One of the major goals for research on adolescent development is to identify the optimal conditions for adolescents to grow up in a complex social world and to understand individual differences in... Show moreOne of the major goals for research on adolescent development is to identify the optimal conditions for adolescents to grow up in a complex social world and to understand individual differences in these trajectories. Based on influential theoretical and empirical work in this field, achieving this goal requires a detailed understanding of the social context in which neural and behavioral development takes place, along with longitudinal measurements at multiple levels (e.g., genetic, hormonal, neural, behavioral). In this perspectives paper, we highlight the promising role of team science in achieving this goal. To illustrate our point, we describe meso (peer relations) and micro (social learning) approaches to understand social development in adolescence as crucial aspects of adolescent mental health. Finally, we provide an overview of how our team has extended our collaborations beyond scientific partners to multiple societal partners for the purpose of informing and including policy makers, education and health professionals, as well as adolescents themselves when conducting and communicating research. Show less
A fundamental task in neuroscience is to characterize the brain's developmental course. While replicable group-level models of structural brain development from childhood to adulthood have recently... Show moreA fundamental task in neuroscience is to characterize the brain's developmental course. While replicable group-level models of structural brain development from childhood to adulthood have recently been identified, we have yet to quantify and understand individual differences in structural brain development. The present study examined inter-individual variability and sex differences in changes in brain structure, as assessed by anatomical MRI, across ages 8.0-26.0 years in 269 participants (149 females) with three time points of data (807 scans), drawn from three longitudinal datasets collected in the Netherlands, Norway, and USA. We further investigated the relationship between overall brain size and developmental changes, as well as how females and males differed in change variability across development. There was considerable inter-individual variability in the magnitude of changes observed for all examined brain measures. The majority of individuals demonstrated decreases in total gray matter volume, cortex volume, mean cortical thickness, and white matter surface area in mid-adolescence, with more variability present during the transition into adolescence and the transition into early adulthood. While most individuals demonstrated increases in white matter volume in early adolescence, this shifted to a majority demonstrating stability starting in mid-to-late adolescence. We observed sex differences in these patterns, and also an association between the size of an individual's brain structure and the overall rate of change for the structure. The present study provides new insight as to the amount of individual variance in changes in structural morphometrics from late childhood to early adulthood in order to obtain a more nuanced picture of brain development. The observed individual-and sex-differences in brain changes also highlight the importance of further studying individual variation in developmental patterns in healthy, at-risk, and clinical populations. Show less
Drunen, L. van; Dobbelaar, S.; Cruijsen, L.W.P. van der; Meulen, M. van der; Achterberg, M.; Wierenga, L.M.; Crone, E.A.M 2021
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... Show moreHow 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. Show less
We tested whether adolescents differ from each other in the structural development of the social brain and whether individual differences in social brain development predicted variability in... Show moreWe tested whether adolescents differ from each other in the structural development of the social brain and whether individual differences in social brain development predicted variability in friendship quality development. Adolescents (N=299, M-age T1=13.98 years) were followed across three biannual waves. We analysed self-reported friendship quality with the best friend at T1 and T3, and bilateral measures of surface area and cortical thickness of the medial prefrontal cortex (mPFC), posterior superior temporal sulcus (pSTS), temporoparietal junction (TPJ) and precuneus across all waves. At the group level, growth curve models confirmed non-linear decreases of surface area and cortical thickness in social brain regions. We identified substantial individual differences in levels and change rates of social brain regions, especially for surface area of the mPFC, pSTS and TPJ. Change rates of cortical thickness varied less between persons. Higher levels of mPFC surface area and cortical thickness predicted stronger increases in friendship quality over time. Moreover, faster cortical thinning of mPFC surface area predicted a stronger increase in friendship quality. Higher levels of TPJ cortical thickness predicted lower friendship quality. Together, our results indicate heterogeneity in social brain development and how this variability uniquely predicts friendship quality development. Show less
Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown... Show moreDelineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes. Show less
Dima, D.; Modabbernia, A.; Papachristou, E.; Doucet, G.E.; Agartz, I.; Aghajani, M.; ... ; Frangou, S. 2021
Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These... Show moreAge has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns. Show less
Becht, A.I.; Klapwijk, E.T.; Wierenga, L.M.; Cruijsen, R. van der; Spaans, J.; Aar, L. van der; ... ; Crone, E.A. 2020
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 ... Show more15.92 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. Show less
For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics... Show moreFor many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders. Show less
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... Show moreProsocial 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. Show less
Crone, E.A.; M. Achterberg, M.; Dobbelaar, S.; Euser, S.; Bulk, B.G. van den; Meulen, M. van der; ... ; IJzendoorn, M.H. van 2020
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... Show moreThe 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. Show less
Adolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward-driven behavior. Although reward-driven behavior is supported by subcortical... Show moreAdolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward-driven behavior. Although reward-driven behavior is supported by subcortical-medial prefrontal cortex (PFC) connectivity, the development of these circuits is not well understood. Particularly, while puberty has been hypothesized to accelerate organization and activation of functional neural circuits, the relationship between age, sex, pubertal change, and functional connectivity has hardly been studied. Here, we present an analysis of resting-state functional connectivity between subcortical structures and the medial PFC, in 661 scans of 273 participants between 8 and 29 years, using a three-wave longitudinal design. Generalized additive mixed model procedures were used to assess the effects of age, sex, and self-reported pubertal status on connectivity between subcortical structures (nucleus accumbens, caudate, putamen, hippocampus, and amygdala) and cortical medial structures (dorsal anterior cingulate, ventral anterior cingulate, subcallosal cortex, frontal medial cortex). We observed an age-related strengthening of subcortico-subcortical and cortico-cortical connectivity. Subcortical-cortical connectivity, such as, between the nucleus accumbens-frontal medial cortex, and the caudate-dorsal anterior cingulate cortex, however, weakened across age. Model-based comparisons revealed that for specific connections pubertal development described developmental change better than chronological age. This was particularly the case for changes in subcortical-cortical connectivity and distinctively for boys and girls. Together, these findings indicate changes in functional network strengthening with pubertal development. These changes in functional connectivity may maximize the neural efficiency of interregional communication and set the stage for further inquiry of biological factors driving adolescent functional connectivity changes. Show less
Wierenga, L.M.; Bos, M.G.N.; Rossenberg, F. van; Crone, E.A. 2019
Although male brains have consistently reported to be 8-10% larger than female brains, it remains not well understood whether there are differences between sexes (average or variance) in... Show moreAlthough male brains have consistently reported to be 8-10% larger than female brains, it remains not well understood whether there are differences between sexes (average or variance) in developmental trajectories. Furthermore, if sex differences in average brain growth or variance are observed, it is unknown whether these sex differences have behavioral relevance. The present longitudinal study aimed to unravel sex effects in cortical brain structure, development, and variance, in relation to the development of educationally relevant cognitive domains and executive functions (EFs). This was assessed with three experimental tasks including working memory, reading comprehension, and fluency. In addition, real-life aspects of EF were assessed with self- and parent-reported Behavior Rating Inventory of Executive Function scores. The full data set included 271 participants (54% female) aged between 8 and 29 years of which three waves were collected at 2-year intervals, resulting in 680 T1-weighted MRI scans and behavioral measures. Analyses of average trajectories confirmed general age-related patterns of brain development but did not support the hypothesis of sex differences in brain development trajectories, except for left banks STS where boys had a steeper decline in surface area than girls. Also, our brain age prediction model (including 270 brain measures) did not indicate delayed maturation in boys compared with girls. Interestingly, support was found for greater variance in male brains than female brains in both structure and development, consistent with prior cross-sectional studies. Behaviorally, boys performed on average better on a working memory task with a spatial aspect and girls performed better on a reading comprehension task, but there was no relation between brain development and cognitive performance, neither for average brain measures, brain age, or variance measures. Taken together, we confirmed the hypothesis of greater males within-group variance in brain structures compared with females, but these were not related to EF. The sex differences observed in EF were not related to brain development, possibly suggesting that these are related to experiences and strategies rather than biological development. Show less
Klapwijk, E.T.; Van de Kamp, F.; Meulen, M. van der; Peters, S.; Wierenga, L.M. 2019
Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long‐lasting reduction in... Show moreMapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long‐lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface‐based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first‐time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first‐time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm3 was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes. Show less
