Alcohol use and brain morphology in adolescence: A longitudinal study in three different cohorts.

Alcohol consumption is commonly initiated during adolescence, but the effects on human brain development remain unknown. In this multisite study, we investigated the longitudinal associations of adolescent alcohol use and brain morphology. Three longitudinal cohorts in the Netherlands (BrainScale n = 200, BrainTime n = 239 and a subsample of the Generation R study n = 318) of typically developing participants aged between 8 and 29 years were included. Adolescent alcohol use was self-reported. Longitudinal neuroimaging data were collected for at least two time points. Processing pipelines and statistical analyses were harmonized across cohorts. Main outcomes were global and regional brain volumes, which were a priori selected. Linear mixed effect models were used to test main effects of alcohol use and interaction effects of alcohol use with age in each cohort separately. Alcohol use was associated with adolescent's brain morphology showing accelerated decrease in grey matter volumes, in particular in the frontal and cingulate cortex volumes, and decelerated increase in white matter volumes. No dose-response association was observed. The findings were most prominent and consistent in the older cohorts (BrainScale and BrainTime). In summary, this longitudinal study demonstrated differences in neurodevelopmental trajectories of grey and white matter volume in adolescents who consume alcohol compared with non-users. These findings highlight the importance to further understand underlying neurobiological mechanisms when adolescents initiate alcohol consumption. Therefore, further studies need to determine to what extent this reflects the causal nature of this association, as this longitudinal observational study does not allow for causal inference.

Opportunities for increased reproducibility and replicability of developmental neuroimaging.

Many workflows and tools that aim to increase the reproducibility and replicability of research findings have been suggested. In this review, we discuss the opportunities that these efforts offer for the field of developmental cognitive neuroscience, in particular developmental neuroimaging. We focus on issues broadly related to statistical power and to flexibility and transparency in data analyses. Critical considerations relating to statistical power include challenges in recruitment and testing of young populations, how to increase the value of studies with small samples, and the opportunities and challenges related to working with large-scale datasets. Developmental studies involve challenges such as choices about age groupings, lifespan modelling, analyses of longitudinal changes, and data that can be processed and analyzed in a multitude of ways. Flexibility in data acquisition, analyses and description may thereby greatly impact results. We discuss methods for improving transparency in developmental neuroimaging, and how preregistration can improve methodological rigor. While outlining challenges and issues that may arise before, during, and after data collection, solutions and resources are highlighted aiding to overcome some of these. Since the number of useful tools and techniques is ever-growing, we highlight the fact that many practices can be implemented stepwise.

Neural processing of socioemotional content in conduct-disordered juvenile offenders with limited prosocial emotions.

BACKGROUND: Reflecting evidence on Callous-Unemotional (CU) traits (e.g., lack of empathy and guilt, shallow affect), the DSM-5 added a categorical CU-based specifier for Conduct Disorder (CD), labeled 'with Limited Prosocial Emotions' (LPE). Theory and prior work suggest that CD youths with and without LPE will likely differ in neural processing of negative socioemotional content. This proposition, however, is mainly derived from studies employing related, yet distinct, operationalizations of CU traits (e.g., dimensional measure/median split/top quartile), thus precluding direct examination of LPE-specific neurocognitive deficits. METHODS: Employing a DSM-5 informed LPE proxy, neural processing of recognizing and resonating negative socioemotional content (angry and fearful faces) was therefore examined here among CD offenders with LPE (CD/LPE+; N = 19), relative to CD offenders without LPE (CD/LPE-; N = 31) and healthy controls (HC; N = 31). RESULTS: Relative to HC and CD/LPE- youths and according to a linearly increasing trend (CD/LPE- < HC < CD/LPE+), CD/LPE+ youths exhibited hyperactivity within dorsolateral, dorsomedial, and ventromedial prefrontal regions during both emotion recognition and resonance. During emotion resonance, CD/LPE+ youths additionally showed increased activity within the posterior cingulate and precuneal cortices in comparison to HC and CD/LPE- youths, which again followed a linearly increasing trend (CD/LPE- < HC < CD/LPE+). These effects moreover seemed specific to the LPE specifier, when compared to a commonly employed method for CU-based grouping in CD (i.e., median split on CU scores). CONCLUSIONS: These data cautiously suggest that CD/LPE+ youths may exhibit an over-reliance on cortical neurocognitive systems when explicitly processing negative socioemotional information, which could have adverse downstream effects on relevant socioemotional functions. The findings thus seem to provide novel, yet preliminary, clues on the neurocognitive profile of CD/LPE+, and additionally highlight the potential scientific utility of the LPE specifier.

Longitudinal associations between structural prefrontal cortex and nucleus accumbens development and daily identity formation processes across adolescence.

We tested whether adolescents with daily high identity uncertainty showed differential structural brain development across adolescence and young adulthood. Participants (N = 150, MageT1 15.92 years) were followed across three waves, covering 4 years. Self-reported daily educational identity and structural brain data of lateral prefrontal cortex (lPFC)/anterior cingulate cortex (ACC), medial PFC, and nucleus accumbens (NAcc) was collected across three waves. All hypotheses were pre-registered. Latent class growth analyses confirmed 2 identity subgroups: an identity synthesis class (characterized by strong commitments, and low uncertainty), and an identity moratorium class (high daily identity uncertainty). Latent growth curve models revealed, on average, delayed maturation of the lateral PFC/ACC and medial PFC and stable NAcc. Yet, adolescents in identity moratorium showed lower levels and less decline in NAcc gray matter volume. Lateral PFC/ACC and medial PFC trajectories did not differ between identity subgroups. Exploratory analyses revealed that adolescents with higher baseline levels and delayed maturation of lateral PFC/ACC and medial PFC gray matter volume, surface area, and cortical thickness reported higher baseline levels and stronger increases of in-depth exploration. These results provide insight into how individual differences in brain development relate to fluctuations in educational identity development across adolescence and young adulthood.

Qoala-T: A supervised-learning tool for quality control of FreeSurfer segmented MRI data.

Performing quality control to detect image artifacts and data-processing errors is crucial in structural magnetic resonance imaging, especially in developmental studies. Currently, many studies rely on visual inspection by trained raters for quality control. The subjectivity of these manual procedures lessens comparability between studies, and with growing study sizes quality control is increasingly time consuming. In addition, both inter-rater as well as intra-rater variability of manual quality control is high and may lead to inclusion of poor quality scans and exclusion of scans of usable quality. In the current study we present the Qoala-T tool, which is an easy and free to use supervised-learning model to reduce rater bias and misclassification in manual quality control procedures using FreeSurfer-processed scans. First, we manually rated quality of N = 784 FreeSurfer-processed T1-weighted scans acquired in three different waves in a longitudinal study. Different supervised-learning models were then compared to predict manual quality ratings using FreeSurfer segmented output data. Results show that the Qoala-T tool using random forests is able to predict scan quality with both high sensitivity and specificity (mean area under the curve (AUC) = 0.98). In addition, the Qoala-T tool was also able to adequately predict the quality of two novel unseen datasets (total N = 872). Finally, analyses of age effects showed that younger participants were more likely to have lower scan quality, underlining that scan quality might confound findings attributed to age effects. These outcomes indicate that this procedure could further help to reduce variability related to manual quality control, thereby benefiting the comparability of data quality between studies.

Interactions Between Oxytocin Receptor Gene Methylation and Callous-Unemotional Traits Impact Socioaffective Brain Systems in Conduct-Disordered Offenders.

BACKGROUND: The developmental trajectory of psychopathy seemingly begins early in life and includes the presence of callous-unemotional (CU) traits (e.g., perturbed socioaffective reactivity and empathy, callousness) in youths with conduct disorder (CD). Whereas oxytocin receptor gene methylation (OXTRMeth) and its downstream neuromodulatory effects are deemed relevant to CU traits, nothing is known of how OXTRMeth interacts with CU traits to impact socioaffective brain systems in youngsters with CD. METHODS: Hence, we uniquely probed OXTRMeth × CU trait interactions on corticolimbic activity and amygdala subregional connections during recognition and resonance of distressing socioaffective stimuli (angry and fearful faces), in juvenile offenders with CD (n = 39) versus matched healthy control youths (n = 27). RESULTS: Relative to healthy control youths, elevated OXTRMeth and CU levels in youths with CD essentially interacted to predict frontoparietal hyperactivity and amygdalo-frontoparietal disconnection during task performance. Specifically, increasing OXTRMeth and CU levels in youths with CD interactively predicted midcingulate hyperactivity during both emotion conditions, with insular, temporoparietal, and precuneal hyperactivity additionally emerging during emotion recognition. Interactions between high OXTRMeth and CU levels in youths with CD additionally predicted centromedial amygdala decoupling from ventromedial/orbitofrontal regions during emotion recognition, along with basolateral amygdala decoupling from precuneal and temporoparietal cortices during emotion resonance. CONCLUSIONS: These results uniquely suggest that interactions between OXTRMeth and CU traits in youths with CD may affect brain systems critical to decoding and integrating socioaffective information. Developmental models of CU traits and psychopathy could thus possibly advance by further examining OXTR epigenetic effects, which may hold promise for indicated prevention and personalized treatment by targeting oxytocinergic function.

Friend versus foe: Neural correlates of prosocial decisions for liked and disliked peers.

Although the majority of our social interactions are with people we know, few studies have investigated the neural correlates of sharing valuable resources with familiar others. Using an ecologically valid research paradigm, this functional magnetic resonance imaging study examined the neural correlates of prosocial and selfish behavior in interactions with real-life friends and disliked peers in young adults. Participants (N = 27) distributed coins between themselves and another person, where they could make selfish choices that maximized their own gains or prosocial choices that maximized outcomes of the other. Participants were more prosocial toward friends and more selfish toward disliked peers. Individual prosociality levels toward friends were associated negatively with supplementary motor area and anterior insula activity. Further preliminary analyses showed that prosocial decisions involving friends were associated with heightened activity in the bilateral posterior temporoparietal junction, and selfish decisions involving disliked peers were associated with heightened superior temporal sulcus activity, which are brain regions consistently shown to be involved in mentalizing and perspective taking in prior studies. Further, activation of the putamen was observed during prosocial choices involving friends and selfish choices involving disliked peers. These findings provide insights into the modulation of neural processes that underlie prosocial behavior as a function of a positive or negative relationship with the interaction partner.

Differential Fairness Decisions and Brain Responses After Expressed Emotions of Others in Boys with Autism Spectrum Disorders.

Little is known about how emotions expressed by others influence social decisions and associated brain responses in autism spectrum disorders (ASD). We investigated the neural mechanisms underlying fairness decisions in response to explicitly expressed emotions of others in boys with ASD and typically developing (TD) boys. Participants with ASD adjusted their allocation behavior in response to the emotions but reacted less unfair than TD controls in response to happiness. We also found reduced brain responses in the precental gyrus in the ASD versus TD group when receiving happy versus angry reactions and autistic traits were positively associated with activity in the postcentral gyrus. These results provide indications for a role of precentral and postcentral gyrus in social-affective difficulties in ASD.

Disorganized Amygdala Networks in Conduct-Disordered Juvenile Offenders With Callous-Unemotional Traits.

BACKGROUND: The developmental trajectory of psychopathy seemingly begins early in life and includes the presence of callous-unemotional (CU) traits (e.g., deficient emotional reactivity, callousness) in conduct-disordered (CD) youth. Though subregion-specific anomalies in amygdala function have been suggested in CU pathophysiology among antisocial populations, system-level studies of CU traits have typically examined the amygdala as a unitary structure. Hence, nothing is yet known of how amygdala subregional network function may contribute to callous-unemotionality in severely antisocial people. METHODS: We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral amygdala (BLA) and centromedial amygdala (CMA) networks across three matched groups of juveniles: CD offenders with CU traits (CD/CU+; n = 25), CD offenders without CU traits (CD/CU-; n = 25), and healthy control subjects (n = 24). We additionally examined whether perturbed amygdala subregional connectivity coincides with altered volume and shape of the amygdaloid complex. RESULTS: Relative to CD/CU- and healthy control youths, CD/CU+ youths showed abnormally increased BLA connectivity with a cluster that included both dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices, along with posterior cingulate, sensory associative, and striatal regions. In contrast, compared with CD/CU- and healthy control youths, CD/CU+ youths showed diminished CMA connectivity with ventromedial/orbitofrontal regions. Critically, these connectivity changes coincided with local hypotrophy of BLA and CMA subregions (without being statistically correlated) and were associated to more severe CU symptoms. CONCLUSIONS: These findings provide unique insights into a putative mechanism for perturbed attention-emotion interactions, which could bias salience processing and associative learning in youth with CD/CU+.

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct-disordered juvenile offenders.

Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N = 50, mean age = 16.83 ± 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these trait-specific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile. Hum Brain Mapp 37:4017-4033, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Fairness decisions in response to emotions: a functional MRI study among criminal justice-involved boys with conduct disorder.

Research suggests that individuals with conduct disorder (CD) are marked by social impairments, such as difficulties in processing the affective reactions of others. Little is known, though, about how they make decisions during social interactions in response to emotional expressions of others. In this study, we therefore investigated the neural mechanisms underlying fairness decisions in response to communicated emotions of others in aggressive, criminal justice-involved boys with CD (N = 32) compared with typically developing (TD) boys (N = 33), aged 15-19 years. Participants received written emotional responses (angry, disappointed or happy) from peers in response to a previous offer and then had to make fairness decisions in a version of the Dictator Game. Behavioral results showed that CD boys did not make differential fairness decisions in response to the emotions, whereas the TD boys did show a differentiation and also responded more unfair to happy reactions than the CD boys. Neuroimaging results revealed that when receiving happy vs disappointed and angry reactions, the CD boys showed less activation than the TD boys in the temporoparietal junction and supramarginal gyrus, regions involved in perspective taking and attention. These results suggest that boys with CD have difficulties with processing explicit emotional cues from others on behavioral and neural levels.

Different brain responses during empathy in autism spectrum disorders versus conduct disorder and callous-unemotional traits.

BACKGROUND: Deficits in empathy are reported in autism spectrum disorders (ASD) and also underlie antisocial behavior of individuals with conduct disorder and callous-unemotional traits (CD/CU+). Many studies suggest that individuals with ASD are typically impaired in cognitive aspects of empathy, and individuals with CD/CU+ typically in affective aspects. In the current study, we compared the neural correlates of cognitive and affective aspects of empathy between youth with ASD and youth with CD/CU+. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess boys with ASD (N = 23), boys with CD/CU+ (N = 23), and typically developing (TD) boys (N = 33), aged 15-19 years. Angry and fearful faces were presented and participants were asked to either infer the emotional state from the face (other-task; emotion recognition) or to judge their own emotional response to the face (self-task; emotional resonance). RESULTS: During emotion recognition, boys with ASD showed reduced responses compared to the other groups in the ventromedial prefrontal cortex (vmPFC). During emotional resonance, the CD/CU+ and ASD groups showed reduced amygdala responses compared to the TD controls, boys with ASD showed reduced responses in bilateral hippocampus, and the CD/CU+ boys showed reduced responses in the inferior frontal gyrus (IFG) and anterior insula (AI). CONCLUSION: Results suggest differential abnormal brain responses associated with specific aspects of empathic functioning in ASD and CD/CU+. Decreased amygdala responses in ASD and CD/CU+ might point to impaired emotion processing in both disorders, whereas reduced vmPFC responses suggest problems in processing cognitive aspects of empathy in ASD. Reduced IFG/AI responses, finally, suggest decreased emotional resonance in CD/CU+.

Emotional reactions of peers influence decisions about fairness in adolescence.

During adolescence, peers take on increasing importance, while social skills are still developing. However, how emotions of peers influence social decisions during that age period is insufficiently known. We therefore examined the effects of three different emotional responses (anger, disappointment, happiness) on decisions about fairness in a sample of 156 adolescents aged 12-17 years. Participants received written emotional responses from peers in a version of the Dictator Game to a previous unfair offer. Adolescents reacted with more generous offers after disappointed reactions compared to angry and happy reactions. Furthermore, we found preliminary evidence for developmental differences over adolescence, since older adolescents differentiated more between the three emotions than younger adolescents. In addition, individual differences in social value orientation played a role in decisions after happy reactions of peers to a previous unfair offer, such that participants with a "proself" orientation made more unfair offers to happy peers than "prosocial" participants. Taken together, our findings demonstrate that adolescents take emotions of peers into account when making social decisions, while individual differences in social value orientation affect these decisions, and age seems to influence the nature of the reaction.

Increased functional connectivity with puberty in the mentalising network involved in social emotion processing.

This article is part of a Special Issue "Puberty and Adolescence". There is increasing evidence that puberty plays an important role in the structural and functional brain development seen in adolescence, but little is known of the pubertal influence on changes in functional connectivity. We explored how pubertal indicators (salivary concentrations of testosterone, oestradiol and DHEA; pubertal stage; menarcheal status) relate to functional connectivity between components of a mentalising network identified to be engaged in social emotion processing by our prior work, using psychophysiological interaction (PPI) analysis. Female adolescents aged 11 to 13years were scanned whilst silently reading scenarios designed to evoke either social emotions (guilt and embarrassment) or basic emotions (disgust and fear), of which only social compared to basic emotions require the representation of another person's mental states. Pubertal stage and menarcheal status were used to assign participants to pre/early or mid/late puberty groups. We found increased functional connectivity between the dorsomedial prefrontal cortex (DMPFC) and the right posterior superior temporal sulcus (pSTS) and right temporo-parietal junction (TPJ) during social relative to basic emotion processing. Moreover, increasing oestradiol concentrations were associated with increased functional connectivity between the DMPFC and the right TPJ during social relative to basic emotion processing, independent of age. Our analysis of the PPI data by phenotypic pubertal status showed that more advanced puberty stage was associated with enhanced functional connectivity between the DMPFC and the left anterior temporal cortex (ATC) during social relative to basic emotion processing, also independent of age. Our results suggest increased functional maturation of the social brain network with the advancement of puberty in girls.