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Emotional facial expressions elicit distinct increased early electrophysiological responses. Many studies report even emotional modulations of very early sensory processing at about 80 and 100 ms after stimulus presentation, indexed by the P1. These early effects are often interpreted to index differential responses to biologically relevant expressions. Since specific spatial frequencies differ between fearful and neutral expressions, it has recently been suggested that these early modulations are substantially driven by such low-level visual differences. However, it remains unclear whether similar P1 effects are also observed in experiments in which no recognizable face information is presented at all. This study investigated this question and explored also whether any effects depend on colour information and attentional conditions. Participants (N = 20) performed a continuous perceptual task of low or high difficultly and were presented with task-irrelevant black/white and colour images of fearful and neutral faces, rendered unrecognizable by doing Fourier phase transformation. ERP findings revealed increased P1 amplitudes for fearful scrambles regardless of experimental conditions. Taken together, our findings show early emotional effects in the absence of any facial expression. Specific low-level frequency information seems to increase P1 amplitudes which thus might have implications for the interpretation of very early sensory emotional expression effects.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

There is an ongoing debate on how different components of the event-related potential (ERP) to threat-related facial expressions are modulated by attentional conditions and interindividual differences in trait anxiety. In the current study (N = 80), we examined ERPs to centrally presented, task-irrelevant fearful and neutral faces, while participants had to solve a face-unrelated visual task, which differed in difficulty and spatial position. Critically, we used a fixation-controlled experimental design and ensured the spatial attention manipulation by spectral analysis of the EEG. Besides the factors emotion, spatial attention, and perceptual load, we also investigated correlations between trait anxiety and ERPs. While P1 emotion effects were insignificant, the N170 was increased to fearful faces regardless of load and spatial attention conditions. During the EPN time window, a significantly increased negativity for fearful faces was observed only during low load and spatial attention to the face. We found no significant relationship between ERPs and trait anxiety, questioning the hypothesis of a general hypersensitivity toward fearful expressions in anxious individuals. These results show a high resistance of the N170 amplitude increase for fearful faces to spatial attention and task load manipulations. By contrast, the EPN modulation by fearful faces index a resource-dependent stage of the ERP, requiring both spatial attention at the location of faces and low load of the face-irrelevant task.

In a previous study, we investigated the resting‐state fMRI effective connectivity (EC) between the bed nucleus of the stria terminalis (BNST) and the laterobasal (LB), centromedial (CM), and superficial (SF) amygdala. We found strong negative EC from all amygdala nuclei to the BNST, while the BNST showed positive EC to the amygdala. However, the validity of these findings remains unclear, since a reproduction in different samples has not been done. Moreover, the association of EC with measures of anxiety offers deeper insight, due to the known role of the BNST and amygdala in fear and anxiety. Here, we aimed to reproduce our previous results in three additional samples. We used spectral Dynamic Causal Modeling to estimate the EC between the BNST, the LB, CM, and SF, and its association with two measures of self‐reported anxiety. Our results revealed consistency over samples with regard to the negative EC from the amygdala nuclei to the BNST, while the positive EC from BNST to the amygdala was also found, but weaker and more heterogenic. Moreover, we found the BNST‐BNST EC showing a positive and the CM‐BNST EC, showing a negative association with anxiety. Our study suggests a reproducible pattern of negative EC from the amygdala to the BNST along with weaker positive EC from the BNST to the amygdala. Moreover, less BNST self‐inhibition and more inhibitory influence from the CM to the BNST seems to be a pattern of EC that is related to higher anxiety., We investigated the reproducibility of resting‐state fMRI effective connectivity (EC) between the bed nucleus of the stria terminalis (BNST) and amygdala nuclei and its relation to anxiety. We found a reproducible pattern of negative EC from the amygdala to the BNST and a positive EC from the BNST to the amygdala. Less BNST self‐inhibition and higher inhibitory influence from the CM to the BNST was associated with higher anxiety.

Higher social relevance has been shown to modulate event-related potentials (ERPs). It is unclear whether such modulations can be observed if one only imagines stimuli to be socially relevant. In a preregistered EEG study (

To date it is poorly understood how and when deviance processing interacts with awareness and task relevance. Furthermore, an important issue in the study of consciousness is the prevalent confound of conscious perception with the requirement of reporting it. This study addresses these topics using a no-report inattentional blindness paradigm with a visual oddball sequence of geometrical shapes presented to male and female human participants. Electrophysiological responses were obtained in three physically identical Phases A–C that differed only with respect to the instructions: (A) participants were uninformed about the shapes and attended an unrelated foreground task (inattentional blind), (B) were informed about the shapes but still attended the foreground task, and (C) attended the shapes. Conscious processing of shapes was indexed by the visual awareness negativity but not a P3. Deviance processing was associated with the visual mismatch negativity independently of consciousness and task relevance. The oddball P3, however, only emerged when the stimuli were task relevant, and was absent for consciously perceived but task irrelevant stimuli. The P3 thus does not represent a reliable marker of stimulus awareness. This result pattern supports the view of hierarchical predictive processing, where lower levels display automatic deviance processing, whereas higher levels require attention and task relevance.SIGNIFICANCE STATEMENTTo react to potentially important changes in our environment it is fundamental to detect deviations from regularities of sensory input. It has yet to be understood how awareness and task relevance of this input interact with deviance processing. We investigated the role of awareness in deviance detection while at the same time circumventing the confound of awareness and report by means of a no-report paradigm. Our results suggest that early processes are elicited automatically, whereas, contrary to prominent theories, late processes do not depend on awareness but on task-based attention.

Until today, there is an ongoing discussion if attention processes interact with the information processing stream already at the level of the C1, the earliest visual electrophysiological response of the cortex. We used two highly powered experiments (each N = 52) and examined the effects of task relevance, spatial attention, and attentional load on individual C1 amplitudes for the upper or lower visual hemifield. Bayesian models revealed evidence for the absence of load effects but substantial modulations by task-relevance and spatial attention. When the C1-eliciting stimulus was a task-irrelevant, interfering distracter, we observed increased C1 amplitudes for spatially unattended stimuli. For spatially attended stimuli, different effects of task-relevance for the two experiments were found. Follow-up exploratory single-trial analyses revealed that subtle but systematic deviations from the eye-gaze position at stimulus onset between conditions substantially influenced the effects of attention and task relevance on C1 amplitudes, especially for the upper visual field. For the subsequent P1 component, attentional modulations were clearly expressed and remained unaffected by these deviations. Collectively, these results suggest that spatial attention, unlike load or task relevance, can exert dissociable top-down modulatory effects at the C1 and P1 levels.

Models of anxiety disorders and the rationale of exposure therapy (ET) are grounded on classical fear conditioning. Yet, it is unclear whether lower fear ratings of conditioned safety versus threat cues and corresponding neural markers of safety-learning and/or fear inhibition assessed before treatment would predict better outcomes of behavioral exposure.Sixty-six patients with spider phobia completed pre-treatment clinical and experimental fear conditioning assessments, one session of virtual reality ET, a post-treatment clinical assessment, and a 6-month follow-up assessment. Tilted Gabor gratings served as conditioned stimuli (CS) that were either paired (CS+) or remained unpaired (CS-) with an aversive phobia-related and phobia-unrelated unconditioned stimulus (UCS). CS+/CS- differences in fear ratings and magnetoencephalographic event-related fields (ERFs) were related to percentual symptom reductions from pre- to post-treatment, as assessed via spider phobia questionnaire (SPQ), behavioral avoidance test (BAT), and remission status at 6-month follow-up.We observed no associations between pre-treatment CS+/CS- differences in fear ratings and any treatment outcome. CS+/CS- differences in source estimations of ERFs revealed that higher CS- activity in bilateral dorsolateral prefrontal cortex (dlPFC) was related with SPQ- and BAT-reductions. Associations between CS+/CS- differences and treatment outcomes were also observed in left ventromedial prefrontal cortex (vmPFC) regions, which additionally revealed associations with the follow-up remission status.Results provide initial evidence that neural pre-treatment CS+/CS- differences may hold predictive information regarding outcomes of behavioral exposure. Our findings highlight a key role of neural responses to safety cues with potentially inhibitory effects on affect-generating structures during fear conditioning.

Prioritized processing of fearful compared to neutral faces has been proposed to result from evolutionary adaptation of the contrast sensitivity function (CSF) to the features of emotionally relevant faces and/or vice versa. However, it is unknown whether a stimulus merely has to feature the amplitude spectrum of a fearful face to be prioritized or whether the relevant spatial frequencies have to occur with specific phases and orientations. Prioritized processing is indexed by specific increases of Event-Related Potentials (ERPs) of the EEG and occurs throughout different early processing stages, indexed by emotion-related modulations of the P1, N170, and EPN. In this pre-registered study, we manipulated phase and amplitude properties of the Fourier spectra of neutral and fearful faces to test the effect of phase coherence (PC, face vs. scramble) and orientation coherence (OC, original vs. rotational average) and their interactions with differential emotion processing. We found that differential emotion processing was not present at the level of P1 but strongly affected N170 and EPN. In both cases, intact phase coherence was required for enhanced processing of fearful faces. OC did not interact with emotion. While faces produced the typical N170 effect, we observed a reversed effect for scrambles. Additional exploratory independent component analysis (ICA) suggests that this reversal could signal a mismatch between an early "perceptual hypothesis" and feedback of configural information. In line with our expectations, fearful-neutral differences for the N170 and EPN depend on configural information, i.e., recognizable faces.

A large body of research suggests that early event-related potentials (ERPs), such as the P1 and N1, are potentiated by attention and represent stimulus amplification. However, recent accounts suggest that the P1 is associated with inhibiting the irrelevant visual field evidenced by a pronounced ipsilateral P1 during sustained attention to peripherally presented stimuli. The current EEG study further investigated this issue to reveal how lateralized ERP findings are modulated by face and emotional information. Therefore, participants were asked to fixate the center of the screen and pay sustained attention either to the right or left visual field, where angry or neutral faces or their Fourier phase-scrambled versions were presented. We found a bilateral P1 to all stimuli with relatively increased, but delayed, ipsilateral P1 amplitudes to faces but not to scrambles. Explorative independent component analyses dissociated an earlier lateralized larger contralateral P1 from a later bilateral P1. By contrast, the N170 showed a contralateral enhancement to all stimuli, which was most pronounced for neutral faces attended in the left hemifield. Finally, increased contralateral alpha power was found for both attended hemifields but was not significantly related to poststimulus ERPs. These results provide evidence against a general inhibitory role of the P1 but suggest stimulus-specific relative enhancements of the ipsilateral P1 for the irrelevant visual hemifield. The lateralized N170, however, is associated with stimulus amplification as a function of facial features.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.

Results of neuroimaging datasets aggregated from multiple sites may be biased by site- specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,343 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,067 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM were more sensitive to the detection of significant case-control differences in regional cortical thickness (X2(3) = 34.339, p < 0.001), and case-control differences in age-related cortical thinning (X2(3) = 15.128, p = 0.002). Specifically, ComBat-GAM led to larger effect size estimates of cortical thickness reductions (corrected p-values < 0.001), smaller age-appropriate declines (corrected p-values < 0.001), and lower female to male contrast (corrected p-values < 0.001) in cases compared to controls relative to other harmonization methods. Harmonization with ComBat-GAM also led to greater estimates of age-related declines in cortical thickness (corrected p-values < 0.001) in both cases and controls compared to other harmonization methods. Our results support the use of ComBat-GAM for harmonizing cortical thickness data aggregated from multiple sites and scanners to minimize confounds and increase statistical power.

A large body of evidence ascribes a pivotal role in emotion processing to the insular cortex. However, the complex structure and lateralization of emotional deficits following insular damage are not understood. Here, we investigated emotional ratings of valence and arousal and skin conductance responses (SCR) to a graded series of emotionally arousing scenes in patients with left (n = 10) or right (n = 9) insular damage and in healthy controls (n = 18). We found a significant reduction in overall SCRs, arousal ratings and valence extremity scores in right-lesioned patients, as compared to left-lesioned patients and healthy controls. The degree of right insular damage was significantly correlated with the degree of arousal, SCR and extremity attenuation. Additional analyses of correlations between subjective arousal ratings resp. SCR and normative arousal ratings revealed that both lesion groups had evaluative and physiological difficulties to discover changes in stimulus arousal. Although no group differences emerged on overall ratings of valence, analysis of correlations between subjective and normative valence ratings displayed markedly reduced accuracy in right-lesioned patients, as compared to left-lesioned patients and healthy controls. Our findings support the hypothesis that the left and right insulae subserve different functions in emotion processing, potentially due to asymmetrical representations of autonomic information in the left and right human forebrain. The right insula may serve as integral node for sympathetic arousal and cognitive-affective processing.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed, which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3,047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1,426 individuals with PTSD and 1,621 controls (2174 males/873 females) between ages 18–83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen’s d=−0.11, p=0.0055). The tapetum connects the left and right hippocampus, structures for which structure and function have been consistently implicated in PTSD. Results remained significant/similar after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Several components of the event-related potential (ERP) are amplified by emotional compared to neutral pictures. This study (N = 80) investigated systematically how attention to specific stimulus features influences ERPs to briefly presented (100 ms) negative and neutral pictures. Participants had to discriminate either (i) the orientation of overlaid lines, (ii) if the picture content was animate or inanimate, or (iii) if the emotional content was negative or neutral. ERP results showed interactions between the attention task and emotion processing for the early posterior negativity (EPN) and the late positive potential (LPP). For the EPN, attention to distracting perceptual information reduced emotional differences, while at the level of the LPP, emotion effects were selectively amplified when participants attended to the emotional content. These findings reveal the time-dependent effects of feature-based attention tasks on ERPs to emotional pictures.

Posttraumatic stress disorder (PTSD) is a complex psychiatric condition that has generated much attention in the neuroimaging literature. A neurocircuitry model supporting fronto-limbic dysfunction as a major player in facilitating clinical symptoms of PTSD is well-characterized; however, recent literature suggests that network-based approaches may provide additional insight into neural dysfunction in PTSD. Our analysis uses resting-state neuroimaging scans of 1063 adults from the PGC-ENIGMA PTSD Consortium to investigate a network-based model of functional connectivity in PTSD. With a novel, resolution limit-free community detection approach, 16 communities corresponding to functionally meaningful networks were detected with high quality. After group-level community detection, participants were classified into three groups (PTSD, n=418, trauma-exposed controls without PTSD, n=434, and non-trauma exposed healthy controls, n=211). Individual network connectivity metrics were calculated, including whole-brain, default mode network, and central executive network participation coefficient and connectivity strength. Linear mixed effects models revealed group differences in the whole-brain, default mode, and central executive network participation coefficient and connectivity strength such that individuals with PTSD demonstrated overall greater values. We also described sex differences such that males demonstrate greater whole-brain participation coefficient vs. females and females demonstrate greater default mode network connectivity strength vs. males. Our results suggest that PTSD in adults is associated with reduced specialization and enhanced inter-module communication throughout the brain network, which may contribute to inefficient information processing and poor emotional regulation. This study presents a novel use of resolution limit-free community detection in a large PTSD sample, revealing robust differences in resting-state network topology.

In neuroscientific studies, the naturalness of face presentation differs; a third of published studies makes use of close-up full coloured faces, a third uses close-up grey-scaled faces and another third employs cutout grey-scaled faces. Whether and how these methodological choices affect emotion-sensitive components of the event-related brain potentials (ERPs) is yet unclear. Therefore, this pre-registered study examined ERP modulations to close-up full-coloured and grey-scaled faces as well as cutout fearful and neutral facial expressions, while attention was directed to no-face oddballs. Results revealed no interaction of face naturalness and emotion for any ERP component, but showed, however, large main effects for both factors. Specifically, fearful faces and decreasing face naturalness elicited substantially enlarged N170 and early posterior negativity amplitudes and lower face naturalness also resulted in a larger P1.This pattern reversed for the LPP, showing linear increases in LPP amplitudes with increasing naturalness. We observed no interaction of emotion with face naturalness, which suggests that face naturalness and emotion are decoded in parallel at these early stages. Researchers interested in strong modulations of early components should make use of cutout grey-scaled faces, while those interested in a pronounced late positivity should use close-up coloured faces.

Background Patients with specific phobia (SP) show altered brain activation when confronted with phobia-specific stimuli. It is unclear whether this pathogenic activation pattern generalizes to other emotional stimuli. This study addresses this question by employing a well-powered sample while implementing an established paradigm using nonspecific aversive facial stimuli. Methods N = 111 patients with SP, spider subtype, and N = 111 healthy controls (HCs) performed a supraliminal emotional face-matching paradigm contrasting aversive faces versus shapes in a 3-T magnetic resonance imaging scanner. We performed region of interest (ROI) analyses for the amygdala, the insula, and the anterior cingulate cortex using univariate as well as machine-learning-based multivariate statistics based on this data. Additionally, we investigated functional connectivity by means of psychophysiological interaction (PPI). Results Although the presentation of emotional faces showed significant activation in all three ROIs across both groups, no group differences emerged in all ROIs. Across both groups and in the HC > SP contrast, PPI analyses showed significant task-related connectivity of brain areas typically linked to higher-order emotion processing with the amygdala. The machine learning approach based on whole-brain activity patterns could significantly differentiate the groups with 73% balanced accuracy. Conclusions Patients suffering from SP are characterized by differences in the connectivity of the amygdala and areas typically linked to emotional processing in response to aversive facial stimuli (inferior parietal cortex, fusiform gyrus, middle cingulate, postcentral cortex, and insula). This might implicate a subtle difference in the processing of nonspecific emotional stimuli and warrants more research furthering our understanding of neurofunctional alteration in patients with SP. Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659

BACKGROUND Because overgeneralization of fear is a pathogenic marker of anxiety disorders, we investigated whether pretreatment levels of fear generalization in spider-phobic patients are related to their response to exposure-based treatment to identify pretreatment moderators of treatment success. METHODS A total of 90 patients with spider phobia completed pretreatment clinical and magnetoencephalography assessments, one session of virtual reality exposure therapy, and a posttreatment clinical assessment. Based on the primary outcome (30% symptom reduction in self-reported symptoms), they were categorized as responders or nonresponders. In a pretreatment magnetoencephalography fear generalization paradigm involving fear conditioning with 2 unconditioned stimuli (UCS), we obtained fear ratings, UCS expectancy ratings, and event-related fields to conditioned stimuli (CS: CS-, CS+) and 7 different generalization stimuli on a perceptual continuum from CS- to CS+. RESULTS Before treatment, nonresponders showed behavioral overgeneralization indicated by more linear generalization gradients in fear ratings. Analyses of magnetoencephalography source estimations revealed that nonresponders showed a decline of their (inhibitory) frontal activations to safety-signaling CS- and generalization stimuli compared with CS+ over time, while responders maintained these activations at early (

The insula plays a central role in empathy. However, the complex structure of empathic deficits following insular damage is not fully understood. While previous lesion research has shown variable deficits in patients with insular damage on basic discrimination tasks or self-report measures, it is unclear in how far patients with insular damage are impaired in cognitive (CE) and affective empathy (AE) functions depending on valence and arousal of stimuli using an ecologically valid paradigm. In the present study, patients with insular lesions (n = 20) and demographically-matched healthy controls (n = 24) viewed 16 videos (duration: 60 sec each) that varied in terms of valence and emotional intensity. The videos showed a person (target) reporting on a personal life event. In CE conditions, subjects continuously rated the affective state of the target, while in AE conditions they continuously rated their own affect. Mean Squared Error (MSE) assessed deviations between subject and target ratings (CE: deviation between targets’ and participants’ ratings of targets’ emotions; AE: deviation between targets’ and participants’ self-ratings of emotion). Patients differed from controls only in negative, low intensity AE, rating their own affective state less negative than the target rated his/her affect. This deficit was not related to trait empathy, neuropsychological or clinical parameters, or laterality of lesion. Our findings provide important insights into the profile of social cognition impairment after insular damage. Empathic functions may be widely spared after insular damage in a naturalistic, dynamic setting, potentially due to the intact interpretation of social context cues by residual networks outside the lesion. The particular role of the insula in AE for negative states may evolve specifically in situations that bear higher uncertainty, which points to a threshold role of the insula in online ratings of AE.

Fearful facial expressions are prioritized across different stages of information processing as reflected by early, mid-latency, and late components of event-related brain potentials (ERP). Trait anxiety has been proposed to modulate these responses, but it is yet unclear how such modulations depend on feature-based attention. In this preregistered study (N = 80), we investigated the effects of trait anxiety on ERP differences between fearful and neutral faces across three different tasks. Participants had to discriminate either the orientation of lines overlaid onto the faces, the gender of the face, or the emotional expression, thus increasing attention to emotionally relevant facial features across the tasks. Fearful versus neutral faces elicited increased P1 and N170 amplitudes across tasks and potentiated amplitudes when attention was directed to faces (early posterior negativity [EPN]) or the expression (EPN and late positive potential). Higher trait anxiety was related to smaller EPN differences between fearful and neutral faces during the perceptual discrimination task. This early relationship suggests reduced instead of amplified processing of fearful faces for high trait anxious participants under perceptual distraction.

IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subjects’ data from 29 cohorts in five countries (n=3439).MethodsUsing Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN.ResultsNotable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comorbid PTSD and MDD showed higher CT-based centrality in the right anterior cingulate gyrus, right parahippocampal gyrus and lower SA-based centrality in left insular gyrus.ConclusionUnlike previous studies with smaller sample sizes (≤318), our study found differences in centrality measures using a sample size of 3439 subjects. This is the first cross-sectional study to examine SCN interactions with age, sex, and comorbid MDD. Although limited to group level inferences, centrality measures offer insights into a node’s relationship to the entire functional connectome unlike approaches like seed-based connectivity or independent component analysis. Nodes having higher centrality have greater structural or functional connections, lending them invaluable for translational treatments like neuromodulation.

Recent animal and human studies highlight the uncertainty about the onset of an aversive event as a crucial factor for the involvement of the centromedial amygdala (CM) and bed nucleus of the stria terminalis (BNST) activity. However, studies investigating temporally predictable or unpredictable threat anticipation and confrontation processes are rare. Furthermore, the few existing fMRI studies analyzing temporally predictable and unpredictable threat processes used small sample sizes or limited fMRI paradigms. Therefore, we measured functional brain activity in 109 predominantly female healthy participants during a temporally predictable-unpredictable threat paradigm, which aimed to solve limited aspects of recent studies. Results showed higher BNST activity compared to the CM during the cue indicating that the upcoming confrontation is aversive relative to the cue indicating an upcoming neutral confrontation. Both the CM and BNST showed higher activity during the confrontation with unpredictable and aversive stimuli, but the reaction to aversive confrontation relative to neutral confrontation was stronger in the CM compared to the BNST. Additional modulation analyses by NPSR1 rs324981 genotype revealed higher BNST activity relative to the CM in unpredictable anticipation relative to predictable anticipation in T-carriers compared to AA carriers. Our results indicate that during the confrontation with aversive or neutral stimuli, temporal unpredictability modulates CM and BNST activity. Further, there is a differential activity concerning threat processing, as BNST is more involved when focussing on fear-related anticipation processes and CM is more involved when focussing on threat confrontation.

Energy consumption by air-conditioning is expansive and leads to the emission of millions of tons of CO

Load Theory assumes that the extent of processing of task-irrelevant information depends on the level (high vs. low load) and type (perceptual vs. working memory) of task load. In this review, we address the neuroscientific perspective on Load Theory by a systematic evaluation of neuroimaging and electrophysiological studies, which manipulated perceptual or working memory load and reported brain responses to task-irrelevant unimodal and crossmodal stimuli. Studies show: (1) Load effects can be observed across the whole processing stream from subcortical areas to higher cortical areas, (2) both higher perceptual and working memory load lead to decreased distractor processing, (3) event-related potential studies suggest that load effects occur more reliably the later the ERP component and (4) load effects occur both within and across modalities. Thus, findings are at least partially consistent with assumptions of Load Theory. Based on the reviewed studies and theoretical and methodological considerations, we provide several suggestions, which might help to improve future research in the field.

In recent years, several ERP components have been identified as potential neural correlates of consciousness (NCC), including early negativities and late positivities. Based on experiments in the visual modality, it has recently been shown that awareness is often confounded with reporting it, possibly overestimating the NCC. It is unknown whether similar constraints also exist in the auditory modality. In order to address this gap, we presented spoken words in a sustained inattentional deafness paradigm. Electrophysiological responses were obtained in three physically identical experimental conditions that differed only with respect to the participants' instructions. Participants were either left uninformed or informed about the presence of spoken words while confronted with an auditory distractor task (U/I condition), informed about the words while exposed to the same task as before (I condition), or requested to respond to the now task-relevant speech stimuli (TR condition). After completion of the U/I condition, only informed participants reported awareness of the words. In ERPs, awareness of words in the U/I and I condition was accompanied by an anterior auditory awareness negativity (AAN). Only when stimuli were task-relevant, i.e., during the TR condition, late positivities emerged. Taken together, these results indicate that early negativities but not late positivities index awareness across sensory modalities. Thus, they provide evidence for a recurrent processing framework, which highlights the importance of early sensory processing in conscious perception.

The temporal dynamics of top-down voluntary and bottom-up driven emotional attention are a matter of debate. Both emotion and task-relevance have been shown to affect the early posterior negativity (EPN) and the late positive potential (LPP) during the processing of emotional pictures, whereas there are mixed findings related to interactions of emotion and task-relevance. In this preregistered study, we used Bayesian models to test this interplay between emotion and task-relevance. Participants (N = 104) were presented negative, neutral, and positive International Affective Picture System (IAPS) pictures, and block-wise were asked to respond either to negative, neutral, or positive pictures, rendering one stimulus category task-relevant and the remaining stimuli task-irrelevant. Bayesian models showed evidence for the absence of interactions between task-relevance and emotion. Furthermore, models showed parallel emotion and task effects for the EPN and late stages of the LPP. Additional interactive effects were found during an early LPP interval (400 to 600 ms), with increased LPP amplitudes when emotion was rendered task-relevant. Taken together, the results revealed distinct but parallel temporal onsets of task-relevance and emotion effects, followed by task and emotion interactions in the early LPP. Thus, based on this high-powered study employing Bayesian analysis, evidence is provided that interactions between task-relevance and emotion do not emerge before the LPP time window. These results further inform theories proposing early parallel and late interactive processes of the emotional salience of stimuli and top-down attention.

Emotional facial expressions lead to modulations of early event-related potentials (ERPs). However, it has so far remained unclear how far these modulations represent face-specific effects rather than differences in low-level visual features, and to which extent they depend on available processing resources. To examine these questions, we conducted two preregistered independent experiments (N = 40 in each experiment) using different variants of a novel task that manipulates peripheral perceptual load across levels but keeps overall visual stimulation constant. At the display center, we presented task-irrelevant angry, neutral, and happy faces and their Fourier phase-scrambled versions, which preserved low-level visual features. The results of both studies showed load-independent P1 and N170 emotional expression effects. Importantly, by using Bayesian analyses we could confirm that these facial expression effects were face-independent for the P1 but not for the N170 component. We conclude that firstly, ERP modulations during the P1 interval strongly depend on low-level visual information, while the N170 modulation requires the processing of figural facial expression features. Secondly, both P1 and N170 modulations appear to be immune to a large range of variations in perceptual load.

Prioritized processing of fearful compared to neutral faces is reflected in behavioral advantages such as lower detection thresholds, but also in enhanced early and late event-related potentials (ERPs). Behavioral advantages have recently been associated with the spatial frequency spectrum of fearful faces, better fitting the human contrast sensitivity function than the spectrum of neutral faces. However, it is unclear whether and to which extent early and late ERP differences are due to low-level spatial frequency spectrum information or high-level representations of the facial expression. In this pre-registered EEG study (N = 38), the effects of fearful-specific spatial frequencies on event-related ERPs were investigated by presenting faces with fearful and neutral expressions whose spatial frequency spectra were manipulated so as to contain either the average power spectra of neutral, fearful, or both expressions combined. We found an enlarged N170 to fearful versus neutral faces, not interacting with spatial frequency. Interactions of emotional expression and spatial frequencies were observed for the P1 and Early Posterior Negativity (EPN). For both components, larger emotion differences were observed when the spectrum contained neutral as opposed to fearful frequencies. Importantly, for the EPN, fearful and neutral expressions did not differ anymore when inserting fearful frequencies into neutral expressions, whereas typical emotion differences were found when faces contained average or neutral frequencies. Our findings show that N170 emotional modulations are unaffected by expression-specific spatial frequencies. However, expression-specific spatial frequencies alter early and mid-latency ERPs. Most notably, the EPN to neutral expressions is boosted by adding fearful spectra-but not vice versa.

Interpersonal violence (IPV) is one of the most frequent causes for the development of posttraumatic stress disorder (PTSD) in women. One key component in PTSD is altered processing of trauma-related cues, leading to emotional symptoms. In the everyday environment, words with trauma-associated semantic content represent typical, albeit abstract, trauma-related stimuli for patients suffering from PTSD. However, the functional neuroanatomy associated with processing single trauma-related words in IPV-PTSD is not understood. The present event-related functional magnetic resonance imaging study investigated the neural basis of trauma-related word processing in women with IPV-PTSD relative to healthy controls (HC) during a non-emotional vigilance task in which the emotional content of the words was task-irrelevant. On the behavioral level, trauma-related relative to neutral word stimuli evoked more unpleasant feelings, higher arousal as well as anxiety in IPV-PTSD patients as compared to HC. Functional imaging data showed hyperactivation to trauma-related versus neutral words in the basolateral amygdala (BLA) and cortical language-processing regions (inferior frontal gyrus, posterior cingulate cortex, angular/supramarginal gyrus) in IPV-PTSD compared to HC. These results propose a role of the BLA in hypervigilant responding to verbal trauma associated cues in IPV-PTSD. Furthermore, the particular involvement of cortical language-processing regions indicates enhanced processing of trauma-related words in brain regions associated with analysis and memory of verbal material. Taken together, our findings suggest that both subcortical and cortical mechanisms contribute to automatic responsivity to verbal trauma cues in PTSD.

Objectives Embedded in the Collaborative Research Center “Fear, Anxiety, Anxiety Disorders” (CRC‐TRR58), this bicentric clinical study aims at identifying biobehavioral markers of treatment (non‐)response by applying machine learning methodology with an external cross‐validation protocol. We hypothesize that a priori prediction of treatment (non‐)response is possible in a second, independent sample based on multimodal markers. Methods One‐session virtual reality exposure treatment (VRET) with patients with spider phobia was conducted on two sites. Clinical, neuroimaging, and genetic data were assessed at baseline, post‐treatment and after 6 months. The primary and secondary outcomes defining treatment response are as follows: 30% reduction regarding the individual score in the Spider Phobia Questionnaire and 50% reduction regarding the individual distance in the behavioral avoidance test. Results N = 204 patients have been included (n = 100 in Würzburg, n = 104 in Münster). Sample characteristics for both sites are comparable. Discussion This study will offer cross‐validated theranostic markers for predicting the individual success of exposure‐based therapy. Findings will support clinical decision‐making on personalized therapy, bridge the gap between basic and clinical research, and bring stratified therapy into reach. The study is registered at ClinicalTrials.gov (ID: NCT03208400).

Emotional facial expressions lead to modulations of early event-related potentials (ERPs). However, it has so far remained unclear in how far these modulations represent face-specific effects rather than differences in low-level visual features, and to which extent they depend on available processing resources. To examine these questions, we conducted two preregistered independent experiments (N = 40 in each experiment) using different variants of a novel task which manipulates peripheral perceptual load across levels but keeps overall visual stimulation constant. Centrally, task-irrelevant angry, neutral and happy faces and their Fourier phase-scrambled versions, which preserved low-level visual features, were presented. The results of both studies showed load-independent P1 and N170 emotion effects. Importantly, we could confirm by using Bayesian analyses that these emotion effects were face-independent for the P1 but not for the N170 component. We conclude that firstly, ERP modulations during the P1 interval strongly depend on low-level visual information, while the emotional N170 modulation requires the processing of figural facial features. Secondly, both P1 and N170 modulations appear to be immune to a large range of variations in perceptual load.

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) is increasingly recognized as a distinct adult electroclinical syndrome. However, functional consequences of morphological alterations of the amygdala in TLE-AE are poorly understood. Here, two emotional stimulation designs were employed to investigate subjective emotional rating and skin conductance responses in a sample of treatment-naïve patients with suspected or confirmed autoimmune TLE-AE (n = 12) in comparison to a healthy control group (n = 16). A subgroup of patients completed follow-up measurements after treatment. As compared to healthy controls, patients with suspected or confirmed autoimmune TLE-AE showed markedly attenuated skin conductance responses and arousal ratings, especially pronounced for anxiety-inducing stimuli. The degree of right amygdala enlargement was significantly correlated with the degree of autonomic arousal attenuation. Furthermore, a decline of amygdala enlargement following prompt aggressive immunotherapy in one patient suffering from severe confirmed autoimmune TLE-AE with a very recent clinical onset was accompanied by a significant improvement of autonomic responses. Findings suggest dual impairments of autonomic and cognitive discrimination of stimulus arousal as hallmarks of emotional processing in TLE-AE. Emotional responses might, at least partially, recover after successful treatment, as implied by first single case data.

While being highly effective on average, exposure-based treatments are not equally effective in all patients. The a priori identification of patients with a poor prognosis may enable the application of more personalized psychotherapeutic interventions. We aimed at identifying sociodemographic and clinical pre-treatment predictors for treatment response in spider phobia (SP). N = 174 patients with SP underwent a highly standardized virtual reality exposure therapy (VRET) at two independent sites. Analyses on group-level were used to test the efficacy. We applied a state-of-the-art machine learning protocol (Random Forests) to evaluate the predictive utility of clinical and sociodemographic predictors for a priori identification of individual treatment response assessed directly after treatment and at 6-month follow-up. The reliability and generalizability of predictive models was tested via external cross-validation. Our study shows that one session of VRET is highly effective on a group-level and is among the first to reveal long-term stability of this treatment effect. Individual short-term symptom reductions could be predicted above chance, but accuracies dropped to non-significance in our between-site prediction and for predictions of long-term outcomes. With performance metrics hardly exceeding chance level and the lack of generalizability in the employed between-site replication approach, our study suggests limited clinical utility of clinical and sociodemographic predictors. Predictive models including multimodal predictors may be more promising.

Several studies reported that the encoding and recognition of emotional target faces are modulated by negative contextual expressions. However, it is unknown whether other contextual expressions, such as emotionally ambiguous expressions, affect the encoding and recognition of target faces. To this end, electroencephalography (EEG) was recorded during the presentation of angry or happy target faces after a random sequence of surprised or neutral contextual faces that did not differ in normative valence ratings. Subsequently, participants were asked to perform an unexpected old/new recognition task in which target faces were shown in either the encoded or a non-encoded expression. During the encoding phase, event-related potential (ERP) results showed that surprised as compared to neutral contextual faces led to smaller late positive potentials (LPP) for happy but not for angry target faces. Similar effects were also observed in the N170, even though the interaction of context and target expression failed to reach statistical significance. In the later recognition phase, recognition rates were lower for encoded happy faces when they had been encountered in surprised as compared to neutral context, regardless of whether the target face showed the encoded or a non-encoded expression. However, this context effect was not observed for angry-encoded faces. Taken together, the present study indicates that ambiguous contextual expressions, e.g., surprised faces, affect structural and cognitive encoding and later recognition of happy target faces to a larger extent than neutral contextual faces; whereas angry faces are more resistant to context effects.

BackgroundAltered amygdala activation to fear-related stimuli has been proposed to be a potential neural correlate of heightened threat sensitivity in anxiety- and stress-related disorders. However, the role of stimulus awareness and disorder specificity remains widely unclear. Here we investigated amygdala responses to conscious and unconscious fearful faces in patients suffering from panic disorder (PD), generalized anxiety disorder (GAD), or post-traumatic stress disorder (PTSD) and in a large sample of healthy controls (HC).MethodsDuring event-related functional magnetic resonance imaging participants (n = 120; 20 PD, 20 GAD, 20 PTSD, 60 HC) were confronted with briefly presented fearful faces, neutral faces, and non-faces in a backward masking paradigm. The design allowed for the analysis of trial-by-trial face detection performance and amygdala responses to fearful v. neutral faces.ResultsAll participants exhibited increased amygdala activation to fearful v. neutral faces during conscious trials. Specifically during unconscious face processing, the PTSD, compared with all other groups, showed higher right basolateral (BLA) amygdala activity to fearful v. neutral faces.ConclusionsThe present study shows that BLA amygdala hyperactivity during unconscious, but not conscious, processing of fearful faces differentiates PTSD from the investigated disorders. This finding suggests an automatic and specific neural hyper-responsivity to general fear cues in PTSD and supports the idea of categorical differences between PTSD and other anxiety-related disorders.

BackgroundPanic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD.MethodsUsing functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations.ResultsPD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks.ConclusionsWe demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

Feelings of uncontrollability and anxiety regarding possibly harmful events are key features of post-traumatic stress disorder (PTSD) symptomatology. Due to a lack of studies, the neural correlates of anticipatory anxiety in PTSD are still poorly understood. During functional magnetic resonance imaging, female PTSD patients with interpersonal violence trauma and healthy controls (HC) anticipated the temporally unpredictable presentation of aversive (human scream) or neutral sounds. Based on separate analysis models, we investigated phasic and sustained brain activations. PTSD patients reported increased anxiety during anticipation of aversive versus neutral sounds. Furthermore, we found both increased initial, phasic amygdala activation and increased sustained activation of the bed nucleus of the stria terminalis (BNST) during anticipation of aversive versus neutral sounds in PTSD patients in comparison to HC. PTSD patients as compared with HC also showed increased phasic responses in mid-cingulate cortex (MCC), posterior cingulate cortex (PCC), mid-insula and lateral prefrontal cortex (PFC) as well as increased sustained responses in MCC, PCC, anterior insula and lateral and medial PFC. Our results demonstrate a relationship between anticipatory anxiety in PTSD patients and hyperresponsiveness of brain regions that have previously been associated with PTSD symptomatology. Additionally, the dissociation between amygdala and BNST indicates distinct temporal and functional characteristics and suggests that phasic fear and sustained anxiety responses are enhanced during unpredictable anticipation of aversive stimuli in PTSD. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

The wet chemical deposition of solution processed transparent conducting oxides (TCO) provides an alternative low cost and economical deposition technique to realize large-areas of conducting films. Since the price for the most common TCO Indium Tin Oxide rises enormously, Aluminum Zinc Oxide (AZO) as alternative TCO reaches more and more interest. The optoelectronical properties of nanoparticle coatings strongly depend beneath the porosity of the coating on the shape and size of the used particles. By using bigger or rod-shaped particles it is possible to minimize the amount of grain boundaries resulting in an improvement of the electrical properties, whereas particles bigger than 100 nm should not be used if highly transparent coatings are necessary as these big particles scatter the visible light and lower the transmittance of the coatings. In this work we present a simple method to synthesize AZO particles with different shape and size, but comparable electronical properties. We use a simple, well reproducible polyol method for synthesis and influence the shape and size of the particles by adding different amounts of water to the precursor solution. We can show that the addition of aluminum as dopant strongly hinders the crystal growth but the addition of water counteracts this, so that both, spherical and rod-shaped particles can be obtained.

Blood-injection-injury (BII) phobia differs from other subtypes of specific phobia in that it is associated with elevated disgust-sensitivity as well as specific autonomic and brain responses during processing of phobia-relevant stimuli. To what extent these features play a role already during threat anticipation is unclear. In the current fMRI experiment, 16 female BII phobics and 16 female healthy controls anticipated the presentation of phobia-specific and neutral pictures. On the behavioral level, anxiety dominated the anticipatory period in BII phobics relative to controls, while both anxiety and disgust were elevated during picture presentation. By applying two different models for the analysis of brain responses to anticipation of phobia-specific versus neutral stimuli, we found initial and sustained increases of activation in anterior cingulate cortex (ACC), insula, lateral and medial prefrontal cortex (PFC), thalamus and visual areas, as well as initial activation in the amygdala for BII phobics as compared to healthy controls. These results suggest that BII phobia is characterized by activation of a typical neural defense network during threat anticipation, with anxiety as the predominant emotion., Highlights • Anxiety, but not disgust, during threat anticipation in blood-injection-injury phobics. • Distinct temporal characteristics of brain regions involved in threat anticipation. • Initial and sustained activation in subregions of a neural defense network.

Unintentional and uncontrollable processing of threat has been suggested to contribute to the pathology of social anxiety disorder (SAD). The present study investigated the neural correlates of processing task-irrelevant, highly ecologically valid, disorder-related stimuli as a function of symptom severity in SAD. Twenty-four SAD patients and 24 healthy controls (HC) performed a feature-based comparison task during functional magnetic resonance imaging, while task-irrelevant, disorder-related or neutral scenes were presented simultaneously at a different spatial position. SAD patients showed greater activity than HC in response to disorder-related versus neutral scenes in brain regions associated with self-referential processing (e.g. insula, precuneus, dorsomedial prefrontal cortex) and emotion regulation (e.g. dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus). Symptom severity was positively associated with amygdala activity, and negatively with activation in dorsal anterior cingulate cortex and dlPFC in SAD patients. Additional correlation analysis revealed that amygdala-prefrontal coupling was positively associated with symptom severity. A network of brain regions is thus involved in SAD patients' processing of task-irrelevant, complex, ecologically valid, disorder-related scenes. Furthermore, increasing symptom severity in SAD patients seems to reflect a growing imbalance between neural mechanisms related to stimulus-driven bottom-up and regulatory top-down processes resulting in dysfunctional regulation strategies., Highlights • SAD patients process task-irrelevant disorder-related scenes automatically. • Automatic threat processing in SAD involves a broad emotion network of brain regions. • Symptom severity has a great impact on automatic disorder-related processing. • Amygdala activity increases with higher levels of symptom severity.

Several regions of the frontal cortex interact with striatal and amygdala regions to mediate the evaluation of reward-related information and subsequent adjustment of response choices. Recent theories discuss the particular relevance of dorsal anterior cingulate cortex (dACC) for switching behavior; consecutively, ventromedial prefrontal cortex (VMPFC) is involved in mediating exploitative behaviors by tracking reward values unfolding after the behavioral switch. Amygdala, on the other hand, has been implied in coding the valence of stimulus-outcome associations and the ventral striatum (VS) has consistently been shown to code a reward prediction error (RPE). Here, we used fMRI data acquired in humans during a reversal task to parametrically model different sequences of positive feedback in order to unravel differential contributions of these brain regions to the tracking and exploitation of rewards. Parameters from an Optimal Bayesian Learner accurately predicted the divergent involvement of dACC and VMPFC during feedback processing: dACC signaled the first, but not later, presentations of positive feedback, while VMPFC coded trial-by-trial accumulations in reward value. Our results confirm that dACC carries a prominent confirmatory signal during processing of first positive feedback. Amygdala coded positive feedbacks more uniformly, while striatal regions were associated with RPE.

BACKGROUNDDysfunctional expectations of impending social or performance outcomes are core features of Social Anxiety Disorder (SAD) but often lack formal definition in clinical research. Reinforcement learning (RL) models offer a framework to define changes in outcome expectations in a formal way by computing the prediction error (PE). This study quantifies the updating of expectations by PEs in SAD and investigates alterations in RL regions associated with PE signaling.METHOD48 adult participants (24 diagnosed with SAD and 24 age-, gender-, and education- matched healthy controls (HC)) underwent event-related functional magnetic resonance imaging while learning from probabilistic feedback. Crucially, both groups completed two parallel versions of the task: one in which they learned under scrutiny (social observation) and one in which they learned without being overtly evaluated (non-social control condition).RESULTSCoupling to prediction errors in SAD was elevated in dorsomedial prefrontal cortex (DMPFC) when learning under observation. These findings provide the first evidence that PE signaling during social performance situations in SAD is associated with hypersensitive response signatures in DMPFC, a brain region associated with using others’ value standards as a proxy for one’s own value standards. Dynamic Causal Modelling further revealed that RPE-modulated connectivity from ventral pallidum to DMPFC during observation was reduced in SAD.CONCLUSIONSThe present results corroborate a crucial role of DMPFC in SAD, which corresponds to dysfunctional expectations about others’ alleged performance standards that play a prominent role in current models of the disorder.

BackgroundPTSD and depression commonly co-occur and have been associated with smaller hippocampal volumes compared to healthy and trauma-exposed controls. However, the hippocampus is heterogeneous, with subregions that may be uniquely affected in individuals with PTSD and depression.MethodsWe used random effects regressions and a harmonized neuroimaging protocol based on FreeSurfer (v6.0) to identify sub-structural hippocampal markers of current PTSD (C-PTSD), depression, and the interaction of these conditions across 31 cohorts worldwide (N=3,115;Mage=38.9±13.9 years). Secondary analyses tested these associations by sex and after modeling the simultaneous effects of remitted PTSD, childhood trauma, mild traumatic brain injury, and alcohol use disorder.ResultsA significant negative main effect of depression (n=800, vs. no depression, n=1456) was observed in the hippocampal tail (ß=−0.13) and CA1 (ß=−0.09) after adjusting for covariates and multiple testing (adjusted p’s (q)=0.028). A main effect of C-PTSD (n=1042 vs. control, n=1359) was not significant, but an interaction between C-PTSD and depression was significant in the CA1 (ß=−0.24, q=0.044). Pairwise comparisons revealed significantly smaller CA1 volumes in individuals with C-PTSD+Depression than controls (ß=−0.12, q=0.012), C-PTSD-only (ß=−0.17, q=0.001), and Depression-only (ß=−0.18, q=0.023). Follow-up analyses revealed sex effects in the hippocampal tail of depressed females, and an interaction effect of C-PTSD and depression in the fimbria of males.ConclusionsCollectively our results suggest that depression is a stronger predictor of hippocampal volumetry than PTSD, particularly in the CA1, and provide compelling evidence of more pronounced hippocampal phenotypes in comorbid PTSD and depression compared to either condition alone.

The ability to learn from feedback, especially under social scrutiny, is an essential prerequisite for successful interaction with the environment. Patients suffering from social anxiety disorder (SAD) have been proposed to show altered processing of and learning from feedback, especially depending on social context. However, the neural basis and behavioral consequences of altered reinforcement learning in SAD are not clear yet. In the present event-related potentials (ERPs) study, 34 SAD patients and 30 healthy control subjects (HC) performed an adapted version of a probabilistic feedback learning task in two distinct social conditions. In the observation condition, participants were observed by a confederate; in the control condition, they performed the task without being observed. Patients as compared to healthy controls experienced more subjective discomfort under social observation. Moreover, they showed better learning from negative feedback in the control condition, but reduced learning from negative feedback in the observation condition. This effect correlated with reduced differentiation of positive and negative feedback in the time range of the feedback-related negativity (FRN) under high action-feedback contingency. In addition, SAD patients demonstrated increased FRN amplitudes in the first half of the observation condition, in particular to positive feedback. The present results demonstrate that processing of and learning from feedback are altered in SAD, especially under social scrutiny. In particular, it appears that SAD patients do not process positive information adequately on the neural level, which may impair their ability to differentiate between negative and positive outcomes.