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Chiara C Brück Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the NetherlandsCorrespondence: Chiara C Brück, Email c.bruck@erasmusmc.nl View the original paper by Dr Zhang and colleagues

Introduction: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. Patients and Methods: 25 patients with Crohn’s disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. Results: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn’s disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p = 1). Discussion: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract Background To date, there are no empirically validated treatments of good quality for adolescents showing suicidality and non-suicidal self-injurious behavior. Risk factors for suicide are impulsive and non-suicidal self-injurious behavior, depression, conduct disorders and child abuse. Behind this background, we tested the main hypothesis of our study; that Dialectical Behavioral Therapy for Adolescents is an effective treatment for these patients. Methods Dialectical Behavioral Therapy (DBT) has been developed by Marsha Linehan - especially for the outpatient treatment of chronically non-suicidal patients diagnosed with borderline personality disorder. The modified version of DBT for Adolescents (DBT-A) from Rathus & Miller has been adapted for a 16-24 week outpatient treatment in the German-speaking area by our group. The efficacy of treatment was measured by a pre-/post- comparison and a one-year follow-up with the aid of standardized instruments (SCL-90-R, CBCL, YSR, ILC, CGI). Results In the pilot study, 12 adolescents were treated. At the beginning of therapy, 83% of patients fulfilled five or more DSM-IV criteria for borderline personality disorder. From the beginning of therapy to one year after its end, the mean value of these diagnostic criteria decreased significantly from 5.8 to 2.75. 75% of patients were kept in therapy. For the behavioral domains according to the SCL-90-R and YSR, we have found effect sizes between 0.54 and 2.14. During treatment, non-suicidal self-injurious behavior reduced significantly. Before the start of therapy, 8 of 12 patients had attempted suicide at least once. There were neither suicidal attempts during treatment with DBT-A nor at the one-year follow-up. Conclusions The promising results suggest that the interventions were well accepted by the patients and their families, and were associated with improvement in multiple domains including suicidality, non-suicidal self-injurious behavior, emotion dysregulation and depression from the beginning of therapy to the one-year follow-up.

Objectives: Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD., Methods: A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop., Results: Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (clinical dementia rating - sum of boxes, clinical dementia rating - global, mini-mental state examination, functional activities questionnaire) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6 to 5.2 years for control strategy and from 0.1 to 1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0 to 0.6 and incremental costs (excluding treatment costs) from -US$66 897 to US$11 896., Conclusions: Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend (1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, (2) a standardized reporting table for model predictions, and (3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health-economic models., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: The credibility of model-based economic evaluations of Alzheimer's disease (AD) interventions is central to appropriate decision-making in a policy context. We report on the International PharmacoEconomic Collaboration on Alzheimer's Disease (IPECAD) Modeling Workshop Challenge., Methods: Two common benchmark scenarios, for the hypothetical treatment of AD mild cognitive impairment (MCI) and mild dementia, were developed jointly by 29 participants. Model outcomes were summarized, and cross-comparisons were discussed during a structured workshop., Results: A broad concordance was established among participants. Mean 10-year restricted survival and time in MCI in the control group ranged across 10 MCI models from 6.7 to 9.5 years and 3.4 to 5.6 years, respectively; and across 4 mild dementia models from 5.4 to 7.9 years (survival) and 1.5 to 4.2 years (mild dementia)., Discussion: The model comparison increased our understanding of methods, data used, and disease progression. We established a collaboration framework to assess cost-effectiveness outcomes, an important step toward transparent and credible AD models., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Deficits in emotional perception are common in autistic people, but it remains unclear to which extent these perceptual impairments are linked to specific sensory modalities, specific emotions or multisensory facilitation., Methods: This study aimed to investigate uni- and bimodal perception of emotional cues as well as multisensory facilitation in autistic ( n  = 18, mean age: 36.72 years, SD: 11.36) compared to non-autistic ( n  = 18, mean age: 36.41 years, SD: 12.18) people using auditory, visual and audiovisual stimuli., Results: Lower identification accuracy and longer response time were revealed in high-functioning autistic people. These differences were independent of modality and emotion and showed large effect sizes (Cohen's d 0.8-1.2). Furthermore, multisensory facilitation of response time was observed in non-autistic people that was absent in autistic people, whereas no differences were found in multisensory facilitation of accuracy between the two groups., Discussion: These findings suggest that processing of auditory and visual components of audiovisual stimuli is carried out more separately in autistic individuals (with equivalent temporal demands required for processing of the respective unimodal cues), but still with similar relative improvement in accuracy, whereas earlier integrative multimodal merging of stimulus properties seems to occur in non-autistic individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hoffmann, Travers-Podmaniczky, Pelzl, Brück, Jacob, Hölz, Martinelli and Wildgruber.)

Laughter plays an important role in group formation, signaling social belongingness by indicating a positive or negative social intention towards the receiver. In adults without autism, the intention of laughter can be correctly differentiated without further contextual information. In autism spectrum disorder (ASD), however, differences in the perception and interpretation of social cues represent a key characteristic of the disorder. Studies suggest that these differences are associated with hypoactivation and altered connectivity among key nodes of the social perception network. How laughter, as a multimodal nonverbal social cue, is perceived and processed neurobiologically in association with autistic traits has not been assessed previously. We investigated differences in social intention attribution, neurobiological activation, and connectivity during audiovisual laughter perception in association with the degree of autistic traits in adults [N = 31, M age (SD) = 30.7 (10.0) years, n female  = 14]. An attenuated tendency to attribute positive social intention to laughter was found with increasing autistic traits. Neurobiologically, autistic trait scores were associated with decreased activation in the right inferior frontal cortex during laughter perception and with attenuated connectivity between the bilateral fusiform face area with bilateral inferior and lateral frontal, superior temporal, mid-cingulate and inferior parietal cortices. Results support hypoactivity and hypoconnectivity during social cue processing with increasing ASD symptoms between socioemotional face processing nodes and higher-order multimodal processing regions related to emotion identification and attribution of social intention. Furthermore, results reflect the importance of specifically including signals of positive social intention in future studies in ASD., (© 2023. The Author(s).)

Background: When receiving mismatching nonverbal and verbal signals, most people tend to base their judgment regarding the current emotional state of others primarily on nonverbal information. However, individuals with high-functioning autism (HFA) have been described as having difficulties interpreting nonverbal signals. Recognizing emotional states correctly is highly important for successful social interaction. Alterations in perception of nonverbal emotional cues presumably contribute to misunderstanding and impairments in social interactions., Methods: To evaluate autism-specific differences in the relative impact of nonverbal and verbal cues, 18 adults with HFA (14 male and four female subjects, mean age 36.7 years (SD 11.4) and 18 age, gender and IQ-matched typically developed controls [14 m/4 f, mean age 36.4 years (SD 12.2)] rated the emotional state of speakers in video sequences with partly mismatching emotional signals. Standardized linear regression coefficients were calculated as a measure of the reliance on the nonverbal and verbal components of the videos for each participant. Regression coefficients were then compared between groups to test the hypothesis that autistic adults base their social evaluations less strongly on nonverbal information. Further exploratory analyses were performed for differences in valence ratings and response times., Results: Compared to the typically developed control group, nonverbal cue reliance was reduced in adults with high-functioning autism [ t (23.14) = -2.44, p = 0.01 (one-sided)]. Furthermore, the exploratory analyses showed a tendency to avoid extreme answers in the HFA group, observable via less positive as well as less negative valence ratings in response to emotional expressions of increasingly strong valence. In addition, response time was generally longer in HFA compared to the control group [ F (1, 33) = 10.65, p = 0.004]., Conclusion: These findings suggest reduced impact of nonverbal cues and longer processing times in the analysis of multimodal emotional information, which may be associated with a subjectively lower relevance of this information and/or more processing difficulties for people with HFA. The less extreme answering tendency may indicate a lower sensitivity for nonverbal valence expression in HFA or result from a tendency to avoid incorrect answers when confronted with greater uncertainty in interpreting emotional states., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pelzl, Travers-Podmaniczky, Brück, Jacob, Hoffmann, Martinelli, Hölz, Wabersich-Flad and Wildgruber.)

Objective: SLE is an autoimmune disease with a complex pathogenesis. T-cell infiltration into organs contributes to inflammation and organ damage in SLE. Recently, G-protein signalling modulator 2 (GPSM2) has been shown to be implicated in T-cell migration., Methods: We analysed the expression levels of GPSM2 and of a truncated isoform of GPSM2 containing the GoLoco motif region in CD4 + T cells from patients with SLE and from healthy individuals by western blot. In a next step, we studied the role of the truncated GPSM2 isoform using a CD4 + T-cell migration assay., Results: Our experiments revealed comparable levels of GPSM2 in CD4 + T cells from patients with SLE and healthy controls. In contrast, the truncated 35 kDa isoform of GPSM2 was significantly more highly expressed in CD4 + T cells from patients with SLE as compared with healthy subjects. Antibody-mediated blockade of the 35 kDa GPSM2 isoform reduced the in vitro capacity of CD4 + T cells to migrate towards the chemokine CCL20., Conclusions: A truncated GPSM2 isoform containing the GoLoco motif region is upregulated in CD4 + T cells from patients with SLE and promotes CD4 + T-cell migration. Targeting this isoform with specific antibodies might be a promising approach to reduce CD4 + T-cell infiltration into inflamed tissues and to prevent organ damage in SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Human nonverbal social signals are transmitted to a large extent by vocal and facial cues. The prominent importance of these cues is reflected in specialized cerebral regions which preferentially respond to these stimuli, e.g. the temporal voice area (TVA) for human voices and the fusiform face area (FFA) for human faces. But it remained up to date unknown whether there are respective specializations during resting state, i.e. in the absence of any cues, and if so, whether these representations share neural substrates across sensory modalities. In the present study, resting state functional connectivity (RSFC) as well as voice- and face-preferential activations were analysed from functional magnetic resonance imaging (fMRI) data sets of 60 healthy individuals. Data analysis comprised seed-based analyses using the TVA and FFA as regions of interest (ROIs) as well as multi voxel pattern analyses (MVPA). Using the face- and voice-preferential responses of the FFA and TVA as regressors, we identified several correlating clusters during resting state spread across frontal, temporal, parietal and occipital regions. Using these regions as seeds, characteristic and distinct network patterns were apparent with a predominantly convergent pattern for the bilateral TVAs whereas a largely divergent pattern was observed for the bilateral FFAs. One region in the anterior medial frontal cortex displayed a maximum of supramodal convergence of informative connectivity patterns reflecting voice- and face-preferential responses of both TVAs and the right FFA, pointing to shared neural resources in supramodal voice and face processing. The association of individual voice- and face-preferential neural activity with resting state connectivity patterns may support the perspective of a network function of the brain beyond an activation of specialized regions., (© 2022. The Author(s).)

Background: The cell surface molecule CD6 is a modulator of T cell receptor (TCR) signaling. Recently, it has been reported that CD6 is downregulated on CD4+ T cells following T cell activation. This mechanism could limit the efficacy of anti-CD6 therapeutical antibodies., Methods: We analyzed CD6 expression on activated and non-activated Th1 cells and Th17 cells by flow cytometry., Results: Our experiments confirmed a significant downregulation of CD6 on IFNγ- and IL17-negative CD4+ T cells from healthy individuals and from patients with rheumatoid arthritis following T cell activation with anti-CD3 and anti-CD28 antibodies. In contrast, CD6 expression remained stable on activated Th17 cells and Th1 cells., Conclusions: Th1 and Th17 cells are resistant towards T cell activation-induced downregulation of CD6. These findings are relevant for the future development of CD6 targeting therapies and show that CD6 expression is differentially regulated in CD4+ T cell subsets., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Faces and voices are very important sources of threat in social anxiety disorder (SAD), a common psychiatric disorder where core elements are fears of social exclusion and negative evaluation. Previous research in social anxiety evidenced increased cerebral responses to negative facial or vocal expressions and also generally increased hemodynamic responses to voices and faces. But it is unclear if also the cerebral process of face-voice-integration is altered in SAD. Applying functional magnetic resonance imaging, we investigated the correlates of the audiovisual integration of dynamic faces and voices in SAD as compared to healthy individuals. In the bilateral midsections of the superior temporal sulcus (STS) increased integration effects in SAD were observed driven by greater activation increases during audiovisual stimulation as compared to auditory stimulation. This effect was accompanied by increased functional connectivity with the visual association cortex and a more anterior position of the individual integration maxima along the STS in SAD. These findings demonstrate that the audiovisual integration of facial and vocal cues in SAD is not only systematically altered with regard to intensity and connectivity but also the individual location of the integration areas within the STS. These combined findings offer a novel perspective on the neuronal representation of social signal processing in individuals suffering from SAD., (Copyright © 2020 Kreifelts, Ethofer, Wiegand, Brück, Wächter, Erb, Lotze and Wildgruber.)

Voices and faces are the most common sources of threat in social anxiety (SA) where the fear of negative evaluation and social exclusion is the central element. SA itself is spectrally distributed among the general population and its clinical manifestation, termed social anxiety disorder, is one of the most common anxiety disorders. While heightened cerebral responses to angry or contemptuous facial or vocal expressions are well documented, it remains unclear if the brain of socially anxious individuals is generally more sensitive to voices and faces. Using functional magnetic resonance imaging, we investigated how SA affects the cerebral processing of voices and faces as compared to various other stimulus types in a study population with greatly varying SA (N = 50, 26 female). While cerebral voice-sensitivity correlated positively with SA in the left temporal voice area (TVA) and the left amygdala, an association of face-sensitivity and SA was observed in the right fusiform face area (FFA) and the face processing area of the right posterior superior temporal sulcus (pSTSFA). These results demonstrate that the increase of cerebral responses associated with social anxiety is not limited to facial or vocal expressions of social threat but that the respective sensory and emotion processing structures are also generally tuned to voices and faces., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Social anxiety (SA) comprises a multitude of persistent fears around the central element of dreaded negative evaluation and exclusion. This very common anxiety is spectrally distributed among the general population and associated with social perception biases deemed causal in its maintenance. Here, we investigated cerebral resting state markers linking SA and biased social perception. To this end, resting state functional connectivity (RSFC) was assessed as the neurobiological marker in a study population with greatly varying SA using fMRI in the first step of the experiment. One month later the impact of unattended laughter-exemplifying social threat-on a face rating task was evaluated as a measure of biased social perception. Applying a dimensional approach, SA-related cognitive biases tied to the valence, dominance and arousal of the threat signal and their underlying RSFC patterns among central nodes of the cerebral emotion, voice and face processing networks were identified. In particular, the connectivity patterns between the amygdalae and the right temporal voice area met all criteria for a cerebral mediation of the association between SA and the laughter valence-related interpretation bias. Thus, beyond this identification of non-state-dependent cerebral markers of biased perception in SA, this study highlights both a starting point and targets for future research on the causal relationships between cerebral connectivity patterns, SA and biased perception, potentially via neurofeedback methods.

Facial expressions and voice modulations are among the most important communicational signals to convey emotional information. The ability to correctly interpret this information is highly relevant for successful social interaction and represents an integral component of emotional competencies that have been conceptualized under the term emotional intelligence. Here, we investigated the relationship of emotional intelligence as measured with the Salovey-Caruso-Emotional-Intelligence-Test (MSCEIT) with cerebral voice and face processing using functional and structural magnetic resonance imaging. MSCEIT scores were positively correlated with increased voice-sensitivity and gray matter volume of the insula accompanied by voice-sensitivity enhanced connectivity between the insula and the temporal voice area, indicating generally increased salience of voices. Conversely, in the face processing system, higher MSCEIT scores were associated with decreased face-sensitivity and gray matter volume of the fusiform face area. Taken together, these findings point to an alteration in the balance of cerebral voice and face processing systems in the form of an attenuated face-vs-voice bias as one potential factor underpinning emotional intelligence.

Building on the assumption of a possible link between biases in social information processing frequently associated with borderline personality disorder (BPD) and the occurrence of gelotophobia (i.e., a fear of being laughed at), the present study aimed at evaluating the prevalence rate of gelotophobia among BPD patients. Using the Geloph<15> , a questionnaire that allows a standardized assessment of the presence and severity of gelotophobia symptoms, rates of gelotophobia were assessed in a group of 30 female BPD patients and compared to data gathered in clinical and non-clinical reference groups. Results indicate a high prevalence of gelotophobia among BPD patients with 87% of BPD patients meeting the Geloph<15> criterion for being classified as gelotophobic. Compared to other clinical and non-clinical reference groups, the rate of gelotophobia among BPD patients appears to be remarkably high, far exceeding the numbers reported for other groups in the literature to date, with 30% of BPD patients reaching extreme levels, 37% pronounced levels, and 20% slight levels of gelotophobia.

Studies conducted in patients diagnosed with borderline personality disorder (BPD) have documented a variety of anomalies concerning patients' abilities to interpret emotional signals. Attempting to clarify the bases of these anomalies, the current literature draws attention to a possible role of dysfunctional expectations, such as the expectation of social rejection. Dysfunctional expectations, however, may not only bias social interpretations, but may also focus attention on social cues most important in conveying emotional messages, such as nonverbal signals. To explore these assumptions, 30 female BPD patients were tasked to judge the valence of emotional states conveyed by combinations of verbal and nonverbal emotional cues. Compared to controls, BPD patients exhibited a negative bias in their interpretations and relied more on available nonverbal cues. Shifts in the relative importance of nonverbal cues appeared to be rooted mainly in a reduced reliance on positive verbal cues presumably deemed less credible by BPD patients.

Social anxiety disorder (SAD) is characterized by negatively biased perception of social cues and deficits in emotion regulation. While negatively biased perception is thought to maintain social anxiety, emotion regulation represents an ability necessary to overcome both biased perception and social anxiety. Here, we used laughter as a social threat in a functional magnetic resonance imaging (fMRI) study to identify cerebral mediators linking SAD with attention and interpretation biases and their modification through cognitive emotion regulation in the form of reappraisal. We found that reappraisal abolished the negative laughter interpretation bias in SAD and that this process was directly mediated through activation patterns of the left dorsolateral prefrontal cortex (DLPFC) serving as a cerebral pivot between biased social perception and its normalization through reappraisal. Connectivity analyses revealed reduced prefrontal control over threat-processing sensory cortices (here: the temporal voice area) during cognitive emotion regulation in SAD. Our results indicate a central role for the left DLPFC in SAD which might represent a valuable target for future research on interventions either aiming to directly modulate cognitive emotion regulation in SAD or to evaluate its potential as physiological marker for psychotherapeutic interventions relying on emotion regulation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

People diagnosed with autism spectrum disorder (ASD) characteristically present with severe difficulties in interpreting every-day social signals. Currently it is assumed that these difficulties might have neurobiological correlates in alterations in activation as well as in connectivity in and between regions of the social perception network suggested to govern the processing of social cues. In this study, we conducted functional magnetic resonance imaging (fMRI)-based activation and connectivity analyses focusing on face-, voice-, and audiovisual-processing brain regions as the most important subareas of the social perception network. Results revealed alterations in connectivity among regions involved in the processing of social stimuli in ASD subjects compared to typically developed (TD) controls-specifically, a reduced connectivity between the left temporal voice area (TVA) and the superior and medial frontal gyrus. Alterations in connectivity, moreover, were correlated with the severity of autistic traits: correlation analysis indicated that the connectivity between the left TVA and the limbic lobe, anterior cingulate and the medial frontal gyrus as well as between the right TVA and the frontal lobe, anterior cingulate, limbic lobe and the caudate decreased with increasing symptom severity. As these frontal regions are understood to play an important role in interpreting and mentalizing social signals, the observed underconnectivity might be construed as playing a role in social impairments in ASD.

In day-to-day social interaction, emotions are usually expressed by verbal (e.g. spoken words) and nonverbal signals (e.g. facial expressions, prosody). In case of conflicting signals nonverbal signals are perceived as being the more reliable source of information. Deficits in interpreting nonverbal signals - as described for patients with schizophrenic disorders - might interfere with the ability to integrate verbal and nonverbal social cues into a meaningful whole. The aim of this study was to examine how schizophrenic disorders influence the integration of verbal and nonverbal signals. For this purpose short video sequences were presented to 21 patients with schizophrenia and 21 healthy controls. Each sequence showed an actor speaking a short sentence with independently varying emotional connotations at the verbal and the nonverbal level. The participants rated the valence of the speaker's emotional state on a four-point scale (from very negative to very positive). The relative impact of nonverbal cues as compared to verbal cues on these ratings was evaluated. Both groups base their decisions primarily on nonverbal information. However, this effect is significantly less prominent in the patient group. Patients tend to base their decisions less on nonverbal signals and more on verbal information than healthy controls., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Impaired interpretation of nonverbal emotional cues in patients with schizophrenia has been reported in several studies and a clinical relevance of these deficits for social functioning has been assumed. However, it is unclear to what extent the impairments depend on specific emotions or specific channels of nonverbal communication., Methods: Here, the effect of cue modality and emotional categories on accuracy of emotion recognition was evaluated in 21 patients with schizophrenia and compared to a healthy control group (n = 21). To this end, dynamic stimuli comprising speakers of both genders in three different sensory modalities (auditory, visual and audiovisual) and five emotional categories (happy, alluring, neutral, angry and disgusted) were used., Results: Patients with schizophrenia were found to be impaired in emotion recognition in comparison to the control group across all stimuli. Considering specific emotions more severe deficits were revealed in the recognition of alluring stimuli and less severe deficits in the recognition of disgusted stimuli as compared to all other emotions. Regarding cue modality the extent of the impairment in emotional recognition did not significantly differ between auditory and visual cues across all emotional categories. However, patients with schizophrenia showed significantly more severe disturbances for vocal as compared to facial cues when sexual interest is expressed (alluring stimuli), whereas more severe disturbances for facial as compared to vocal cues were observed when happiness or anger is expressed., Conclusion: Our results confirmed that perceptual impairments can be observed for vocal as well as facial cues conveying various social and emotional connotations. The observed differences in severity of impairments with most severe deficits for alluring expressions might be related to specific difficulties in recognizing the complex social emotional information of interpersonal intentions as compared to "basic" emotional states. Therefore, future studies evaluating perception of nonverbal cues should consider a broader range of social and emotional signals beyond basic emotions including attitudes and interpersonal intentions. Identifying specific domains of social perception particularly prone for misunderstandings in patients with schizophrenia might allow for a refinement of interventions aiming at improving social functioning.

Background: Laughter is a powerful signal of social acceptance or rejection while the fear of being embarrassed and humiliated is central in social anxiety (SA). This type of anxiety is associated with cognitive biases indicating increased sensitivity to social threat as well as with deficits in emotion regulation. Both are thought to be implicated in the maintenance of social anxiety., Method: Using laughter as a novel stimulus, we investigated cognitive biases and their modulation through emotion regulation and cue ambiguity in individuals with varying degrees of SA (N = 60)., Results: A combination of a negative laughter interpretation bias and an attention bias away from joyful/social inclusive laughter in SA was observed. Both biases were not attributable to effects of general anxiety and were closely correlated with the concept of gelotophobia, the fear of being laughed at., Discussion: Thus, our study demonstrates altered laughter perception in SA. Furthermore, it highlights the usefulness of laughter as a highly prevalent social signal for future research on the interrelations of interpretation and attention biases in SA and their modulation through emotion regulation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

While non-verbal affective voice cues are generally recognized as a crucial behavioral guide in any day-to-day conversation their role as a powerful source of information may extend well beyond close-up personal interactions and include other modes of communication such as written discourse or literature as well. Building on the assumption that similarities between the different 'modes' of voice cues may not only be limited to their functional role but may also include cerebral mechanisms engaged in the decoding process, the present functional magnetic resonance imaging study aimed at exploring brain responses associated with processing emotional voice signals described in literary texts. Emphasis was placed on evaluating 'voice' sensitive as well as task- and emotion-related modulations of brain activation frequently associated with the decoding of acoustic vocal cues. Obtained findings suggest that several similarities emerge with respect to the perception of acoustic voice signals: results identify the superior temporal, lateral and medial frontal cortex as well as the posterior cingulate cortex and cerebellum to contribute to the decoding process, with similarities to acoustic voice perception reflected in a 'voice'-cue preference of temporal voice areas as well as an emotion-related modulation of the medial frontal cortex and a task-modulated response of the lateral frontal cortex., (© The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

A great number of functional imaging studies contributed to developing a cerebral network model illustrating the processing of prosody in the brain. According to this model, the processing of prosodic emotional signals is divided into three main steps, each related to different brain areas. The present study sought to evaluate parts of the aforementioned model by using low-frequency repetitive transcranial magnetic stimulation (rTMS) over two important brain regions identified by the model: the superior temporal cortex (Experiment 1) and the inferior frontal cortex (Experiment 2). The aim of both experiments was to reduce cortical activity in the respective brain areas and evaluate whether these reductions lead to measurable behavioral effects during prosody processing. However, results obtained in this study revealed no rTMS effects on the acquired behavioral data. Possible explanations for these findings are discussed in the paper.

The fear of embarrassment and humiliation is the central element of social anxiety. This frequent condition is associated with cognitive biases indicating increased sensitivity to signals of social threat, which are assumed to play a causal role in the maintenance of social anxiety. Here, we employed laughter, a potent medium for the expression of acceptance and rejection, as an experimental stimulus in participants selected for varying degrees of social anxiety to identify cerebral mediators of cognitive biases in social anxiety using functional magnetic resonance imaging in combination with mediation analysis. We directly demonstrated that cerebral activation patterns within the dorsal attention network including the left dorsolateral and dorsomedial prefrontal cortex mediate the influence of social anxiety on laughter perception. This mediation proved to be specific for social anxiety after correction for measures of general state and trait anxiety and occurred most prominently under bimodal audiovisual laughter presentation when compared with monomodal auditory or visual laughter cues. Considering the possibility to modulate cognitive biases and cerebral activity by neuropsychological trainings, non-invasive electrophysiological stimulation and psychotherapy, this study represents a starting point for a whole line of translational research projects and identifies promising targets for electrophysiological interventions aiming to alleviate cognitive biases and symptom severity in social anxiety.

Emotional information can be conveyed by verbal and nonverbal cues with the latter often suggested to exert a greater influence in shaping our perceptions of others. The present functional magnetic resonance imaging study sought to explore attentional biases toward nonverbal signals by investigating the interaction of verbal and nonverbal cues. Results obtained in this study underline the previous suggestions of a "nonverbal dominance" in emotion communication by evidencing implicit effects of nonverbal cues on emotion judgements even when attention is directed away from nonverbal signals and focused on verbal cues. Attentional biases toward nonverbal signals appeared to be reflected in increasing activation of the dorsolateral prefrontal cortex (DLPFC) assumed to reflect increasing difficulties to suppress nonverbal cues during task conditions that asked to shift attention away from nonverbal signals. Aside the DLPFC, results suggest the right amygdala to play a role in attention control mechanisms related to the processing of emotional cues. Analyses conducted to determine the cerebral correlates of the individual ability to shift attention between verbal and nonverbal sources of information indicated that higher task-switching abilities seem to be associated with the up-regulation of right amygdala activation during explicit judgments of nonverbal cues, whereas difficulties in task-switching seem to be related to a down-regulation.

The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure.

Laughter is an ancient signal of social communication among humans and non-human primates. Laughter types with complex social functions (e.g., taunt and joy) presumably evolved from the unequivocal and reflex-like social bonding signal of tickling laughter already present in non-human primates. Here, we investigated the modulations of cerebral connectivity associated with different laughter types as well as the effects of attention shifts between implicit and explicit processing of social information conveyed by laughter using functional magnetic resonance imaging (fMRI). Complex social laughter types and tickling laughter were found to modulate connectivity in two distinguishable but partially overlapping parts of the laughter perception network irrespective of task instructions. Connectivity changes, presumably related to the higher acoustic complexity of tickling laughter, occurred between areas in the prefrontal cortex and the auditory association cortex, potentially reflecting higher demands on acoustic analysis associated with increased information load on auditory attention, working memory, evaluation and response selection processes. In contrast, the higher degree of socio-relational information in complex social laughter types was linked to increases of connectivity between auditory association cortices, the right dorsolateral prefrontal cortex and brain areas associated with mentalizing as well as areas in the visual associative cortex. These modulations might reflect automatic analysis of acoustic features, attention direction to informative aspects of the laughter signal and the retention of those in working memory during evaluation processes. These processes may be associated with visual imagery supporting the formation of inferences on the intentions of our social counterparts. Here, the right dorsolateral precentral cortex appears as a network node potentially linking the functions of auditory and visual associative sensory cortices with those of the mentalizing-associated anterior mediofrontal cortex during the decoding of social information in laughter.

Emotional communication uses verbal and nonverbal means. In case of conflicting signals, nonverbal information is assumed to have a stronger impact. It is unclear, however, whether perceptual nonverbal dominance varies between individuals and whether it is linked to emotional intelligence. Using audiovisual stimulus material comprising verbal and nonverbal emotional cues that were varied independently, perceptual nonverbal dominance profiles and their relations to emotional intelligence were examined. Nonverbal dominance was found in every participant, ranging from 55 to 100%. Moreover, emotional intelligence, particularly the ability to understand emotions, correlated positively with nonverbal dominance. Furthermore, higher overall emotional intelligence as well as a higher ability to understand emotions were linked to smaller reaction time differences between emotionally incongruent and congruent stimuli. The association between perceptual nonverbal dominance and emotional intelligence, and more specifically the ability to understand emotions, might reflect an adaptive process driven by the experience of higher authenticity in nonverbal cues.

Emotional communication is essential for successful social interactions. Emotional information can be expressed at verbal and nonverbal levels. If the verbal message contradicts the nonverbal expression, usually the nonverbal information is perceived as being more authentic, revealing the "true feelings" of the speaker. The present fMRI study investigated the cerebral integration of verbal (sentences expressing the emotional state of the speaker) and nonverbal (facial expressions and tone of voice) emotional signals using ecologically valid audiovisual stimulus material. More specifically, cerebral activation associated with the relative impact of nonverbal information on judging the affective state of a speaker (individual nonverbal dominance index, INDI) was investigated. Perception of nonverbally expressed emotions was associated with bilateral activation within the amygdala, fusiform face area (FFA), temporal voice area (TVA), and the posterior temporal cortex as well as in the midbrain and left inferior orbitofrontal cortex (OFC)/left insula. Verbally conveyed emotions were linked to increased responses bilaterally in the TVA. Furthermore, the INDI correlated with responses in the left amygdala elicited by nonverbal and verbal emotional stimuli. Correlation of the INDI with the activation within the medial OFC was observed during the processing of communicative signals. These results suggest that individuals with a higher degree of nonverbal dominance have an increased sensitivity not only to nonverbal but to emotional stimuli in general., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Just as eyes are often considered a gateway to the soul, the human voice offers a window through which we gain access to our fellow human beings' minds - their attitudes, intentions and feelings. Whether in talking or singing, crying or laughing, sighing or screaming, the sheer sound of a voice communicates a wealth of information that, in turn, may serve the observant listener as valuable guidepost in social interaction. But how do human beings extract information from the tone of a voice? In an attempt to answer this question, the present article reviews empirical evidence detailing the cerebral processes that underlie our ability to decode emotional information from vocal signals. The review will focus primarily on two prominent classes of vocal emotion cues: laughter and speech prosody (i.e. the tone of voice while speaking). Following a brief introduction, behavioral as well as neuroimaging data will be summarized that allows to outline cerebral mechanisms associated with the decoding of emotional voice cues, as well as the influence of various context variables (e.g. co-occurring facial and verbal emotional signals, attention focus, person-specific parameters such as gender and personality) on the respective processes. Building on the presented evidence, a cerebral network model will be introduced that proposes a differential contribution of various cortical and subcortical brain structures to the processing of emotional voice signals both in isolation and in context of accompanying (facial and verbal) emotional cues., (Copyright © 2011 Elsevier B.V. All rights reserved.)

While several studies have focused on identifying common brain mechanisms governing the decoding of emotional speech melody, interindividual variations in the cerebral processing of prosodic information, in comparison, have received only little attention to date: Albeit, for instance, differences in personality among individuals have been shown to modulate emotional brain responses, personality influences on the neural basis of prosody decoding have not been investigated systematically yet. Thus, the present study aimed at delineating relationships between interindividual differences in personality and hemodynamic responses evoked by emotional speech melody. To determine personality-dependent modulations of brain reactivity, fMRI activation patterns during the processing of emotional speech cues were acquired from 24 healthy volunteers and subsequently correlated with individual trait measures of extraversion and neuroticism obtained for each participant. Whereas correlation analysis did not indicate any link between brain activation and extraversion, strong positive correlations between measures of neuroticism and hemodynamic responses of the right amygdala, the left postcentral gyrus as well as medial frontal structures including the right anterior cingulate cortex emerged, suggesting that brain mechanisms mediating the decoding of emotional speech melody may vary depending on differences in neuroticism among individuals. Observed trait-specific modulations are discussed in the light of processing biases as well as differences in emotion control or task strategies which may be associated with the personality trait of neuroticism., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Although impaired decoding of emotional prosody has frequently been associated with Parkinson's disease (PD), to date only few reports have sought to explore the effect of Parkinson's treatment on disturbances of prosody decoding. In particular, little is known about how surgical treatment approaches such as high frequency deep brain stimulation (DBS) affect emotional speech perception in patients with PD. Accordingly, the objective of this study was to evaluate the effect of subthalamic nucleus (STN) stimulation on prosody processing., Methodology/principal Findings: To this end the performance of 13 PD patients on three tasks requiring the decoding of emotional speech was assessed and subsequently compared to the performance of healthy control individuals. To delineate the effect of STN-DBS, all patients were tested with stimulators turned on as well as with stimulators turned off. Results revealed that irrespective of whether assessments were made "on" or "off" stimulation, patients' performance was less accurate as compared to healthy control participants on all tasks employed in this study. However, while accuracy appeared to be unaffected by stimulator status, a facilitation of reactions specific to highly conflicting emotional stimulus material (i.e. stimulus material presenting contradicting emotional messages on a verbal and non-verbal prosodic level) was observed during "on" stimulation assessments., Conclusion: In sum, presented results suggest that the processing of emotional speech is indeed modulated by STN-DBS. Observed alterations might, on the one hand, reflect a more efficient processing of highly conflicting stimulus material following DBS. However, on the other hand, given the lack of an improvement in accuracy, increased impulsivity associated with STN stimulation needs to be taken into consideration.