Research Publications

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To assess the association between sexual orientation and screen use (screen time and problematic screen use) in a demographically diverse national sample of early adolescents in the United States.

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Childhood obesity is a serious health concern that is not yet fully understood. Previous research has linked obesity with neurobehavioral factors such as behavior, cognition, and brain morphology. The causal directions of these relationships remain mostly untested. We filled this gap by using the Adolescent Brain Cognitive Development study cohort comprising 11,875 children aged 9-10. First, correlations between the age- and sex-specific 95th BMI percentile (%BMIp95) and neurobehavioral measures were cross-sectionally analyzed. Effects were then aggregated by neurobehavioral domain for causal analyses. Behavioral genetic Direction of Causation modeling was used to test the direction of each relationship. Findings were validated by longitudinal cross-lagged panel modeling. %BMIp95 correlated with impulsivity, motivation, psychopathology, eating behavior, and cognitive tests (executive functioning, language, memory, perception, working memory). Greater %BMIp95 was also associated with reduced cortical thickness in frontal and temporal brain areas but with increased thickness in parietal and occipital areas. Similar although weaker patterns emerged for cortical surface area and volume. Behavioral genetic modeling suggested causal effects of %BMIp95 on eating behavior (β = 0.26), cognition (β = 0.05), cortical thickness (β = 0.15), and cortical surface area (β = 0.07). Personality/psychopathology (β = 0.09) and eating behavior (β = 0.16) appeared to influence %BMIp95. Longitudinal evidence broadly supported these findings. Results regarding cortical volume were inconsistent. Results supported causal effects of obesity on brain functioning and morphology. The present study highlights the importance of physical health for brain development and may inform interventions aimed at preventing or reducing pediatric obesity. RESEARCH HIGHLIGHTS: A continuous measure related to obesity, %BMIp95, has correlations with various measures of brain functioning and structure Behavioral genetic and longitudinal modeling suggest causal links from personality, psychopathology, and eating behavior to %BMIp95 Results also indicate directional links from %BMIp95 to eating behavior, cognition, cortical thickness, and cortical surface area Obesity may play a role for healthy brain development during childhood.

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Despite the numerous studies in favor of breastfeeding for its benefits in cognition and mental health, the long-term effects of breastfeeding on brain structure are still largely unknown. Our main objective was to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also explored the potential mediatory role of brain volumes on behavior.

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This study investigates the capacity of pre/perinatal factors to predict attention-deficit/hyperactivity disorder (ADHD) symptoms in childhood. It also explores whether predictive accuracy of a pre/perinatal model varies for different groups in the population. We used the ABCD (Adolescent Brain Cognitive Development) cohort from the United States ( = 9975). Pre/perinatal information and the Child Behavior Checklist were reported by the parent when the child was aged 9-10. Forty variables which are generally known by birth were input as potential predictors including maternal substance-use, obstetric complications and child demographics. Elastic net regression with 5-fold validation was performed, and subsequently stratified by sex, race/ethnicity, household income and parental psychopathology. Seventeen pre/perinatal variables were identified as robust predictors of ADHD symptoms in this cohort. The model explained just 8.13% of the variance in ADHD symptoms on average (95% CI = 5.6%-11.5%). Predictive accuracy of the model varied significantly by subgroup, particularly across income groups, and several pre/perinatal factors appeared to be sex-specific. Results suggest we may be able to predict childhood ADHD symptoms with modest accuracy from birth. This study needs to be replicated using prospectively measured pre/perinatal data.

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Screen media activity (SMA) consumes considerable time in youth’s lives, raising concerns about the effects it may have on youth development. Disentangling mixed associations between SMA of youth and developmental measures should move beyond overall screen time and consider types and patterns of SMA. This study aimed to identify reliable and generalizable SMA patterns among youth and examine their associations with behavioral developmental measures and developing brain functional connectivity.

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The purpose of this study was to examine associations between sexual minority status (e.g., gay or bisexual) and sleep problems in a demographically diverse, national sample of U.S. early adolescents. We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 2, 2018-2020) to estimate associations between sexual orientation and sleep problems or disturbance, adjusting for confounders and testing potential mediators (depressive problems, stress problems, family conflict, and parental monitoring). In a sample of 8563 adolescents 10- to 14-years-old, 4.4% identified as sexual minority individuals. Sexual minority status was associated with self-reported trouble falling or staying asleep (risk ratio [RR] = 2.24, 95% confidence interval [CI] = 1.88-2.68) and caregiver-reported sleep disturbance (RR = 1.50, 95% CI = 1.29-1.75). The association between sexual minority status and trouble falling or staying asleep was partially mediated by greater depressive problems, more family conflict, and less parental monitoring, whereas the association between sexual minority status and caregiver-reported sleep disturbance was partially mediated by greater depressive problems, higher stress, and greater family conflict. Our results indicate that sexual minority status may be linked to sleep disturbance in early adolescence. Depressive problems, stress, family conflict, and less parental monitoring partially mediate disparities in sleep health for sexual minority youth. Future research could test interventions to promote family and caregiver acceptance and mental health support for sexual minority youth to improve their sleep and other health outcomes.

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Childhood obesity has become a global health problem. Previous studies showed that childhood obesity is associated with brain structural differences relative to controls. However, few studies have been performed with longitudinal evaluations of brain structural developmental trajectories in childhood obesity. We employed voxel-based morphometry (VBM) analysis to assess gray matter (GM) volume at baseline and 2-year follow-up in 258 obese children (OB) and 265 normal weight children (NW), recruited as part of the National Institutes of Health Adolescent Brain and Cognitive Development study. Significant group × time effects on GM volume were observed in the prefrontal lobe, thalamus, right precentral gyrus, caudate, and parahippocampal gyrus/amygdala. OB compared with NW had greater reductions in GM volume in these regions over the 2-year period. Body mass index (BMI) was negatively correlated with GM volume in prefrontal lobe and with matrix reasoning ability at baseline and 2-year follow-up. In OB, Picture Test was positively correlated with GM volume in the left orbital region of the inferior frontal gyrus (OFCinf_L) at baseline and was negatively correlated with reductions in OFCinf_L volume (2-year follow-up vs. baseline). These findings indicate that childhood obesity is associated with GM volume reduction in regions involved with reward evaluation, executive function, and cognitive performance.

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Familial, obstetric, and early-life environmental risks for schizophrenia spectrum disorder (SSD) alter normal cerebral development, leading to the formation of characteristic brain deficit patterns prior to onset of symptoms. We hypothesized that the insidious effects of these risks may increase brain similarity to adult SSD deficit patterns in prepubescent children.

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Sipping, an early form of alcohol initiation, is associated with aspects of psychopathology and personality that reflect long-term risk for harmful alcohol use. In the Adolescent Brain and Cognitive Development cohort ( = 11,872), sipping by age 9-10 was concurrently associated with impulsivity, other aspects of externalizing, and prodromal schizophrenia symptoms. Still, these associations were cross-sectional in nature, leaving open the possibility that these features of psychopathology and personality might not reflect long-term risk for alcohol consumption and related harm across development. Here, we attempted to replicate baseline concurrent associations across three waves of data to extend concurrent associations to prospective ones. Most cross-sectional associations replicated across waves, such that impulsivity, other aspects of externalizing, reward sensitivity (e.g., surgency, sensation seeking), and prodromal schizophrenia symptoms were associated with increased odds of having sipped alcohol by the age of 12. Nevertheless, not all concurrent associations replicated prospectively; impulsigenic features did not reflect long-term risk for sipping. Thus, some psychopathology features appeared to reflect stable risk factors, whereas others appeared to reflect state-dependent risk factors. All told, sipping might not reflect long-term risk for harmful alcohol use, and the nature of sipping may change across development.

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Data from multisite magnetic resonance imaging (MRI) studies contain variance attributable to the scanner that can reduce statistical power and potentially bias results if not appropriately managed. The Adolescent Cognitive Brain Development (ABCD) study is an ongoing, longitudinal neuroimaging study acquiring data from over 11,000 children starting at 9-10 years of age. These scans are acquired on 29 different scanners of 5 different model types manufactured by 3 different vendors. Publicly available data from the ABCD study include structural MRI (sMRI) measures such as cortical thickness and diffusion MRI (dMRI) measures such as fractional anisotropy. In this work, we 1) quantify the variance attributable to scanner effects in the sMRI and dMRI datasets, 2) demonstrate the effectiveness of the data harmonization approach called ComBat to address scanner effects, and 3) present a simple, open-source tool for investigators to harmonize image features from the ABCD study. Scanner-induced variance was present in every image feature and varied in magnitude by feature type and brain location. For almost all features, scanner variance exceeded variability attributable to age and sex. ComBat harmonization was shown to effectively remove scanner induced variance from all image features while preserving the biological variability in the data. Moreover, we show that for studies examining relatively small subsamples of the ABCD dataset, the use of ComBat harmonized data provides more accurate estimates of effect sizes compared to controlling for scanner effects using ordinary least squares regression.

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Resting-state functional connectivity (RSFC) is widely used to predict behavioral measures. To predict behavioral measures, representing RSFC with parcellations and gradients are the two most popular approaches. Here, we compare parcellation and gradient approaches for RSFC-based prediction of a broad range of behavioral measures in the Human Connectome Project (HCP) and Adolescent Brain Cognitive Development (ABCD) datasets. Among the parcellation approaches, we consider group-average “hard” parcellations (Schaefer et al., 2018), individual-specific “hard” parcellations (Kong et al., 2021a), and an individual-specific “soft” parcellation (spatial independent component analysis with dual regression; Beckmann et al., 2009). For gradient approaches, we consider the well-known principal gradients (Margulies et al., 2016) and the local gradient approach that detects local RSFC changes (Laumann et al., 2015). Across two regression algorithms, individual-specific hard-parcellation performs the best in the HCP dataset, while the principal gradients, spatial independent component analysis and group-average “hard” parcellations exhibit similar performance. On the other hand, principal gradients and all parcellation approaches perform similarly in the ABCD dataset. Across both datasets, local gradients perform the worst. Finally, we find that the principal gradient approach requires at least 40 to 60 gradients to perform as well as parcellation approaches. While most principal gradient studies utilize a single gradient, our results suggest that incorporating higher order gradients can provide significant behaviorally relevant information. Future work will consider the inclusion of additional parcellation and gradient approaches for comparison.

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About 1/3 of youth spend more than four hours/day engaged in screen media activity (SMA). This investigation utilized longitudinal brain imaging and mediation analyses to examine relationships among SMA, brain patterns, and internalizing problems.

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Adolescence is a period of significant brain development and maturation, and it is a time when many mental health problems first emerge. This study aimed to explore a comprehensive map that describes possible pathways from genetic and environmental risks to structural brain organization and psychopathology in adolescents. We included 32 environmental items on developmental adversity, maternal substance use, parental psychopathology, socioeconomic status (SES), school and family environment; 10 child psychopathological scales; polygenic risk scores (PRS) for 10 psychiatric disorders, total problems, and cognitive ability; and structural brain networks in the Adolescent Brain Cognitive Development study (ABCD, n = 9168). Structural equation modeling found two pathways linking SES, brain, and psychopathology. Lower SES was found to be associated with lower structural connectivity in the posterior default mode network and greater salience structural connectivity, and with more severe psychosis and internalizing in youth (p < 0.001). Prematurity and birth weight were associated with early-developed sensorimotor and subcortical networks (p < 0.001). Increased parental psychopathology, decreased SES and school engagement was related to elevated family conflict, psychosis, and externalizing behaviors in youth (p < 0.001). Increased maternal substance use predicted increased developmental adversity, internalizing, and psychosis (p < 0.001). But, polygenic risks for psychiatric disorders had moderate effects on brain structural connectivity and psychopathology in youth. These findings suggest that a range of genetic and environmental factors can influence brain structural organization and psychopathology during adolescence, and that addressing these risk factors may be important for promoting positive mental health outcomes in young people.

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attention-deficit/hyperactivity disorder (ADHD) is associated with both polygenic liability and environmental exposures, both intrinsic to the family, such as family conflict, and extrinsic, such as air pollution. However, much less is known about the interplay between environmental and genetic risks relevant to ADHD-a better understanding of which could inform both mechanistic models and clinical prediction algorithms.

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In adulthood, stress exposure and genetic risk heighten psychological vulnerability by accelerating neurobiological senescence. To investigate whether molecular and brain network maturation processes play a similar role in adolescence, we analysed genetic, as well as longitudinal task neuroimaging (inhibitory control, incentive processing) and early life adversity (i.e., material deprivation, violence) data from the Adolescent Brain and Cognitive Development study (N = 980, age range: 9-13 years). Genetic risk was estimated separately for Major Depressive Disorder (MDD) and Alzheimer’s Disease (AD), two pathologies linked to stress exposure and allegedly sharing a causal connection (MDD-to-AD). Adversity and genetic risk for MDD/AD jointly predicted functional network segregation patterns suggestive of accelerated (GABA-linked) visual/attentional, but delayed (dopamine [D2]/glutamate [GLU5R]-linked) somatomotor/association system development. A positive relationship between brain maturation and psychopathology emerged only among the less vulnerable adolescents, thereby implying that normatively maladaptive neurodevelopmental alterations could foster adjustment among the more exposed and genetically more stress susceptible youths. Transcriptomic analyses suggested that sensitivity to stress may underpin the joint neurodevelopmental effect of adversity and genetic risk for MDD/AD, in line with the proposed role of negative emotionality as a precursor to AD, likely to account for the alleged causal impact of MDD on dementia onset.

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Resting-state functional connectivity (RSFC) is a powerful tool for characterizing brain changes, but it has yet to reliably predict higher-order cognition. This may be attributed to small effect sizes of such brain-behavior relationships, which can lead to underpowered, variable results when utilizing typical sample sizes (N∼25). Inspired by techniques in genomics, we implement the polyneuro risk score (PNRS) framework – the application of multivariate techniques to RSFC data and validation in an independent sample. Utilizing the Adolescent Brain Cognitive Development® cohort split into two datasets, we explore the framework’s ability to reliably capture brain-behavior relationships across 3 cognitive scores – general ability, executive function, learning & memory. The weight and significance of each connection is assessed in the first dataset, and a PNRS is calculated for each participant in the second. Results support the PNRS framework as a suitable methodology to inspect the distribution of connections contributing towards behavior, with explained variance ranging from 1.0 % to 21.4 %. For the outcomes assessed, the framework reveals globally distributed, rather than localized, patterns of predictive connections. Larger samples are likely necessary to systematically identify the specific connections contributing towards complex outcomes. The PNRS framework could be applied translationally to identify neurologically distinct subtypes of neurodevelopmental disorders.

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In this work, we expand the normative model repository introduced in Rutherford et al., 2022a to include normative models charting lifespan trajectories of structural surface area and brain functional connectivity, measured using two unique resting-state network atlases (Yeo-17 and Smith-10), and an updated online platform for transferring these models to new data sources. We showcase the value of these models with a head-to-head comparison between the features output by normative modeling and raw data features in several benchmarking tasks: mass univariate group difference testing (schizophrenia versus control), classification (schizophrenia versus control), and regression (predicting general cognitive ability). Across all benchmarks, we show the advantage of using normative modeling features, with the strongest statistically significant results demonstrated in the group difference testing and classification tasks. We intend for these accessible resources to facilitate the wider adoption of normative modeling across the neuroimaging community.

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Youth with incarcerated parents experience more adverse childhood experiences than other youth, placing them at higher risk for mental health and substance use disorders. Despite their increased risk, these youth may be less likely to access mental health services, particularly given their racial and ethnic makeup. Therefore, this study aimed to assess racial and ethnic disparities in access to mental health services for youth with incarcerated parents.

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Resting-state fMRI is commonly used to derive brain parcellations, which are widely used for dimensionality reduction and interpreting human neuroscience studies. We previously developed a model that integrates local and global approaches for estimating areal-level cortical parcellations. The resulting local-global parcellations are often referred to as the Schaefer parcellations. However, the lack of homotopic correspondence between left and right Schaefer parcels has limited their use for brain lateralization studies. Here, we extend our previous model to derive homotopic areal-level parcellations. Using resting-fMRI and task-fMRI across diverse scanners, acquisition protocols, preprocessing and demographics, we show that the resulting homotopic parcellations are as homogeneous as the Schaefer parcellations, while being more homogeneous than five publicly available parcellations. Furthermore, weaker correlations between homotopic parcels are associated with greater lateralization in resting network organization, as well as lateralization in language and motor task activation. Finally, the homotopic parcellations agree with the boundaries of a number of cortical areas estimated from histology and visuotopic fMRI, while capturing sub-areal (e.g., somatotopic and visuotopic) features. Overall, these results suggest that the homotopic local-global parcellations represent neurobiologically meaningful subdivisions of the human cerebral cortex and will be a useful resource for future studies. Multi-resolution parcellations estimated from 1479 participants are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Yan2023_homotopic).

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The amygdala is a crucial interconnecting structure in the brain that performs several regulatory functions, yet its genetic architectures and involvement in brain disorders remain largely unknown. We carried out the first multivariate genome-wide association study (GWAS) of amygdala subfield volumes in 27,866 UK Biobank individuals. The whole amygdala was segmented into nine nuclei groups using Bayesian amygdala segmentation. The post-GWAS analysis allowed us to identify causal genetic variants in phenotypes at the SNP, locus, and gene levels, as well as genetic overlap with brain health-related traits. We further generalized our GWAS in Adolescent Brain Cognitive Development (ABCD) cohort. The multivariate GWAS identified 98 independent significant variants within 32 genomic loci associated (P < 5 × 10) with amygdala volume and its nine nuclei. The univariate GWAS identified significant hits for eight of the ten volumes, tagging 14 independent genomic loci. Overall, 13 of the 14 loci identified in the univariate GWAS were replicated in the multivariate GWAS. The generalization in ABCD cohort supported the GWAS results with the 12q23.2 (RNA gene RP11-210L7.1) being discovered. All of these imaging phenotypes are heritable, with heritability ranging from 15% to 27%. Gene-based analyses revealed pathways relating to cell differentiation/development and ion transporter/homeostasis, with the astrocytes found to be significantly enriched. Pleiotropy analyses revealed shared variants with neurological and psychiatric disorders under the conjFDR threshold of 0.05. These findings advance our understanding of the complex genetic architectures of amygdala and their relevance in neurological and psychiatric disorders.

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Despite decades of costly research, we still cannot accurately predict individual differences in cognition from task-based functional magnetic resonance imaging (fMRI). Moreover, aiming for methods with higher prediction is not sufficient. To understand brain-cognition relationships, we need to explain how these methods draw brain information to make the prediction. Here we applied an explainable machine-learning (ML) framework to predict cognition from task-based fMRI during the n-back working-memory task, using data from the Adolescent Brain Cognitive Development (n = 3,989). We compared 9 predictive algorithms in their ability to predict 12 cognitive abilities. We found better out-of-sample prediction from ML algorithms over the mass-univariate and ordinary least squares (OLS) multiple regression. Among ML algorithms, Elastic Net, a linear and additive algorithm, performed either similar to or better than nonlinear and interactive algorithms. We explained how these algorithms drew information, using SHapley Additive explanation, eNetXplorer, Accumulated Local Effects, and Friedman’s H-statistic. These explainers demonstrated benefits of ML over the OLS multiple regression. For example, ML provided some consistency in variable importance with a previous study and consistency with the mass-univariate approach in the directionality of brain-cognition relationships at different regions. Accordingly, our explainable-ML framework predicted cognition from task-based fMRI with boosted prediction and explainability over standard methodologies.

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Stressful childhood experiences are associated with unique brain activity patterns during emotional processing. Specifically, pediatric stress is linked to activation in the insulae, superior temporal and parahippocampal gyri, and the amygdalae, as well as differential activation in the dorsal anterior cingulate cortex when viewing emotional faces. Gender diversity is broadly associated with higher victimization and mental health disparities in children aged 9/10, but whether it is associated with stress-like alterations in brain function (BOLD signal during task-based fMRI) remains unknown. We investigate the functional brain correlates of this relationship to determine if gender-diverse youth show patterns of functional activity during an emotional task consistent with those of other populations that experience heightened stress.

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Our understanding of the mechanisms relating pubertal timing to mental health problems via brain development remains rudimentary.

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Human cortical expansion has occurred non-uniformly across the brain. We assessed the genetic architecture of cortical global expansion and regionalization by comparing two sets of genome-wide association studies of 24 cortical regions with and without adjustment for global measures (i.e., total surface area, mean cortical thickness) using a genetically informed parcellation in 32,488 adults. We found 393 and 756 significant loci with and without adjusting for globals, respectively, where 8% and 45% loci were associated with more than one region. Results from analyses without adjustment for globals recovered loci associated with global measures. Genetic factors that contribute to total surface area of the cortex particularly expand anterior/frontal regions, whereas those contributing to thicker cortex predominantly increase dorsal/frontal-parietal thickness. Interactome-based analyses revealed significant genetic overlap of global and dorsolateral prefrontal modules, enriched for neurodevelopmental and immune system pathways. Consideration of global measures is important in understanding the genetic variants underlying cortical morphology.

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Psychiatric disorders commonly emerge prior to adulthood. Identification and intervention may vary significantly across populations. We leveraged a large population-based study to estimate the prevalence of psychiatric disorders and treatments, and evaluate predictors of treatment, in children ages 9-10 in the United States.

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Increased expression of the complement component 4A (C4A) gene is associated with a greater lifetime risk of schizophrenia. In the brain, C4A is involved in synaptic pruning; yet, it remains unclear the extent to which upregulation of C4A alters brain development or is associated with the risk for psychotic symptoms in childhood. Here, we perform a multi-ancestry phenome-wide association study in 7789 children aged 9-12 years to examine the relationship between genetically regulated expression (GREx) of C4A, childhood brain structure, cognition, and psychiatric symptoms.

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Alcohol expectancies are beliefs regarding positive (e.g., tension reduction) or negative (e.g., loss of motor coordination) effects of alcohol. Based on Social Learning Theory, social media can influence alcohol expectancies in adolescents. In particular, problematic social media use – which can reflect elements of addiction, including mood modification, tolerance, withdrawal, conflict, and relapse – could be linked to alcohol expectancies. We aimed to determine the associations between problematic social media use and alcohol expectancies in a national (U.S.) cohort of 10-14-year-old early adolescents.

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The current study investigated symptom network patterns in adolescents from a gut-brain-axis (GBA) biopsychosocial perspective. Our secondary analysis of data from the Adolescent Brain Cognitive Development Study assessed symptom relationships using network analysis to provide information about multivariate structural dependencies among 41 signs and symptoms. Cross-sectional EBICglasso symptom networks were evaluated to assess patterns associated with anhedonia and depressed mood. Significant differences were identified between symptom neighbors of anhedonia compared with depressed mood based on stratification by age. The GBA perspective revealed several symptom neighbors that could expand clinical assessment, diagnosing criteria, education, and interventions for adolescents at risk for, or with, anhedonia or depressed mood. Results speak to the unique impact of symptoms on health that are not interchangeable with other symptoms and do not have equal effects. Mental health nurses should consider a holistic and proactive precision health approach to improving health and well-being through evidence-based assessment of symptom associations. [(7), 29-38.].

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Sleep plays an important role in healthy neurocognitive development, and poor sleep is linked to cognitive and emotional dysfunction. Studies in adults suggest that shorter sleep duration and poor sleep quality may disrupt core neurocognitive networks, particularly the default mode network (DMN)-a network implicated in internal cognitive processing and rumination. Here, we examine the relationships between sleep and within- and between-network resting-state functional connectivity (rs-FC) of the DMN in youth.

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The adverse effects of COVID-19 containment policies disrupting child mental health and sleep have been debated. However, few current estimates correct biases of these potential effects.

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Early detection of attention-deficit/hyperactivity disorder (ADHD) and sleep problems is paramount for children’s mental health. Interview-based diagnostic approaches have drawbacks, necessitating the development of an evaluation method that uses digital phenotypes in daily life.

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The use of consumer-grade wearable devices for collecting data for biomedical research may be associated with social determinants of health (SDoHs) linked to people’s understanding of and willingness to join and remain engaged in remote health studies.

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Childhood mild traumatic brain injury (mTBI) is associated with elevated risk of developing social problems, which may be underpinned by changes in the structural developmental trajectory of the social brain, a network of cortical regions supporting social cognition and behavior. However, limited sample sizes and cross-sectional designs generally used in neuroimaging studies of pediatric TBI have prevented explorations of this hypothesis. This longitudinal retrospective study examined the development of parent-reported social problems and cortical thickness in social brain regions following childhood mTBI using data from the large population-based Adolescent Brain Cognitive Development (ABCD) Study. Two-group latent change score models revealed different developmental trajectories from ages 10-12 years in the level of social problems between children with (n = 345) and without (n = 7,089) mTBI. Children with mTBI showed higher, but non-clinical, levels of social problems than controls at age 10. Then, social problems decreased over 2 years, but still remained higher, but non-clinical, than in controls in which they stayed stable. Both groups showed similar decreases in social brain cortical thickness between ages 10 and 12 years. Further studies providing detailed information on the injury mechanism and acute symptoms are needed to better understand individual differences in social functioning and brain development in pediatric TBI.

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Studies suggest prenatal cannabis exposure is associated with mood/behavioral problems in children. However, it is unclear if targeting modifiable domains like sleep behaviors would improve outcomes in exposed youth. Using a causal inference framework, the effect of changing sleep-hours on changing internalizing/externalizing problems in children was examined using the Adolescent Brain Cognitive Development™ study baseline (ages 9-10; collected during 2016-2018) and year-1 follow-up data (N = 9825; 4663 female; 5196 white). Average treatment effects (ATE) indicated that more sleep predicted less internalizing (ATE = -.34, SE = .08, p < .001) and externalizing (ATE = -.29, SE = .07, p < .001) problems over time. However, prenatal cannabis exposure moderated the ATE on internalizing (conditional-ATE = .91, SE = .39, p = .019), whereby participants with exposure (n = 605) did not show any effect of changing sleep-hours on mood (B = .09, SE = .24).

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Earlier pubertal timing is associated with higher rates of depressive disorders in adolescence. Neuroimaging studies report brain structural associations with both pubertal timing and depression. However, whether brain structure mediates the relationship between pubertal timing and depression remains unclear.

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The temporal characteristics of adolescent neurodevelopment are shaped by a complex interplay of genetic, biological, and environmental factors. Using a large longitudinal dataset of children aged 9-13 from the Adolescent Brain Cognitive Development (ABCD) study we tested the associations between pubertal status and brain maturation. Brain maturation was assessed using brain age prediction based on convolutional neural networks and minimally processed T1-weighted structural MRI data. Brain age prediction provided highly accurate and reliable estimates of individual age, with an overall mean absolute error of 0.7 and 1.4 years at the two timepoints respectively, and an intraclass correlation of 0.65. Linear mixed effects (LME) models accounting for age and sex showed that on average, a one unit increase in pubertal maturational level was associated with a 2.22 months higher brain age across time points (β = 0.10, p < .001). Moreover, annualized change in pubertal development was weakly related to the rate of change in brain age (β = .047, p = 0.04). These results demonstrate a link between sexual development and brain maturation in early adolescence, and provides a basis for further investigations of the complex sociobiological impacts of puberty on life outcomes.

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Leveraging a large population-level morphologic, microstructural, and functional neuroimaging dataset, we aimed to elucidate the underlying neurobiology of attention-deficit hyperactivity disorder (ADHD) in children. In addition, we evaluated the applicability of machine learning classifiers to predict ADHD diagnosis based on imaging and clinical information.

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Suicide is a leading cause of death among adolescents. Emerging literature has described relationships between excessive screen time and suicidal behaviors, though findings have been mixed. The objective of this study is to determine the prospective associations between screen time and suicidal behaviors two-years later in a national (U.S.) cohort of 9-11-year-old-children. We analyzed prospective cohort data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 11,633). Logistic regression analyses were estimated to determine the associations between baseline self-reported screen time (exposure) and suicidal behaviors (outcome) based on the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-5) at two-year-follow-up. Participants reported an average of 4.0 h of total screen time per day at baseline. At two-year-follow-up, 1.38% of the sample reported at least one suicidal behavior. Each additional hour of total screen time was prospectively associated with 1.09 higher odds of suicidal behaviors at 2-year-follow-up (95% CI 1.03-1.14), after adjusting for covariates. For specific screen time modalities, each additional hour of texting (aOR 1.36, 95% CI 1.06-1.74), video chatting (aOR 1.30, 95% CI 1.03-1.65), watching videos (aOR 1.21, 95% CI 1.04-1.39), and playing video games (aOR 1.18, 95% CI 1.01-1.38) was associated with higher odds of subsequent suicidal behaviors. Higher screen time is associated with higher odds of reporting suicidal behaviors at two-year-follow-up. Future research should seek to identify how specific screen time experiences may influence suicidal behaviors.

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The objective of this study was to explore the relationship between accumulating adverse childhood experiences (ACEs) and sipping alcohol in a large, nationwide sample of 9-to-10-year-old U.S. children. We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study (2016-2018). Of 10,853 children (49.1 % female), 23.4 % reported ever sipping alcohol. A greater ACE score was associated with a higher risk of sipping alcohol. Having 4 or more ACEs placed children at 1.27 times the risk (95 % CI 1.11-1.45) of sipping alcohol compared to children with no ACEs. Among the nine distinct ACEs examined, household violence (Risk Ratio [RR] = 1.13, 95 % CI 1.04-1.22) and household alcohol abuse (RR = 1.14, 95 % CI 1.05-1.22) were associated with sipping alcohol during childhood. Our findings indicate a need for increased clinical attention to alcohol sipping among ACE-exposed children.

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Characterizing the optimal fMRI paradigms for detecting behaviorally relevant functional connectivity (FC) patterns is a critical step to furthering our knowledge of the neural basis of behavior. Previous studies suggested that FC patterns derived from task fMRI paradigms, which we refer to as task-based FC, are better correlated with individual differences in behavior than resting-state FC, but the consistency and generalizability of this advantage across task conditions was not fully explored. Using data from resting-state fMRI and three fMRI tasks from the Adolescent Brain Cognitive Development Study ® (ABCD), we tested whether the observed improvement in behavioral prediction power of task-based FC can be attributed to changes in brain activity induced by the task design. We decomposed the task fMRI time course of each task into the task model fit (the fitted time course of the task condition regressors from the single-subject general linear model) and the task model residuals, calculated their respective FC, and compared the behavioral prediction performance of these FC estimates to resting-state FC and the original task-based FC. The FC of the task model fit was better than the FC of the task model residual and resting-state FC at predicting a measure of general cognitive ability or two measures of performance on the fMRI tasks. The superior behavioral prediction performance of the FC of the task model fit was content-specific insofar as it was only observed for fMRI tasks that probed similar cognitive constructs to the predicted behavior of interest. To our surprise, the task model parameters, the beta estimates of the task condition regressors, were equally if not more predictive of behavioral differences than all FC measures. These results showed that the observed improvement of behavioral prediction afforded by task-based FC was largely driven by the FC patterns associated with the task design. Together with previous studies, our findings highlighted the importance of task design in eliciting behaviorally meaningful brain activation and FC patterns.

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Obesity pandemic is reaching an alarming level globally, including in childhood, with a strong tendency to carry it over in adulthood. Obesity induces deleterious neurobiological outcomes; however, Morys et al. investigated how genetic predisposition to obesity — not obesity itself — impacts the brain and behavior. “We focused on children, as the effects of chronic obesity on the brain are possibly low, so any brain changes associated with genetic risk for obesity would likely constitute vulnerability factors rather than secondary effects of obesity,” explains Filip Morys, the first author of the study.

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Population-based neuroscience offers opportunities to examine important but understudied sociocultural factors such as acculturation. Acculturation refers to the extent to which an individual retains their cultural heritage and/or adopts the receiving society’s culture and is particularly salient among Hispanic/Latinx immigrants. Specific acculturative orientations have been linked to vulnerability to substance use, depression, and suicide and are known to influence family dynamics between caregivers and their children.

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This study tested whether multiple domains of social adversity, including neighborhood opportunity/deprivation and life stress, moderate genetic (A), common environmental (C), and unique environmental (E) influences on externalizing behaviors in 760 same-sex twin pairs (332 monozygotic; 428 dizygotic) ages 10-11 from the ABCD Study. Proportion of C influences on externalizing behavior increased at higher neighborhood adversity (lower overall opportunity). A decreased and C and E increased at lower levels of educational opportunity. A increased at lower health-environment and social-economic opportunity levels. For life stress, A decreased and E increased with number of experienced events. Results for educational opportunity and stressful life experiences suggest a bioecological gene-environment interaction pattern such that environmental influences predominate at higher levels of adversity, whereas limited access to healthcare, housing, and employment stability may potentiate genetic liability for externalizing behavior via a diathesis-stress mechanism. More detailed operationalization of social adversity in gene-environment interaction studies is needed.

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The COVID-19 pandemic has made an unprecedented shift in children’s daily lives. Children are increasingly spending time with screens to learn and connect with others. As the online environment rapidly substitutes in-person experience, understanding children’s neuropsychological trajectories associated with screen experiences is important. Previous findings suggest that excessive screen use can lead children to prefer more immediate rewards over delayed outcomes. We hypothesized that increased screen time delays a child’s development of inhibitory control system in the brain (i.e., fronto-striatal circuitry). By analyzing neuropsychological data from 8324 children (9-11ys) from the ABCD Study, we found that children who had more screen time showed a higher reward orientation and weaker fronto-striatal connectivity. Importantly, we found that the daily screen exposure mediated the effect of reward sensitivity on the development of the inhibitory control system in the brain over a two year period. These findings suggest possible negative long-term impacts of increased daily screen time on children’s neuropsychological development. The results further demonstrated that screen time influences dorsal striatum connectivity, which suggests that the effect of daily screen use is a habitual seeking behavior. The study provides neural and behavioral evidence for the negative impact of daily screen use on developing children.

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There is emerging evidence that the neuroanatomy of autism forms a spectrum which extends into the general population. However, whilst several studies have identified cortical morphology correlates of autistic traits, it is not established whether morphological differences are present in the subcortical structures of the brain. Additionally, it is not clear to what extent previously reported structural associations may be confounded by co-occurring psychopathology. To address these questions, we utilised neuroimaging data from the Adolescent Brain Cognitive Development Study to assess whether a measure of autistic traits was associated with differences in child subcortical morphology, and if any observed differences persisted after adjustment for child internalising and externalising symptoms.

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Physical activity is associated with mental health benefits in youth. Here, we used causal inference and triangulation with 2 levels of biology to substantiate relationships between sports participation and dimensional psychopathology in youths.

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Music engagement is a powerful, influential experience that often begins early in life. Music engagement is moderately heritable in adults (~ 41-69%), but fewer studies have examined genetic influences on childhood music engagement, including their association with language and executive functions. Here we explored genetic and environmental influences on music listening and instrument playing (including singing) in the baseline assessment of the Adolescent Brain Cognitive Development study. Parents reported on their 9-10-year-old children’s music experiences (N = 11,876 children; N = 1543 from twin pairs). Both music measures were explained primarily by shared environmental influences. Instrument exposure (but not frequency of instrument engagement) was associated with language skills (r = .27) and executive functions (r = .15-0.17), and these associations with instrument engagement were stronger than those for music listening, visual art, or soccer engagement. These findings highlight the role of shared environmental influences between early music experiences, language, and executive function, during a formative time in development.

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A general psychopathology (p) factor captures shared variation across mental disorders. Structural neural alterations have been associated with the p factor concurrently, but less is known about whether these alterations relate to within-person change in the p factor over time, especially during preadolescence, a period of neurodevelopmental changes.

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Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in school-aged children. Its accurate diagnosis looks after patients’ interests well with effective treatment, which is important to them and their family. Resting-state functional magnetic resonance imaging (rsfMRI) has been widely used to characterize the abnormal brain function by computing the voxel-wise measures and Pearson’s correlation (PC)-based functional connectivity (FC) for ADHD diagnosis. However, exploring the powerful measures of rsfMRI to improve ADHD diagnosis remains a particular challenge. To this end, this paper proposes an automated ADHD classification framework by fusion of multiple measures of rsfMRI in adolescent brain. First, we extract the voxel-wise measures and ROI-wise time series from the brain regions of rsfMRI after preprocessing. Then, to extract the multiple functional connectivities, we compute the PC-derived FCs including the topographical information-based high-order FC (tHOFC) and dynamics-based high-order FC (dHOFC), the sparse representation (SR)-derived FCs including the group SR (GSR), the strength and similarity guided GSR (SSGSR), and sparse low-rank (SLR). Finally, these measures are combined with multiple kernel learning (MKL) model for ADHD classification. The proposed method is applied to the Adolescent Brain and Cognitive Development (ABCD) dataset. The results show that the FCs of dHOFC and SLR perform better than the others. Fusing multiple measures achieves the best classification performance (AUC = 0.740, accuracy = 0.6916), superior to those from the single measure and the previous studies. We have identified the most discriminative FCs and brain regions for ADHD diagnosis, which are consistent with those of published literature.

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Although cannabis use during pregnancy is increasing widely, the effects of cannabis on developmental trajectories, such as whether its effects during pregnancy remain the same between time points or gradually increase, are unclear. This study aimed to examine whether cannabis use during pregnancy affects the process of change in cognition and brain volume. Data from two-time points measured longitudinally were analyzed. We used data from the Adolescent Brain and Cognitive Development Study. Participants included 11,876 children aged 9-11 years participated at baseline, and 10,414 participated at 2-year follow-up from 22 sites across the United States. We explored the associations between prenatal cannabis exposure and cognitive abilities and brain volumes developmental trajectories. Among 11,530 children with valid data for prenatal cannabis exposure, 10,833 had no prenatal cannabis use, and 697 had cannabis use during their pregnancy. There was a significant interaction between time points and cannabis use during pregnancy on visuo-perceptual processing ability (b = -0.019, p = .009) and intracranial volumes (b = -6338.309, p = .009). We found that the effects of exposure to cannabis during pregnancy are not uniform at all times and may gradually become more apparent and magnified as development progresses.

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Morphological features of the lateral prefrontal cortex (PFC) in late childhood and early adolescence may provide important clues as to the developmental etiology of clinical conditions such as obesity. Body composition measurements and structural brain imaging were performed on 11 226 youth at baseline (age 9 or 10 years) and follow-up (age 11 or 12 years). Baseline morphological features of the lateral PFC were examined as predictors of body composition. Findings revealed reliable associations between middle frontal gyrus volume, thickness and surface area and multiple indices of body composition. These findings were consistent across both time points and remained significant after covariate adjustment. Cortical thicknesses of the inferior frontal gyrus and lateral orbitofrontal cortex were also reliable predictors. Morphology effects on body composition were mediated by performance on a non-verbal reasoning task. Modest but reliable moderation effects were observed with respect to environmental self-regulatory demand after controlling for sex, race/ethnicity, income and methodological variables. Overall findings suggest that PFC morphology is a reliable predictor of body composition in early adolescence, as mediated through select cognitive functions and partially moderated by environmental characteristics.

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Early adolescence is a critical period for eating behaviors as children gain autonomy around food choice and peer influences increase in potency. From a neurodevelopmental perspective, significant structural changes take place in the prefrontal cortex during this time, including the orbitofrontal cortex (OFC), which is involved in socially contextualized decision-making. We examined the morphological features of the OFC in relation to food choice in a sample of 10 309 early adolescent children from the Adolescent Brain and Cognitive Development Study. Structural parameters of the OFC and insula were examined for relationships with two important aspects of food choice: limiting the consumption of fast/fried food and maximizing the consumption of nutritious foods. Raw, partially adjusted and fully adjusted models were evaluated. Findings revealed that a larger surface area of the lateral OFC was associated with higher odds of limiting fast/fried food consumption in raw [odds ratio (OR) = 1.07, confidence interval (CI): 1.02, 1.12, P = 0.002, PFDR = 0.012], partially adjusted (OR = 1.11, CI: 1.03, 1.19, P = 0.004, PFDR = 0.024) and fully adjusted models (OR = 1.11, CI: 1.03, 1.19, P = 0.006, PFDR = 0.036). In contrast, a larger insula volume was associated with lower odds of maximizing healthy foods in raw (OR = 0.94, CI: 0.91, 0.97, P <0.001, PFDR = 0.003) and partially adjusted (OR = 0.93, CI: 0.88, 0.98, P = 0.008, PFDR = 0.048) models. These findings refine our understanding of the OFC as a network node implicated in socially mediated eating behaviors.

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Mapping the connectome of the human brain using structural or functional connectivity has become one of the most pervasive paradigms for neuroimaging analysis. Recently, Graph Neural Networks (GNNs) motivated from geometric deep learning have attracted broad interest due to their established power for modeling complex networked data. Despite their superior performance in many fields, there has not yet been a systematic study of how to design effective GNNs for brain network analysis. To bridge this gap, we present BrainGB, a benchmark for brain network analysis with GNNs. BrainGB standardizes the process by (1) summarizing brain network construction pipelines for both functional and structural neuroimaging modalities and (2) modularizing the implementation of GNN designs. We conduct extensive experiments on datasets across cohorts and modalities and recommend a set of general recipes for effective GNN designs on brain networks. To support open and reproducible research on GNN-based brain network analysis, we host the BrainGB website at https://braingb.us with models, tutorials, examples, as well as an out-of-box Python package. We hope that this work will provide useful empirical evidence and offer insights for future research in this novel and promising direction.

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Black Americans in the United States are disproportionately exposed to childhood adversity compared with White Americans. Such disparities may contribute to race-related differences in brain structures involved in regulating the emotional response to stress, such as the amygdala, hippocampus, and prefrontal cortex (PFC). The authors investigated neuroanatomical consequences of racial disparities in adversity.

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The Physical Activity Guidelines Advisory Committee Scientific Report identified important research gaps to inform future guidance for adolescents, including limited evidence on the importance of sedentary behaviors (screen time) and their interactions with physical activity for adolescent health outcomes, including overweight and obesity.

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Most epidemiologic studies examine the brain as an outcome in relation to adiposity (ie, the brain-as-outcome perspective), but it is also a potential risk factor associated with adiposity accumulation over time (ie, the brain-as-risk factor perspective). The bidirectionality hypothesis has not been fully explored in adolescent samples previously.

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The neurobiological underpinnings underlying sex differences in cognition during adolescence are largely unknown.

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Studies demonstrate that individuals with diagnoses for Major Depressive Disorder (MDD), Post-traumatic Stress Disorder (PTSD), and Schizophrenia (SCZ) may exhibit smaller hippocampal gray matter relative to otherwise healthy controls, although the effect sizes vary in each disorder. Existing work suggests that hippocampal abnormalities in each disorder may be attributable to genetic liability and/or environmental variables. The following study uses baseline data from the Adolescent Brain and Cognitive Development[Formula: see text] Study (ABCD Study[Formula: see text]) to address three open questions regarding the relationship between genetic risk for each disorder and hippocampal volume reductions: (a) whether polygenic risk scores (PGRS) for MDD, PTSD, and SCZ are related to hippocampal volume; (b) whether PGRS for MDD, PTSD, and SCZ are differentially related to specific hippocampal subregions along the longitudinal axis; and (c) whether the association between PGRS for MDD, PTSD, and SCZ and hippocampal volume is moderated by sex and/or environmental adversity. In short, we did not find associations between PGRS for MDD, PTSD, and SCZ to be significantly related to any hippocampal subregion volumes. Furthermore, neither sex nor enviornmental adversity significantly moderated these associations. Our study provides an important null finding on the relationship genetic risk for MDD, PTSD, and SCZ to measures of hippocampal volume.

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Neuroimaging studies showing the adverse effects of air pollution on neurodevelopment have largely focused on smaller samples from limited geographical locations and have implemented univariant approaches to assess exposure and brain macrostructure. Herein, we implement restriction spectrum imaging and a multivariate approach to examine how one year of annual exposure to daily fine particulate matter (PM), daily nitrogen dioxide (NO), and 8-h maximum ozone (O) at ages 9-10 years relates to subcortical gray matter microarchitecture in a geographically diverse subsample of children from the Adolescent Brain Cognitive Development (ABCD) Study. Adjusting for confounders, we identified a latent variable representing 66% of the variance between one year of air pollution and subcortical gray matter microarchitecture. PM was related to greater isotropic intracellular diffusion in the thalamus, brainstem, and accumbens, which related to cognition and internalizing symptoms. These findings may be indicative of previously identified air pollution-related risk for neuroinflammation and early neurodegenerative pathologies.

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To investigate the strength and reproducibility of the teratogenic impact of prenatal tobacco exposure (PTE) on child physical health and neurodevelopmental outcomes, in the context of intersecting sociodemographic and other prenatal correlates, and test if early postnatal health mediates PTE associations with childhood outcomes.

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Neighborhood threats can increase risk for externalizing problems, including aggressive, oppositional, and delinquent behavior. Yet, there is substantial variability in how youth respond to neighborhood threats. Difficulty with cognitive functioning, particularly in the face of emotional information, may increase risk for externalizing in youth who live in neighborhoods with higher threats. However, little research has examined: 1) associations between neighborhood threats and executive networks involved in cognitive functioning or 2) whether executive networks may amplify risk for externalizing in the context of neighborhood threats. Further, most research on neighborhood threats does not account for youth’s experiences in other social contexts. Utilizing the large, sociodemographically diverse cohort of youth (ages 9-10) included in the Adolescent Brain Cognitive Development Study, we identified four latent profiles of youth based on threats in their neighborhoods, families, and schools: low threat in all contexts, elevated family threat, elevated neighborhood threat, and elevated threat in all contexts. The elevated neighborhood threat and elevated all threat profiles showed lower behavioral performance on an emotional n-back task relative to low threat and elevated family threat profiles. Lower behavioral performance in the elevated neighborhood threat profile specifically was paralleled by lower executive network activity during a cognitive challenge. Moreover, among youth with lower executive network activity, higher probability of membership in the elevated neighborhood threat profile was associated with higher externalizing. Together, these results provide evidence that interactions between threats that are concentrated in youth’s neighborhoods and attenuated executive network function may contribute to risk for externalizing problems.

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Diffusion MRI tractography is an advanced imaging technique that enables in vivo mapping of the brain’s white matter connections. White matter parcellation classifies tractography streamlines into clusters or anatomically meaningful tracts. It enables quantification and visualization of whole-brain tractography. Currently, most parcellation methods focus on the deep white matter (DWM), whereas fewer methods address the superficial white matter (SWM) due to its complexity. We propose a novel two-stage deep-learning-based framework, Superficial White Matter Analysis (SupWMA), that performs an efficient and consistent parcellation of 198 SWM clusters from whole-brain tractography. A point-cloud-based network is adapted to our SWM parcellation task, and supervised contrastive learning enables more discriminative representations between plausible streamlines and outliers for SWM. We train our model on a large-scale tractography dataset including streamline samples from labeled long- and medium-range (over 40 mm) SWM clusters and anatomically implausible streamline samples, and we perform testing on six independently acquired datasets of different ages and health conditions (including neonates and patients with space-occupying brain tumors). Compared to several state-of-the-art methods, SupWMA obtains highly consistent and accurate SWM parcellation results on all datasets, showing good generalization across the lifespan in health and disease. In addition, the computational speed of SupWMA is much faster than other methods.

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Caffeine is the most consumed drug in the world, and it is commonly used by children. Despite being considered relatively safe, caffeine can have marked effects on sleep. Studies in adults suggest that genetic variants in the adenosine A2A receptor (, rs5751876) and cytochrome P450 1A (, rs2472297, rs762551) loci are correlated with caffeine-associated sleep disturbances and caffeine intake (dose), but these associations have not been assessed in children. We examined the independent and interaction effects of daily caffeine dose and candidate variants in and on the sleep quality and duration in 6112 children aged 9-10 years who used caffeine and were enrolled in the Adolescent Brain Cognitive Development (ABCD) study. We found that children with higher daily caffeine doses had lower odds of reporting > 9 h of sleep per night (OR = 0.81, 95% CI = 0.74-0.88, and = 1.2 × 10). For every mg/kg/day of caffeine consumed, there was a 19% (95% CI = 12-26%) decrease in the odds of children reporting > 9 h of sleep. However, neither nor genetic variants were associated with sleep quality, duration, or caffeine dose. Likewise, genotype by caffeine dose interactions were not detected. Our findings suggest that a daily caffeine dose has a clear negative correlation with sleep duration in children, but this association is not moderated by the or genetic variation.

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Mild traumatic brain injuries (mTBI) are considered self-limiting and full recovery is expected. Recent studies identify deficits persisting years after mTBI. Large-scale prospective data permit testing the hypothesis that mTBI increases incidence of affective and behavioral symptoms after new, past , or new and past mTBI.

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Alcohol expectancies (AEs) are associated with likelihood of alcohol initiation and subsequent alcohol use disorders. It is unclear whether genetic predisposition to alcohol use and/or related traits contributes to shaping how one expects to feel when drinking alcohol. We used the Adolescent Brain Cognitive Development study to examine associations between genetic propensities (i.e., polygenic risk for problematic alcohol use, depression, risk-taking), sociodemographic factors (i.e., parent income), and the immediate social environment (i.e., peer use and disapproval toward alcohol) and positive and negative AEs in alcohol-naïve children (max analytic N = 5,352). Mixed-effect regression models showed that age, parental education, importance of the child’s religious beliefs, adverse childhood experiences, and peer disapproval of alcohol use were associated with positive and/or negative AEs, to varying degrees. Overall, our results suggest several familial and psychosocial predictors of AEs but little evidence of contributions from polygenic liability to problematic alcohol use or related phenotypes.

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The prefrontal cortex and the frontoparietal network are associated with a variety of regulatory behaviors. Functional connections between these brain regions and the amygdala are implicated in risk for anxiety disorders. The prefrontal cortex and frontoparietal network are also linked to executive functioning, or behaviors that help orient action towards higher order goals. Where much research has been focused on deleterious effects of under-controlled behavior, a body of work suggests that over-controlled behavior may also pose a risk for internalizing problems. Indeed, while work suggests that high levels of attention shifting may still be protective against internalizing problems, there is evidence that high levels of inhibitory control may be a risk factor for socioemotional difficulties. In the ABCD sample, which offers large sample sizes as well as sociodemographic diversity, we test the interaction between frontoparietal network-amygdala resting state functional connectivity and executive functioning behaviors on longitudinal changes in internalizing symptoms from approximately 10 to 12 years of age. We found that higher proficiency in attention shifting indeed predicts fewer internalizing behaviors over time. In addition, higher proficiency in inhibitory control predicts fewer internalizing symptoms over time, but only for children showing resting state connectivity moderately above the sample average between the frontoparietal network and amygdala. This finding supports the idea that top-down control may not be adaptive for all children, and relations between executive functioning and anxiety risk may vary as a function of trait-level regulation.

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Early life adversity (ELA) tends to accelerate neurobiological ageing, which, in turn, is thought to heighten vulnerability to both major depressive disorder (MDD) and Alzheimer’s disease (AD). The two conditions are putatively related, with MDD representing either a risk factor or early symptom of AD. Given the substantial environmental susceptibility of both disorders, timely identification of their neurocognitive markers could facilitate interventions to prevent clinical onset. To this end, we analysed multimodal data from the Adolescent Brain and Cognitive Development study (ages 9-10 years). To disentangle genetic from correlated genetic-environmental influences, while also probing gene-adversity interactions, we compared adoptees, a group generally exposed to substantial ELA, with children raised by their biological families via genetic risk scores (GRS) from genome-wide association studies. AD and MDD GRSs predicted overlapping and widespread neurodevelopmental alterations associated with superior fluid cognition. Specifically, among adoptees only, greater AD GRS were related to accelerated structural maturation (i.e., cortical thinning) and higher MDD GRS were linked to delayed functional neurodevelopment, as reflected in compensatory brain activation on an inhibitory control task. Our study identifies compensatory mechanisms linked to MDD risk and highlights the potential cognitive benefits of accelerated maturation linked to AD vulnerability in late childhood.

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Executive Functions (EF) is an umbrella term for a set of mental processes geared towards goal-directed behavior supporting academic skills such as reading abilities. One of the brain’s functional networks implicated in EF is the Default Mode Network (DMN). The current study uses measures of inhibitory control, a main sub-function of EF, to create cognitive and neurobiological “inhibitory control profiles” and relate them to reading abilities in a large sample (N = 5055) of adolescents aged 9-10 from the Adolescent Brain Cognitive Development (ABCD) study. Using a Latent Profile Analysis (LPA) approach, data related to inhibitory control was divided into four inhibition classes. For each class, functional connectivity within the DMN was calculated from resting-state data, using a non-parametric algorithm for detecting group similarities. These inhibitory control profiles were then related to reading abilities. The four inhibitory control groups showed significantly different reading abilities, with neurobiologically different DMN segregation profiles for each class versus controls. The current study demonstrates that a community sample of children is not entirely homogeneous and is composed of different subgroups that can be differentiated both behaviorally/cognitively and neurobiologically, by focusing on inhibitory control and the DMN. Educational implications relating these results to reading abilities are noted.

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To determine how environmental factors are associated with physical health conditions in 9- to 10-year-old participants in the Adolescent Brain Cognitive Development (ABCD) Study, and how they are moderated by family-level socioeconomic status (SES).

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Population-based neuroimaging studies that feature complex sampling designs enable researchers to generalize their results more widely. However, several theoretical and analytical questions pose challenges to researchers interested in these data. The following is a resource for researchers interested in using population-based neuroimaging data. We provide an overview of sampling designs and describe the differences between traditional model-based analyses and survey-oriented design-based analyses. To elucidate key concepts, we leverage data from the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), a population-based sample of 11,878 9-10-year-olds in the United States. Analyses revealed modest sociodemographic discrepancies between the target population of 9-10-year-olds in the U.S. and both the recruited ABCD sample and the analytic sample with usable structural and functional imaging data. In evaluating the associations between socioeconomic resources (i.e., constructs that are tightly linked to recruitment biases) and several metrics of brain development, we show that model-based approaches over-estimated the associations of household income and under-estimated the associations of caregiver education with total cortical volume and surface area. Comparable results were found in models predicting neural function during two fMRI task paradigms. We conclude with recommendations for ABCD Study® users and users of population-based neuroimaging cohorts more broadly.

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Attention deficit hyperactivity disorder (ADHD) is associated with reduction of cortical and subcortical gray matter volumes (GMVs). The kinectin 1 gene (KTN1) has recently been reported to significantly regulate GMVs and ADHD risk. In this study, we aimed to identify sex-specific, replicable risk KTN1 alleles for ADHD and to explore their regulatory effects on mRNA expression and cortical and subcortical GMVs. We examined a total of 1020 KTN1 SNPs in one discovery sample (ABCD cohort: 5573 males and 5082 females) and three independent replication European samples (Samples #1 and #2 each with 802/122 and 472/141 male/female offspring with ADHD; and Sample #3 with 14,154/4945 ADHD and 17,948/16,246 healthy males/females) to identify replicable associations within each sex. We examined the regulatory effects of ADHD-risk alleles on the KTN1 mRNA expression in two European brain cohorts (n = 348), total intracranial volume (TIV) in 46 European cohorts (n = 18,713) and the ABCD cohort, as well as the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258) and of 118 cortical and subcortical regions in the ABCD cohort. We found that four KTN1 variants significantly regulated the risk of ADHD with the same direction of effect in males across discovery and replication samples (0.003 ≤ p ≤ 0.041), but none in females. All four ADHD-risk alleles significantly decreased KTN1 mRNA expression in all brain regions examined (1.2 × 10 ≤ p ≤ 0.039). The ADHD-risk alleles significantly increased basal ganglia (2.8 × 10 ≤ p ≤ 0.040) and hippocampus (p = 0.010) GMVs but reduced amygdala GMV (p = 0.030) and TIV (0.010 < p ≤ 0.013). The ADHD-risk alleles also significantly reduced some cortical (right superior temporal pole, right rectus) and cerebellar but increased other cortical (0.007 ≤ p ≤ 0.050) GMVs. To conclude, we identified a set of replicable and functional risk KTN1 alleles for ADHD, specifically in males. KTN1 may play a critical role in the pathogenesis of ADHD, and the reduction of specific cortical and subcortical, including amygdalar but not basal ganglia or hippocampal, GMVs may serve as a neural marker of the genetic effects.

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The childhood-to-adolescence transition is a notable period of change including pubertal development, neurodevelopment, and psychopathology onset, that occurs in divergent patterns between sexes. This study examined the effects of sex and puberty on cortical thickness (CT) in children and explored whether CT changes over time related to emergence of psychopathology in early adolescence.

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Obesity has a strong genetic component, with up to 20% of variance in body mass index (BMI) being accounted for by common polygenic variation. Most genetic polymorphisms associated with BMI are related to genes expressed in the central nervous system. At the same time, higher BMI is associated with neurocognitive changes. However, the direct link between genetics of obesity and neurobehavioral mechanisms related to weight gain is missing. Here, we use a large sample of participants (n > 4000) from the Adolescent Brain Cognitive Development cohort to investigate how genetic risk for obesity, expressed as polygenic risk score for BMI (BMI-PRS), is related to brain and behavioral measures in adolescents. In a series of analyses, we show that BMI-PRS is related to lower cortical volume and thickness in the frontal and temporal areas, relative to age-expected values. Relatedly, using structural equation modeling, we find that lower overall cortical volume is associated with higher impulsivity, which in turn is related to an increase in BMI 1 year later. In sum, our study shows that obesity might partially stem from genetic risk as expressed in brain changes in the frontal and temporal brain areas, and changes in impulsivity.

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Accurate drug use identification through subjective self-report and toxicological biosample (hair) analysis are necessary to determine substance use sequelae in youth. Yet consistency between self-reported substance use and robust, toxicological analysis in a large sample of youth is understudied. We aim to assess concordance between self-reported substance use and hair toxicological analysis in community-based adolescents. Hair results by LC-MS/MS and GC-MS/MS and self-reported past-year substance use from an Adolescent Brain Cognitive Development (ABCD) Study subsample ( = 1,390; ages 9-13; 48% female) were compared. The participants were selected for hair selection through two methods: high scores on a substance risk algorithm selected 93%; 7% were low-risk, randomly selected participants. Kappa coefficients the examined concordance between self-report and hair results. 10% of youth self-reported any past-year substance use (e.g. alcohol, cannabis, nicotine, and opiates), while a mostly non-overlapping 10% had hair results indicating recent substance use (cannabis, alcohol, non-prescription amphetamines, cocaine, nicotine, opiates, and fentanyl). In randomly selected low-risk cases, 7% were confirmed positive in hair. Combining methods, 19% of the sample self-reported substance use and/or had a positive hair sample. Kappa coefficient of concordance between self-report and hair results was low (kappa = 0.07;  = .007). Hair toxicology identified substance use in high-risk and low-risk ABCD cohort subsamples. Given low concordance between hair results and self-report, reliance on either method alone would incorrectly categorize 9% as non-users. Multiple methods for characterizing substance use history in youth improves accuracy. Larger representative samples are needed to assess the prevalence of substance use in youth.

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Mood and anxiety disorders typically begin in adolescence and have overlapping clinical features but marked inter-individual variation in clinical presentation. The use of multimodal neuroimaging data may offer novel insights into the underlying brain mechanisms. We applied Heterogeneity Through Discriminative Analysis (HYDRA) to measures of regional brain morphometry, neurite density, and intracortical myelination to identify subtypes of youth, aged 9-10 years, with mood and anxiety disorders (N = 1931) compared to typically developing youth (N = 2823). We identified three subtypes that were robust to permutation testing and sample composition. Subtype 1 evidenced a pattern of imbalanced cortical-subcortical maturation compared to the typically developing group, with subcortical regions lagging behind prefrontal cortical thinning and myelination and greater cortical surface expansion globally. Subtype 2 displayed a pattern of delayed cortical maturation indicated by higher cortical thickness and lower cortical surface area expansion and myelination compared to the typically developing group. Subtype 3 showed evidence of atypical brain maturation involving globally lower cortical thickness and surface coupled with higher myelination and neural density. Subtype 1 had superior cognitive function in contrast to the other two subtypes that underperformed compared to the typically developing group. Higher levels of parental psychopathology, family conflict, and social adversity were common to all subtypes, with subtype 3 having the highest burden of adverse exposures. These analyses comprehensively characterize pre-adolescent mood and anxiety disorders, the biopsychosocial context in which they arise, and lay the foundation for the examination of the longitudinal evolution of the subtypes identified as the study sample transitions through adolescence.

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To determine the association between cyberbullying (victimization and perpetration) and sleep disturbance among a demographically diverse sample of 10-14-year-old early adolescents.

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Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent, inheritable, and heterogeneous neurodevelopmental disorder. Children with a family history of ADHD are at elevated risk of having ADHD and persisting its symptoms into adulthood. The objective of this study was to investigate the influence of having or not having positive family risk factor in the neuroanatomy of the brain in children with ADHD. Cortical thickness-, surface area-, and volume-based measures were extracted and compared in a total of 606 participants, including 132, 165, and 309 in groups of familial ADHD (ADHD-F), non-familial ADHD (ADHD-NF), and typically developed children, respectively. Compared to controls, ADHD probands showed significantly reduced gray matter surface area in the left cuneus. Among the ADHD subgroups, ADHD-F showed significantly increased gray matter volume in the right thalamus and significantly thinner cortical thickness in the right pars orbitalis. Among ADHD-F, an increased volume of the right thalamus was significantly correlated with a reduced DSM-oriented t-score for ADHD problems. The findings of this study may suggest that a positive family history of ADHD is associated with the structural abnormalities in the thalamus and inferior frontal gyrus; these anatomical abnormalities may significantly contribute to the emergence of ADHD symptoms.

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Transgender individuals are at heightened risk for self-injurious thoughts and behaviors (SITBs). Evidence suggests that middle childhood-aged transgender individuals experience elevated rates of non-suicidal self-injury (NSSI) and passive suicidal ideation (SI), compared to cisgender children. Little is known about gender identity-based disparities in SI more broadly and suicidal behavior (SB) in children aged 9 and 10. The aim of this study was to examine gender identity-based disparities in SITBs among children in middle childhood (pre-teens) in a US-based sample.

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The general psychopathology factor (p-factor) represents shared variance across mental disorders based on psychopathologic symptoms. The Adolescent Brain Cognitive Development (ABCD) Study offers an unprecedented opportunity to investigate functional networks (FNs) from functional magnetic resonance imaging (fMRI) associated with the psychopathology of an adolescent cohort (n > 10,000). However, the heterogeneities associated with the use of multiple sites and multiple scanners in the ABCD Study need to be overcome to improve the prediction of the p-factor using fMRI. We proposed a scanner-generalization neural network (SGNN) to predict the individual p-factor by systematically reducing the scanner effect for resting-state functional connectivity (RSFC). We included 6905 adolescents from 18 sites whose fMRI data were collected using either Siemens or GE scanners. The p-factor was estimated based on the Child Behavior Checklist (CBCL) scores available in the ABCD study using exploratory factor analysis. We evaluated the Pearson’s correlation coefficients (CCs) for p-factor prediction via leave-one/two-site-out cross-validation (LOSOCV/LTSOCV) and identified important FNs from the weight features (WFs) of the SGNN. The CCs were higher for the SGNN than for alternative models when using both LOSOCV (0.1631 ± 0.0673 for the SGNN vs. 0.1497 ± 0.0710 for kernel ridge regression [KRR]; p < 0.05 from a two-tailed paired t-test) and LTSOCV (0.1469 ± 0.0381 for the SGNN vs. 0.1394 ± 0.0359 for KRR; p = 0.01). It was found that (a) the default-mode and dorsal attention FNs were important for p-factor prediction, and (b) the intra-visual FN was important for scanner generalization. We demonstrated the efficacy of our novel SGNN model for p-factor prediction while simultaneously eliminating scanner-related confounding effects for RSFC.

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The Adolescent Brain Cognitive Development (ABCD) Study is a longitudinal neuroimaging study of unprecedented scale that is in the process of following over 11,000 youth from middle childhood though age 20. However, a design feature of the study’s stop-signal task violates “context independence”, an assumption critical to current non-parametric methods for estimating stop-signal reaction time (SSRT), a key measure of inhibitory ability in the study. This has led some experts to call for the task to be changed and for previously collected data to be used with caution. We present a cognitive process modeling framework, the RDEX-ABCD model, that provides a parsimonious explanation for the impact of this design feature on “go” stimulus processing and successfully accounts for key behavioral trends in the ABCD data. Simulation studies using this model suggest that failing to account for the context independence violations in the ABCD design can lead to erroneous inferences in several realistic scenarios. However, we demonstrate that RDEX-ABCD effectively addresses these violations and can be used to accurately measure SSRT along with an array of additional mechanistic parameters of interest (e.g., attention to the stop signal, cognitive efficiency), advancing investigators’ ability to draw valid and nuanced inferences from ABCD data. AVAILABILITY OF DATA AND MATERIALS: Data from the ABCD Study are available through the NIH Data Archive (NDA): nda.nih.gov/abcd. Code for all analyses featured in this study is openly available on the Open Science Framework (OSF): osf.io/2h8a7/.

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Sustained attention (SA) and working memory (WM) are critical processes, but the brain networks supporting these abilities in development are unknown. We characterized the functional brain architecture of SA and WM in 9- to 11-year-old children and adults. First, we found that adult network predictors of SA generalized to predict individual differences and fluctuations in SA in youth. A WM model predicted WM performance both across and within children-and captured individual differences in later recognition memory-but underperformed in youth relative to adults. We next characterized functional connections differentially related to SA and WM in youth compared to adults. Results revealed 2 network configurations: a dominant architecture predicting performance in both age groups and a secondary architecture, more prominent for WM than SA, predicting performance in each age group differently. Thus, functional connectivity (FC) predicts SA and WM in youth, with networks predicting WM performance differing more between youths and adults than those predicting SA.

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The stop-signal task (SST) is one of the most common fMRI tasks of response inhibition, and its performance measure, the stop-signal reaction-time (SSRT), is broadly used as a measure of cognitive control processes. The neurobiology underlying individual or clinical differences in response inhibition remain unclear, consistent with the general pattern of quite modest brain-behavior associations that have been recently reported in well-powered large-sample studies. Here, we investigated the potential of multivariate, machine learning (ML) methods to improve the estimation of individual differences in SSRT with multimodal structural and functional region of interest-level neuroimaging data from 9- to 11-year-olds children in the ABCD Study. Six ML algorithms were assessed across modalities and fMRI tasks. We verified that SST activation performed best in predicting SSRT among multiple modalities including morphological MRI (cortical surface area/thickness), diffusion tensor imaging, and fMRI task activations, and then showed that SST activation explained 12% of the variance in SSRT using cross-validation and out-of-sample lockbox data sets (n = 7298). Brain regions that were more active during the task and that showed more interindividual variation in activation were better at capturing individual differences in performance on the task, but this was only true for activations when successfully inhibiting. Cortical regions outperformed subcortical areas in explaining individual differences but the two hemispheres performed equally well. These results demonstrate that the detection of reproducible links between brain function and performance can be improved with multivariate approaches and give insight into a number of brain systems contributing to individual differences in this fundamental cognitive control process.

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This study examined the independent and interactive effects of genetic risk for alcohol use disorder (AUD), parenting behaviors, and family environment on childhood impulsivity. Data were drawn from White ( = 5,991), Black/African American ( = 1,693), and Hispanic/Latino ( = 2,118) youth who completed the baseline assessment (age 9-10) and had genotypic data available from the Adolescent Brain Cognitive Development Study. Participants completed questionnaires and provided saliva or blood samples for genotyping. Results indicated no significant main effects of AUD genome-wide polygenic scores (AUD-PRS) on childhood impulsivity as measured by the UPPS-P scale across racial/ethnic groups. In general, parental monitoring and parental acceptance were associated with lower impulsivity; family conflict was associated with higher impulsivity. There was an interaction effect between AUD-PRS and family conflict, such that family conflict exacerbated the association between AUD-PRS and positive urgency, only among Black/African American youth. This was the only significant interaction effect detected from a total of 45 tests (five impulsivity dimensions, three subsamples, and three family factors), and thus may be a false positive and needs to be replicated. These findings highlight the important role of parenting behaviors and family conflict in relation to impulsivity among children.

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Adherence to 24-hour movement guidelines of ≥60 minutes of physical activity, ≤2 hours of screen time, and 9-11 hours of sleep has been shown to benefit cognitive, physical, and psychosocial health in children and young adolescents aged 5-13 years. However, these findings have mostly been based on cross-sectional studies or relatively small samples and the associations between adherence to guidelines and brain structure remain to be evaluated.

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Environmental resources are related to childhood obesity risk and altered brain development, but whether these relationships are stable or if they have sustained impact is unknown. Here, we utilized a multidimensional index of childhood neighborhood conditions to compare the influence of various social and environmental disparities (SED) on body mass index (BMI)-brain relationships over a 2-year period in early adolescence.

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The use of predefined parcellations on surface-based representations of the brain as a method for data reduction is common across neuroimaging studies. In particular, prediction-based studies typically employ parcellation-driven summaries of brain measures as input to predictive algorithms, but the choice of parcellation and its influence on performance is often ignored. Here we employed preprocessed structural magnetic resonance imaging (sMRI) data from the Adolescent Brain Cognitive Development Study® to examine the relationship between 220 parcellations and out-of-sample predictive performance across 45 phenotypic measures in a large sample of 9- to 10-year-old children (N = 9,432). Choice of machine learning (ML) pipeline and use of alternative multiple parcellation-based strategies were also assessed. Relative parcellation performance was dependent on the spatial resolution of the parcellation, with larger number of parcels (up to ~4,000) outperforming coarser parcellations, according to a power-law scaling of between 1/4 and 1/3. Performance was further influenced by the type of parcellation, ML pipeline, and general strategy, with existing literature-based parcellations, a support vector-based pipeline, and ensembling across multiple parcellations, respectively, as the highest performing. These findings highlight the choice of parcellation as an important influence on downstream predictive performance, showing in some cases that switching to a higher resolution parcellation can yield a relatively large boost to performance.

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While childhood attention-deficit/hyperactivity disorder (ADHD) is more prevalent in males than females, genetic contributors to this effect have not been established. Here, we explore sex differences in the contribution of common and/or rare genetic variants to ADHD. Participants were from the Adolescent Brain and Cognitive Development study (N = 1253 youth meeting DSM-5 criteria for ADHD [mean age = 11.46 years [SD = 0.87]; 31% female] and 5577 unaffected individuals [mean age = 11.42 years [SD = 0.89]; 50% female], overall 66% White, non-Hispanic (WNH), 19% Black/African American, and 15% other races. Logistic regression tested for interactions between sex (defined genotypically) and both rare copy number variants (CNV) and polygenic (common variant) risk in association with ADHD. There was a significant interaction between sex and the presence of a CNV deletion larger than 200 kb, both in the entire cohort (β = -0.74, CI = [-1.27 to -0.20], FDR-corrected p = 0.048) and, at nominal significance levels in the WNH ancestry subcohort (β = -0.86, CI = [-1.51 to -0.20], p = 0.010). Additionally, the number of deleted genes interacted with sex in association with ADHD (whole cohort. β = -0.13, CI = [-0.23 to -0.029], FDR-corrected p = 0.048; WNH. β = -0.17, CI = [-0.29 to -0.050], FDR-corrected p = 0.044) as did the total length of CNV deletions (whole cohort. β = -0.12, CI = [-0.19 to -0.044], FDR-corrected p = 0.028; WNH. β = -0.17, CI = [-0.28 to -0.061], FDR-corrected p = 0.034). This sex effect was driven by increased odds of childhood ADHD for females but not males in the presence of CNV deletions. No similar sex effect was found for CNV duplications or polygenic risk scores. The association between CNV deletions and ADHD was partially mediated by measures of cognitive flexibility. In summary, CNV deletions were associated with increased odds for childhood ADHD in females, but not males.

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The aim of this study is to determine the prospective associations between baseline screen time and obsessive-compulsive disorder (OCD) at 2-year follow-up in a national (United States) cohort of 9- to 10-year-old children.

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Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene-environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene-environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.

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It is important to develop statistical techniques to analyze high-dimensional data in the presence of both complex dependence and possible heavy tails and outliers in real-world applications such as imaging data analyses. We propose a new robust high-dimensional regression with coefficient thresholding, in which an efficient nonconvex estimation procedure is proposed through a thresholding function and the robust Huber loss. The proposed regularization method accounts for complex dependence structures in predictors and is robust against heavy tails and outliers in outcomes. Theoretically, we rigorously analyze the landscape of the population and empirical risk functions for the proposed method. The fine landscape enables us to establish both statistical consistency and computational convergence under the high-dimensional setting. We also present an extension to incorporate spatial information into the proposed method. Finite-sample properties of the proposed methods are examined by extensive simulation studies. An application concerns a scalar-on-image regression analysis for an association of psychiatric disorder measured by the general factor of psychopathology with features extracted from the task functional MRI data in the Adolescent Brain Cognitive Development (ABCD) study.

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Childhood internalizing and externalizing problems frequently co-occur. Many studies report neural correlates of either internalizing or externalizing problems, but few account for their co-occurrence. We aimed to assess specific cortical substrates of these psychiatric problems.

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Preadolescence is a critical period characterized by dramatic morphological changes and accelerated cortico-subcortical development. Moreover, the coordinated development of cortical and subcortical regions underlies the emerging cognitive functions during this period. Deviations in this maturational coordination may underlie various psychiatric disorders that begin during preadolescence, but to date these deviations remain largely uncharted. We constructed a comprehensive whole-brain morphometric similarity network (MSN) from 17 neuroimaging modalities in a large preadolescence sample (N = 8908) from Adolescent Brain Cognitive Development (ABCD) study and investigated its association with 10 cognitive subscales and 27 psychiatric subscales or diagnoses. Based on the MSNs, each brain was clustered into five modules with distinct cytoarchitecture and evolutionary relevance. While morphometric correlation was positive within modules, it was negative between modules, especially between isocortical and paralimbic/subcortical modules; this developmental dissimilarity was genetically linked to synapse and neurogenesis. The cortico-subcortical dissimilarity becomes more pronounced longitudinally in healthy children, reflecting developmental differentiation of segregated cytoarchitectonic areas. Higher cortico-subcortical dissimilarity (between the isocortical and paralimbic/subcortical modules) were related to better cognitive performance. In comparison, children with poor modular differentiation between cortex and subcortex displayed higher burden of externalizing and internalizing symptoms. These results highlighted cortical-subcortical morphometric dissimilarity as a dynamic maturational marker of cognitive and psychiatric status during the preadolescent stage and provided insights into brain development.

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We evaluated whether relationships between area deprivation (ADI), body mass index (BMI) and brain structure (e.g., cortical thickness, subcortical volume) during preadolescence supported the immunologic model of self-regulation failure (NI) and/or neuronal stress (NS) theories of overeating. The NI theory proposes that ADI causes structural alteration in the brain due to the neuroinflammatory effects of overeating unhealthy foods. The NS theory proposes that ADI-related stress negatively impacts brain structure, which causes stress-related overeating and subsequent obesity.

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