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Objective To examine whether the occipito-temporal visual N700 component of the event-related potential is sensitive to stimulus probabilities. Methods P1, N1, P3, and, in particular, the occipito-temporal N700 component of the event-related potential were analysed in response to frequent and rare non-target letters of a continuous performance task in 200 healthy adolescents. Additionally, amplitude habituation with time was examined for the occipito-temporal N700 and N1 components. Results The visual P1, N1, and occipito-temporal N700 components were significantly larger in response to rare letters than to frequent letters, whereas the P3 component demonstrated no amplitude difference. Over time, the occipito-temporal N700 amplitude decreased in response to the rare letters, while the N1 amplitude increased, to both, frequent and rare letters. Conclusions This study provides first evidence that the visual occipito-temporal N700 is sensitive to stimulus probabilities, suggesting an enhanced post-processing of rare stimuli in secondary visual areas. The distinct habituation patterns of occipito-temporal N700 and N1 amplitudes distinguish repetition effects on stimulus post-processing (N700) from those on perception (N1). Significance The enhanced N700 component to rare stimuli might reflect an orienting response and underlying attentional processes. The N700 sensitivity to stimulus probabilities should be examined in patient groups with attentional deficits.

ObjectiveMaladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated this association in predefined regions of interest.MethodT1-weighted magnetic resonance images were acquired from 158 children and adolescents with aggressive behavior (ODD/CD) and 96 controls in a multi-centre study. Aggression subtypes were assessed by questionnaires. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models.ResultsIn cases only proactive aggression was negatively associated with amygdala volume (b=−11.82, p=0.05), while reactive aggression was negatively associated with insula volume (b=−46.41, p=0.01). Classical group comparison showed that children and adolescents with aggressive behavior had smaller volumes than controls in (bilateral) ventral striatum (p=0.003), ACC (p=0.01), and vmPFC (p=0.003) with modest effect sizes.ConclusionsAggression was associated with reduced volume in brain regions involved in decision making. Negative associations were found between reactive aggression and volumes in regions involved in threat responsivity and between proactive aggression and regions linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure.

ObjectiveThere is increasing evidence for altered resting state functional connectivity (rsFC) in adolescents with disruptive behavior. Despite considerable ongoing behavioral research suggesting also important differences relating to reactive and proactive aggression, the corresponding rsFC correlates have not been studied to date. We therefore examined associations between these aggression subtypes along with subdimensions of callous-unemotional (CU) traits and rsFC using predefined seeds in aggression-related salience network (SN) and default mode network (DMN).MethodAggression subtype-specific whole-brain rsFC of SN and DMN seeds was investigated in a resting state sequence (mean acquisition time = 8 min 25 sec) acquired from 207 children and adolescents of both sexes aged 8 - 18 years (mean age (SD) = 13.30 (2.60) years; range = 8.02 – 18.35) in a multi-center study. One hundred eighteen individuals exhibited disruptive behavior (conduct disorder/oppositional defiant disorder) with different levels of comorbid ADHD symptoms, 89 were healthy.ResultsCompared to healthy controls, cases demonstrated reduced DMN and – after controlling for ADHD scores – SN seed-based rsFC with left hemispheric frontal clusters. We found increased and distinct aggression-subtype specific rsFC patterns. Specifically, reactive and proactive aggression correlated with distinct SN and DMN seed-based rsFC patterns. CU dimensions led to different DMN and SN rsFC with clusters including frontal, parietal, and cingulate areas.ConclusionsThis first study investigating reactive and proactive aggression along with CU dimensions reveals new subtype-specific whole-brain rsFC patterns in brain regions linked to processes like emotion, empathy, moral, and cognitive control.

Reports of current ADHD symptoms in adults with a childhood diagnosis of ADHD are often discrepant: While one subgroup reports a particularly high level of current ADHD symptoms, another reports-in contrast-a very low level. The reasons for this difference remain unclear. Although sex might play a moderating role, it has not yet been examined in this regard. In an epidemiological cohort study from birth to young adulthood, childhood ADHD diagnoses were assessed at the ages of 4.5, 8, and 11 years based on parent ratings. Sex-specific development of ADHD symptoms was analyzed from the age of 15 to 25 years via self-reported ADHD symptoms in participants with (n = 47) and without childhood ADHD (n = 289) using a random coefficient regression model. The congruence between parent reports and adolescents' self-ratings was examined, and the role of childhood ADHD diagnosis, childhood OCC/CD, and childhood internalizing disorder as possible sex-specific predictors of self-reported ADHD symptoms at age 25 years was investigated. With regard to self-reported ADHD symptoms, females with a childhood ADHD diagnosis reported significantly more ADHD symptoms compared to females without childhood ADHD and males with and without ADHD throughout adolescence and young adulthood. In contrast, males with childhood ADHD did not differ from control males either at age 15 or at age 25 years. Only in females did a childhood diagnosis of an externalizing disorder (ADHD and CD/ODD) predict self-reported ADHD symptoms by age 25 years. Our findings suggest that self-reports of young adults with a childhood diagnosis of ADHD are influenced by sex. Specifically, females with childhood ADHD report increased levels of ADHD symptoms upon reaching adulthood. To correctly evaluate symptoms and impairment in this subgroup, other, more objective, sources of information may be advisable, such as neurophysiological measures.

A recent study (James et al. 2016) found that attention-deficit/hyperactivity disorder (ADHD) was associated with hypo-arousal, indexed by low electrodermal activity, during a low-demand reaction-time task, which normalized in a fast-incentive condition. We now investigate if (1) autonomic arousal in individuals with ADHD changes over a long testing session and (2) across time, to clarify if arousal profiles are context-dependent. We also examine (3) how autonomic arousal relates to each ADHD symptom domain, and specificity of arousal profiles to ADHD, by controlling for oppositional defiant/conduct disorder (ODD/CD) symptoms. Skin conductance level and non-specific fluctuations were measured during four successive resting-state and cognitive conditions (Resting-state time 1, Continuous Performance Task, Fast Task: Baseline and Fast-Incentive conditions, Resting-state time 2) from 71 adolescents/young adults with ADHD and 140 controls. Lower arousal was observed in individuals with ADHD only during a slow, low-demanding task, and more fluctuating arousal was observed towards the end of assessment. Both inattentive and hyperactive-impulsive symptoms were associated with arousal levels and fluctuations, independently from ODD/CD. Overall, we extend previous findings showing that under-arousal, but also fluctuating arousal, are context-specific rather than stable impairments in ADHD.

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) often present with overlapping symptoms and cognitive impairments, such as increased fluctuations in attentional performance measured by increased reaction-time variability (RTV). We previously provided initial evidence of shared and distinct event-related potential (ERP) impairments in ADHD and BD in a direct electrophysiological comparison, but no study to date has compared neural mechanisms underlying attentional impairments with finer-grained brain oscillatory markers. Here, we aimed to compare the neural underpinnings of impaired attentional processes in ADHD and BD, by examining event-related brain oscillations during a reaction-time task under slow-unrewarded baseline and fast-incentive conditions. We measured cognitive performance, ERPs and brain-oscillatory modulations of power and phase variability in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. Compared to controls, both ADHD and BD groups showed increased RTV in the baseline condition and increased RTV, theta phase variability and lower contingent negative variation in the fast-incentive condition. Unlike controls, neither clinical group showed an improvement from the slow-unrewarded baseline to the fast-incentive condition in attentional P3 amplitude or alpha power suppression. Most impairments did not differ between the disorders, as only an adjustment in beta suppression between conditions (lower in the ADHD group) distinguished between the clinical groups. These findings suggest shared impairments in women with ADHD and BD in cognitive and neural variability, preparatory activity and inability to adjust attention allocation and activation. These overlapping impairments may represent shared neurobiological mechanisms of attentional dysfunction in ADHD and BD, and potentially underlie common symptoms in both disorders. Electronic supplementary material The online version of this article (10.1007/s10548-018-0625-z) contains supplementary material, which is available to authorized users.

A time-processing deficit has been proposed as a neuropsychological candidate endophenotype for Attention Deficit Hyperactivity Disorder (ADHD), but its developmental trajectory still needs to be explored. In the present study, children (N = 33) and adults (N = 22) with ADHD were compared to normal controls on two time-processing tasks. For time reproduction, ADHD-related impairment was found in the full group, but not when adults were analyzed separately. For the discrimination of brief intervals, children and adults with ADHD showed different patterns of deficit. We conclude that in ADHD some time-processing deficits are still present in adults, but may take on age-related different forms.

Neurofeedback of specific brain activity patterns allows perceiving and learning to gain control over these otherwise unaware neuronal processes. Neurofeedback may improve underlying neuronal deficits, and/or establish more general self-regulatory skills for compensating behavioural difficulties in other domains. Treating ADHD is the most common clinical neurofeedback application. Standard neurofeedback protocols based on electroencephalography train self-regulation of oscillatory activity in certain frequency bands (targeting theta/beta ratio) or slow cortical potential shifts. Both protocols have demonstrated promising outcomes, particularly in improving inattention symptoms, although controlled effects remain heterogeneous and often attenuated in blinded ratings. Further randomized controlled and (as far as possible) blinded evaluation studies are needed for better understanding of the mode of action and to establish robust standard training protocols for routine care. In the current state of evidence, neurofeedback can be recommended as part of a multimodal treatment of ADHD.

Neurophysiology allows us to understand and modulate the neural mechanisms in ADHD with high time- and/or frequency-resolution. These non-invasive methods include electroencephalographic recordings at rest and during tasks, with spontaneous and event-related oscillations and potentials tracking covert processing and transcranial neuromodulation through magnetic or electric fields. The findings indicate consistent cognitive and neural deficits in ADHD related to impaired attention and deficient inhibition. Advanced signal processing and source imaging methods often converge with other imaging approaches. Neurophysiological findings also reveal considerable heterogeneity in ADHD regarding cognitive, affective, and genetic subtypes. This illustrates the importance of dimensional approaches and of pathophysiological mechanisms partly shared with other disorders. Although several potential neurophysiological markers of ADHD have been considered, a clinical use for individual diagnostics and classification is not supported to date. More research should clarify the clinical potential of multivariate multimodal classification and prediction of treatment outcome to advance individualized treatment.

Developmental dyslexia (DD) is one of the most prevalent learning disorders among children and is characterized by deficits in different cognitive skills, including reading, spelling, short term memory and others. To help unravel the genetic basis of these skills, we conducted a Genome Wide Association Study (GWAS), including nine cohorts of reading-impaired and typically developing children of European ancestry, recruited across different countries (N=2,562-3,468).We observed a genome-wide significant effect (p−8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2 withinMIR924HG (micro-RNA 924 host gene;p= 4.73×10−9), and a suggestive association on 8q12.3 withinNKAIN3(encoding a cation transporter;p= 2.25 ×10−8). RAN represents one of the best universal predictors of reading fluency across orthographies and linkage to RAN has been previously reported withinCELF4(18q12.2), a gene highly expressed in the fetal brain which is co-expressed withNKAIN3and predicted to be a target ofMIR924. These findings suggest new candidate DD susceptibility genes and provide insights into the genetics and neurobiology of dyslexia.

The JCPP works at the cutting edge of clinical science to publish ground-breaking research across the full range of topics in the field of child psychology and psychiatry. As JCPP editors, who are also active researchers in our own right, we are conscious of the threat posed to our field by what has come to be known as the reproducibility crisis - the fact that many published findings, initially trumpeted as important developments in the field, cannot be replicated and are therefore likely to be spurious (Nature Human Behaviour, 1, 2017, 21). The JCPP is conscious of its responsibility to play its part in addressing this issue as best it can. The roots of the problem are complex and its causes multifaceted. As one part of its response, the JCPP embraces the principles of open science and encourage preregistration of study protocols. Furthermore, we are working towards implementing new systems to promote preregistration with the hope of increasing scientific transparency and accountability and reducing the risks of selective reporting and posthoc rationalisation of findings (Journal of Child Psychology & Psychiatry, 59, 2018, 1).

Spontaneous EEG signal can be parsed into sub-second periods of stable functional states (microstates) that assumingly correspond to brief large scale synchronization events. In schizophrenia, a specific class of microstate (class "D") has been found to be shorter than in healthy controls and to be correlated with positive symptoms. To explore potential new treatment options in schizophrenia, we tested in healthy controls if neurofeedback training to self-regulate microstate D presence is feasible and what learning patterns are observed. Twenty subjects underwent EEG-neurofeedback training to up-regulate microstate D presence. The protocol included 20 training sessions, consisting of baseline trials (resting state), regulation trials with auditory feedback contingent on microstate D presence, and a transfer trial. Response to neurofeedback was assessed with mixed effects modelling. All participants increased the percentage of time spent producing microstate D in at least one of the three conditions (p

Recent longitudinal studies have indicated that affective and behavioral dysregulation in childhood is associated with an increased risk for various negative outcomes in later life. However, few studies to date have examined early mechanisms preceding dysregulation during early childhood. Aim of this study was to elucidate early mechanisms relating to dysregulation in later life using data from an epidemiological cohort study on the long-term outcome of early risk factors from birth to adulthood. At age 3 months, mothers and infants were videotaped during a nursing and playing situation. Maternal responsiveness was evaluated by trained raters. Infant regulatory problems were assessed on the basis of a parent interview and direct observation by trained raters. At age 8 and 11 years, 290 children (139 males) were rated on the Child Behavior Checklist (CBCL). Additionally, participants were genotyped for the dopamine D4 receptor (DRD4) exon 3 VNTR polymorphism. A significant three-way interaction between maternal responsiveness, DRD4 genotype and infant regulatory problems was detected predicting the CBCL-dysregulation profile (CBCL-DP). Carriers of the DRD4 7r allele with regulatory problems at age 3 months showed significantly more behavior problems associated with the CBCL-DP during childhood when exposed to less maternal responsiveness. In contrast, no effect of maternal responsiveness was observed in DRD4 7r carriers without infant regulatory problems and in non-carriers of the DRD4 7r allele. This prospective longitudinal study extends earlier findings regarding the association of the CBCL-DP with early parenting and later psychopathology, introducing both DRD4 genotype and infant regulatory problems as important moderators.

Attention problems affect a substantial number of children and adolescents and are predictive of academic underachievement and lower global adaptive functioning. Considerable variability has been observed with regard to the individual development of attention problems over time. In particular, the period of adolescence is characterized by substantial maturation of executive functioning including attentional processing, with the influence of genetic and environmental factors on individual trajectories not yet well understood. In the present investigation, we evaluated whether the monoamine oxidase A functional promoter polymorphism, MAOA-LPR, plays a role in determining continuity of parent-rated attention problems during adolescence. At the same time, a potential effect of severe life events (SLEs) was taken into account. A multi-group path analysis was used in a sample of 234 adolescents (149 males, 85 females) who took part in an epidemiological cohort study at the ages of 11 and 15 years. Attention problems during early adolescence were found to be a strong predictor of attention problems in middle adolescence. However, in carriers of the MAOA-LPR low-activity variant (MAOA-L), stability was found to be significantly higher than in carriers of the high-activity variant (MAOA-H). Additionally, only in MAOA-L carriers did SLEs during adolescence significantly impact on attention problems at the age of 15 years, implying a possible gene × environment interaction. To conclude, we found evidence that attention problems during adolescence in carriers of the MAOA-L allele are particularly stable and malleable to life stressors. The present results underline the usefulness of applying a more dynamic GxE perspective.

Symptomatology and behavioral characteristics in autism spectrum disorders (ASD) have increasingly been linked to abnormalities in early brain growth patterns of affected children. Studies investigating specific components of gray matter structure, such as cortical thickness (CT), have produced conflicting results, and have rarely included additional measures of social impairment. In the present study, we applied a surface-based whole brain analysis to investigate CT in a sample of 36 pre-adolescent children [18 subjects with ASD (IQ mean: 111) and 18 healthy controls (IQ mean: 112.8), age range 6-12 years]. The CT analysis revealed widespread, but mostly left-hemispheric thinning in frontal, temporal, parietal and occipital brain areas related to the theory-of-mind network and the heteromodal association cortex. In an exploratory analysis, CT was observed to be differently associated with social impairment in children with ASD compared with typically developing children. The affected neuroanatomical regions are related to characteristic deficits in language, cognition and behavior that are often observed in the disorder. The relationship between social impairment and CT in children with ASD and controls seems to indicate aberrant developmental trajectories in ASD emerging early in life.

Emotionally biased information processing towards sad and away from happy information characterises individuals with major depression. To learn more about the nature of these dysfunctional modulations, developmental and neural aspects of emotional face processing have to be considered. By combining measures of performance (attention control, inhibition) in an emotional Go/NoGo task with an event-related potential (ERP) of early face processing (N170), we obtained a multifaceted picture of emotional face processing in a sample of children and adolescents (11-14 years) with major depression (MDD, n = 26) and healthy controls (CTRL, n = 26). Subjects had to respond to emotional faces (fearful, happy or sad) and withhold their response to calm faces or vice versa. Children of the MDD group displayed shorter N170 latencies than children of the CTRL group. Typical right lateralisation of the N170 was observed for all faces in the CTRL but not for happy and calm faces in the MDD group. However, the MDD group did not differ in their behavioural reaction to emotional faces, and effects of interference by emotional information on the reaction to calm faces in this group were notably mild. Although we could not find a typical pattern of emotional bias, the results suggest that alterations in face processing of children with major depression can be seen at early stages of face perception indexed by the N170. The findings call for longitudinal examinations considering effects of development in children with major depression as well as associations to later stages of processing.

Learning a foreign language in a natural immersion context with high exposure to the new language has been shown to change the way speech sounds of that language are processed at the neural level. It remains unclear, however, to what extent this is also the case for classroom-based foreign language learning, particularly in children. To this end, we presented a mismatch negativity (MMN) experiment during EEG recordings as part of a longitudinal developmental study: 38 monolingual (Swiss-) German speaking children (7.5 years) were tested shortly before they started to learn English at school and followed up one year later. Moreover, 22 (Swiss-) German adults were recorded. Instead of the originally found positive mismatch response in children, an MMN emerged when applying a high-pass filter of 3 Hz. The overlap of a slow-wave positivity with the MMN indicates that two concurrent mismatch processes were elicited in children. The children's MMN in response to the non-native speech contrast was smaller compared to the native speech contrast irrespective of foreign language learning, suggesting that no additional neural resources were committed to processing the foreign language speech sound after one year of classroom-based learning.

Epigenetic modulations are a hypothesized link between environmental factors and the development of psychiatric disorders. Research has suggested that patients with depression or bipolar disorder exhibit higher methylation levels in the glucocorticoid receptor gene NR3C1. We aimed to investigate whether NR3C1 methylation changes are similarly associated with externalizing disorders such as aggressive behavior and conduct disorder. NR3C1 exon 1F methylation was analyzed in young adults with a lifetime diagnosis of an externalizing disorder (N = 68) or a depressive disorder (N = 27) and healthy controls (N = 124) from the Mannheim Study of Children at Risk. The externalizing disorders group had significantly lower NR3C1 methylation levels than the lifetime depressive disorder group (p = 0.009) and healthy controls (p = 0.001) This report of lower methylation levels in NR3C1 in externalizing disorders may indicate a mechanism through which the differential development of externalizing disorders as opposed to depressive disorders might occur.

Variation in the gene encoding for the norepinephrine transporter (NET, SLC6A2) has repeatedly been linked with ADHD, although there is some inconsistency regarding the association with specific genes. The variants for which most consistent association has been found are the NET variants rs3785157 and rs28386840. Here, we tested for their association with ADHD diagnosis and ADHD-related phenotypes during development in a longitudinal German community sample. Children were followed from age 4 to age 15, using diagnostic interviews to assess ADHD. Between the ages of 8 and 15 years, the Child Behavior Checklist (CBCL) was administered to the primary caregivers. The continuous performance task (CPT) was performed at age 15. Controlling for possible confounders, we found that homozygous carriers of the major A allele of the functional promoter variant rs28386840 displayed a higher rate of ADHD lifetime diagnosis. Moreover, homozygous carriers of the minor T allele of rs3785157 were more likely to develop ADHD and showed higher scores on the CBCL externalizing behavior scales. Additionally, we found that individuals heterozygous for rs3785157 made fewer omission errors in the CPT than homozygotes. This is the first longitudinal study to report associations between specific NET variants and ADHD-related phenotypes during the course of development. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Brain activation stability is crucial to understanding attention lapses. EEG methods could provide excellent markers to assess neuronal response variability with respect to temporal (intertrial coherence) and spatial variability (topographic consistency) as well as variations in activation intensity (low frequency variability of single trial global field power). We calculated intertrial coherence, topographic consistency and low frequency amplitude variability during target P300 in a continuous performance test in 263 15-year-olds from a cohort with psychosocial and biological risk factors. Topographic consistency and low frequency amplitude variability predicted reaction time fluctuations (RTSD) in a linear model. Higher RTSD was only associated with higher psychosocial adversity in the presence of the homozygous 6R-10R dopamine transporter haplotype. We propose that topographic variability of single trial P300 reflects noise as well as variability in evoked cortical activation patterns. Dopaminergic neuromodulation interacted with environmental and biological risk factors to predict behavioural reaction time variability. (C) 2015 Elsevier B.V. All rights reserved.

Background: Preterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown. We aimed to investigate whether the association of preterm birth with cognitive-neurophysiological impairments and increased ADHD symptoms is consistent with a causal preterm birth inference, or due to familial confounds. Methods: We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents, recruited from South East England schools, and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task that we previously found to be impaired in the preterm group when compared to an unrelated control group. Outcomes: Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (β=0.18, p=0.01, 95%CI=0.02,0.36) and specific cognitive-ERP impairments, such as IQ (β=- 0.20, p=0.02, 95%CI=-0.40,-0.01), preparation-vigilance measures and measures of error processing (ranging from β=0.71, -0.35). There was no significant within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β=-0.07, p=0.45, 95%CI=-0.33,0.15) or verbal working memory (digit span backward, β=-0.05, p=0.63, 95%CI=-0.30,0.18). Interpretation: The robust within-sibling associations of preterm birth with specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) and with ADHD symptoms indicate that these associations are independent of family-level risk and consistent with a causal inference. In contrast, the negligible within-sibling association between preterm birth and executive control processes of inhibition and working memory implies that familial risk factors associated with preterm birth underlie these previously observed associations. By distinguishing impairments that are consistent with a causal inference of preterm birth from those that are instead linked to background characteristics of families with a preterm-born child, these results suggest that interventions need to target both preterm-birth specific and family-level risk factors. Funding Statement: Action Medical Research and the Medical Research Council. Declaration of Interests: Prof Asherson has acted in an advisory role for Shire, Janssen-Cilag, Eli Lilly and Flynn Pharma. He has received education or research grants from Shire, Janssen-Cilag and Eli-Lilly. He has given talks at educational events sponsored by the above companies. Prof Kuntsi has given talks at educational events sponsored by Medice; all funds are received by King’s College London and used for studies of ADHD. Dr. Banaschewski served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Novartis, Shire. He received conference support or speaker’s fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. The other authors report no conflicts of interest. Ethics Approval Statement: Written informed consent was obtained following procedures approved by the National Research Ethics Service Committee London - Bromley (13/LO/0068).

Reward processing is altered in various psychopathologies and has been shown to be susceptible to genetic and environmental influences. Here, we examined whether maternal care may buffer familial risk for psychiatric disorders in terms of reward processing. Functional magnetic resonance imaging during a monetary incentive delay task was acquired in participants of an epidemiological cohort study followed since birth (N = 172, 25 years). Early maternal stimulation was assessed during a standardized nursing/playing setting at the age of 3 months. Parental psychiatric disorders (familial risk) during childhood and the participants’ previous psychopathology were assessed by diagnostic interview. With high familial risk, higher maternal stimulation was related to increasing activation in the caudate head, the supplementary motor area, the cingulum and the middle frontal gyrus during reward anticipation, with the opposite pattern found in individuals with no familial risk. In contrast, higher maternal stimulation was associated with decreasing caudate head activity during reward delivery and reduced levels of attention deficit hyperactivity disorder (ADHD) in the high-risk group. Decreased caudate head activity during reward anticipation and increased activity during delivery were linked to ADHD. These findings provide evidence of a long-term association of early maternal stimulation on both adult neurobiological systems of reward underlying externalizing behavior and ADHD during development., Social Cognitive and Affective Neuroscience, 13 (11), ISSN:1749-5016, ISSN:1749-5024

Journal of Neural Transmission, 122 (8), ISSN:1435-1463, ISSN:0300-9564

This review evaluates the clinical utility of tools for systematic behavioral observation in different settings for children and adolescents with ADHD. A comprehensive search yielded 135 relevant results since 1990. Observations from naturalistic settings were grouped into observations of classroom behavior (n = 58) and of social interactions (n = 25). Laboratory observations were subdivided into four contexts: independent play (n = 9), test session (n = 27), parent interaction (n = 11), and peer interaction (n = 5). Clinically relevant aspects of reliability and validity of employed instruments are reviewed. The results confirm the usefulness of systematic observations. However, no procedure can be recommended as a stand-alone diagnostic method. Psychometric properties are often unsatisfactory, which reduces the validity of observational methods, particularly for measuring treatment outcome. Further efforts are needed to improve the specificity of observational methods with regard to the discrimination of comorbidities and other disorders.

Background: Behavioural interventions are recommended for use with children and young people with ADHD, however specific guidance for their implementation based on the best available evidence is currently lacking. Methods: This review used an explicit question and answer format to address issues of clinical concern, based on expert interpretation of the evidence with precedence given to meta-analyses of randomised controlled trials. Results: On the basis of current evidence that takes into account whether outcomes are blinded, behavioural intervention cannot be supported as a front-line treatment for core ADHD symptoms. There is however, evidence from measures that are probably blinded that these interventions benefit parenting practices and improve conduct problems which commonly co-occur with ADHD, and are often the main reason for referral. Initial positive results have also been found in relation to parental knowledge, children’s emotional, social and academic functioning – although most studies have not used blinded outcomes. Generic as well as specialised ADHD parent training approaches - delivered either individually or in groups – have reported beneficial effects. High quality training, supervision of therapists and practice with the child, may improve outcomes but further evidence is required. Evidence for who benefits the most from behavioural interventions is scant. There is no evidence to limit behavioural treatments to parents with parenting difficulties or children with conduct problems. There are positive effects of additive school based intervention for the inattentive subtype. Targeting parental depression may enhance the effects of behavioural interventions. Conclusion: Parent training is an important part of the multi-modal treatment of children with ADHD which improves parenting, reduces levels of oppositional and non-compliant behaviours and may improve other aspects of functioning. However, blinded evidence does not support it as a specific treatment for core ADHD symptoms. More research is required to understand how to optimise treatment effectiveness either in general or for individual patients and explore potential barriers to treatment uptake and engagement. In terms of selecting which intervention formats to use it seems important to acknowledge and respond to parental treatment preferences. ispartof: Journal of Child Psychology and Psychiatry vol:59 issue:9 pages:932-947 ispartof: location:England status: published

Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. Electronic supplementary material The online version of this article (doi:10.1186/s13229-017-0146-8) contains supplementary material, which is available to authorized users.

Contains fulltext : 169834.pdf (Publisher’s version ) (Open Access) Contains fulltext : 169834pos.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS: In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0.0156. FINDINGS: Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0.15), amygdala (d=-0.19), caudate (d=-0.11), hippocampus (d=-0.11), putamen (d=-0.14), and intracranial volume (d=-0.10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0.95) and thalamus (p=0.39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=-0.19 vs -0.10), amygdala (d=-0.18 vs -0.14), caudate (d=-0.13 vs -0.07), hippocampus (d=-0.12 vs -0.06), putamen (d=-0.18 vs -0.08), and intracranial volume (d=-0.14 vs 0.01). There was no difference between children and adults for the pallidum (p=0.79) or thalamus (p=0.89). Case-control differences in adults were non-significant (all p>0.03). Psychostimulant medication use (all p>0.15) or symptom scores (all p>0.02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0.5). INTERPRETATION: With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING: National Institutes of Health. 10 p.

There has been an increasing interest in and the use of computer-based cognitive training as a treatment of attention-deficit/hyperactivity disorder (ADHD). The authors' review of current evidence, based partly on a stringent meta-analysis of 6 randomized controlled trials (RCTs) published in 2013, and an overview of 8 recently published RCTs highlights the inconsistency of findings between trials and across blinded and nonblinded ADHD measures within trials. Based on this, they conclude that more evidence from well-blinded studies is required before cognitive training can be supported as a frontline treatment of core ADHD symptoms.

Considerable scientific effort has been directed at developing effective treatments for attention-deficit/hyperactivity disorder (ADHD). Among alternative treatment approaches, neurofeedback has gained some promising empirical support in recent years from controlled studies as a treatment of core ADHD symptoms. However, a recent stringent meta-analysis of 8 randomized controlled trials published in 2013 found that the effects were stronger for unblinded measures and 3 recent subsequently published well-controlled trials found no effects for the most blinded ADHD outcome. Firmer conclusions must await upcoming evidence from larger controlled studies and future meta-analyses contrasting different forms of neurofeedback and different outcome measures.

Elevated theta or theta/beta ratio is often reported in attention deficit hyperactivity disorder (ADHD), but the consistency across studies and the relation to hypoarousal are increasingly questioned. Reports of elevated delta related to maturational lag and of attenuated beta activity are less well replicated. Some critical inconsistencies could relate to differences in recording context. We examined if resting-state EEG power or global field synchronization (GFS) differed between recordings made at the beginning and end of a 1.5 h testing session in 76 adolescents and young adults with ADHD, and 85 controls. In addition, we aimed to examine the effect of IQ on any potential group differences. Both regional and midline electrodes yielded group main effects for delta, trends in theta, but no differences in alpha or theta/beta ratio. An additional group difference in beta was detected when using regions. Group by time interactions in delta and theta became significant when controlling for IQ. The ADHD group had higher delta and theta power at time-1, but not at time-2, whereas beta power was elevated only at time-2. GFS did not differ between groups or condition. We show some ADHD-control differences on EEG spectral power varied with recording time within a single recording session, with both IQ and electrode selection having a small but significant influence on observed differences. Our findings demonstrate the effect of recording context on resting-state EEG, and highlight the importance of accounting for these variables to ensure consistency of results in future studies. Electronic supplementary material The online version of this article (doi:10.1007/s10548-014-0395-1) contains supplementary material, which is available to authorized users.

The classical phonological deficit account of dyslexia is increasingly linked to impairments in grapho-phonological conversion, and to dysfunctions in superior temporal regions associated with audiovisual integration. The present study investigates mechanisms of audiovisual integration in typical and impaired readers at the critical developmental stage of adolescence. Congruent and incongruent audiovisual as well as unimodal (visual only and auditory only) material was presented. Audiovisual presentations were single letters and three-letter (consonant–vowel–consonant) stimuli accompanied by matching or mismatching speech sounds. Three-letter stimuli exhibited fast phonetic transitions as in real-life language processing and reading. Congruency effects, i.e. different brain responses to congruent and incongruent stimuli were taken as an indicator of audiovisual integration at a phonetic level (grapho-phonological conversion). Comparisons of unimodal and audiovisual stimuli revealed basic, more sensory aspects of audiovisual integration. By means of these two criteria of audiovisual integration, the generalizability of audiovisual deficits in dyslexia was tested. Moreover, it was expected that the more naturalistic three-letter stimuli are superior to single letters in revealing group differences. Electrophysiological and hemodynamic (EEG and fMRI) data were acquired simultaneously in a simple target detection task. Applying the same statistical models to event-related EEG potentials and fMRI responses allowed comparing the effects detected by the two techniques at a descriptive level. Group differences in congruency effects (congruent against incongruent) were observed in regions involved in grapho-phonological processing, including the left inferior frontal and angular gyri and the inferotemporal cortex. Importantly, such differences also emerged in superior temporal key regions. Three-letter stimuli revealed stronger group differences than single letters. No significant differences in basic measures of audiovisual integration emerged. Convergence of hemodynamic and electrophysiological signals appeared to be limited and mainly occurred for highly significant and large effects in visual cortices. The findings suggest efficient superior temporal tuning to audiovisual congruency in controls. In impaired readers, however, grapho-phonological conversion is effortful and inefficient, although basic audiovisual mechanisms seem intact. This unprecedented demonstration of audiovisual deficits in adolescent dyslexics provides critical evidence that the phonological deficit might be explained by impaired audiovisual integration at a phonetic level, especially for naturalistic and word-like stimulation.

Two types of biofeedback (BF), tomographic electroencephalogram (EEG) neurofeedback (NF) and electromyographic biofeedback (EMG-BF), both with phasic and tonic protocols, were compared for treatment effects and specificity in attention-deficit/hyperactivity disorder (ADHD). Thirteen children with ADHD trained their brain activity in the anterior cingulate cortex (ACC), and twelve trained activity of arm muscles involved in fine motor skills. In each training session, resting state 24-channel EEG and training performances were recorded. Both groups showed similar behavioral improvements and artifact reduction in selected conditions, with no significant advantages despite medium effect sizes on primary outcomes for NF. Only the EMG-BF group, however, showed clear improvement in training regulation performance, and specific motor coordination effects. The NF group tended to present individual normalization of trained frequency bands in the ACC during rest across training. The results provide evidence for some specific effects in our small sample, albeit only to a small extent.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to study the neural correlates of reward anticipation, but the interrelation of EEG and fMRI measures remains unknown. The goal of the present study was to investigate this relationship in response to a well established reward anticipation paradigm using simultaneous EEG-fMRI recording in healthy human subjects. Analysis of causal interactions between the thalamus (THAL), ventral-striatum (VS), and supplementary motor area (SMA), using both mediator analysis and dynamic causal modeling, revealed that (1) THAL fMRI blood oxygenation level-dependent (BOLD) activity is mediating intermodal correlations between the EEG contingent negative variation (CNV) signal and the fMRI BOLD signal in SMA and VS, (2) the underlying causal connectivity network consists of top-down regulation from SMA to VS and SMA to THAL along with an excitatory information flow through a THAL→VS→SMA route during reward anticipation, and (3) the EEG CNV signal is best predicted by a combination of THAL fMRI BOLD response and strength of top-down regulation from SMA to VS and SMA to THAL. Collectively, these findings represent a likely neurobiological mechanism mapping a primarily subcortical process, i.e., reward anticipation, onto a cortical signature.

BackgroundObsessive–compulsive disorder (OCD) has been linked to functional abnormalities in fronto-striatal networks as well as impairments in decision making and learning. Little is known about the neurocognitive mechanisms causing these decision-making and learning deficits in OCD, and how they relate to dysfunction in fronto-striatal networks.MethodWe investigated neural mechanisms of decision making in OCD patients, including early and late onset of disorder, in terms of reward prediction errors (RPEs) using functional magnetic resonance imaging. RPEs index a mismatch between expected and received outcomes, encoded by the dopaminergic system, and are known to drive learning and decision making in humans and animals. We used reinforcement learning models and RPE signals to infer the learning mechanisms and to compare behavioural parameters and neural RPE responses of the OCD patients with those of healthy matched controls.ResultsPatients with OCD showed significantly increased RPE responses in the anterior cingulate cortex (ACC) and the putamen compared with controls. OCD patients also had a significantly lower perseveration parameter than controls.ConclusionsEnhanced RPE signals in the ACC and putamen extend previous findings of fronto-striatal deficits in OCD. These abnormally strong RPEs suggest a hyper-responsive learning network in patients with OCD, which might explain their indecisiveness and intolerance of uncertainty.

Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors., Social Cognitive and Affective Neuroscience, 12 (2), ISSN:1749-5016, ISSN:1749-5024

Contains fulltext : 181911.pdf (Publisher’s version ) (Closed access) Autism spectrum disorders (ASDs) and obsessive compulsive disorder (OCD) are often comorbid with the overlap based on compulsive behaviors. Although previous studies suggest glutamatergic deficits in fronto-striatal brain areas in both disorders, this is the first study to directly compare the glutamate concentrations across the two disorders with those in healthy control participants using both categorical and dimensional approaches. In the current multi-center study (four centers), we used proton magnetic resonance spectroscopy in 51 children with ASD, 29 with OCD, and 53 healthy controls (aged 8-13 years) to investigate glutamate (Glu) concentrations in two regions of the fronto-striatal circuit: midline anterior cingulate cortex (ACC) and left dorsal striatum. Spectra were processed with Linear Combination Model. Group comparisons were performed with one-way analyses of variance including sex, medication use, and scanner site as covariates. In addition, a dimensional analysis was performed, linking glutamate with a continuous measure of compulsivity across disorders. There was a main group effect for ACC glutamate (p=0.019). Contrast analyses showed increased glutamate both in children with ASD and OCD compared with controls (p=0.007), but no differences between the two disorders (p=0.770). Dimensional analyses revealed a positive correlation between compulsive behavior (measured with the Repetitive Behavior Scale) and ACC glutamate (rho=0.24, p=0.03). These findings were robust across sites. No differences were found in the striatum. The current findings confirm overlap between ASD and OCD in terms of glutamate involvement. Glutamate concentration in ACC seems to be associated with the severity of compulsive behavior.

Objective: Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments.Method: Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome.Results: Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments.Conclusions: Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.

INTRODUCTION Sleep slow wave activity (SWA EEG power between 1 and 4.5 Hz) is a major characteristic of non rapid eye movement (NREM) sleep which seems to be critically involved in cortical plasticity. Studies using high density electroencephalography (hd EEG) showed that the topographical distribution of SWA mirrors cortical maturation expressing a local maximum that is characteristic for a certain age range. We compared the sleep EEG of children with attention deficit/hyperactivity disorder (ADHD) with healthy controls to explore differences in sleep SWA. METHODS All night hd EEG recordings (128 electrodes) were performed in a group of nine children diagnosed with ADHD and nine age and sex matched healthy controls. SWA topography was calculated and contrasted between the groups. RESULTS We found a local increase of SWA in a cluster of six electrodes over central regions in children with ADHD compared to control children (+17 ± 6 SE p < .01). This group difference was specific for the SWA range and stable across the night. CONCLUSIONS Children with ADHD showed a less mature topographical SWA distribution in comparison to healthy children of the same age and sex. This neuromaturational delay in ADHD is in accordance with neuroimaging and behavioral studies. Thus our study supports the use of sleep SWA topography as a reliable imaging tool for the study of cortical plasticity.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self‐control, underpinned by inferior fronto‐striatal deficits. Real‐time functional magnetic resonance neurofeedback (rtfMRI‐NF) allows participants to gain self‐control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological‐NF on ADHD symptoms, no study has applied the spatially superior rtfMRI‐NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI‐NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region‐specificity, an active control group received rtfMRI‐NF of the left parahippocampal gyrus (lPHG). Thirty‐one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI‐NF runs over 2 weeks. Feedback was provided through a video‐clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11‐month follow‐up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof‐of‐concept study demonstrates for the first time feasibility, safety, and shorter‐ and longer‐term efficacy of rtfMRI‐NF of rIFG in adolescents with ADHD. Hum Brain Mapp 38:3190–3209, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Dr. Micoulaud-Franchi et al. raise concerns relating to our 2016 meta-analysis1 of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD). It is encouraging that Dr. Micoulaud-Franchi et al. agree with us that there is “an urgent need to conduct future research that associates both high quality of [randomized controlled trial] RCT and high quality of [electroencephalography] EEG-neurofeedback sessions.” Consistent with this, we wrote, “Future efforts should focus on implementing standard neurofeedback protocols, ensuring learning, and optimizing clinically relevant transfer.”1(p444) This is in line with the significant advantage for neurofeedback demonstrated in our additional preliminary analysis of the few studies meeting such standards.

Background Depressed mood is prevalent during pregnancy, with accumulating evidence suggesting an impact on developmental outcome in the offspring. However, the long-term effects of prenatal maternal depression regarding internalizing psychopathology in the offspring are as yet unclear. Methods As part of an ongoing epidemiological cohort study, prenatal maternal depressed mood was assessed at the child's age of 3 months. In a sample of n=307 offspring, depressive symptoms were obtained via questionnaire at the ages of 19, 22, 23 and 25 years. At age 25 years, diagnoses of depressive disorder were obtained using a diagnostic interview. In a subsample of currently healthy participants, voxel-based morphometry was conducted and amygdala volume was assessed. Results In n=85 young adults exposed to prenatal maternal depressed mood, no significantly higher risk for a diagnosis of depressive disorder was observed. However, they reported significantly lower levels of depressive symptoms. This association was especially pronounced when prenatal maternal depressed mood was present during the first trimester of pregnancy and when maternal mood was depressed pre- as well as postnatally. At an uncorrected level only, prenatal maternal depressed mood was associated with decreased amygdala volume. Limitations Prenatal maternal depressed mood was not assessed during pregnancy, but shortly after childbirth. No diagnoses of maternal clinical depression during pregnancy were available. Conclusions Self-reported depressive symptoms do not imply increased, but rather decreased symptom levels in young adults who were exposed to prenatal maternal depressed mood. A long-term perspective may be important when considering consequences of prenatal risk factors.

In today's 24/7 society, sleep restriction is a common phenomenon which leads to increased levels of sleep pressure in daily life. However, the magnitude and extent of impairment of brain functioning due to increased sleep pressure is still not completely understood. Resting state network (RSN) analyses have become increasingly popular because they allow us to investigate brain activity patterns in the absence of a specific task and to identify changes under different levels of vigilance (e.g. due to increased sleep pressure). RSNs are commonly derived from BOLD fMRI signals but studies progressively also employ cerebral blood flow (CBF) signals. To investigate the impact of sleep pressure on RSNs, we examined RSNs of participants under high (19 h awake) and normal (10 h awake) sleep pressure with three imaging modalities (arterial spin labeling, BOLD, pseudo BOLD) while providing confirmation of vigilance states in most conditions. We demonstrated that CBF and pseudo BOLD signals (measured with arterial spin labeling) are suited to derive independent component analysis based RSNs. The spatial map differences of these RSNs were rather small, suggesting a strong biological substrate underlying these networks. Interestingly, increased sleep pressure, namely longer time awake, specifically changed the functional network connectivity (FNC) between RSNs. In summary, all FNCs of the default mode network with any other network or component showed increasing effects as a function of increased 'time awake'. All other FNCs became more anti-correlated with increased 'time awake'. The sensorimotor networks were the only ones who showed a within network change of FNC, namely decreased connectivity as function of 'time awake'. These specific changes of FNC could reflect both compensatory mechanisms aiming to fight sleep as well as a first reduction of consciousness while becoming drowsy. We think that the specific changes observed in functional network connectivity could imply an impairment of information transfer between the affected RSNs.

Previous research suggests a role of the dorsomedial prefrontal cortex (dmPFC) in metacognitive representation of social information, while the right posterior superior temporal sulcus (pSTS) has been linked to social perception. This study targeted these functional roles in the context of spontaneous mentalizing. An animated shapes task was presented to 46 subjects during functional magnetic resonance imaging. Stimuli consisted of video clips depicting animated shapes whose movement patterns prompt spontaneous mentalizing or simple intention attribution. Based on their differential response during spontaneous mentalizing, both regions were characterized with respect to their task‐dependent connectivity profiles and their associations with autistic traits. Functional network analyses revealed highly localized coupling of the right pSTS with visual areas in the lateral occipital cortex, while the dmPFC showed extensive coupling with instances of large‐scale control networks and temporal areas including the right pSTS. Autistic traits were related to mentalizing‐specific activation of the dmPFC and to the strength of connectivity between the dmPFC and posterior temporal regions. These results are in good agreement with the hypothesized roles of the dmPFC and right pSTS for metacognitive representation and perception‐based processing of social information, respectively, and further inform their implication in social behavior linked to autism. Hum Brain Mapp 38:3791–3803, 2017. © 2017 Wiley Periodicals, Inc.

Developmental dyslexia is a highly prevalent and specific disorder of reading acquisition characterised by impaired reading fluency and comprehension. We have previously identified fMRI- and ERP-based neural markers of impaired sentence reading in dyslexia that indicated both deviant basic word processing and deviant semantic incongruency processing. However, it remained unclear how specific these impairments are for dyslexia, as they occurred when children with dyslexia (DYS) were compared to chronological age-matched controls (CA) who also differ in the amount of reading experience. Adding a younger control group at a similar reading level (RL) as the dyslexic group, we examined here which of these markers would be specific for dyslexia despite matched performance, and which would resemble a developmental delay. Both the RL group and the DYS group showed a similar reversal of incongruency effects in the inferior parietal region (fMRI data) and similarly reduced incongruency effects around 400 ms (ERP data) compared to the CA group, suggesting that the semantic impairment in dyslexia resembles a developmental delay. Furthermore, the DYS group showed reduced sentence reading-related activation in the inferior parietal cortex in the fMRI data, and at around 100 ms (trend) and 400 ms in the ERP data when compared to both CA and RL groups, suggesting dyslexia-specific deficits in basic word processing during sentence reading. Low reading skills due to young age and due to dyslexia-specific word processing deficits thus reflect different pathways which impair semantic processing in similar ways.