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In cognitive neurosciences, fundamental principles of mental processes and functional brain organization have been established with highly controlled tasks and testing environments. Recent technical advances allowed the investigation of these functions and their brain mechanisms in naturalistic settings. The diversity in those approaches have been recently (Matusz, P. J., Dikker, S., Huth, A. G., & Perrodin, C. (2019). Are we ready for real-world neuroscience? Journal of Cognitive Neuroscience, 31(3), 327–338. doi:10.1162/jocn_e_01276) classified via a three-category cycle, including controlled laboratory, partially naturalistic laboratory, and naturalistic real-world research. Based on this model, we developed the Multidimensional Assessment of Research in Context (MARC) tool to easily delineate the approach researchers have taken in their study. MARC provides means to describe the degree of ecological validity for each component of a study (e.g., sample, stimuli, measures, etc.), and the study's location on the cycle. The tool comprises seven questions concerning a study's characteristics. It outputs a summary of those and a compass plot, which can be used for presentations, preregistration, grant proposals, and papers. It aims to improve drawing conclusions across studies and raise awareness about the generalizability of research findings.

This paper is about the assessment of masonry arch bridges in the Netherlands, whether or not founded on wooden foundation piles. A large part of the public road network in old city centres is still formed by masonry arch bridges crossing the canals. The general question of the local authorities is: “Can these masonry arch bridges withstand motorised traffic including busses and occasionally heavy trucks?” Nonlinear finite element analysis in PLAXIS is applied for the assessment of the failure behaviour of the masonry structure and its shallow or pile foundation. The structural limits are related to cracking, continuous deformations and instability. A proof-loading of a real bridge increased the reliability of the calculation methodology. With NLFEA it can be demonstrated that these historic bridges still meet the current loads from heavy motorised traffic. With a quick scan method based on the MEXE theory, a large group of arches can be quickly classified, so the assessment with NLFEA can start with the riskiest objects. In many cases lifetime extension of these bridges is possible, whether or not by strengthening the superstructure. This means that the shallow foundation or pile foundation is reused., Paper presentation

Contains fulltext : 288062.pdf (Publisher’s version ) (Closed access) There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE

Background: Social reticence in early childhood is characterized by shy and anxiously avoidant behavior, and it confers risk for pediatric anxiety disorders later in development. Aberrant threat processing may play a critical role in this association between early reticent behavior and later psychopathology. The goal of this longitudinal study is to characterize developmental trajectories of neural mechanisms underlying threat processing and relate these trajectories to associations between early-childhood social reticence and adolescent anxiety. Methods: In this 16-year longitudinal study, social reticence was assessed from 2 to 7 years of age; anxiety symptoms and neural mechanisms during the dot-probe task were assessed at 10, 13, and 16 years of age. The sample included 144 participants: 71 children provided data at age 10 (43 girls, meanage = 10.62), 85 at age 13 (46 girls, meanage = 13.25), and 74 at age 16 (36 girls, meanage = 16.27). Results: A significant interaction manifested among social reticence, anxiety symptoms, and time, on functional connectivity between the left amygdala and the left dorsolateral prefrontal cortex, voxelwise p < .001, clusterwise familywise error p < .05. Children with high social reticence showed a negative association between amygdala–dorsolateral prefrontal cortex connectivity and anxiety symptoms with age, compared to children with low social reticence, suggesting distinct neurodevelopmental pathways to anxiety. Conclusions: These findings were present across all conditions, suggesting task-general effects in potential threat processing. Additionally, the timing of these neurodevelopmental pathways differed for children with high versus low social reticence, which could affect the timing of effective preventive interventions.

Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Here, we built and validated neurostructural machine learning (ML) models for individual-level inferences based on the largest-ever multi-site neuroimaging sample of youth with anxiety disorders (age: 10-25 years, N=3,343 individuals from 32 global sites), as compiled by three ENIGMA Anxiety Working Groups: Panic Disorder (PD), Generalized Anxiety Disorder (GAD), and Social Anxiety Disorder (SAD). ML classifiers were trained on MRI-derived regional measures of cortical thickness, surface area, and subcortical volumes to classify patients and healthy controls (HC) for each anxiety disorder separately and across disorders (transdiagnostic classification). Modest, yet robust, classification performance was achieved for PD vs. HC (AUC=0.62), but other disorder-specific and transdiagnostic classifications were not significantly different from chance. However, above chance-level transdiagnostic classifications were obtained in exploratory subgroup analyses of male patients vs. male HC, unmedicated patients vs. HC, and patients with low anxiety severity vs. HC (AUC 0.59-0.63). The above chance-level classifications were based on plausible and specific neuroanatomical features in fronto-striato-limbic and temporo-parietal regions. This study provides a realistic estimate of classification performance in a large, ecologically valid, multi-site sample of youth with anxiety disorders, and may as such serve as a benchmark.

While it is normal to be scared of things, some children are so scared that it disrupts their lives. This is called an anxiety disorder. To help children with anxiety disorders, we need to know how anxiety disorders start. From other research we knew that toddlers who avoid new situations are more likely to become anxious later in life. They are more likely, which does not mean they all become more anxious, just some of them. We wanted to know if brain activity could predict which children would become anxious. We studied avoidance in toddlers and invited them back as preteens. We studied their brains while they were resting and while they were making mistakes in front of somebody else. We found that brain responses to mistakes predicted which avoidant toddlers became very anxious as preteens. This helps us understand who might develop anxiety, so that we can help!

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.

The COVID-19 pandemic is a chronically stressful event, particularly for youth. Here, we examine (i) changes in mood and anxiety symtpoms, (ii) pandemic-related stress as a mediator of change in symptoms, and (ii) threat processing biases as a predictor of increased anxiety during the pandemic. A clinically well-characterized sample of 81 youth ages 8–18 years (M = 13.8 years, SD = 2.65; 40.7% female) including youth with affective and/or behavioral psychiatric diagnoses and youth without psychopathology completed pre- and during pandemic assessments of anxiety and depression and COVID-related stress. Forty-six youth also completed a threat processing fMRI task pre-pandemic. Anxiety and depression significantly increased during the pandemic (all ps Fs(1.95,81.86) > 14.44, ps

This report examines the relationship between pediatric anxiety disorders and implicit bias evoked by threats. To do so, the report uses two tasks that assess implicit bias to negative-valence faces, the first by eye-gaze and the second by measuring body-movement parameters. The report contrasts task performance in 51 treatment-seeking, medication-free pediatric patients with anxiety disorders and 36 healthy peers. Among these youth, 53 completed an eye-gaze task, 74 completed a body-movement task, and 40 completed both tasks. On the eye-gaze task, patients displayed longer gaze duration on negative relative to non-negative valence faces than healthy peers, F(1, 174) = 8.27, p = .005. In contrast, on the body-movement task, patients displayed a greater tendency to behaviorally avoid negative-valence faces than healthy peers, F(1, 72) = 4.68, p = .033. Finally, implicit bias measures on the two tasks were correlated, r(38) = .31, p = .049. In sum, we found an association between pediatric anxiety disorders and implicit threat bias on two tasks, one measuring eye-gaze and the other measuring whole-body movements. Converging evidence for implicit threat bias encourages future research using multiple tasks in anxiety.

The authors examined temperamental and sociocognitive predictors of socially anxious behavior from preschool to early adolescence. Children (N = 227; 59% male; 69% White) completed a speech task at ages 5, 7, 10, and 13 and socially anxious behaviors were coded. Behavioral inhibition (BI) was assessed at ages 2/3 and Theory of Mind (ToM) was assessed at age 4. Data collection occurred between 2003 and 2016. Three trajectories of socially anxious behavior were identified: high stable, average increasing, and low stable. Higher BI was related to the high stable trajectory, whereas lower ToM was related to the increasing trajectory of socially anxious behavior. There are heterogenous pathways of socially anxious behavior, which may be uniquely influenced by early temperamental and sociocognitive factors.

Irritability, defined as proneness to anger, is among the most common reasons youth are seen for psychiatric care. Youth with irritability demonstrate aberrant processing of anger-related stimuli; however, the neural mechanisms remain unknown. We applied a drift-diffusion model (DDM), a computational tool, to derive a latent behavioral metric of attentional bias to angry faces in youth with varying levels of irritability during functional magnetic resonance imaging (fMRI). We examined associations among irritability, task behavior using a DDM-based index for preferential allocation of attention to angry faces (i.e., extra-decisional time bias; Δt0), and amygdala context-dependent connectivity during the dot-probe task. Our transdiagnostic sample, enriched for irritability, included 351 youth (ages 8–18; M = 12.92 years, 51% male, with primary diagnoses of either attention deficit/hyperactivity disorder [ADHD], disruptive mood dysregulation disorder [DMDD], an anxiety disorder, or healthy controls). Models accounted for age, sex, in-scanner motion, and co-occurring symptoms of anxiety. Youth and parents rated youth’s irritability using the Affective Reactivity Index. An fMRI dot-probe task was used to assess attention orienting to angry faces. In the angry-incongruent vs. angry-congruent contrast, amygdala connectivity with the bilateral inferior frontal gyrus (IFG), insula, caudate, and thalamus/pulvinar was modulated by irritability level and attention bias to angry faces, Δt0, all ts350 > 4.46, ps t0 was associated with a weaker amygdala connectivity. In contrast, in youth with low irritability, elevated Δt0 was associated with stronger connectivity in those regions. No main effect emerged for irritability. As irritability is associated with reactive aggression, these results suggest a potential neural regulatory deficit in irritable youth who have elevated attention bias to angry cues.

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders., Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

To arrive at a coherent understanding of the relation between glucocorticoids and the human brain, we systematically reviewed the literature for studies examining the associations between endogenous or exogenous cortisol and human brain function. Higher levels of endogenous cortisol during psychological stress were related to increased activity in the middle temporal gyrus and perigenual anterior cingulate cortex (ACC), decreased activity in the ventromedial prefrontal cortex, and altered function (i.e., mixed findings, increased or decreased) in the amygdala, hippocampus and inferior frontal gyrus. Moreover, endogenous cortisol response to psychological stress was related to increased activity in the inferior temporal gyrus and altered function in the amygdala during emotional tasks that followed psychological stress. Exogenous cortisol administration was related to increased activity in the postcentral gyrus, superior frontal gyrus and ACC, and altered function in the amygdala and hippocampus during conditioning, emotional and reward-processing tasks after cortisol administration. These findings were in line with those from animal studies on amygdala activity during and after stress.

Excessive expression of threat-anticipatory defensive responses is central in anxiety. Animal research indicates that anticipatory responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from translational work on threat imminence could guide mechanistic research mapping abnormal function in this circuitry to aberrant defensive responses in anxiety. Here, we initiate such research.Fifty pediatric anxiety patients and healthy-comparisons (33 females) completed a threat-anticipation task whereby cues signaled delivery of highly-painful (threat) or non-painful (safety) heat. Temporal changes in skin-conductance indexed defensive responding as function of threat imminence. Resting-state functional connectivity data were used to identify intrinsic-function correlates of anticipatory response within a specific functional network derived from translational research.Results indicate that anxiety was associated with greater increase in anticipatory response as threats became more imminent. Magnitude of increase in threat-anticipatory responses corresponded to intrinsic connectivity within a cortical-subcortical circuit; importantly, more severe anxiety was associated with greater connectivity between ventromedial prefrontal cortex and hippocampus and basolateral amygdala, a circuit implicated in animal models of anxiety. These findings link basic-translational and clinical research, highlighting aberrant intrinsic function in conserved defensive circuitry as potential pathophysiological mechanism in anxiety.

Background Aberrations in both neural reward processing and stress reactivity are associated with increased risk for mental illness; yet, how these two factors relate to each other remains unclear. Several studies suggest that stress exposure impacts reward function, thus increasing risk for psychopathology. However, the alternative hypothesis, in which reward dysfunction impacts stress reactivity, has been rarely examined. The current study aimed to test both hypotheses using a longitudinal design. Methods Participants were 38 children (23 girls; 61%) from a prospective cohort study. A standard stress-exposure measure was collected at 7 years of age. Children performed a well-validated imaging reward paradigm at age 10, and a standardized acute psychological stress laboratory protocol was administered both at age 10 and at age 13. Structural equation modeling was used to examine bidirectional associations between stress and neural response to reward anticipation. Results Higher exposure to stressful life events at age 7 predicted lower neural response to reward anticipation in regions of the basal ganglia at age 10, which included ventral caudate, nucleus accumbens, putamen, and globus pallidus. Lower response to reward anticipation in medial prefrontal and anterior cingulate cortex predicted higher stress reactivity at age 13. Conclusions Our findings provide support for bidirectional associations between stress and reward processing, in that stress may impact reward anticipation, but also in that reduced reward anticipation may increase susceptibility to stress.

This study identified a shared pathophysiological mechanism of pediatric anxiety and irritability. Clinically, anxiety and irritability are common, co-occurring problems, both characterized by high-arousal negative affective states. Behaviorally, anxiety and irritability are associated with aberrant threat processing. To build on these findings, we examined eye-tracking measures of attention bias in relation to the unique and shared features of anxiety and irritability in a transdiagnostic sample of youth (n = 97, 58% female, Mage = 13.03, SDage = 2.82). We measured attention bias to negative versus non-negative emotional faces during a passive viewing task. We employed bifactor analysis to parse the unique and shared variance of anxiety and irritability symptoms from self- and parent-report questionnaires. Negative affectivity is the derived latent factor reflecting shared variance of anxiety and irritability. We found that higher negative affectivity was associated with looking longer at negative versus non-negative faces, reflecting a shared mechanism of anxiety and irritability. This finding suggests that modification of elevated attention to negative emotional faces may represent a common potential treatment target of anxiety and irritability.