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Abstract Previous research on the neural correlates of consciousness (NCC) in visual perception revealed an early event-related potential (ERP), the visual awareness negativity (VAN), to be associated with stimulus awareness. However, due to the use of brief stimulus presentations in previous studies, it remains unclear whether awareness-related negativities represent a transient onset-related response or correspond to the duration of a conscious percept. Studies are required that allow prolonged stimulus presentation under aware and unaware conditions. The present ERP study aimed to tackle this challenge by using a novel stimulation design. Male and female human participants (n = 62) performed a visual task while task-irrelevant line stimuli were presented in the background for either 500 or 1000 ms. The line stimuli sometimes contained a face, which needed so-called visual one-shot learning to be seen. Half of the participants were informed about the presence of the face, resulting in faces being perceived by the informed but not by the uninformed participants. Comparing ERPs between the informed and uninformed group revealed an enhanced negativity over occipitotemporal electrodes that persisted for the entire duration of stimulus presentation. Our results suggest that sustained visual awareness negativities (SVAN) are associated with the duration of stimulus presentation.

Abstract Although highly effective on average, exposure-based treatments do not work equally well for all patients with anxiety disorders. The identification of pre-treatment response-predicting patient characteristics may enable patient stratification. Preliminary research highlights the relevance of inhibitory fronto-limbic networks as such. We aimed to identify pre-treatment neural signatures differing between exposure treatment responders and non-responders in spider phobia and to validate results through rigorous replication. Data of a bi-centric intervention study comprised clinical phenotyping and pre-treatment resting-state functional connectivity (rsFC) data of n = 79 patients with spider phobia (discovery sample) and n = 69 patients (replication sample). RsFC data analyses were accomplished using the Matlab-based CONN-toolbox with harmonized analyses protocols at both sites. Treatment response was defined by a reduction of >30% symptom severity from pre- to post-treatment (Spider Phobia Questionnaire Score, primary outcome). Secondary outcome was defined by a reduction of >50% in a Behavioral Avoidance Test (BAT). Mean within-session fear reduction functioned as a process measure for exposure. Compared to non-responders and pre-treatment, results in the discovery sample seemed to indicate that responders exhibited stronger negative connectivity between frontal and limbic structures and were characterized by heightened connectivity between the amygdala and ventral visual pathway regions. Patients exhibiting high within-session fear reduction showed stronger excitatory connectivity within the prefrontal cortex than patients with low within-session fear reduction. Whereas these results could be replicated by another team using the same data (cross-team replication), cross-site replication of the discovery sample findings in the independent replication sample was unsuccessful. Results seem to support negative fronto-limbic connectivity as promising ingredient to enhance response rates in specific phobia but lack sufficient replication. Further research is needed to obtain a valid basis for clinical decision-making and the development of individually tailored treatment options. Notably, future studies should regularly include replication approaches in their protocols.

Faces can acquire emotional meaning by learning to associate individuals with specific behaviors. Here, we investigated emotional evaluation and brain activations toward faces of persons who had given negative or positive evaluations to others. Furthermore, we investigated how emotional evaluations and brain activation generalize to perceptually similar faces. Valence ratings indicated learning and generalization effects for both positive and negative faces. Brain activation, measured with functional magnetic resonance imaging (fMRI), showed significantly increased activation in the fusiform gyrus (FG) to negatively associated faces but not positively associated ones. Remarkably, brain activation in FG to faces to which emotional meaning (negative and positive) was successfully generalized was decreased compared to neutral faces. This suggests that the emotional relevance of faces is not simply associated with increased brain activation in visual areas. While, at least for negative conditions, faces paired with negative feedback behavior are related to potentiated brain responses, the opposite is seen for perceptually very similar faces despite generalized emotional responses.

Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.

Abstract While inattentional blindness and deafness studies have revealed neural correlates of consciousness (NCC) without the confound of task relevance in the visual and auditory modality, comparable studies for the somatosensory modality are lacking. Here, we investigated NCC using functional magnetic resonance imaging (fMRI) in an inattentional numbness paradigm. Participants (N = 44) received weak electrical stimulation on the left hand while solving a demanding visual task. Half of the participants were informed that task-irrelevant weak tactile stimuli above the detection threshold would be applied during the experiment, while the other half expected stimuli below the detection threshold. Unexpected awareness assessments after the experiment revealed that altogether 10 participants did not consciously perceive the somatosensory stimuli during the visual task. Awareness was not significantly modulated by prior information. The fMRI data show that awareness of stimuli led to increased activation in the contralateral secondary somatosensory cortex. We found no significant effects of stimulus awareness in the primary somatosensory cortex or frontoparietal areas. Thus, our results support the hypothesis that somatosensory stimulus awareness is mainly based on activation in higher areas of the somatosensory cortex and does not require strong activation in extended anterior or posterior networks, which is usually seen when perceived stimuli are task-relevant.

Abstract Negative emotional content is prioritized across different stages of information processing as reflected by different components of the event-related potential (ERP). In this preregistered study (N = 40), we investigated how varying the attentional focus allows us to dissociate the involvement of specific ERP components in the processing of negative and neutral words. Participants had to discriminate the orientation of lines overlaid onto the words, the word type (adjective/noun), or the emotional content (negative/neutral). Thus, attention was either not focused on words (distraction task), non-emotional aspects, or the emotional relevance of words. Regardless of the task, there were no significant differences between negative and neutral words for the P1, N1, or P2 components. In contrast, interactions between emotion and task were observed for the early posterior negativity (EPN) and late positive potential (LPP). EPN differences were absent during the distraction task but were present in the other two tasks. LPP emotion differences were found only when attention was directed to the emotional content of words. Our study adds to the evidence that early ERP components do not reliably separate negative and neutral words. However, results show that mid-latency and late stages of emotion processing are separable by different attention tasks. The EPN represents a stage of attentional enhancement of negative words given sufficient attentional resources. Differential activations during the LPP stage are associated with more elaborative processing of the emotional meaning of words.

This article details a correction to: Röseler, L., Weber, L., Helgerth, K., Stich, E., Günther, M., Tegethoff, P., … Schütz, A. (2022). The Open Anchoring Quest Dataset: Anchored Estimates from 96 Studies on Anchoring Effects. Journal of Open Psychology Data, 10(1), 16. DOI: https://doi.org/10.5334/jopd.67

Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Abstract Load theory assumes that neural activation to distractors in early sensory cortices is modulated by the perceptual load of a main task, regardless of whether task and distractor share the same sensory modality or not. While several studies have investigated the question of load effects on distractor processing in early sensory areas, there is no functional magnetic resonance imaging (fMRI) study regarding load effects on somatosensory stimuli. Here, we used fMRI to investigate effects of visual perceptual load on neural responses to somatosensory stimuli applied to the wrist in a study with 44 participants. Perceptual load was manipulated by an established sustained visual detection task, which avoided simultaneous target and distractor presentations. Load was operationalized by detection difficulty of subtle or clear color changes of one of 12 rotating dots. While all somatosensory stimuli led to activation in somatosensory areas SI and SII, we found no statistically significant difference in brain activation to these stimuli under high compared to low sustained visual load. Moreover, exploratory Bayesian analyses supported the absence of differences. Thus, our findings suggest a resistance of somatosensory processing to at least some forms of visual perceptual load, possibly due to behavioural relevance of discrete somatosensory stimuli and separable attentional resources for the somatosensory and visual modality.

Abstract While perceptual load has been proposed to reduce the processing of task-unrelated stimuli, theoretical arguments and empirical findings for other forms of task load are inconclusive. Here, we systematically investigated the detection and neural processing of auditory stimuli varying in stimulus intensity during a stimuli-unrelated visual working memory task alternating between low and high load. We found, depending on stimulus strength, decreased stimulus detection and reduced P3, but unaffected N1 amplitudes of the event-related potential to auditory stimuli under high as compared to low load. In contrast, load independent awareness effects were observed during both early (N1) and late (P3) time windows. Findings suggest a late neural effect of visual working memory load on auditory stimuli leading to lower probability of reported awareness of these stimuli.

Abstract Prioritized processing of fearful compared to neutral faces is reflected in increased amplitudes of components of the event-related potential (ERP). It is unknown whether specific face parts drive these modulations. Here, we investigated the contributions of face parts on ERPs to task-irrelevant fearful and neutral faces using an ERP-dependent facial decoding technique and a large sample of participants (N = 83). Classical ERP analyses showed typical and robust increases of N170 and EPN amplitudes by fearful relative to neutral faces. Facial decoding further showed that the absolute amplitude of these components, as well as the P1, was driven by the low-frequency contrast of specific face parts. However, the difference between fearful and neutral faces was not driven by any specific face part, as supported by Bayesian statistics. Furthermore, there were no correlations between trait anxiety and main effects or interactions. These results suggest that increased N170 and EPN amplitudes to task-irrelevant fearful compared to neutral faces are not driven by specific facial regions but represent a holistic face processing effect.

Load Theory states that perceptual load prevents, or at least reduces, the processing of task-unrelated stimuli. This study systematically examined the detection and neural processing of auditory stimuli unrelated to a visual foreground task. The visual task was designed to create continuous perceptual load, alternated between low and high load, and contained performance feedback to motivate participants to focus on the visual task instead of the auditory stimuli presented in the background. The auditory stimuli varied in intensity, and participants signaled their subjective perception of these stimuli without receiving feedback. Depending on stimulus intensity, we observed load effects on detection performance and P3 amplitudes of the event-related potential (ERP). N1 amplitudes were unaffected by perceptual load, as tested by Bayesian statistics. Findings suggest that visual perceptual load affects the processing of auditory stimuli in a late time window, which is associated with a lower probability of reported awareness of these stimuli.

Thin, flat textile roofing offers negligible heat insulation. In warm areas, such roofing membranes are therefore equipped with metallized surfaces to reflect solar heat radiation, thus reducing the warming inside a textile building. Heat reflection effects achieved by metallic coatings are always accompanied by shading effects as the metals are non-transparent for visible light (VIS). Transparent conductive oxides (TCOs) are transparent for VIS and are able to reflect heat radiation in the infrared. TCOs are, e.g., widely used in the display industry. To achieve the perfect coatings needed for electronic devices, these are commonly applied using costly vacuum processes at high temperatures. Vacuum processes, on account of the high costs involved and high processing temperatures, are obstructive for an application involving textiles. Accepting that heat-reflecting textile membranes demand less perfect coatings, a wet chemical approach has been followed here when producing transparent heat-reflecting coatings. Commercially available TCOs were employed as colloidal dispersions or nanopowders to prepare sol–gel-based coating systems. Such coatings were applied to textile membranes as used for architectural textiles using simple coating techniques and at moderate curing temperatures not exceeding 130 °C. The coatings achieved about 90% transmission in the VIS spectrum and reduced near-infrared transmission (at about 2.5 µm) to nearly zero while reflecting up to 25% of that radiation. Up to 35% reflection has been realized in the far infrared, and emissivity values down to ε = 0.5777 have been measured.

Background: Fear generalization is pivotal for the survival-promoting avoidance of potential danger, but, if too pronounced, it promotes pathological anxiety. Similar to adult patients with anxiety disorders, healthy children tend to show overgeneralized fear responses. Objective: This study aims to investigate neuro-developmental aspects of fear generalization in adolescence – a critical age for the development of anxiety disorders. Methods: We compared healthy adolescents (14–17 years) with healthy adults (19–34 years) regarding their fear responses towards tilted Gabor gratings (conditioned stimuli, CS; and slightly differently titled generalization stimuli, GS). In the conditioning phase, CS were paired (CS+) or remained unpaired (CS-) with an aversive stimulus (unconditioned stimuli, US). In the test phase, behavioral, peripheral and neural responses to CS and GS were captured by fear- and UCS expectancy ratings, a perceptual discrimination task, pupil dilation and source estimations of event-related magnetic fields. Results: Closely resembling adults, adolescents showed robust generalization gradients of fear ratings, pupil dilation, and estimated neural source activity. However, in the UCS expectancy ratings, adolescents revealed shallower generalization gradients indicating overgeneralization. Moreover, adolescents showed stronger visual cortical activity after as compared to before conditioning to all stimuli. Conclusion: Various aspects of fear learning and generalization appear to be mature in healthy adolescents. Yet, cognitive aspects might show a slower course of development.

Several event-related potentials (ERPs) have been proposed as neural correlates of consciousness (NCC), most prominently the early visual awareness negativity (VAN) and the late P3b component. Highly influential support for the P3b comes from studies utilizing the attentional blink (AB), where conscious perception of a first visual target (T1) impairs reporting a second target (T2) presented shortly afterwards. Recent no-report studies using other paradigms suggest that the P3b component may reflect post-perceptual processes associated with decision-making rather than awareness. However, no-report studies are limited in their awareness assessment, and their conclusions have not been tested in an AB paradigm. The present study (N = 38) addressed these issues using a novel AB paradigm, which reduced decision-making processes by omitting a discrimination task on T2 stimuli and rendering their relevance uncertain. Nevertheless, awareness was assessed trial by trial. Comparing ERPs in response to seen versus unseen T2 stimuli revealed a VAN but no enhanced P3b regardless of whether they were marked as distinct from distractor stimuli or not. Our results corroborate the VAN and challenge the P3b as NCC despite rigorous trial-by-trial assessment of conscious perception. Thus, they support the idea that awareness emerges during early sensory processing.

Abstract 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.

Abstract Previous studies on the associations between trait anxiety and amygdalar responses to threat stimuli have resulted in mixed findings, possibly due to sample characteristics, specific tasks, and analytical methods. The present functional magnetic resonance imaging (fMRI) study aimed to investigate linear or non-linear associations between trait anxiety and amygdalar responses in a sample of participants with low, medium, and high trait anxiety scores. During scanning, participants were presented with threat-related or neutral pictures and had either to solve an emotional task or an emotional-unrelated distraction task. Results showed that only during the explicit task trait anxiety was associated with right amygdalar responses to threat-related pictures as compared to neutral pictures. The best model was a cubic model with increased amygdala responses for very low and medium trait anxiety values but decreased amygdala activation for very high trait anxiety values. The findings imply a non-linear relation between trait anxiety and amygdala activation depending on task conditions.

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 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 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 was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

Detection of regularities and their violations in sensory input is key to perception. Violations are indexed by an early EEG component called the mismatch negativity (MMN) – even if participants are distracted or unaware of the stimuli. On a mechanistic level, two dominant models have been suggested to contribute to the MMN: adaptation and prediction. Whether and how context conditions, such as awareness and task relevance, modulate the mechanisms of MMN generation is unknown. We conducted an EEG study disentangling influences of task relevance and awareness on the visual MMN. Then, we estimated different computational models for the generation of single-trial amplitudes in the MMN time window. Amplitudes were best explained by a prediction error model when stimuli were task-relevant but by an adaptation model when task-irrelevant and unaware. Thus, mismatch generation does not rely on one predominant mechanism but mechanisms vary with task relevance of stimuli.

There is an ongoing debate on the neural correlates of consciousness (NCC) in the attentional blink (AB). Theoretical accounts propose that NCC during the attentional blink occur late in the processing hierarchy and that this quality is specific to the AB. We investigated this question by recording event-related potentials during an AB experiment with faces as T2. We analyzed ERPs to T2 stimuli inside (short lag) and outside (long lag) the AB window after carefully calibrating T2 stimuli to ensure equal visibility ratings across lags. We found that the N170, the visual awareness negativity (VAN), and the P3b showed an increased amplitude for seen compared to unseen face stimuli regardless of stimulus lag and that all these components scale linearly with subjective visibility. These findings suggest similar early and late mechanisms of graded perceptual awareness within and outside the AB across perceptual (N170, VAN) and post-perceptual (P3b) processing stages.

Neural mismatch responses have been proposed to rely on different mechanisms, including prediction error-related activity and adaptation to frequent stimuli. However, the hierarchical cortical structure of these mechanisms is unknown. To investigate this question, we recorded hemodynamic responses while participants (N = 54) listened to an auditory oddball sequence as well as a suited control condition. In addition to effects in sensory processing areas (Heschl's gyrus, superior temporal gyrus (STG)), we found several distinct clusters that indexed deviance processing in frontal and parietal regions (anterior cingulate cortex/supplementary motor area (ACC/SMA), inferior parietal lobule (IPL), anterior insula (AI), inferior frontal junction (IFJ)). Comparing responses to the control stimulus with the deviant and standard enabled us to delineate the contributions of prediction error- or adaptation-related brain activation, respectively. We observed significant effects of adaptation in Heschl's gyrus, STG and ACC/SMA, while prediction error-related activity was observed in STG, IPL, AI and IFJ. Additional dynamic causal modeling confirmed the superiority of a hierarchical processing structure compared to a flat structure. Thus, we found that while prediction-error related processes increased with the hierarchical level of the brain area, adaptation declined. This suggests that the relative contribution of different mechanisms in deviance processing varies across the cortical hierarchy.

Abstract Examining personality traits as predictors of human behaviour is of high interest. There are several but inconclusive reported relationships of personality and the susceptibility to the “anchoring effect”, a tendency to adjust estimates towards a given anchor. To provide an answer to variably reported links between personality traits and the anchoring effect, we collected data from 1000 participants in the lab and validated typical anchoring effects and representative personality scores of the sample. Using Bayesian statistical data analyses, we found evidence for the absence of a relationship between anchoring effects and personality scores. We, therefore, conclude that there are no specific personality traits that relate to a higher susceptibility to the anchoring effect. The lack of a relationship between personality and the susceptibility to the anchoring effect might be due to the specific anchoring design, be limited to specific cognitive domains, or the susceptibility to anchors might reflect no reliable individual cognitive phenomena. In the next step, studies should examine the reliability of anchoring effects on the individual level, and testing relationships of individual traits and anchoring effects for other types of anchors, anchoring designs, or cognitive domains.

Abstract Background Posttraumatic stress disorder (PTSD) is associated with markers of accelerated aging. Estimates of brain age, compared to chronological age, may clarify the effects of PTSD on the brain and may inform treatment approaches targeting the neurobiology of aging in the context of PTSD. Method Adult subjects (N = 2229; 56.2% male) aged 18–69 years (mean = 35.6, SD = 11.0) from 21 ENIGMA‐PGC PTSD sites underwent T1‐weighted brain structural magnetic resonance imaging, and PTSD assessment (PTSD+, n = 884). Previously trained voxel‐wise (brainageR) and region‐of‐interest (BARACUS and PHOTON) machine learning pipelines were compared in a subset of control subjects (n = 386). Linear mixed effects models were conducted in the full sample (those with and without PTSD) to examine the effect of PTSD on brain predicted age difference (brain PAD; brain age − chronological age) controlling for chronological age, sex, and scan site. Results BrainageR most accurately predicted brain age in a subset (n = 386) of controls (brainageR: ICC = 0.71, R = 0.72, MAE = 5.68; PHOTON: ICC = 0.61, R = 0.62, MAE = 6.37; BARACUS: ICC = 0.47, R = 0.64, MAE = 8.80). Using brainageR, a three‐way interaction revealed that young males with PTSD exhibited higher brain PAD relative to male controls in young and old age groups; old males with PTSD exhibited lower brain PAD compared to male controls of all ages. Discussion Differential impact of PTSD on brain PAD in younger versus older males may indicate a critical window when PTSD impacts brain aging, followed by age‐related brain changes that are consonant with individuals without PTSD. Future longitudinal research is warranted to understand how PTSD impacts brain aging across the lifespan.

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.

A growing body of evidence suggests a role of the insular cortex (IC) and the basal ganglia (BG) in the experience, expression, and recognition of disgust. However, human lesion research, probing this structure-function link, has yielded rather disparate findings in single cases of unilateral and bilateral damage to these areas. Comparative group approaches are needed to elucidate whether disgust-related deficits specifically follow damage to the IC-BG system, or whether there might be a differential hemispheric contribution to disgust processing. We examined emotional processing by means of a comprehensive emotional test battery in four patients with left- and four patients with right-hemispheric lesions to the IC-BG system as well as in 19 healthy controls. While single tests did not provide clear-cut separations of patient groups, composite scores indicated selective group effects for disgust. Importantly, left-lesioned patients presented attenuated disgust composites, while right-lesioned patients showed increased disgust composites, as compared to each other and controls. These findings propose a left-hemispheric basis of disgust, potentially due to asymmetrical representations of autonomic information in the human forebrain. The present study provides the first behavioral evidence of hemispheric lateralization of a specific emotion in the human brain, and contributes to neurobiological models of disgust.

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.

Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples.An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n=174) and healthy control (HC)-participants (n=213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium. Keywords: Social anxiety disorder, Structural MRI, Voxel-based morphometry, Gray matter, Mega-analysis, Striatum

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.

Anticipation of potentially threatening social situations is a key process in social anxiety disorder (SAD). In other anxiety disorders, recent research of neural correlates of anticipation of temporally unpredictable threat suggests a temporally dissociable involvement of amygdala and bed nucleus of the stria terminalis (BNST) with phasic amygdala responses and sustained BNST activation. However, the temporal profile of amygdala and BNST responses during temporal unpredictability of threat has not been investigated in patients suffering from SAD. We used functional magnetic resonance imaging (fMRI) to investigate neural activation in the central nucleus of the amygdala (CeA) and the BNST during anticipation of temporally unpredictable aversive (video camera observation) relative to neutral (no camera observation) events in SAD patients compared to healthy controls (HC). For the analysis of fMRI data, we applied two regressors (phasic/sustained) within the same model to detect temporally dissociable brain responses. The aversive condition induced increased anxiety in patients compared to HC. SAD patients compared to HC showed increased phasic activation in the CeA and the BNST for anticipation of aversive relative to neutral events. SAD patients as well as HC showed sustained activity alterations in the BNST for aversive relative to neutral anticipation. No differential activity during sustained threat anticipation in SAD patients compared to HC was found. Taken together, our study reveals both CeA and BNST involvement during threat anticipation in SAD patients. The present results point towards potentially SAD-specific threat processing marked by elevated phasic but not sustained CeA and BNST responses when compared to HC. Keywords: FMRI, Threat anticipation, Social anxiety disorder, Bed nucleus of stria terminalis, Amygdala

Background: Despite considerable effort, the neurobiological underpinnings of hyper-responsive threat processing specific to patients suffering from generalized anxiety disorder (GAD) remain poorly understood. The current functional magnetic resonance imaging (fMRI) study aims to delineate GAD-specific brain activity during immediate threat processing by comparing GAD patients to healthy controls (HC), to social anxiety disorder (SAD) and to panic disorder (PD) patients. Method: Brain activation and functional connectivity patterns to threat vs. neutral pictures were investigated using event-related fMRI. The sample consisted of 21 GAD, 21 PD, 21 SAD and 21 HC. Results: GAD-specific elevated activity to threat vs. neutral pictures was found in cingulate cortex, dorsal anterior insula/frontal operculum (daI/FO) and posterior dorsolateral prefrontal cortex (dlPFC). Defining these effects as seed regions, we detected GAD-specific increased functional connectivity to threat vs. neutral pictures between posterior dlPFC and ventrolateral prefrontal cortex, between cingulate cortex and amygdala, between cingulate cortex and anterior insula, as well as decreased functional connectivity between daI/FO and mid-dlPFC. Conclusion: The findings present the first evidence for GAD-specific neural correlates of hyper-responsive threat processing, possibly reflecting exaggerated threat sensitivity, maladaptive appraisal and attention-allocation processes.

BACKGROUND: Negative affective and pain-related cues, such as pictures or words, have been shown to act as primes and enhance the perceived intensity of subsequent painful events. For pain-related semantic primes, it remains unclear whether this effect depends on negative valence itself or, specifically, on the pain-relatedness of the words.

For several stimulus categories (e.g., pictures, odors and words), the arousal of both negative and positive stimuli has been shown to modulate amygdalar activation. In contrast, previous studies did not observe similar amygdalar effects in response to negative and positive facial expressions with varying intensity of facial expressions. Reasons for this discrepancy may be related to analytical strategies, experimental design and stimuli. Therefore, the present study aimed at re-investigating whether the intensity of facial expressions modulates amygdalar activation by circumventing limitations of previous research. Event-related functional magnetic resonance imaging (fMRI) was used to assess brain activation while participants observed a static neutral expression and positive (happy) and negative (angry) expressions of either high or low intensity from an ecologically valid, novel stimulus set. The ratings of arousal and intensity were highly correlated. We found that amygdalar activation followed a u-shaped activation pattern with highest activation to high intense facial expressions as compared to low intensity facial expressions and to the neutral expression irrespective of valence, suggesting a critical role of the amygdala in valence-independent arousal processing of facial expressions. Additionally, consistent with previous studies, intensity effects were also found in visual areas and generally increased activation to angry vs. happy faces were found in visual cortex and insula, indicating enhanced visual representations of high arousing facial expressions and increased visual and somatosensory representations of threat.

Disorder-relevant but task-unrelated stimuli impair cognitive performance in social anxiety disorder (SAD); however, time course and neural correlates of emotional interference are unknown. The present study investigated time course and neural basis of emotional interference in SAD using event-related functional magnetic resonance imaging (fMRI). Patients with SAD and healthy controls performed an emotional stroop task which allowed examining interference effects on the current and the succeeding trial. Reaction time data showed an emotional interference effect in the current trial, but not the succeeding trial, specifically in SAD. FMRI data showed greater activation in the left amygdala, bilateral insula, medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (ACC), and left opercular part of the inferior frontal gyrus during emotional interference of the current trial in SAD patients. Furthermore, we found a positive correlation between patients' interference scores and activation in the mPFC, dorsal ACC and left angular/supramarginal gyrus. Taken together, results indicate a network of brain regions comprising amygdala, insula, mPFC, ACC, and areas strongly involved in language processing during the processing of task-unrelated threat in SAD. However, specifically the activation in mPFC, dorsal ACC, and left angular/supramarginal gyrus is associated with the strength of the interference effect, suggesting a cognitive network model of attentional bias in SAD. This probably comprises exceeded allocation of attentional resources to disorder-related information of the presented stimuli and increased self-referential and semantic processing of threat words in SAD.

Time processing critically relies on the mesencephalic dopamine system and striato-prefrontal projections and has thus been suggested to play a key role in schizophrenia. Previous studies have provided evidence for an acceleration of the internal clock in schizophrenia that may be linked to dopaminergic pathology. The present study aimed to assess the relationship between altered time processing in schizophrenia and symptom manifestation in 22 patients and 22 controls. Subjects were required to estimate the time needed for a visual stimulus to complete a horizontal movement towards a target position on trials of varying cognitive demand. It was hypothesized that patients - compared to controls - would be less accurate at estimating the movement time, and that this effect would be modulated by symptom manifestation and task difficulty. In line with the notion of an accelerated internal clock due to dopaminergic dysregulation, particularly patients with severe positive symptoms were expected to underestimate movement time. However, if altered time perception in schizophrenia was better explained in terms of cognitive deficits, patients with severe negative symptoms should be specifically impaired, while generally, task performance should correlate with measures of processing speed and cognitive flexibility. Patients underestimated movement time on more demanding trials, although there was no link to disease-related cognitive dysfunction. Task performance was modulated by symptom manifestation. Impaired estimation of movement time was significantly correlated with PANSS positive symptom scores, with higher positive symptom scores associated with stronger underestimation of movement time. The present data thus support the notion of a deficit in anticipatory and predictive mechanisms in schizophrenia that is modulated both by symptom manifestation and by cognitive demand.