Computational modeling of social evaluative decision-making elucidates individual differences in adolescent anxiety.

Adolescents experience significant developmental changes during a time of heightened sensitivity to social cues, particularly rejection by peers, which can be especially overwhelming for those with elevated levels of social anxiety. Social evaluative decision-making tasks have been useful in uncovering the neural correlates of information processing biases; however, linking youths' task-based performance to individual differences in psychopathology (e.g., anxiety symptoms) has proven more elusive. Here, we address this weakness with drift diffusion modeling to decompose youths' performance on the social judgment paradigm (SJP) to determine if this approach is useful in discovering individual differences in anxiety symptoms, as well as puberty, age, and sex. A sample of 103 adolescents (55 males, Mage = 14.49, SD = 1.69) completed the SJP and self-report measures of anxiety, as well as self- and parent-reported measures of puberty. The decision threshold parameter, reflecting the amount of evidence needed to make a social evaluative decision, predicted youth self-reported anxiety, above and beyond typical metrics of SJP performance. Our results highlight the potential advantage of parsing task performance according to the underlying cognitive processes. Future research would likely benefit from applying computational modeling approaches to social judgment tasks when attempting to uncover performance-based individual differences in psychopathology.

Graph Analysis of EEG Functional Connectivity Networks During a Letter-Speech Sound Binding Task in Adult Dyslexics.

We performed an EEG graph analysis on data from 31 typical readers (22.27 ± 2.53 y/o) and 24 dyslexics (22.99 ± 2.29 y/o), recorded while they were engaged in an audiovisual task and during resting-state. The task simulates reading acquisition as participants learned new letter-sound mappings via feedback. EEG data was filtered for the delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) bands. We computed the Phase Lag Index (PLI) to provide an estimate of the functional connectivity between all pairs of electrodes per band. Then, networks were constructed using a Minimum Spanning Tree (MST), a unique sub-graph connecting all nodes (electrodes) without loops, aimed at minimizing bias in between groups and conditions comparisons. Both groups showed a comparable accuracy increase during task blocks, indicating that they correctly learned the new associations. The EEG results revealed lower task-specific theta connectivity, and lower theta degree correlation over both rest and task recordings, indicating less network integration in dyslexics compared to typical readers. This pattern suggests a role of theta oscillations in dyslexia and may reflect differences in task engagement between the groups, although robust correlations between MST metrics and performance indices were lacking.

As they wait: Anticipatory neural response to evaluative peer feedback varies by pubertal status and social anxiety.

Adolescence is a developmental period characterized by substantial biological, neural, behavioral, and social changes. Learning to navigate the complex social world requires adaptive skills. Although anticipation of social situations can serve an adaptive function, providing opportunity to adjust behavior, socially anxious individuals may engage in maladaptive anticipatory processing. Importantly, elevated social anxiety often coincides with adolescence. This study investigated cortical electroencephalogram (EEG) responses during anticipation of evaluative feedback in 106 healthy adolescents aged 12-17 years. We examined differences in anticipatory event-related potentials (i.e., stimulus preceding negativity [SPN]) in relation to social anxiety levels and pubertal maturation. As expected, the right frontal SPN was more negative during feedback anticipation, particularly for adolescents with higher social anxiety and adolescents who were at a more advanced pubertal stage. Effects for the left posterior SPN were the opposite of those for the right frontal SPN consistent with a dipole. Anticipatory reactivity in adolescence was related to social anxiety symptom severity, especially in females, and pubertal maturation in a social evaluative situation. This study provides evidence for the development of social anticipatory processes in adolescence and potential mechanisms underlying maladaptive anticipation in social anxiety.

Improvement in left ventricular ejection fraction after pharmacological up-titration in new-onset heart failure with reduced ejection fraction.

OBJECTIVE: Recent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality. METHODS: From 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients. RESULTS: Of 345 HFrEF patients with a follow-up visit after 9 months, 69% reached ≥ 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached ≥ 50% of the recommended dose of beta-blockers and 77% reached ≥ 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75-0.94, p = 0.002) for mortality and 0.85 (0.78-0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years. CONCLUSIONS: This study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF.

Short- and long-term haemodynamic consequences of transcatheter closure of atrial septal defect and patent foramen ovale.

BACKGROUND: Transcatheter atrial septal defect (ASD) and patent foramen ovale (PFO) closure might have opposite short- and long-term haemodynamic consequences compared with restricted interatrial shunt creation, which recently emerged as a potential treatment modality for patients with heart failure with preserved ejection fraction (HFpEF). Given the opposing approaches of ASD and PFO closure versus shunt creation, we investigated the early and sustained cardiac structural and functional changes following transcatheter ASD or PFO closure. METHODS: In this retrospective study, adult secundum-type ASD and PFO patients with complete echocardiography examinations at baseline and at 1­day and 1­year follow-up who also underwent transcatheter closure between 2013 and 2017 at the University Medical Centre Groningen, the Netherlands were included. RESULTS: Thirty-nine patients (mean age 48 ± standard deviation 16 years, 61.5% women) were included. Transcatheter ASD/PFO closure resulted in an early and persistent decrease in right ventricular systolic and diastolic function. Additionally, transcatheter ASD/PFO closure resulted in an early and sustained favourable response of left ventricular (LV) systolic function, but also in deterioration of LV diastolic function with an increase in LV filling pressure (LVFP), as assessed by echocardiography. Age (ß = 0.31, p = 0.009) and atrial fibrillation (AF; ß = 0.24, p = 0.03) were associated with a sustained increase in LVFP after transcatheter ASD/PFO closure estimated by mean E/e' ratio (i.e. ratio of mitral peak velocity of early filling to diastolic mitral annular velocity). In subgroup analysis, this was similar for ASD and PFO closure. CONCLUSION: Older patients and patients with AF were predisposed to sustained increases in left-sided filling pressures resembling HFpEF following ASD or PFO closure. Consequently, these findings support the current concept that creating a restricted interatrial shunt might be beneficial, particularly in elderly HFpEF patients with AF.

Corrigendum: Graph Analysis of EEG Functional Connectivity Networks During a Letter-Speech Sound Binding Task in Adult Dyslexics.

[This corrects the article DOI: 10.3389/fpsyg.2021.767839.].

The aortic root in repaired tetralogy of Fallot: Serial measurements and impact of losartan treatment.

BACKGROUND: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and the effect of pharmaceutical treatment. This study aims to determine factors associated with aortic growth and investigate effects of losartan. METHODS AND RESULTS: We performed a prespecified analysis from the 1:1 randomized, double-blind REDEFINE trial. Aortic root diameters were measured at baseline and after 2.0 ± 0.3 years of follow-up using cardiovascular magnetic resonance (CMR) imaging. A total of 66 patients were included (68% men, age 40 ± 12 years, baseline aortic root 37 ± 6 mm, 32% aortic dilatation (>40 mm)). There was a trend towards slow aortic root growth (+0.6 ± 2.3 mm after two years, p = 0.06) (n = 60). LV stroke volume was the only factor associated with both a larger baseline aortic root (ß: 0.09 mm/ml (95% C.I.:0.02, 0.15), p = 0.010) and with aortic growth during follow-up (ß: 0.04 mm/ml (95% C.I.:0.005, 0.066), p = 0.024), after correction for age, sex, and body surface area using linear regression analysis. No treatment effect of losartan was found (p = 0.17). CONCLUSIONS: Aortic root dilatation was present in about one-third of rTOF patients. A larger LV stroke volume was associated with both a larger baseline aortic root and ongoing growth. Our findings provide no arguments for lower aortic diameter thresholds for prophylactic surgery compared to the general population.

Infective endocarditis in the Netherlands: current epidemiological profile and mortality : An analysis based on partial ESC EORP collected data.

INTRODUCTION: Infective endocarditis (IE) is associated with a high in-hospital and long term mortality. Although progress has been made in diagnostic approach and management of IE, morbidity and mortality of IE remain high. In the latest European guidelines, the importance of the multi-modality imaging in diagnosis and follow up of IE is emphasized. AIM: The aim was to provide information regarding mortality and adverse events of IE, to determine IE characteristics and to assess current use of imaging in the diagnostic workup of IE. METHODS: This is a prospective observational cohort study. We used data from the EURO-ENDO registry. Seven hospitals in the Netherlands have participated and included patients with IE between April 2016 and April 2018. RESULTS: A total of 139 IE patients were included. Prosthetic valve endocarditis constituted 32.4% of the cases, cardiac device related IE 7.2% and aortic root prosthesis IE 3.6%. In-hospital mortality was 14.4% (20 patients) and one-year mortality was 21.6% (30 patients). The incidence of embolic events under treatment was 16.5%, while congestive heart failure or cardiogenic shock occurred in 15.1% of the patients. Transthoracic and transoesophageal echocardiography were performed most frequently (97.8%; 81.3%) and within 3 days after IE suspicion, followed by 18F­fluorodeoxyglucose positron emission tomography/computed tomography (45.3%) within 6 days and multi-slice computed tomography (42.4%) within 7 days. CONCLUSION: We observed a high percentage of prosthetic valve endocarditis, rapid and extensive use of imaging and a relatively low in-hospital and one-year mortality of IE in the Netherlands. Limitations include possible selection bias.

EEG Resting State Functional Connectivity in Adult Dyslexics Using Phase Lag Index and Graph Analysis.

Developmental dyslexia may involve deficits in functional connectivity across widespread brain networks that enable fluent reading. We investigated the large-scale organization of electroencephalography (EEG) functional networks at rest in 28 dyslexics and 36 typically reading adults. For each frequency band (delta, theta alpha and beta), we assessed functional connectivity strength with the phase lag index (PLI). Network topology was examined using minimum spanning tree (MST) graphs derived from the functional connectivity matrices. We found significant group differences in the alpha band (8-13 Hz). The graph analysis indicated more interconnected nodes, in dyslexics compared to typical readers. The graph metrics were significantly correlated with age in dyslexics but not in typical readers, which may indicate more heterogeneity in maturation of brain networks in dyslexics. The present findings support the involvement of alpha oscillations in higher cognition and the sensitivity of graph metrics to characterize functional networks in adult dyslexia. Finally, the current results extend our previous findings on children.

Frontal delta-beta cross-frequency coupling in high and low social anxiety: An index of stress regulation?

Cross-frequency coupling (CFC) between frontal delta (1-4 Hz) and beta (14-30 Hz) oscillations has been suggested as a candidate neural correlate of social anxiety disorder, a disorder characterized by fear and avoidance of social and performance situations. Prior studies have used amplitude-amplitude correlation (AAC) as a CFC measure and hypothesized it as a candidate neural mechanism of affective control. However, using this metric has yielded inconsistent results regarding the direction of CFC, and the functional significance of coupling strength is uncertain. To offer a better understanding of CFC in social anxiety, we compared frontal delta-beta AAC with phase-amplitude coupling (PAC) - a mechanism for information transfer through neural circuits. Twenty high socially anxious (HSA) and 32 low socially anxious (LSA) female undergraduates participated in a social performance task (SPT). Delta-beta PAC and AAC were estimated during the resting state, as well as the anticipation and recovery conditions. Results showed significantly more AAC in LSA than HSA participants during early anticipation, as well as significant values during all conditions in LSA participants only. PAC did not distinguish between LSA and HSA participants, and instead was found to correlate with state nervousness during early anticipation, but in LSA participants only. Together, these findings are interpreted to suggest that delta-beta AAC is a plausible neurobiological index of adaptive stress regulation and can distinguish between trait high and low social anxiety during stress, while delta-beta PAC might be sensitive enough to reflect mild state anxiety in LSA participants.

Variable heart rate and a flexible mind: Higher resting-state heart rate variability predicts better task-switching.

The neurovisceral integration model proposes that heart rate variability (HRV) is linked to prefrontal cortex activity via the vagus nerve, which connects the heart and the brain. HRV, an index of cardiac vagal tone, has been found to predict performance on several cognitive control tasks that rely on the prefrontal cortex. However, the link between HRV and the core cognitive control function "shifting" between tasks and mental sets is under-investigated. Therefore, the present study tested the neurovisceral integration model by examining, in 90 participants, the relationship between vagally mediated resting-state HRV and performance in a task-switching paradigm that provides a relatively process-pure measure of cognitive flexibility. As predicted, participants with higher resting-state HRV (indexed both by time domain and frequency domain measures) showed smaller switch costs (i.e., greater flexibility) than individuals with lower resting-state HRV. Our findings support the neurovisceral integration model and indicate that higher levels of vagally mediated resting-state HRV promote cognitive flexibility.

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes.

OBJECTIVES: Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so-called "endophenotypes". These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. METHODS: The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. RESULTS: The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self-reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. CONCLUSIONS: By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD.

Community structure analysis of rejection sensitive personality profiles: A common neural response to social evaluative threat?

Monitoring social threat is essential for maintaining healthy social relationships, and recent studies suggest a neural alarm system that governs our response to social rejection. Frontal-midline theta (4-8 Hz) oscillatory power might act as a neural correlate of this system by being sensitive to unexpected social rejection. Here, we examined whether frontal-midline theta is modulated by individual differences in personality constructs sensitive to social disconnection. In addition, we examined the sensitivity of feedback-related brain potentials (i.e., the feedback-related negativity and P3) to social feedback. Sixty-five undergraduate female participants (mean age = 19.69 years) participated in the Social Judgment Paradigm, a fictitious peer-evaluation task in which participants provided expectancies about being liked/disliked by peer strangers. Thereafter, they received feedback signaling social acceptance/rejection. A community structure analysis was employed to delineate personality profiles in our data. Results provided evidence of two subgroups: one group scored high on attachment-related anxiety and fear of negative evaluation, whereas the other group scored high on attachment-related avoidance and low on fear of negative evaluation. In both groups, unexpected rejection feedback yielded a significant increase in theta power. The feedback-related negativity was sensitive to unexpected feedback, regardless of valence, and was largest for unexpected rejection feedback. The feedback-related P3 was significantly enhanced in response to expected social acceptance feedback. Together, these findings confirm the sensitivity of frontal midline theta oscillations to the processing of social threat, and suggest that this alleged neural alarm system behaves similarly in individuals that differ in personality constructs relevant to social evaluation.

Behavioral and EEG responses to social evaluation: A two-generation family study on social anxiety.

Social anxiety disorder is an invalidating psychiatric disorder characterized by extreme fear and avoidance of one or more social situations in which patients might experience scrutiny by others. The goal of this two-generation family study was to delineate behavioral and electrocortical endophenotypes of social anxiety disorder related to social evaluation. Nine families of patients with social anxiety disorder (their spouse and children, and siblings of these patients with spouse and children) performed a social judgment paradigm in which they believed to be evaluated by peers. For each peer, participants indicated their expectation about the evaluative outcome, after which they received social acceptance or rejection feedback. Task behavior, as well as the feedback-related EEG brain potentials (N1, FRN, P3) and theta power were tested as candidate endophenotypes based on two criteria: co-segregation with social anxiety disorder within families and heritability. Results indicated that reaction time for indicating acceptance-expectations might be a candidate behavioral endophenotype of social anxiety disorder, possibly reflecting increased uncertainty or self-focused attention and vigilance during the social judgment paradigm. N1 in response to expected rejection feedback and P3 in response to acceptance feedback might be candidate electrocortical endophenotypes of social anxiety disorder, although the heritability analyses did not remain significant after correcting for multiple tests. Increased N1 possibly reflects hypervigilance to socially threatening stimuli, and increased P3 might reflect that positive feedback is more important for, and/or less expected by, participants with social anxiety disorder. Finally, increased feedback-related negativity and theta power in response to unexpected rejection feedback compared to the other conditions co-segregated with social anxiety disorder, but these EEG measures were not heritable. The candidate endophenotypes might play a new and promising role in future research on genetic mechanisms, early detection and/or prevention of social anxiety disorder.

Will they like me? Neural and behavioral responses to social-evaluative peer feedback in socially and non-socially anxious females.

The current study examined neural and behavioral responses to social-evaluative feedback processing in social anxiety. Twenty-two non-socially and 17 socially anxious females (mean age = 19.57 years) participated in a Social Judgment Paradigm in which they received peer acceptance/rejection feedback that was either congruent or incongruent with their prior predictions. Results indicated that socially anxious participants believed they would receive less social acceptance feedback than non-socially anxious participants. EEG results demonstrated that unexpected social rejection feedback elicited a significant increase in theta (4-8 Hz) power relative to other feedback conditions. This theta response was only observed in non-socially anxious individuals. Together, results corroborate cognitive-behavioral studies demonstrating a negative expectancy bias in socially anxiety with respect to social evaluation. Furthermore, the present findings highlight a functional role for theta oscillatory dynamics in processing cues that convey social-evaluative threat, and this social threat-monitoring mechanism seems less sensitive in socially anxious females.

Delta-beta correlation as a candidate endophenotype of social anxiety: A two-generation family study.

BACKGROUND: Social anxiety disorder (SAD) is characterized by an extreme and intense fear and avoidance of social situations. In this two-generation family study we examined delta-beta correlation during a social performance task as candidate endophenotype of SAD. METHODS: Nine families with a target participant (diagnosed with SAD), their spouse and children, as well as target's siblings with spouse and children performed a social performance task in which they gave a speech in front of a camera. EEG was measured during resting state, anticipation, and recovery. Our analyses focused on two criteria for endophenotypes: co-segregation within families and heritability. RESULTS: Co-segregation analyses revealed increased negative delta-low beta correlation during anticipation in participants with (sub)clinical SAD compared to participants without (sub)clinical SAD. Heritability analyses revealed that delta-low beta and delta-high beta correlation during anticipation were heritable. Delta-beta correlation did not differ between participants with and without (sub)clinical SAD during resting state or recovery, nor between participants with and without SAD during all phases of the task. LIMITATIONS: It should be noted that participants were seen only once, they all performed the EEG tasks in the same order, and some participants were too anxious to give a speech. CONCLUSIONS: Delta-low beta correlation during anticipation of giving a speech might be a candidate endophenotype of SAD, possibly reflecting increased crosstalk between cortical and subcortical regions. If validated as endophenotype, delta-beta correlation during anticipation could be useful in studying the genetic basis, as well as improving treatment and early detection of persons at risk for developing SAD.

Electrocortical measures of information processing biases in social anxiety disorder: A review.

Social anxiety disorder (SAD) is characterized by information processing biases, however, their underlying neural mechanisms remain poorly understood. The goal of this review was to give a comprehensive overview of the most frequently studied EEG spectral and event-related potential (ERP) measures in social anxiety during rest, anticipation, stimulus processing, and recovery. A Web of Science search yielded 35 studies reporting on electrocortical measures in individuals with social anxiety or related constructs. Social anxiety was related to increased delta-beta cross-frequency correlation during anticipation and recovery, and information processing biases during early processing of faces (P1) and errors (error-related negativity). These electrocortical measures are discussed in relation to the persistent cycle of information processing biases maintaining SAD. Future research should further investigate the mechanisms of this persistent cycle and study the utility of electrocortical measures in early detection, prevention, treatment and endophenotype research.

Appropriate use criteria for echocardiography in the Netherlands.

INTRODUCTION: Appropriate use criteria (AUC) for echocardiography based on clinical scenarios were previously published by an American Task Force. We determined whether members of the Dutch Working Group on Echocardiography (WGE) would rate these scenarios in a similar way. METHODS: All 32 members of the WGE were invited to judge clinical scenarios independently using a blanked version of the previously published American version of AUC for echocardiography. During a face-to-face meeting, consensus about the final rating was reached by open discussion for each indication. For reasons of simplicity, the scores were reduced from a 9-point scale to a 3-point scale (indicating an appropriate, uncertain or inappropriate echo indication, respectively). RESULTS: Nine cardiologist members of the WGE reported their judgment on the echo cases (n = 153). Seventy-one indications were rated as appropriate, 35 were rated as uncertain, and 47 were rated as inappropriate. In 5% of the cases the rating was opposite to that in the original (appropriate compared with inappropriate and vice versa), whereas in 20% judgements differed by 1 level of appropriateness. After the consensus meeting, the appropriateness of 7 (5%) cases was judged differently compared with the original paper. CONCLUSIONS: Echocardiography was rated appropriate when it is applied for an initial diagnosis, a change in clinical status or a change in patient management. However, in about 5% of the listed clinical scenarios, members of the Dutch WGE rated the AUC for echocardiography differently as compared with their American counterparts. Further research is warranted to analyse this decreased external validity.

NT-proBNP and exercise capacity in adult patients with congenital heart disease and a prosthetic valve: a multicentre PROSTAVA study.

OBJECTIVES: N-terminal B­type natriuretic peptide (NT-proBNP) is an important biomarker for the detection of heart failure. Adults with congenital heart disease (ACHD) and a prosthetic heart valve are at risk for heart failure. This study aimed to determine the value of NT-proBNP in ACHD patients with a prosthetic valve and investigate its relationship with cardiac function and exercise capacity. METHODS: In this multi-centre cross-sectional observational study, data regarding medical history, echocardiography, exercise testing (VO2peak) and laboratory blood evaluation (including NT-proBNP) were collected in ACHD patients with a single prosthetic valve (either homografts, heterografts or mechanical valves). RESULTS: A total of 306 ACHD patients with pulmonary valve replacement (PVR, n = 139), aortic valve replacement (n = 141), mitral valve replacement (n = 21) or tricuspid valve replacement (n = 5) were investigated. The majority of patients (77 %) were in NYHA class I or II. Elevated NT-proBNP levels (cut-off ≥125 pg/ml) were found in 50 % of the patients, with the highest levels in patients with mitral valve replacements. In this study population, NT-proBNP levels were associated with gender (p = 0.029) and VO2max (p < 0.001). In PVR patients, NT-proBNP levels were associated with lower VO2peak, also after adjustment for age, gender and age at valve replacement in a multivariate model (p = 0.015). CONCLUSIONS: In patients with ACHD and a prosthetic valve, elevated NT-proBNP levels are frequently observed despite preserved NYHA class. In PVR patients, a higher NT-proBNP level was associated with a lower VO2peak. These results may be of importance in the ongoing discussion about the timing of valve replacement in patients with CHD.