Longitudinal changes in DLPFC activation during childhood are related to decreased aggression following social rejection.

Regulating aggression after social feedback is an important prerequisite for developing and maintaining social relations, especially in the current times with larger emphasis on online social evaluation. Studies in adults highlighted the role of the dorsolateral prefrontal cortex (DLPFC) in regulating aggression. Little is known about the development of aggression regulation following social feedback during childhood, while this is an important period for both brain maturation and social relations. The current study used a longitudinal design, with 456 twins undergoing two functional MRI sessions across the transition from middle (7 to 9 y) to late (9 to 11 y) childhood. Aggression regulation was studied using the Social Network Aggression Task. Behavioral aggression after social evaluation decreased over time, whereas activation in the insula, dorsomedial PFC and DLPFC increased over time. Brain-behavior analyses showed that increased DLPFC activation after negative feedback was associated with decreased aggression. Change analyses further revealed that children with larger increases in DLPFC activity from middle to late childhood showed stronger decreases in aggression over time. These findings provide insights into the development of social evaluation sensitivity and aggression control in childhood.

The nature of the self: Neural analyses and heritability estimates of self-evaluations in middle childhood.

How neural correlates of self-concept are influenced by environmental versus genetic factors is currently not fully understood. We investigated heritability estimates of behavioral and neural correlates of self-concept in middle childhood since this phase is an important time window for taking on new social roles in academic and social contexts. To do so, a validated self-concept fMRI task was applied in a twin sample of 345 participants aged between 7 and 9 years. In the self-concept condition, participants were asked to indicate whether academic and social traits applied to them whereas the control condition required trait categorization. The self-processing activation analyses (n = 234) revealed stronger medial prefrontal cortex (mPFC) activation for self than for control conditions. This effect was more pronounced for social-self than academic self-traits, whereas stronger dorsolateral prefrontal cortex (DLPFC) activation was observed for academic versus social self-evaluations. Behavioral genetic modeling (166 complete twin pairs) revealed that 25-52% of the variation in academic self-evaluations was explained by genetic factors, whereas 16-49% of the variation in social self-evaluations was explained by shared environmental factors. Neural genetic modeling (91 complete twin pairs) for variation in mPFC and anterior prefrontal cortex (PFC) activation for academic self-evaluations confirmed genetic and unique environmental influences, whereas anterior PFC activation for social self-evaluations was additionally influenced by shared environmental influences. This indicates that environmental context possibly has a larger impact on the behavioral and neural correlates of social self-concept at a young age. This is the first study demonstrating in a young twin sample that self-concept depends on both genetic and environmental factors, depending on the specific domain.

Distinctive heritability patterns of subcortical-prefrontal cortex resting state connectivity in childhood: A twin study.

Connectivity between limbic/subcortical and prefrontal-cortical brain regions develops considerably across childhood, but less is known about the heritability of these networks at this age. We tested the heritability of limbic/subcortical-cortical and limbic/subcortical-subcortical functional brain connectivity in 7- to 9-year-old twins (N = 220), focusing on two key limbic/subcortical structures: the ventral striatum and the amygdala, given their combined influence on changing incentivised behavior during childhood and adolescence. Whole brain analyses with ventral striatum (VS) and amygdala as seeds in genetically independent groups showed replicable functional connectivity patterns. The behavioral genetic analyses revealed that in general VS and amygdala connectivity showed distinct influences of genetics and environment. VS-prefrontal cortex connections were best described by genetic and unique environmental factors (the latter including measurement error), whereas amygdala-prefrontal cortex connectivity was mainly explained by environmental influences. Similarities were also found: connectivity between both the VS and amygdala and ventral anterior cingulate cortex (vACC) showed influences of shared environment, while connectivity with the orbitofrontal cortex (OFC) showed heritability. These findings may inform future interventions that target behavioral control and emotion regulation, by taking into account genetic dispositions as well as shared and unique environmental factors such as child rearing.

Heritability of aggression following social evaluation in middle childhood: An fMRI study.

Middle childhood marks an important phase for developing and maintaining social relations. At the same time, this phase is marked by a gap in our knowledge of the genetic and environmental influences on brain responses to social feedback and their relation to behavioral aggression. In a large developmental twin sample (509 7- to 9-year-olds), the heritability and neural underpinnings of behavioral aggression following social evaluation were investigated, using the Social Network Aggression Task (SNAT). Participants viewed pictures of peers that gave positive, neutral, or negative feedback to the participant's profile. Next, participants could blast a loud noise toward the peer as an index of aggression. Genetic modeling revealed that aggression following negative feedback was influenced by both genetics and environmental (shared as well as unique environment). On a neural level (n = 385), the anterior insula and anterior cingulate cortex gyrus (ACCg) responded to both positive and negative feedback, suggesting they signal for social salience cues. The medial prefrontal cortex (mPFC) and inferior frontal gyrus (IFG) were specifically activated during negative feedback, whereas positive feedback resulted in increased activation in caudate, supplementary motor cortex (SMA), and dorsolateral prefrontal cortex (DLPFC). Decreased SMA and DLPFC activation during negative feedback was associated with more aggressive behavior after negative feedback. Moreover, genetic modeling showed that 13%-14% of the variance in dorsolateral PFC activity was explained by genetics. Our results suggest that the processing of social feedback is partly explained by genetic factors, whereas shared environmental influences play a role in behavioral aggression following feedback.

Frontostriatal White Matter Integrity Predicts Development of Delay of Gratification: A Longitudinal Study.

The ability to delay gratification increases considerably across development. Here, we test the hypothesis that this impulse control capacity is driven by increased maturation of frontostriatal circuitry using a fiber-tracking approach combined with longitudinal imaging. In total, 192 healthy volunteers between 8 and 26 years underwent diffusion tensor imaging scanning and completed a delay-discounting task twice, separated by a 2-year interval. We investigated dynamic associations between frontostriatal white matter (WM) integrity and delay of gratification skills. Moreover, we examined the predictive value of frontostriatal WM integrity for future delay of gratification skills. Results showed that delay discounting increases with age in a quadratic fashion, with greatest patience during late adolescence. Data also indicated nonlinear development of frontostriatal WM, with relative fast development during childhood and early adulthood and--on average--little change during mid-adolescence. Furthermore, the positive association between age and delay discounting was further increased in individuals with higher WM integrity of the frontostriatal tracts. Predictive analysis showed that frontostriatal WM development explained unique variance in current and future delay of gratification skills. This study adds to a descriptive relation between WM integrity and delay of gratification by showing that maturation of frontostriatal connectivity predicts changes in delay of gratification skills. These findings have implications for studies examining deviances in impulse control by showing that the developmental path between striatum and prefrontal cortex may be an important predictor for when development goes astray. SIGNIFICANCE STATEMENT: During the transition from childhood to adulthood, individuals generally show increased patience and become better in delaying gratification. The exact neural correlates of delay of gratification, however, remain poorly understood. By measuring both frontostriatal white matter (WM) integrity and delay of gratification skills at two time points, we were able to provide links for our understanding of the neural mechanisms underlying this type of impulse regulation capacity. We demonstrate that the ability to delay gratification improves between childhood and young adulthood and this improvement is predicted by the integrity of frontostriatal WM connections. This study adds to a descriptive relation between WM quality and delay of gratification by showing that maturation of frontostriatal connectivity predicts improvements in delay of gratification skills.

Structural and functional connectivity in children and adolescents with and without attention deficit/hyperactivity disorder.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) has frequently been associated with changes in resting-state functional connectivity, and decreased white matter (WM) integrity. In the current study, we investigated functional connectivity within Default Mode and frontal control resting-state networks (RSNs) in children with and without ADHD. We hypothesized the RSNs of interest would show a pattern of impaired functional integration and segregation and corresponding changes in WM structure. METHODS: Resting-state fMRI and diffusion-weighted imaging data were acquired from 35 participants with ADHD and 36 matched typically developing peers, aged 6 through 18 years. Functional connectivity was assessed using independent component analysis. Network topology and WM connectivity were further investigated using graph theoretical measures and tract-based spatial statistics (TBSS). RESULTS: Resting-state fMRI analyses showed increased functional connectivity in right inferior frontal gyrus (IFG), and bilateral medial prefrontal cortex (mPFC) within the Default Mode and frontal control networks. Furthermore, a more diffuse spatial pattern of functional connectivity was found in children with ADHD. We found no group differences in structural connectivity as assessed with TBSS or graph theoretical measures. CONCLUSIONS: Resting-state networks show a more diffuse pattern of connectivity in children with ADHD. The increases in functional connectivity in right IFG and bilateral mPFC in children with ADHD may reflect reduced or delayed functional segregation of prefrontal brain regions. As these functional changes were not accompanied by changes in WM, they may precede the development of the frequently reported changes in WM structure.

Behavioral and neural responses to social rejection: Individual differences in developmental trajectories across childhood and adolescence.

Dealing with social rejection is challenging, especially during childhood when behavioral and neural responses to social rejection are still developing. In the current longitudinal study, we used a Bayesian multilevel growth curve model to describe individual differences in the development of behavioral and neural responses to social rejection in a large sample (n > 500). We found a peak in aggression following negative feedback (compared to neutral feedback) during late childhood, as well as individual differences during this developmental phase, possibly suggesting a sensitive window for dealing with social rejection across late childhood. Moreover, we found evidence for individual differences in the linear development of neural responses to social rejection in our three brain regions of interest: The anterior insula, the medial prefrontal cortex, and the dorsolateral prefrontal cortex. In addition to providing insights in the individual trajectories of dealing with social rejection during childhood, this study also makes a meaningful methodological contribution: Our statistical analysis strategy (and can be found in this study's online supplementary materials at https://jeroendmulder.github.io/social-emotion-regulation/) can be used as an example on how to take into account the many complexities of developmental neuroimaging datasets, while still enabling researchers to answer interesting questions about individual-level relationships.

Developmental patterns and individual differences in responding to social feedback: A longitudinal fMRI study from childhood to adolescence.

Learning to control behavior when receiving feedback underlies social adaptation in childhood and adolescence, and is potentially strengthened by environmental support factors, such as parents. This study examined the neural development of responding to social feedback from childhood to adolescence, and effects of parental sensitivity on this development. We studied these questions in a 3-wave longitudinal fMRI sample (ages 7-13 years, n = 512). We measured responses to feedback using the fMRI Social Network Aggression Task through noise blasts following peer feedback and associated neural activity, and parental sensitivity using observations of parent-child interactions during Etch-a-Sketch. Results revealed largest reductions in noise blasts following positive feedback between middle and late childhood and following negative feedback between late childhood and early adolescence. Additionally, brain-behavior associations between dorsolateral prefrontal cortex activation and noise blast durations became more differentiated across development. Parental sensitivity was only associated with noise blast duration following positive feedback in childhood, but not in adolescence. There was no relation between parental sensitivity and neural activity. Our findings contribute to our understanding of neural development and individual differences in responding to social feedback, and the role of parenting in supporting children's adaption to social feedback.

Development of social feedback processing and responses in childhood: an fMRI test-replication design in two age cohorts.

This study investigated behavioral and neural correlates underlying social feedback processing and subsequent aggressive behaviors in childhood in two age cohorts (test sample: n = 509/n = 385 and replication sample: n = 354/n = 195, 7-9 years old). Using a previously validated Social Network Aggression Task, we showed that negative social feedback resulted in most behavioral aggression, followed by less aggression after neutral and least aggression after positive feedback. Receiving positive and negative social feedback was associated with increased activity in the insula, medial prefrontal cortex and ventrolateral prefrontal cortex. Responding to feedback was associated with additional activation in the dorsolateral prefrontal cortex (DLPFC) following positive feedback. This DLPFC activation correlated negatively with aggression. Furthermore, age analyses showed that older children showed larger reductions in aggression following positive feedback and more neural activation in the DLPFC when responding to positive feedback compared to younger children. To assess the robustness of our results, we examined these processes in two independent behavioral/functional magnetic resonance imaging samples using equivalence testing, thereby contributing to replicable reports. Together, these findings demonstrate an important role of social saliency and regulatory processes where regulation of aggression rapidly develops between the ages of 7 and 9 years.

Prosocial development in adolescence.

In this review, we describe the development of prosocial behavior in adolescence as a critical inflection period for social adjustment. Experimental research using prosocial giving tasks demonstrates that adolescents differentiate more between recipients and contexts, suggesting increasing ingroup-outgroup differentiation during adolescence. We also demonstrate that social brain development during adolescence is partly driven by environmental influences, further underlining adolescence as a critical period for social development. The COVID-19 pandemic has had and will have long-term effects on the current generation of adolescents, for which we describe both the risks, resilience factors, and opportunities for engaging in prosocial acts of kindness.

Longitudinal associations between prosocial behavior and behavioral problems across childhood: A robust random-intercept cross-lagged panel model.

Prior studies have indicated that prosocial behavior might be a protective factor for developing internalizing and externalizing behavioral problems. However, little research has been conducted on within-person changes of prosocial behavior and behavioral problems over time. With random-intercept cross-lagged panel models (RI-CLPMs), the current study analyzed longitudinal associations between prosocial behavior and behavioral problems in two twin cohorts (98% Western European): in early childhood (age M = 4.77, SD = .58, 52% girls, N = 440) and middle childhood (age M = 7.94, SD = .67, 51% girls, N = 512). To obtain robust results, two parental reported questionnaires and an observational task were used as prosocial behavior assessments. In line with the literature, we found a significant between-person association between externalizing behavior and parent reported prosocial behavior in middle childhood, but not in early childhood. Some evidence indicated that changes in externalizing problems affect later prosocial behavior in middle childhood. Overall, however, the RI-CLPMs provided most support for the hypothesis that within-person changes in prosocial behavior are not related to within-person changes in behavioral problems. Thus, our findings did not support the hypothesis that increased prosocial behavior directly results in decreased behavioral problems, but emphasizes the need to take into account the multifaceted nature of prosocial behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Longitudinal associations between social media use, mental well-being and structural brain development across adolescence.

Youth of today grow up in a digital social world but the effects on well-being and brain development remain debated. This study tracked longitudinal associations between structural brain development, social media use and mental well-being. The study demonstrated two pathways of heterogeneity in brain development. First, adolescents who used social media more than their peers showed higher baseline cortical thickness in lateral prefrontal cortex (PFC) and medial PFC; and stronger decreases in the lateral PFC and temporal parietal junction. In contrast, adolescents with lower mental well-being showed lower baseline levels of surface area in the medial PFC and posterior superior temporal sulcus relative to their peers. Whereas the associations between structural brain development and well-being remained significant after correction for multiple testing, the results for social media use did not survive FDR correction. These findings demonstrate that although social media use and mental well-being were both associated with differential trajectories of brain development, the associations we report are distinct. These results show a nuanced perspective on the presumed relations between social media use and well-being and provide a starting point to further examine neural mechanisms that could explain which adolescents thrive by social media and which might be harmed.

Perceived stress as mediator for longitudinal effects of the COVID-19 lockdown on wellbeing of parents and children.

Dealing with a COVID-19 lockdown may have negative effects on children, but at the same time might facilitate parent-child bonding. Perceived stress may influence the direction of these effects. Using a longitudinal twin design, we investigated how perceived stress influenced lockdown induced changes in wellbeing of parents and children. A total of 106 parents and 151 children (10-13-year-olds) filled in questionnaires during lockdown and data were combined with data of previous years. We report a significant increase in parental negative feelings (anxiety, depression, hostility and interpersonal sensitivity). Longitudinal child measures showed a gradual decrease in internalizing and externalizing behavior, which seemed decelerated by the COVID-19 lockdown. Changes in parental negative feelings and children's externalizing behavior were mediated by perceived stress: higher scores prior to the lockdown were related to more stress during the lockdown, which in turn was associated with an increase in parental negative feelings and children's' externalizing behavior. Perceived stress in parents and children was associated with negative coping strategies. Additionally, children's stress levels were influenced by prior and current parental overreactivity. These results suggest that children in families with negative coping strategies and (a history of) parental overreactivity might be at risk for negative consequences of the lockdown.

Overlapping and distinct neural correlates of self-evaluations and self-regulation from the perspective of self and others.

Prior research has implicated the medial and lateral prefrontal cortex (PFC) in processing evaluations from the perspective of self (self-traits) and evaluations from others (peer feedback), suggesting that these areas form a neural substrate that serves an intertwined function in monitoring self in relation to others. To test this possibility, we examined neural activation overlap in medial and lateral PFC after processing self- and other-informed evaluations. Young adults (age range 18-30-yrs, n = 40) performed two fMRI tasks. The self-concept task involved rating whether positive and negative traits described themselves. The Social Network Aggression Task involved processing positive, neutral or negative feedback from others, with the possibility to retaliate by blasting a loud noise following feedback. The results show that rating positive self traits and receiving positive peer feedback was associated with increased activity in an overlapping region in medial PFC. There were no significant correlations on a behavioral level and medial PFC activity for self-versus-other evaluations. The study further replicated the finding from previous research showing that higher activity in dorsolateral PFC (dlPFC) when receiving negative social feedback was associated with reduced noise blast aggression. Finally, during retaliatory responses after receiving positive feedback, participants showed increased activity in the dlPFC. Together these findings suggest that medial PFC is more strongly involved in protecting positive self-views from both internal (self traits) and external (peer feedback) points of view, whereas dlPFC is more strongly involved in regulating retaliatory responses following social rejection, and actively inhibiting aggressive behavior after receiving positive peer feedback.

Genetic and environmental influences on structure of the social brain in childhood.

Prosocial behavior and empathy are important aspects of developing social relations in childhood. Prior studies showed protracted structural development of social brain regions associated with prosocial behavior. However, it remains unknown how structure of the social brain is influenced by genetic or environmental factors, and whether overlapping heritability factors explain covariance in structure of the social brain and behavior. The current study examined this hypothesis in a twin sample (aged 7-9-year; N = 512). Bilateral measures of surface area and cortical thickness of the medial prefrontal cortex (mPFC), temporo-parietal junction (TPJ), posterior superior temporal sulcus (pSTS), and precuneus were analyzed. Results showed genetic contributions to surface area and cortical thickness for all brain regions. We found additional shared environmental influences for TPJ, suggesting that this region might be relatively more sensitive to social experiences. Genetic factors also influenced parent-reported prosocial behavior (A = 45%) and empathy (A = 59%). We provided initial evidence that the precuneus shares genetically determined variance with empathy, suggesting a possible small genetic overlap (9%) in brain structure and empathy. These findings show that structure of the social brain and empathy are driven by a combination of genetic and environmental factors, with some factors overlapping for brain structure and behavior.

A Bi-Dimensional Taxonomy of Social Responsivity in Middle Childhood: Prosociality and Reactive Aggression Predict Externalizing Behavior Over Time.

Developing social skills is essential to succeed in social relations. Two important social constructs in middle childhood, prosocial behavior and reactive aggression, are often regarded as separate behaviors with opposing developmental outcomes. However, there is increasing evidence for the co-occurrence of prosociality and aggression, as both might indicate responsivity to the social environment. Here, we tested whether a bi-dimensional taxonomy of prosociality and reactive aggression could predict internalizing and externalizing problems over time. We re-analyzed data of two well-validated experimental tasks for prosociality (the Prosocial Cyberball Game) and reactive aggression (the Social Network Aggression Task) in a developmental population sample (n = 496, 7-9 years old). Results revealed no associations between prosociality and reactive aggression, confirming the independence of those constructs. Interestingly, although prosociality and reactive aggression independently did not predict problem behavior, the interaction of both was negatively predictive of changes in externalizing problems over time. Specifically, only children who scored low on both prosociality and reactive aggression showed an increase in externalizing problems 1 year later, whereas levels of externalizing problems did not change for children who scored high on both types of behavior. Thus, our results suggest that at an individual level, reactive aggression in middle childhood might not always be maladaptive when combined with prosocial behavior, thereby confirming the importance of studying social competence across multiple dimensions.

Neural and behavioral signatures of social evaluation and adaptation in childhood and adolescence: The Leiden consortium on individual development (L-CID).

The transition period between early childhood and late adolescence is characterized by pronounced changes in social competence, or the capacity for flexible social adaptation. Here, we propose that two processes, self-control and prosociality, are crucial for social adaptation following social evaluation. We present a neurobehavioral model showing commonalities in neural responses to experiences of social acceptance and rejection, and multiple pathways for responding to social context. The Leiden Consortium on Individual Development (L-CID) provides a comprehensive approach towards understanding the longitudinal developmental pathways of, and social enrichment effects on, social competence, taking into account potential differential effects of such enrichment. Using Neurosynth based brain maps we point towards the medial prefrontal cortex as an important region integrating social cognition, self-referential processing and self-control for learning to respond flexibly to changing social contexts. Based on their role in social evaluation processing, we suggest to examine medial prefrontal cortex connections with lateral prefrontal cortex and the ventral striatum as potential neural differential susceptibility markers, in addition to previously established markers of differential susceptibility.

Genetic and environmental influences on MRI scan quantity and quality.

The current study provides an overview of quantity and quality of MRI data in a large developmental twin sample (N = 512, aged 7-9), and investigated to what extent scan quantity and quality were influenced by genetic and environmental factors. This was examined in a fixed scan protocol consisting of two functional MRI tasks, high resolution structural anatomy (3DT1) and connectivity (DTI) scans, and a resting state scan. Overall, scan quantity was high (88% of participants completed all runs), while scan quality decreased with increasing session length. Scanner related distress was negatively associated with scan quantity (i.e., completed runs), but not with scan quality (i.e., included runs). In line with previous studies, behavioral genetic analyses showed that genetics explained part of the variation in head motion, with heritability estimates of 29% for framewise displacement and 65% for absolute displacement. Additionally, our results revealed that subtle head motion (after exclusion of excessive head motion) showed lower heritability estimates (0-14%), indicating that findings of motion-corrected and quality-controlled MRI data may be less confounded by genetic factors. These findings provide insights in factors contributing to scan quality in children, an issue that is highly relevant for the field of developmental neuroscience.

Heritability of neural reactions to social exclusion and prosocial compensation in middle childhood.

Experiencing and observing social exclusion and inclusion, as well as prosocial behavior, are important aspects of social relationships in childhood. However, it is currently unknown to what extent these processes and their neural correlates differ in heritability. We investigated influences of genetics and environment on experiencing social exclusion and compensating for social exclusion of others with the Prosocial Cyberball Game using fMRI in a twin sample (aged 7-9; N = 500). Neuroimaging analyses (N = 283) revealed that experiencing possible self-exclusion resulted in activity in inferior frontal gyrus and medial prefrontal cortex, which was influenced by genetics and unique environment. Experiencing self-inclusion was associated with activity in anterior cingulate cortex, insula and striatum, but this was not significantly explained by genetics or shared environment. We found that children show prosocial compensating behavior when observing social exclusion. Prosocial compensating behavior was associated with activity in posterior cingulate cortex/precuneus, and showed unique environmental effects or measurement error at both behavioral and neural level. Together, these findings show that in children neural activation for experiencing possible self-exclusion and self-inclusion, and for displaying prosocial compensating behavior, is accounted for by unique environmental factors and measurement error, with a small genetic effect on possible self-exclusion.

The neural and behavioral correlates of social evaluation in childhood.

Being accepted or rejected by peers is highly salient for developing social relations in childhood. We investigated the behavioral and neural correlates of social feedback and subsequent aggression in 7-10-year-old children, using the Social Network Aggression Task (SNAT). Participants viewed pictures of peers that gave positive, neutral or negative feedback to the participant's profile. Next, participants could blast a loud noise towards the peer, as an index of aggression. We included three groups (N=19, N=28 and N=27) and combined the results meta-analytically. Negative social feedback resulted in the most behavioral aggression, with large combined effect-sizes. Whole brain condition effects for each separate sample failed to show robust effects, possibly due to the small samples. Exploratory analyses over the combined test and replication samples confirmed heightened activation in the medial prefrontal cortex (mPFC) after negative social feedback. Moreover, meta-analyses of activity in predefined regions of interest showed that negative social feedback resulted in more neural activation in the amygdala, anterior insula and the mPFC/anterior cingulate cortex. Together, the results show that social motivation is already highly salient in middle childhood, and indicate that the SNAT is a valid paradigm for assessing the neural and behavioral correlates of social evaluation in children.