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BackgroundExperimental work in animals has shown that DNA methylation (DNAm), an epigenetic mechanism regulating gene expression, is influenced by typical variation in maternal care. While emerging research in humans supports a similar association, studies to date have been limited to candidate gene and cross-sectional approaches, with a focus on extreme deviations in the caregiving environment.MethodsHere, we explored the prospective association between typical variation in maternal sensitivity and offspring epigenome-wide DNAm, in a population-based cohort of children (N = 235). Maternal sensitivity was observed when children were 3- and 4-years-old. DNAm, quantified with the Infinium 450 K array, was extracted at age 6 (whole blood). The influence of methylation quantitative trait loci (mQTLs), DNAm at birth (cord blood), and confounders (socioeconomic status, maternal psychopathology) was considered in follow-up analyses.ResultsGenome-wide significant associations between maternal sensitivity and offspring DNAm were observed at 13 regions (p < 1.06 × 10−07), but not at single sites. Follow-up analyses indicated that associations at these regions were in part related to genetic factors, confounders, and baseline DNAm levels at birth, as evidenced by the presence of mQTLs at five regions and estimate attenuations. Robust associations with maternal sensitivity were found at four regions, annotated to ZBTB22, TAPBP, ZBTB12, and DOCK4.ConclusionsThese findings provide novel leads into the relationship between typical variation in maternal caregiving and offspring DNAm in humans, highlighting robust regions of associations, previously implicated in psychological and developmental problems, immune functioning, and stress responses.

Social isolation has been suggested to foster paranoia. Here we investigate whether social company (i.e., being alone vs. not) and its nature (i.e., stranger/distant vs. familiar other) affects paranoia differently depending on psychosis risk. Social interactions and paranoid thinking in daily life were investigated in 29 patients with clinically stable non-affective psychotic disorders, 20 first-degree relatives, and 26 controls (n = 75), using the experience sampling method (ESM). ESM was completed up to ten times daily for 1 week. Patients experienced marginally greater paranoia than relatives [b = 0.47, p = 0.08, 95% CI (− 0.06, 1.0)] and significantly greater paranoia than controls [b = 0.55, p = 0.03, 95% CI (0.5, 1.0)], but controls and relatives did not differ [b = 0.07, p = 0.78, 95% CI (− 0.47, 0.61)]. Patients were more often alone [68.5% vs. 44.8% and 56.2%, respectively, p = 0.057] and experienced greater paranoia when alone than when in company [b = 0.11, p = 0.016, 95% CI (0.02, 0.19)]. In relatives this was reversed [b = − 0.17, p b = − 0.02, p = 0.67, 95% CI (− 0.09, 0.06)]. The time-lagged association between being in social company and subsequent paranoia was non-significant and paranoia did not predict the likelihood of being in social company over time (both p’s = 0.68). All groups experienced greater paranoia in company of strangers/distant others than familiar others [X2(2) = 4.56, p = 0.03] and being with familiar others was associated with lower paranoia over time [X2(2) = 4.9, p = 0.03]. Patients are frequently alone. Importantly, social company appears to limit their paranoia, particularly when being with familiar people. The findings stress the importance of interventions that foster social engagement and ties with family and friends.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

Objective: Recent findings suggest that diminished processing of positive contextual information about others during interactions may contribute to social impairment in the schizophrenia spectrum. This could be due to general social context processing deficits or specific biases against positive information. We studied the impact of positive and negative social contextual information during social interactions using functional neuroimaging and probed whether these neural mechanisms were associated with real-life social functioning in schizophrenia spectrum disorders. Methods: Patients with a schizophrenia spectrum disorder ( N = 23) and controls disorder ( N = 25) played three multi-round trust games during functional magnetic resonance imaging scanning, with no, positive and negative information about the counterpart’s trustworthiness, while all counterparts were programmed to behave trustworthy. The main outcome variable was the height of the shared amount in the trust game, i.e. investment, representing an indication of trust. The first investment in the game was considered to be basic trust, since no behavioural feedback was given yet. We performed region-of-interest analyses and examined the association with real-life social functioning using the experience sampling method. Results: Social contextual information had no effect on patients’ first investments, whereas controls made the lowest investment after negative and the highest investments after positive contextual information was provided. Over trials, patients decreased investments, suggesting reduced social reward learning, whereas controls increased investments in response to behavioural feedback in the negative context. Patients engaged the dorsolateral prefrontal cortex less than controls during context presentation and showed reduced activity within the caudate during repayments. In patients, lower investments were associated with more time spent alone and social exclusion and lower caudate activation was marginally significantly associated with higher perceived social exclusion. Conclusion: The failure to adapt trust to positive and negative social contexts suggests that patients have a general insensitivity to prior social information, indicating top-down processing impairments. In addition, patients show reduced sensitivity to social reward, i.e. bottom-up processing deficits. Moreover, lower trust and lower neural activation were related to lower real-life social functioning. Together, these findings indicate that improving trust and social interactions in schizophrenia spectrum needs a multi-faceted approach that targets both mechanisms.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic had brought negative consequences and new stressors to mothers. The current study aims to compare factors predicting maternal mental health during the COVID-19 lockdown in China, Italy, and the Netherlands.MethodsThe sample consisted of 900 Dutch, 641 Italian, and 922 Chinese mothers (age M = 36.74, s.d. = 5.58) who completed an online questionnaire during the lockdown. Ten-fold cross-validation models were applied to explore the predictive performance of related factors for maternal mental health, and also to test similarities and differences between the countries.ResultsCOVID-19-related stress and family conflict are risk factors and resilience is a protective factor in association with maternal mental health in each country. Despite these shared factors, unique best models were identified for each of the three countries. In Italy, maternal age and poor physical health were related to more mental health symptoms, while in the Netherlands maternal high education and unemployment were associated with mental health symptoms. In China, having more than one child, being married, and grandparental support for mothers were important protective factors lowering the risk for mental health symptoms. Moreover, high SES (mother's high education, high family income) and poor physical health were found to relate to high levels of mental health symptoms among Chinese mothers.ConclusionsThese findings are important for the identification of at-risk mothers and the development of mental health promotion programs during COVID-19 and future pandemics.

Key Points Question Does a brief video-feedback parenting intervention delivered in a routine health context improve behavior outcomes for at-risk children aged 12 to 36 months? Findings This randomized clinical trial that included 300 children and their caregivers found lower levels of behavior problems among families allocated to receive the intervention vs those who received usual care. In particular, conduct problems decreased. Meaning This brief parenting intervention can benefit the mental health of very young children and can be delivered by frontline staff in a routine community health service setting., Importance Behavior problems are one of the most common mental health disorders in childhood and can undermine children’s health, education, and employment outcomes into adulthood. There are few effective interventions for early childhood. Objective To test the clinical effectiveness of a brief parenting intervention, the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD), in reducing behavior problems in children aged 12 to 36 months. Design, Setting, and Participants The Healthy Start, Happy Start study was a 2-group, parallel-group, researcher-blind, multisite randomized clinical trial conducted via health visiting services in 6 National Health Service trusts in England. Baseline and 5-month follow-up data were collected between July 30, 2015, and April 27, 2018. Of 818 eligible families, 227 declined to participate, and 300 were randomized into the trial. Target participants were caregivers of children who scored in the top 20% for behavior problems on the Strengths and Difficulties Questionnaire. Participants were randomly allocated on a 1:1 basis to receive either VIPP-SD (n = 151) or usual care (n = 149), stratified by site and number of participating caregivers. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from September 5, 2019, to January 17, 2020. Interventions All families continued to access usual care. Families allocated to VIPP-SD were offered 6 home-based video-feedback sessions of 1 to 2 hours’ duration every 2 weeks. Main Outcomes and Measures The primary outcome was the score on an early childhood version of the Preschool Parental Account of Children’s Symptoms, a semistructured interview of behavior symptoms, at 5 months after randomization. Secondary outcomes included caregiver-reported behavior problems on the Child Behavior Checklist and the Strengths and Difficulties Questionnaire. Results Among 300 participating children (163 boys [54%]; mean [SD] age, 23.0 [6.7] months), primary outcome data were available for 140 of 151 VIPP-SD participants (93%) and 146 of 149 usual care participants (98%). There was a mean difference in the total Preschool Parental Account of Children’s Symptoms score of 2.03 (95% CI, 0.06-4.01; P = .04; Cohen d = 0.20 [95% CI, 0.01-0.40]) between trial groups, with fewer behavior problems in the VIPP-SD group, particularly conduct symptoms (mean difference, 1.61 [95% CI, 0.44-2.78]; P = .007; d = 0.30 [95% CI, 0.08-0.51]). Other child behavior outcomes showed similar evidence favoring VIPP-SD. No treatment or trial-related adverse events were reported. Conclusions and Relevance This study found that VIPP-SD was effective in reducing symptoms of early behavior problems in young children when delivered in a routine health service context. Trial Registration isrctn.org Identifier: ISRCTN58327365, This randomized clinical trial tests the clinical effectiveness of a brief video feedback–based parenting intervention in reducing behavior problems in children aged 12 to 36 months.

BACKGROUND: Professionals in child healthcare increasingly endorse the support of self-management in paediatric rehabilitation services for children with physical disability. Less understood though are their views regarding the role of the children's parents, as well as their own role in supporting parents. This study aimed to investigate the motivation of rehabilitation professionals to support self-management of parents regarding their child with physical disability, professionals' beliefs about parental self-management, and the perceptions underlying their motivation.METHODS: A mixed-methods strategy was followed using a survey among rehabilitation professionals (n = 175) and consecutive semi-structured interviews (n = 16). Associations between autonomous (intrinsic) versus controlled (extrinsic) motivation and beliefs on parental self-management were tested. For deeper understanding of their motivation, directed content analysis was used to address key themes in the qualitative data extracts.RESULTS: Professionals reported autonomous motivation for parental self-management support more often than controlled motivation (t(174) = 29.95, p < .001). Autonomous motivation was associated with the beliefs about the importance of parental self-management (r = .29, p < .001). Approximately 90% of the professionals believed that parents should have an active role, though less than ten percent considered it important that parents also are independent actors and initiative takers in the rehabilitation process. Interviews revealed that individual professionals struggled with striking a balance between keeping control and "giving away responsibility" to parents. A "professional-like" attitude was expected of parents with "involvement" and "commitment" as essential preconditions. Furthermore, professionals expressed the need for additional coaching skills to support parental self-management.CONCLUSION: Professionals were predominantly autonomously motivated to support self-management of parents. However, the dilemmas in giving or taking responsibilities within the partnership with parents, may limit their effectiveness in empowering parents. Reflection on the potential gaps between professionals' motivation, beliefs, and actual behaviour might be crucial to support parental self-management.

Infant protection is an important but largely neglected aspect of parental care. Available theory and research suggest that endocrine levels and neural responses might be biological correlates of protective behavior. However, no research to date examined associations between these neurobiological and behavioral aspects. This study, preregistered on https://osf.io/2acxd, explored the psychobiology of paternal protection in 77 new fathers by combining neural responses to infant-threatening situations, self-reported protective behavior, behavioral observations in a newly developed experimental set-up (Auditory Startling Task), and measurements of testosterone and vasopressin. fMRI analyses validated the role of several brain networks in the processing of infant-threatening situations and indicated replicable findings with the infant-threat paradigm. We found little overlap between observed and reported protective behavior. Robust associations between endocrine levels, neural responses, and paternal protective behavior were absent. ispartof: Developmental Psychobiology vol:63 issue:5 pages:1358-1369 ispartof: location:United States status: published

© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Introduction: For Small-Group Active Learning (SMAL) to be effective, students need to engage meaningfully in learning activities to construct their knowledge. Teachers can have difficulty engaging their students in this process. To improve engagement, we aimed to identify the diversity in medical students’ appreciation of SMAL, using the concepts of epistemic beliefs and approaches to learning. Method: Q-methodology is a mixed-method research design used for the systematic study of subjectivity. We developed a set of 54 statements on active learning methods. In individual interviews, first-year medical students rank ordered their agreement with these statements and explained their reasons. Data were analyzed using a by-person factor analysis to group participants with shared viewpoints. Results: A four-factor solution (i.e. profiles) fit the data collected from 52 students best and explained 52% of the variance. Each profile describes a shared viewpoint on SMAL. We characterized the profiles as ‘understanding-oriented’, ‘assessment-oriented’, ‘group-oriented’, and ‘practice-oriented’. Discussion: The four profiles describe how and why students differ in their appreciation of SMAL. Teachers can use the profiles to make better-informed decisions when designing and teaching their SMAL classes, by relating to students’ epistemic beliefs, and approaches to learning. This may improve student motivation and engagement for SMAL.

Building knowledge schemas that organize information and guide future learning is of great importance in everyday life. Such knowledge building is suggested to occur through reinstatement of prior knowledge during new learning, yielding integration of new with old memories supported by the medial prefrontal cortex (mPFC) and medial temporal lobe (MTL). Congruency with prior knowledge is also known to enhance subsequent memory. Yet, how reactivation and congruency interact to optimize memory integration is unknown. To investigate this question, we used an adapted AB-AC inference paradigm in combination with functional Magnetic Resonance Imaging (fMRI). Participants first studied an AB-association followed by an AC-association, so B (a scene) and C (an object) were indirectly linked through A (a pseudoword). BC-associations were either congruent or incongruent with prior knowledge (e.g. bathduck or hammer in a bathroom), and participants reported subjective B-reactivation strength while learning AC. Behaviorally, both congruency and reactivation enhanced memory integration. In the brain, these behavioral effects related to univariate and multivariate parametric effects in the MTL, mPFC, and Parahippocampal Place Area (PPA). Moreover, mPFC exhibited larger PPA-connectivity for more congruent associations. These outcomes provide insights into the neural mechanisms underlying memory enhancement, which has value for educational learning.

Background Maternal smoking and stress during pregnancy are associated with adverse health effects for women themselves and are risk factors for adverse developmental outcomes of the unborn child. Smoking and stress seem to be intertwined in various ways. First, the majority of smoking pregnant women is of lower socio-economic status, which is associated with higher levels of perceived stress. Second, smoking women often report to smoke because they feel stressed. Third, quitting smoking often increases perceived stress levels initially. Therefore, effective interventions are needed to support women with smoking cessation by reducing stress. The aim of this study is to test the effectiveness of an eHealth intervention on stress reduction and smoking cessation. Methods/design The Stress- and Smoke Free Start of Life (SSFSL) study is a randomized controlled trial (RCT) comparing a personalized eHealth intervention with a control condition. Inclusion criteria for the women are: (1) > 18 years of age, (2) Discussion If the eHealth intervention is effective in smoking cessation among pregnant smoking women, it can be implemented as a tool into the health care in the Netherlands. Trial registration Netherlands Trial Register, ID: NL8156. Registered on 11 November 2019.

Contains fulltext : 236261.pdf (Publisher’s version ) (Open Access) New fathers may grow into their parental role through active involvement in childcare. Spending time in physical contact with the child may promote an adaptive transition to fatherhood. In this randomized controlled trial, we tested the effects of a baby carrier intervention on fathers' hormonal and neural functioning. Using functional magnetic resonance imaging (fMRI), we examined whether infant carrying affects neural reactivity to infant crying in first-time fathers, taking into account the role of the hormone oxytocin as a mediating mechanism and fathers' own childhood experiences as a potential moderating factor. Sixty first-time fathers (infant age M = 11.18 weeks, SD = 2.08) were randomly assigned to a baby carrier intervention group (n = 32 fathers) or a control group (n = 28 fathers). Fathers in the intervention group were instructed to use a baby carrier for three weeks, whereas fathers in the control group were instructed to use a baby seat. Before and after the intervention salivary oxytocin was measured and neural reactivity to infant crying was assessed using fMRI. Results showed that the infant carrier intervention increased amygdala reactivity to infant crying compared to the infant seat users. This effect was most pronounced in fathers with experiences of childhood abuse. The carrier intervention did not affect fathers' oxytocin levels. Our findings indicate that spending time in physical contact with the infant may promote attention to and accurate perception of infant signals, in particular in fathers with more adverse childhood experiences. Soft baby carriers may, therefore, facilitate an adaptive transition to fatherhood. 10 p.

Contains fulltext : 236748.pdf (Publisher’s version ) (Open Access) Objectives: The goal of the present study was to identify the role of the medial temporal lobe (MTL) in the detection and later processing of novelty. Methods: Twenty-one epilepsy patients with unilateral MTL resection (10 left-sided; 11 right-sided) and 26 matched healthy controls performed an adapted visual novelty oddball task. In this task two streams of stimuli were presented on the left and right of fixation while the patients’ electroencephalogram was measured. The participants had to respond to infrequent target stimuli, while ignoring frequent standard, and infrequent novel stimuli that were presented to the left or right, appearing either contra- or ipsilateral to the patients’ resections. Results: Novelty detection, as indexed by the N2 ERP component elicited by novels, was reduced by the MTL resections, as evidenced by a smaller N2 for patients than healthy controls. Later processing of novels, as indexed by the novelty P3 ERP component, was reduced for novels presented contra- versus ipsilateral to the resected side. Moreover, at a frontal electrode site, the N2-P3 complex showed reduced novelty processing in patients with MTL resections compared to healthy controls. The ERP differences were specific for the novel stimuli, as target processing, as indexed by the P3b, was unaffected in the patients: No P3b differences were found between targets presented ipsi- or contralaterally to the resected side, nor between patients and healthy controls. Conclusions: The current results suggest that MTL structures play a role in novelty processing. In contrast, target processing was unaffected by MTL resections. 11 p.

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

According to several computational models, novel items can create a learning mode with dynamics favorable to new learning, and not to memory retrieval. In line with that idea, a new item in a recognition test has been found to create a bias toward calling subsequent items new as well. Here, we tested whether this bias, which we termed the afterglow effect, is indeed caused by a general learning mode, or is caused by perceptual overlap between preceding and current items. In two experiments, we show that a preceding recognition judgment biases the current one, but only if the preceding and current items are of the same perceptual category. In contrast, we did not find strong bias effects from perceptually novel fractal images, as would be predicted if novel items induce a learning mode that then biases recognition judgments. We conclude that the afterglow effect is more likely to reflect perceptual phenomena than a learning mode. We suggest how this can be reconciled with what is known about familiarity at the neural level.

During reading, word recognition speed is influenced by the amount of orthographic overlap with surrounding words. The nature of this phenomenon is not understood: some theories attribute it to low-level visual operations (i.e., parafoveal feature detectors influencing foveal letter detectors), whereas other theories assume that orthographic processing (i.e., letter position coding and word activation) occurs across multiple words in parallel. To arbitrate between these theories, we used electroencephalography to reveal the time course of orthographic spatial integration in a lexical decision task. Foveal target words were flanked on each side by parafoveal words, manipulated across three conditions: repetition flankers (e.g. rock rock rock), unrelated flankers (step rock step) and a no-flanker condition. Linear mixed-effect models were constructed to analyze EEG data on a trial-by-trial basis. Word recognition was worse in the unrelated flanker condition than in the repetition and no-flanker conditions. This behavioral pattern was accompanied by increased negativity in the N250 and N400 windows, associated with the activation of sub-lexical and lexico-semantic representations, respectively. Crucially, the absence of effects prior to 200 ms post-stimulus onset provides evidence against the involvement of low-level visual processes. We conclude that orthographic spatial integration is driven by parallel processing of multiple words, which leads to the activation of a larger set of sub-lexical nodes and more difficult processing at the lexical level when those words are orthographically unrelated., Highlights • Words are recognized faster when they share many letters with surrounding words. • EEG measurements suggest that this effect unfolds 200 ms after stimulus onset. • The locus of effects contradicts the involvement of low-level visual processing. • Instead, the phenomenon appears to be driven by parallel orthographic processing.

Background Behaviour problems emerge early in childhood and place children at risk for later psychopathology. Objectives To evaluate the clinical effectiveness and cost-effectiveness of a parenting intervention to prevent enduring behaviour problems in young children. Design A pragmatic, assessor-blinded, multisite, two-arm, parallel-group randomised controlled trial. Setting Health visiting services in six NHS trusts in England. Participants A total of 300 at-risk children aged 12–36 months and their parents/caregivers. Interventions Families were allocated in a 1 : 1 ratio to six sessions of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) plus usual care or usual care alone. Main outcome measures The primary outcome was the Preschool Parental Account of Children’s Symptoms, which is a structured interview of behaviour symptoms. Secondary outcomes included caregiver-reported total problems on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The intervention effect was estimated using linear regression. Health and social care service use was recorded using the Child and Adolescent Service Use Schedule and cost-effectiveness was explored using the Preschool Parental Account of Children’s Symptoms. Results In total, 300 families were randomised: 151 to VIPP-SD plus usual care and 149 to usual care alone. Follow-up data were available for 286 (VIPP-SD, n = 140; usual care, n = 146) participants and 282 (VIPP-SD, n = 140; usual care, n = 142) participants at 5 and 24 months, respectively. At the post-treatment (primary outcome) follow-up, a group difference of 2.03 on Preschool Parental Account of Children’s Symptoms (95% confidence interval 0.06 to 4.01; p = 0.04) indicated a positive treatment effect on behaviour problems (Cohen’s d = 0.20, 95% confidence interval 0.01 to 0.40). The effect was strongest for children’s conduct [1.61, 95% confidence interval 0.44 to 2.78; p = 0.007 (d = 0.30, 95% confidence interval 0.08 to 0.51)] versus attention deficit hyperactivity disorder symptoms [0.29, 95% confidence interval –1.06 to 1.65; p = 0.67 (d = 0.05, 95% confidence interval –0.17 to 0.27)]. The Child Behaviour Checklist [3.24, 95% confidence interval –0.06 to 6.54; p = 0.05 (d = 0.15, 95% confidence interval 0.00 to 0.31)] and the Strengths and Difficulties Questionnaire [0.93, 95% confidence interval –0.03 to 1.9; p = 0.06 (d = 0.18, 95% confidence interval –0.01 to 0.36)] demonstrated similar positive treatment effects to those found for the Preschool Parental Account of Children’s Symptoms. At 24 months, the group difference on the Preschool Parental Account of Children’s Symptoms was 1.73 [95% confidence interval –0.24 to 3.71; p = 0.08 (d = 0.17, 95% confidence interval –0.02 to 0.37)]; the effect remained strongest for conduct [1.07, 95% confidence interval –0.06 to 2.20; p = 0.06 (d = 0.20, 95% confidence interval –0.01 to 0.42)] versus attention deficit hyperactivity disorder symptoms [0.62, 95% confidence interval –0.60 to 1.84; p = 0.32 (d = 0.10, 95% confidence interval –0.10 to 0.30)], with little evidence of an effect on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The primary economic analysis showed better outcomes in the VIPP-SD group at 24 months, but also higher costs than the usual-care group (adjusted mean difference £1450, 95% confidence interval £619 to £2281). No treatment- or trial-related adverse events were reported. The probability of VIPP-SD being cost-effective compared with usual care at the 24-month follow-up increased as willingness to pay for improvements on the Preschool Parental Account of Children’s Symptoms increased, with VIPP-SD having the higher probability of being cost-effective at willingness-to-pay values above £800 per 1-point improvement on the Preschool Parental Account of Children’s Symptoms. Limitations The proportion of participants with graduate-level qualifications was higher than among the general public. Conclusions VIPP-SD is effective in reducing behaviour problems in young children when delivered by health visiting teams. Most of the effect of VIPP-SD appears to be retained over 24 months. However, we can be less certain about its value for money. Trial registration Current Controlled Trials ISRCTN58327365. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 29. See the NIHR Journals Library website for further project information.

The development of social-cognitive abilities in infancy is subject to an intricate interaction between maturation of neural systems and environmental input. We investigated the role of infants’ attachment relationship quality in shaping infants’ neural responses to observed social interactions. One-hundred thirty 10-month-old infants participated in an EEG session while they watched animations involving a distressing separation event that ended with either comforting or ignoring behavior. Frontal asymmetry (FA) in the alpha range - which is indicative of approach-withdrawal tendencies - was measured with EEG. Attachment quality was assessed using the Strange Situation procedure at 12 months. Overall, infants with disorganized attachment showed a lack of right-sided – withdrawal related – FA compared to secure and insecure infants. Furthermore, only avoidant infants exhibited reduced right-sided FA responses following the separation. Contrary to our expectations, the type of response (comforting vs. ignoring) did not elicit differences in FA patterns, and attachment quality did not moderate the effects of the type of response on frontal asymmetry. Implications for research on attachment-related biases in social information processing and on the neural underpinnings of prosocial behaviors are discussed.

Special Issue: The ENIGMA Consortium: the first 10 years.-- Karolinska Schizophrenia Project (KaSP)., Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns., National Institute of Mental Health, Grant/Award Numbers: MH104284, MH116147, R01MH113619, R01 MH090553, R01MH117014, R01MH042191; Karolinska Institutet; Stockholm County Council; Southern and Eastern Norway Regional Health Authority; German Centre for Cardiovascular Research; DZHK; Siemens Healthineers; University of Queensland; US National Institute of Child Health and Human Development, Grant/Award Number: RO1HD050735; Australian National Health and Medical Research Council; Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Institute on Drug Abuse, Grant/Award Numbers: UL1 TR000153, 1 U24 RR025736-01, 1 U24 RR021992; Brain Injury Fund Research Grant Program; Indiana State Department of Health Spinal Cord; Parents Against Childhood Epilepsy; Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures; Epilepsy Foundation; American Epilepsy Society; Knut and Alice Wallenberg Foundation; European Community's Horizon 2020 Programme; Vici Innovation Program; NWO Brain & Cognition Excellence Program; Netherlands Organization for Scientific Research; Hersenstichting Nederland; Netherlands Organization for Health Research and Development; Geestkracht Programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; Universiteit Utrecht; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; National Center for Advancing Translational Sciences; National Institutes of Health; National Center for Research Resources; Consortium grant, Grant/Award Number: U54 EB020403; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Number: G0500092; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; the Research Council, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Swedish Research Council; European Community's Seventh Framework Programme, Grant/Award Number: 602450; King's College London; South London and Maudsley NHS Foundation Trust; Biomedical Research Centre; National Institute for Health Research.

International audience; When reading, orthographic information is extracted not only from the word the reader is looking at, but also from adjacent words in the parafovea. Here we examined, using the recently introduced OB1-reader computational model, how orthographic information can be processed in parallel across multiple words and how orthographic information can be integrated across time and space. Although OB1-reader is a model of text reading, here we used it to simulate single-word recognition experiments in which parallel processing has been shown to play a role by manipulating the surrounding context in flanker and priming paradigms. In flanker paradigms, observers recognize a central word flanked by other letter strings located left and right of the target and separated from the target by a space. The model successfully accounts for the finding that such flankers can aid word recognition when they contain bigrams of the target word, independent of where those flankers are in the visual field. In priming experiments, in which the target word is preceded by a masked prime, the model accounts for the finding that priming occurs independent of whether the prime and target word are in the same location or not. Crucial to these successes is the key role that spatial attention plays within OB1-reader, as it allows the model to receive visual input from multiple locations in parallel, while limiting the kinds of errors that can potentially occur under such spatial pooling of orthographic information.

Selective attention plays a prominent role in prioritizing information in working memory (WM), improving performance for attended representations. However, it remains unclear whether unattended WM representations suffer from information loss. Here we tested the hypothesis that within WM, selectively attending to an item and stopping storing other items are independent mechanisms. We recorded EEG while participants performed a WM recall task in which the item most likely to be tested was cued retrospectively during retention. By manipulating retro-cue reliability (i.e., the ratio of valid to invalid cue trials), we varied the incentive to retain non-cued items. Storage and selective attention in WM were measured during the retention interval by contralateral delay activity (CDA) and contralateral alpha power suppression, respectively. Soon after highly reliable cues, the cued item was attended, and non-cued items suffered information loss. However, for less reliable cues, initially the cued item was attended, but unattended items were kept in WM. Later during the delay, previously unattended items suffered information loss despite now attention being reallocated to their locations, presumably to strengthen their weakening traces. These results show that storage and attention in WM are distinct processes that can behave differently depending on the relative importance of representations.

In a warned reaction time task, the warning stimulus (S1) initiates a process of temporal preparation, which promotes a speeded response to the impending target stimulus (S2). According to the multiple trace theory of temporal preparation (MTP), participants learn the timing of S2 by storing a memory trace on each trial, which contains a temporal profile of the events on that trial. On each new trial, S1 serves as a retrieval cue that implicitly and associatively activates memory traces created on earlier trials, which jointly drive temporal preparation for S2. The idea that S1 assumes this role as a retrieval cue was tested across eight experiments, in which two different S1s were associated with two different distributions of S1-S2 intervals: one with predominantly short and one with predominantly long intervals. Experiments differed regarding the S1 features that made up a pair, ranging from highly distinct (e.g., tone and flash) to more similar (e.g., red and green flash) and verbal (i.e., “short” vs “long”). Exclusively for pairs of highly distinct S1s, the results showed that the S1 cue modified temporal preparation, even in participants who showed no awareness of the contingency. This cueing effect persisted in a subsequent transfer phase, in which the contingency between S1 and the timing of S2 was broken – a fact participants were informed of in advance. Together, these findings support the role of S1 as an implicit retrieval cue, consistent with MTP.

Mother-child relationships change considerably in adolescence, but it is not yet understood how mothers experience vicarious rewards for their adolescent children. In the current study, we investigated neural responses of twenty mothers winning and losing money for their best friend and for their adolescent child in a gambling task. During the task, functional neuroimaging data were acquired. We examined the activation patterns when playing for or winning for self, adolescent children and friends in four a-priori selected ROIs (nucleus accumbens, dorsomedial prefrontal cortex, precuneus and temporo-parietal junction). Behaviorally, mothers indicated that they experienced most enjoyment when they gained money for their children and that their children deserved to win more, relative to friends and self. At the neural level, nucleus accumbens activity was stronger when winning versus losing. This pattern was not only found when playing for self, but also for friends and children, possibly reflecting the rewarding value of vicarious prosocial gains. In addition, dorsomedial prefrontal cortex, precuneus, and temporo-parietal junction were more active when receiving outcomes for children and friends compared to self, possibly reflecting increased recruitment of mentalizing processes. Interestingly, activity in this network was stronger for mothers who indicated that their children and friends deserved to win more. These findings provide initial evidence that vicarious rewards for one’s children are processed similarly as rewards for self, and that activation in social brain regions are related to social closeness.

The current generation of adolescents grows up in a media-saturated world. However, it is unclear how media influences the maturational trajectories of brain regions involved in social interactions. Here we review the neural development in adolescence and show how neuroscience can provide a deeper understanding of developmental sensitivities related to adolescents’ media use. We argue that adolescents are highly sensitive to acceptance and rejection through social media, and that their heightened emotional sensitivity and protracted development of reflective processing and cognitive control may make them specifically reactive to emotion-arousing media. This review illustrates how neuroscience may help understand the mutual influence of media and peers on adolescents’ well-being and opinion formation., The current generation of adolescents grows up in a media-saturated world. Here, Crone and Konijn review the neural development in adolescence and show how neuroscience can provide a deeper understanding of developmental sensitivities related to adolescents’ media use.

Fulfilled predictions lead to neural suppression akin to repetition suppression, but it is currently unclear if such effects generalize to broader stimulus categories in the absence of exact expectations. In particular, does expecting novelty alter the way novel stimuli are processed? In the present study, the effects of expectations on novelty processing were investigated using event-related potentials, while controlling for the effect of repetition. Sequences of five stimuli were presented in a continuous way, such that the last stimulus of a 5-stimulus sequence was followed by the first stimulus of a new 5-stimulus sequence without interruption. The 5-stimulus sequence was predictable: the first three stimuli were preceded by a cue indicating that the next stimulus was likely to be a standard stimulus, and the last two by a cue indicating that the next stimulus was likely to be novel. On some trials a cue typically predicting a standard was in fact followed by an unexpected novel stimulus. This design allowed to investigate the independent effects of (violated) expectations and repetition on novelty processing. The initial detection of expected novels was enhanced compared to unexpected novels, as indexed by a larger anterior N2. In contrast, the orienting response, as reflected by a novelty P3, was reduced for expected compared to unexpected novels. Although the novel stimuli were never repeated themselves, they could be presented after one another in the sequence. Such a category repetition affected the processing of novelty, as evidenced by an enhanced anterior N2, and a reduced novelty P3 for novels preceded by other novels. Taken together, the current study shows that novelty processing is influenced by expectations.

Background In several developed countries women with a low risk of complications during pregnancy and childbirth can make choices regarding place of birth. In the Netherlands, these women receive midwife-led care and can choose between a home or hospital birth. The declining rate of midwife-led home births alongside the recent debate on safety of home births in the Netherlands, however, suggest an association of choice of birth place with psychological factors related to safety and risk perception. In this study associations of pregnancy related anxiety and general anxious or depressed mood with (changes in) planned place of birth were explored in low risk women in midwife-led care until the start of labour. Methods Data (n = 2854 low risk women in midwife-led care at the onset of labour) were selected from the prospective multicenter DELIVER study. Women completed the Pregnancy Related Anxiety Questionnaire-Revised (PRAQ-R) to assess pregnancy related anxiety and the EuroQol-6D (EQ-6D) for an anxious and/or depressed mood. Results A high PRAQ-R score was associated with planned hospital birth in nulliparous (aOR 1.92; 95% CI 1.32–2.81) and parous women (aOR 2.08; 95% CI 1.55–2.80). An anxious or depressed mood was associated with planned hospital birth (aOR 1.58; 95% CI 1.20–2.08) and with being undecided (aOR 1.99; 95% CI 1.23–2.99) in parous women only. The majority of women did not change their planned place of birth. Changing from an initially planned home birth to a hospital birth later in pregnancy was, however, associated with becoming anxious or depressed after 35 weeks gestation in nulliparous women (aOR 4.17; 95% CI 1.35–12.89) and with pregnancy related anxiety at 20 weeks gestation in parous women (aOR 3.91; 95% CI 1.32–11.61). Conclusion Low risk women who planned hospital birth (or who were undecided) more often reported pregnancy related anxiety or an anxious or depressed mood. Women who changed from home to hospital birth during pregnancy more often reported pregnancy related anxiety or an anxious or depressed mood in late pregnancy. Anxiety should be adequately addressed in the process of informed decision-making regarding planned place of birth in low risk women.

Contains fulltext : 157159.pdf (Publisher’s version ) (Closed access) Objective: Youth who report risky substance use and who have a familial history of substance use disorders (SUDs) are at increased risk for developing SUDs themselves later in life. Physiological stress reactivity may be a potential biological mechanism underlying this increased risk. In the current study, we examined (a) whether physiological stress reactivity to a psychosocial stressor was prospectively related to risky substance use later in adolescence and (b) whether this relation was moderated by a familial history of SUDs. Method: Youth from the general population (n = 220) and the children of a parent/parents with an SUD (CPSUDs; n = 60) participated in a psychosocial stress procedure at Time 1. Cortisol and heart rate reactivity were measured during the procedure. Four years later, on average, risky substance use was self-reported (Time 2). Results: Logistic regression analyses showed that youth who had lower cortisol reactivity at Time 1 were more likely to report risky substance use at Time 2. Heart rate reactivity was not related to risky substance use at Time 2, and the relation between stress reactivity and risky substance use was not more pronounced in CPSUDs compared with youth from the general population. These analyses were controlled for alcohol use at Time 1. Conclusions: The present findings suggest hyporeactivity of the hypothalamic pituitary adrenal axis in youth who are more likely to engage in risky substance use later in adolescence. These individuals may be inherently hypoaroused, which leads them to seek out substances in order to achieve a more normalized level of arousal. 12 p.

Maternal prenatal stress has been related to infant negative affect. However, it is still unclear how different sources of maternal prenatal stress such as depressive, anxiety and pregnancy-specific anxiety symptoms are associated with reactivity outcomes. This study aimed to test the associations between different sources of maternal prenatal stress and the aspects of infant emotional reactivity at six months.Our study population (n=282) was drawn from the FinnBrain Birth Cohort Study. Prenatal stress was measured by questionnaires on maternal depression, general anxiety and pregnancy-specific anxiety at three time points across pregnancy (gwk 14, 24, 34). Based on the symptom scores, the sample was divided into mothers with high stress during pregnancy (n=110) and mothers with low stress during pregnancy (n=172). Mother-reported infant emotional reactivity and its subscales were measured six months postpartum.After controlling for background variables and maternal postnatal symptoms, overall negative emotional reactivity (β=0.20, p0.01), and its aspects fearfulness (β=0.15, p=.057) and falling reactivity (β=-0.22, p0.01), were predicted by only pregnancy-specific anxiety. No significant predictors were found for infant positive reactivity after adjusting for confounders.Mother reports of both maternal symptoms and infant reactivity were used, which might increase the risk of reporting bias.The findings suggest that mothers experiencing stress should be provided intervention during pregnancy, and that screening should have a particular focus on pregnancy-related worries.

Background: We examined the longitudinal associations of autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis rest and reactivity measures with anxiety and depressive symptoms at one-year follow-up in children with anxiety disorders. Methods: In a clinical sample of 152 children with a primary DSM-IV anxiety disorder, aged 8 to 12 years, anxiety and depressive symptoms were assessed with the Multidimensional Anxiety Scale for Children and the Children's Depression Inventory at pre-treatment baseline and one year later, after treatment with cognitive behavioral therapy. At baseline, children participated in a 70 min stress task. Salivary cortisol was measured directly prior to and 20 min post stress task. Skin conductance level (SCL), heart rate and high frequency heart rate variability (HRV) were continuously measured during rest and the stress task. To investigate if rest or reactivity measures predicted anxiety and depressive symptoms at one year follow-up, linear regression analyses were conducted for rest and reactivity measures of SCL, heart rate, HRV and cortisol separately. Results: Higher SCL reactivity predicted less decrease of anxiety symptoms at one-year follow-up. Cortisol reactivity showed a weak association with depressive symptoms at one-year follow-up: lower cortisol reactivity predicted less decrease in depressive symptoms. Limitations: Only self-reported anxiety and depressive symptoms were used. However, all predictors were objective biological measures, hence there is no risk of shared method variance bias. Conclusions: These findings suggest that pre-treatment HPA and ANS responsiveness to stress are predictive biomarkers for a lack of symptom improvement in children with a clinical anxiety disorder. (C) 2016 Elsevier B.V. All rights reserved.

Contains fulltext : 157470.pdf (Publisher’s version ) (Closed access) The current study examined mean level and change in extraversion and neuroticism across adolescence in relation to physiological stress reactivity to social evaluation. Adolescents (n = 327) from the Dutch general population reported on personality measures at five annual assessments. At age 17 years, adolescents participated in a psychosocial stress procedure characterized by social evaluation during which cortisol, heart rate, pre-ejection period (PEP) and heart rate variability were assessed. Dual latent growth curve models were fitted in which the intercepts (mean level) and slopes (change) of personality across adolescence predicted the intercepts (baseline) and slopes (reactivity) of the physiological stress measures. Most comparisons revealed no relation between personality and stress reactivity. Adolescents with higher mean level scores on extraversion did show lower cortisol reactivity. Adolescents with higher mean level neuroticism scores showed higher PEP reactivity. Our findings lend partial support for a relation between personality and physiological stress reactivity. 13 p.

Contains fulltext : 226919.pdf (Publisher’s version ) (Open Access) The ability to provide appropriate responses to infant distress is vital to paternal care, but may be affected by fathers' experiences of childhood maltreatment. Detrimental effects of childhood maltreatment have been found in the adult brain's white matter fibers, accompanied with impaired emotional and cognitive functioning. In the current study (N = 121), we examined new and expectant fathers' childhood maltreatment experiences (i.e. emotional and physical abuse and neglect), current behavioral responses (i.e. handgrip force) to infant cry sounds, and white matter integrity using diffusion tensor imaging. First, more exposure to childhood maltreatment was associated with more use of excessive handgrip force in response to infant crying by fathers. Second, the association between experienced childhood maltreatment and white matter integrity was not significant in whole-brain analyses. Lastly, we found that the association between maltreatment exposure and excessive handgrip force during infant crying was absent in fathers with high tract integrity in the bilateral uncinate fasciculus. These findings possibly point to insufficient behavioral inhibition or emotional dysregulation in fathers who experienced childhood maltreatment, but buffering for this effect in those with larger integrity in brain fibers connecting the amygdala and prefrontal cortex. 16 p.

Decades of reading research have led to sophisticated accounts of single-word recognition and, in parallel, accounts of eye-movement control in text reading. Although these two endeavors have strongly advanced the field, their relative independence has precluded an integrated account of the reading process. To bridge the gap, we here present a computational model of reading, OB1-reader, which integrates insights from both literatures. Key features of OB1 are as follows: (1) parallel processing of multiple words, modulated by an attentional window of adaptable size; (2) coding of input through a layer of open bigram nodes that represent pairs of letters and their relative position; (3) activation of word representations based on constituent bigram activity, competition with other word representations and contextual predictability; (4) mapping of activated words onto a spatiotopic sentence-level representation to keep track of word order; and (5) saccade planning, with the saccade goal being dependent on the length and activation of surrounding word units, and the saccade onset being influenced by word recognition. A comparison of simulation results with experimental data shows that the model provides a fruitful and parsimonious theoretical framework for understanding reading behavior. (PsycINFO Database Record (c) 2018 APA, all rights reserved).