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Abstract Intrinsic brain dynamics play a fundamental role in cognitive function, but their development is incompletely understood. We investigated pubertal changes in temporal fluctuations of intrinsic network topologies (focusing on the strongest connections and coordination patterns) and signals, in an early longitudinal sample from the Adolescent Brain Cognitive Development (ABCD) study, with resting-state fMRI (n = 4,099 at baseline; n = 3,376 at follow-up [median age = 10.0 (1.1) and 12.0 (1.1) years; n = 2,116 with both assessments]). Reproducible, inverse associations between low-frequency signal and topological fluctuations were estimated (p < 0.05, β = −0.20 to −0.02, 95% confidence interval (CI) = [−0.23, −0.001]). Signal (but not topological) fluctuations increased in somatomotor and prefrontal areas with pubertal stage (p < 0.03, β = 0.06–0.07, 95% CI = [0.03, 0.11]), but decreased in orbitofrontal, insular, and cingulate cortices, as well as cerebellum, hippocampus, amygdala, and thalamus (p < 0.05, β = −0.09 to −0.03, 95% CI = [−0.15, −0.001]). Higher temporal signal and topological variability in spatially distributed regions were estimated in girls. In racial/ethnic minorities, several associations between signal and topological fluctuations were in the opposite direction of those in the entire sample, suggesting potential racial differences. Our findings indicate that during puberty, intrinsic signal dynamics change significantly in developed and developing brain regions, but their strongest coordination patterns may already be sufficiently developed and remain temporally consistent. 

Abstract Social isolation during development, especially in adolescence, has detrimental but incompletely understood effects on the brain. This study investigated the neural correlates of preference for solitude and social withdrawal in a sample of 2809 youth [median (IQR) age = 12.0 (1.1) years, 1440 (51.26%) females] from the Adolescent Brain Cognitive Development study. Older youth whose parents had mental health issues more frequently preferred solitude and/or were socially withdrawn (β = 0.04 to 0.14, CI = [0.002, 0.19], P < 0.05), both of which were associated with internalizing and externalizing behaviors, depression, and anxiety (β = 0.25 to 0.45, CI = [0.20, 0.49], P < 0.05). Youth who preferred solitude and/or were socially withdrawn had lower cortical thickness in regions involved in social function (cuneus, insula, anterior cingulate, and superior temporal gyri) and/or mental health (β = −0.09 to −0.02, CI = [−0.14, −0.003], P < 0.05), and higher amygdala, entorhinal cortex, parahippocampal gyrus, and basal ganglia volume (β = 2.62 to 668.10, CI = [0.13, 668.10], P < 0.05). Youth who often preferred solitude had more topologically segregated dorsal attention, temporoparietal, and social networks (β = 0.07 to 0.10, CI = [0.02, 0.14], P ≤ 0.03). Socially withdrawn youth had a less topologically robust and efficient (β = −0.05 to −0.80, CI = [−1.34,−0.01], P < 0.03) and more fragile cerebellum (β = 0.04, CI = [0.01, 0.07], P < 0.05). These findings suggest that social isolation in adolescence may be a risk factor for widespread alterations in brain regions supporting social function and mental health. 

Abstract The COVID-19 pandemic has had profound but incompletely understood adverse effects on youth. To elucidate the role of brain circuits in how adolescents responded to the pandemic’s stressors, we investigated their prepandemic organization as a predictor of mental/emotional health in the first ~15 months of the pandemic. We analyzed resting-state networks from n = 2,641 adolescents [median age (interquartile range) = 144.0 (13.0) months, 47.7% females] in the Adolescent Brain Cognitive Development study, and longitudinal assessments of mental health, stress, sadness, and positive affect, collected every 2 to 3 months from May 2020 to May 2021. Topological resilience and/or network strength predicted overall mental health, stress and sadness (but not positive affect), at multiple time points, but primarily in December 2020 and May 2021. Higher resilience of the salience network predicted better mental health in December 2020 (β = 0.19, 95% CI = [0.06, 0.31], P = 0.01). Lower connectivity of left salience, reward, limbic, and prefrontal cortex and its thalamic, striatal, amygdala connections, predicted higher stress (β = −0.46 to −0.20, CI = [−0.72, −0.07], P < 0.03). Lower bilateral robustness (higher fragility) and/or connectivity of these networks predicted higher sadness in December 2020 and May 2021 (β = −0.514 to −0.19, CI = [−0.81, −0.05], P < 0.04). These findings suggest that the organization of brain circuits may have played a critical role in adolescent stress and mental/emotional health during the pandemic. 

Abstract Community structure is a fundamental topological characteristic of optimally organized brain networks. Currently, there is no clear standard or systematic approach for selecting the most appropriate community detection method. Furthermore, the impact of method choice on the accuracy and robustness of estimated communities (and network modularity), as well as method‐dependent relationships between network communities and cognitive and other individual measures, are not well understood. This study analyzed large datasets of real brain networks (estimated from resting‐state fMRI from = 5251 pre/early adolescents in the adolescent brain cognitive development [ABCD] study), and = 5338 synthetic networks with heterogeneous, data‐inspired topologies, with the goal to investigate and compare three classes of community detection methods: (i) modularity maximization‐based (Newman and Louvain), (ii) probabilistic (Bayesian inference within the framework of stochastic block modeling (SBM)), and (iii) geometric (based on graph Ricci flow). Extensive comparisons between methods and their individual accuracy (relative to the ground truth in synthetic networks), and reliability (when applied to multiple fMRI runs from the same brains) suggest that the underlying brain network topology plays a critical role in the accuracy, reliability and agreement of community detection methods. Consistent method (dis)similarities, and their correlations with topological properties, were estimated across fMRI runs. Based on synthetic graphs, most methods performed similarly and had comparable high accuracy only in some topological regimes, specifically those corresponding to developed connectomes with at least quasi‐optimal community organization. In contrast, in densely and/or weakly connected networks with difficult to detect communities, the methods yielded highly dissimilar results, with Bayesian inference within SBM having significantly higher accuracy compared to all others. Associations between method‐specific modularity and demographic, anthropometric, physiological and cognitive parameters showed mostly method invariance but some method dependence as well. Although method sensitivity to different levels of community structure may in part explain method‐dependent associations between modularity estimates and parameters of interest, method dependence also highlights potential issues of reliability and reproducibility. These findings suggest that a probabilistic approach, such as Bayesian inference in the framework of SBM, may provide consistently reliable estimates of community structure across network topologies. In addition, to maximize robustness of biological inferences, identified network communities and their cognitive, behavioral and other correlates should be confirmed with multiple reliable detection methods. 

Abstract Parental religious beliefs and practices (religiosity) may have profound effects on youth, especially in neurodevelopmentally complex periods such as adolescence. In n = 5566 children (median age = 120.0 months; 52.1% females; 71.2% with religious affiliation) from the Adolescent Brain Cognitive Development study, relationships between parental religiosity and non-religious beliefs on family values (data on youth beliefs were not available), topological properties of youth resting-state brain networks, and executive function, inhibitory control, and cognitive flexibility were investigated. Lower caregiver education and family income were associated with stronger parental beliefs (p < 0.01). Strength of both belief types was correlated with lower efficiency, community structure, and robustness of frontoparietal control, temporoparietal, and dorsal attention networks (p < 0.05), and lower Matrix Reasoning scores. Stronger religious beliefs were negatively associated (directly and indirectly) with multiscale properties of salience and default-mode networks, and lower Flanker and Dimensional Card Sort scores, but positively associated with properties of the precuneus. Overall, these effects were small (Cohen’s d ~ 0.2 to ~ 0.4). Overlapping neuromodulatory and cognitive effects of parental beliefs suggest that early adolescents may perceive religious beliefs partly as context-independent rules on expected behavior. However, religious beliefs may also differentially affect cognitive flexibility, attention, and inhibitory control and their neural substrates. 

The COVID-19 pandemic had profound effects on developing adolescents that, to date, remain incompletely understood. Youth with preexisting mental health problems and associated brain alterations were at increased risk for higher stress and poor mental health. This study investigated impacts of adolescent pre-pandemic mental health problems and their neural correlates on stress, negative emotions and poor mental health during the first 15 months of the COVID-19 pandemic. N = 2,641 adolescents (median age = 12.0 years) from the Adolescent Brain Cognitive Development (ABCD) cohort were studied, who had pre-pandemic data on anxiety, depression, and behavioral (attention, aggression, social withdrawal, internalizing, externalizing) problems, longitudinal survey data on mental health, stress and emotions during the first 15 months following the outbreak, structural MRI, and resting-state fMRI. Data were analyzed using mixed effects mediation and moderation models. Preexisting mental health and behavioral problems predicted higher stress, negative affect and negative emotions (β = 0.09–0.21, CI=[0.03,0.32]), and lower positive affect (β = −0.21 to −0.09, CI=[−0.31,-0.01]) during the first ~6 months of the outbreak. Pre-pandemic structural characteristics of brain regions supporting social function and emotional processing (insula, superior temporal gyrus, orbitofrontal cortex, and the cerebellum) mediated some of these relationships (β = 0.10–0.15, CI=[0.01,0.24]). The organization of pre-pandemic brain circuits moderated (attenuated) associations between preexisting mental health and pandemic stress and negative emotions (β = −0.17 to −0.06, CI=[−0.27,-0.01]). Preexisting mental health problems and their structural brain correlates were risk factors for youth stress and negative emotions during the early months of the outbreak. In addition, the organization of some brain circuits was protective and attenuated the effects of preexisting mental health issues on youth responses to the pandemic’s stressors. 

Empathy is at the core of our social world, yet multidomain factors that affect its development in socially sensitive periods, such as adolescence, are incompletely understood. To address this gap, this study investigated associations between social, environmental and mental health factors, and their temporal changes, on adolescent empathetic behaviors/emotions and, for comparison, callous unemotional (CU) traits and behaviors, in the early longitudinal Adolescent Brain Cognitive Development sample (baseline: n = 11062; 2-year follow-up: n = 9832, median age = 119 and 144 months, respectively). Caregiver affection towards the youth, liking school, having a close friend, and importance of religious beliefs/spirituality in the youth’s life were consistently positively correlated with empathetic behaviors/emotions across assessments (p<0.001, Cohen’s f = ~0.10). Positive family dynamics and cohesion, living in a neighborhood that shared the family’s values, but also parent history of substance use and (aggregated) internalizing problems were additionally positively associated with one or more empathetic behaviors at follow-up (p<0.001, f = ~0.10). In contrast, externalizing problems, anxiety, depression, fear of social situations, and being withdrawn were negatively associated with empathetic behaviors and positively associated with CU traits and behaviors (p<0.001, f = ~0.1–0.44). The latter were also correlated with being cyberbullied and/or discriminated against, anhedonia, and impulsivity, and their interactions with externalizing and internalizing issues. Significant positive temporal correlations of behaviors at the two assessments indicated positive (early) developmental empathetic behavior trajectories, and negative CU traits’ trajectories. Negative changes in mental health adversely moderated positive trajectories and facilitated negative ones. These findings highlight that adolescent empathetic behaviors/emotions are positively related to multidomain protective social environmental factors, but simultaneously adversely associated with risk factors in the same domains, as well as bully victimization, discrimination, and mental health problems. Risk factors instead facilitate the development of CU traits and behaviors.