the classic version of the experiment faces with negative emotional expression and scenes depicting distressing events are compared with geometric shapes instead of neutral stimuli of the same category (i.e. faces or scenes). This makes it difficult to clearly attribute amygdala activation to the emotional valence and not to the social content. To improve this paradigm, we conducted a functional magnetic resonance imaging study in which emotionally neutral and, additionally, positive stimuli within each stimulus category (i.e. faces, social and non-social scenes) were included. These categories enabled us to differentiate the exact nature of observed effects in the amygdala. First, the main findings of the original paradigm were replicated. Second, we observed amygdala activation when comparing negative to neutral stimuli of the same category. However, for negative faces, the amygdala response habituated rapidly. Third, positive stimuli were associated with widespread activation including the insula and the caudate. This validated adaption study enables more precise statements on the neural activation underlying emotional processing. These advances may benefit future studies on identifying selective impairments in emotional and social stimulus processing. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Social interactions are dynamic, context-dependent, and reciprocal events that influence prospective strategies and require constant practice and adaptation. This complexity of social interactions creates several research challenges. We propose a new framework encouraging future research to investigate not only individual differences in capacities relevant for social functioning and their underlying mechanisms, but also the flexibility to adapt or update one's social abilities. We suggest three key capacities relevant for social functioning: (1) social perception, (2) sharing emotions or empathizing, and (3) mentalizing. We elaborate on how adaptations in these capacities may be investigated on behavioral and neural levels. Research on these flexible adaptations of one's social behavior is needed to specify how humans actually "learn to be social". Learning to adapt implies plasticity of the relevant brain networks involved in the underlying social processes, indicating that social abilities are malleable for different contexts. To quantify such measures, researchers need to find ways to investigate learning through dynamic changes in adaptable social paradigms and examine several factors influencing social functioning within the three aformentioned social key capacities. This framework furthers insight concerning individual differences, provides a holistic approach to social functioning, and may improve interventions for ameliorating social abilities in patients. • We propose a novel framework challenging the possibility to (un)learn, modify, or improve the capacity to "be social". • Researchers need to find ways to investigate learning through dynamic changes in adaptable social paradigms. • This framework enables a dimensional and transdiagnostic approach to study social capacities in line with the RDoC proposal. [ABSTRACT FROM AUTHOR]

The feedback people receive on their behavior shapes the process of belief formation and self-efficacy in mastering a particular task. However, the neural and computational mechanisms of how the subjective value of self-efficacy beliefs, and the corresponding affect, influence the learning process remain unclear. We investigated these mechanisms during self-efficacy belief formation using fMRI, pupillometry, and computational modeling, and by analyzing individual differences in affective experience. Biases in the formation of self-efficacy beliefs were associated with affect, pupil dilation, and neural activity within the anterior insula, amygdala, ventral tegmental area/ substantia nigra, and mPFC. Specifically, neural and pupil responses mapped the valence of the prediction errors in correspondence with individuals' experienced affective states and learning biases during self-efficacy belief formation. Together with the functional connectivity dynamics of the anterior insula within this network, our results provide evidence for neural and computational mechanisms of how we arrive at affected beliefs. Analyses of learning mechanisms, pupillometry, and fMRI data from healthy participants in a cognitive estimation task reveal neural dynamics related to how self-efficacy beliefs are formed, as well as how this process is impacted by emotions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This document is a correction to an article titled "The effect of the COMT val158met polymorphism on neural correlates of semantic verbal fluency." The correction provides a list of brain regions and their coordinates that are associated with semantic verbal fluency and reading aloud. The original article contained incorrect data in Table 2. The correction was made by Axel Krug and includes the contact information for the authors and their affiliations. [Extracted from the article]

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 &y& Elsevier]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dynamic causal modeling (DCM) is a Bayesian framework for inferring effective connectivity among brain regions from neuroimaging data. While the validity of DCM has been investigated in various previous studies, the reliability of DCM parameter estimates across sessions has been examined less systematically. Here, we report results of a software comparison with regard to test-retest reliability of DCM for fMRI, using a challenging scenario where complex models with many parameters were applied to relatively few data points. Specifically, we examined the reliability of different DCM implementations (in terms of the intra-class correlation coefficient, ICC) based on fMRI data from 35 human subjects performing a simple motor task in two separate sessions, one month apart. We constructed DCMs of motor regions with fair to excellent reliability of conventional activation measures. Using classical DCM (cDCM) in SPM5, we found that the test-retest reliability of DCM results was high, both concerning the model evidence (ICC = 0.94) and the model parameter estimates (median ICC = 0.47). However, when using a more recent DCM version (DCM10 in SPM8), test-retest reliability was reduced notably. Analyses indicated that, in our particular case, the prior distributions played a crucial role in this change in reliability across software versions. Specifically, when using cDCM priors for model inversion in DCM10, this not only restored reliability but yielded even better results than in cDCM. Analyzing each component of the objective function in DCM, we found a selective change in the reliability of posterior mean estimates. This suggests that tighter regularization afforded by cDCM priors reduces the possibility of local extrema in the objective function. We conclude this paper with an outlook to ongoing developments for overcoming the software-dependency of reliability observed in this study, including global optimization and empirical Bayesian procedures. [ABSTRACT FROM AUTHOR]

Abstract: We studied the somatovisceral response pattern of vicarious embarrassment for someone else''s inappropriate condition. Participants (N =54) were confronted with hand-drawn sketches depicting public situations and were instructed to rate the intensity of their vicarious embarrassment. The inappropriate condition varied according to the attribution of intentionality (absent/present) and awareness (absent/present). Irrespective of these attributions, participants reported stronger vicarious embarrassment in comparison to neutral situations. Across a set of eleven somatovisceral variables vicarious embarrassment elicited a pattern of increased autonomic activation which was modulated by the awareness of the protagonist about the ongoing norm violation. The somatovisceral response pattern matches previous findings for the first-person experience of embarrassment. Together, these results support the hypothesis that processes of perspective taking also mediate the vicarious experience of embarrassment. [Copyright &y& Elsevier]

Abstract: Ten years ago, neuroscientists began to study cultural phenomena by using functional MRI. Since then the number of publications in this field, termed cultural neuroscience (CN), has tremendously increased. In these studies, particular concepts of culture are implied, but rarely explicitly discussed. We argue that it is necessary to make these concepts a topic of debate in order to unravel the foundations of CN. From 40 fMRI studies we extracted two strands of reasoning: models investigating universal mechanisms for the formation of cultural groups and habits and, models assessing differences in characteristics among cultural groups. Both strands simplify culture as an inflexible set of traits and specificities. We question this rigid understanding of culture and highlight its hidden evaluative nature. [Copyright &y& Elsevier]

Abstract: Rhyming words, as in songs or poems, is a universal feature of human language across all ages. In the present fMRI study a novel overt rhyming task was applied to determine the neural correlates of rhyme production. Fifteen right-handed healthy male volunteers participated in this verbal fluency study. Participants were instructed to overtly articulate as many words as possible either to a given initial letter (LVF) or to a semantic category (SVF). During the rhyming verbal fluency task (RVF), participants had to generate words that rhymed with pseudoword stimuli. On-line overt verbal responses were audiotaped in order to correct the imaging results for the number of generated words. Fewer words were generated in the rhyming compared to both the lexical and the semantic condition. On a neural level, all language tasks activated a language network encompassing the left inferior frontal gyrus, the middle and superior temporal gyri as well as the contralateral right cerebellum. Rhyming verbal fluency compared to both lexical and semantic verbal fluency demonstrated significantly stronger activation of left inferior parietal region. Generating novel rhyme words seems to be mainly mediated by the left inferior parietal lobe, a region previously found to be associated with meta-phonological as well as sub-lexical linguistic processes. [Copyright &y& Elsevier]

Abstract: Background: Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be overrepresented in patients suffering from bipolar disorder, schizophrenia or major depression. While the functions underlying the pathophysiology of these psychiatric disorders are yet unknown, impaired performance in verbal fluency tasks is an often replicated finding. We investigated the influence of the rs1006737 single nucleotide polymorphism (SNP) on verbal fluency and its neural correlates. Methods: Brain activation was measured with functional magnetic resonance imaging (fMRI) during a semantic verbal fluency task in 63 healthy male individuals. They additionally performed more demanding verbal fluency tasks outside the scanner. All subjects were genotyped for CACNA1C rs1006737. Results: For the behavioral measures outside the scanner, rs1006737genotype had an effect on semantic but not on lexical verbal fluency with decreased performance in risk-allele carriers. In the fMRI experiment, while there were no differences in behavioural performance, increased activation in the left inferior frontal gyrus as well as the left precuneus was found in risk-allele carriers in the semantic verbal fluency task. Conclusions: The rs1006737 variant does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in bipolar disorder, schizophrenia and major depression and may explain some of the cognitive and brain activation variation found in these disorders. [Copyright &y& Elsevier]

Abstract: The ability to segment continuous linguistic information online into larger, meaningful units is a key element in narrative comprehension. Narrative shifts, i.e. transitions between individual units, are postulated to continuously update the mental situation model. Their cerebral correlates, however, have hardly been investigated. Under highly naturalistic conditions this study seeks to identify the neural correlates of implicit processing of narrative shifts during continuous speech comprehension. 16 male native German speakers listened passively to a German novella for 23 min while BOLD signal was recorded with fMRI. Text comprehension was tested in a short post-scan interview asking for critical episodes of the story. Narrative shifts were defined on the basis of a macropropositional analysis. Compared to listening to text passages of the narrative that neither contained narrative shifts nor structurally similar linguistic control events (i.e., sentence boundaries), narrative shifts evoked increased BOLD signal changes in the right temporal gyrus, precuneus and posterior/middle cingulate cortex bilaterally. When narrative shifts were contrasted with sentence boundaries, activation in the right precuneus and cingulate cortex remained significant. The results strengthen the relevance of medial parietal structures for natural language comprehension. More precisely, the precuneus and posterior cingulate appear to be the neural substrate for updating mental story representations and can be regarded as critical parts of a more complex, distributed neural network underlying story comprehension. [Copyright &y& Elsevier]