| A mega-analytic study of white matter differences in attention deficit hyperactivity disorder seen across multiple cohorts | Context: Previous research has explored the relationship between attention-deficit/hyperactivity disorder (ADHD) and variations in the brain's white matter tract connections, as observed through structural differences. However, these investigations have produced inconsistent outcomes, which may be attributed to the relatively small participant groups in these studies. Consequently, we embarked on a comprehensive analysis involving over 6000 participants from five distinct cohorts. We aimed to examine white matter microstructure using diffusion tensor imaging in vivo.
Approach: Employing a mega-analysis approach, we employed linear mixed models to investigate potential links between ADHD traits and diagnosis with the fractional anisotropy of 42 white matter tracts. We also contrasted these associations against measurements of mood, anxiety, and other outward behavioral issues.
Findings: Our study encompassed a total of 6993 participants, aged 6 to 18 years, with a mean age of 10.62 years (standard deviation 1.99). This group included 3368 girls and 3625 boys from diverse racial and ethnic backgrounds, including 764 African American individuals, 4146 non-Hispanic White individuals, and 2083 from other racial/ethnic groups. Among these participants, data was available for ADHD and other emotional/behavioral symptoms (N = 6933). Additionally, clinical information was adequate for the diagnosis of ADHD (n = 951) or the absence of such a diagnosis (n = 4884). Our analysis revealed that both ADHD diagnosis and traits were linked to decreased fractional anisotropy in the inferior longitudinal and left uncinate fasciculi (at a statistically adjusted false discovery rate of p < .05). Notably, the observed effect sizes were modest (the most robust association with ADHD traits had a partial r effect size of -0.14, while the most significant difference between cases and controls had a d effect size of -0.3). Conversely, no similar microstructural irregularities were observed in relation to anxiety, mood, or externalizing issues. These findings persisted even when ADHD cases and control subjects were matched based on their in-scanner motion.
Conclusion: Although the microstructural distinctions associated with ADHD were evident across the various cohorts, their effects were minor. This underscores the limited clinical usefulness of relying solely on this imaging technique in isolation. | 10073/12537 | Secondary Analysis | Shared |
| Environmental Risk Factors and Psychotic-like Symptoms in Children Aged 9-11 | Objective: Research implicates environmental risk factors, including correlates of urbanicity, deprivation, and environmental toxins, in psychotic-like experiences (PLEs). The current study examined associations between several types of environmental risk factors and PLEs in school-age children, whether these associations were specific to PLEs or generalized to other psychopathology, and examined possible neural mechanisms for significant associations.
Method: The current study used data from 10,328 9-11-year-olds from the Adolescent Brain Cognitive Development (ABCD) study. Hierarchical linear models examined associations between PLEs and geocoded environmental risk factors, and whether associations generalized to internalizing/externalizing symptoms. Mediation models examined whether structural MRI abnormalities (e.g., intracranial volume) mediated associations between PLEs and environmental risk factors.
Results: The results found specific types of environmental risk factors, namely measures of urbanicity (i.e., drug offense exposure, less perception of neighborhood safety), deprivation (including overall deprivation, rate of poverty, fewer years at residence), and lead exposure risk, were associated with PLEs. These associations showed evidence of stronger associations with PLEs than internalizing/externalizing symptoms (especially overall deprivation, poverty, drug offense exposure, and lead exposure risk). There was evidence that brain volume mediated between 11-25% of the associations between poverty, perception of neighborhood safety, and lead exposure risk with PLEs.
Conclusions: These results are the first to find support for neural measures partially mediating the association between PLEs and environmental exposures. Furthermore, the current study replicated and extended recent findings of the association between PLEs and environmental exposures, finding evidence for specific associations with correlates of urbanicity, deprivation, and lead exposure risk.
| 9701/11898 | Secondary Analysis | Shared |
| Longitudinally stable, brain-based predictive models mediate the relationships between childhood cognition and socio-demographic, psychological and genetic factors. | Cognitive abilities are one of the major transdiagnostic domains in the National Institute of Mental Health's Research Domain Criteria (RDoC). Following RDoC's integrative approach, we aimed to develop brain-based predictive models for cognitive abilities that (a) are developmentally stable over years during adolescence and (b) account for the relationships between cognitive abilities and socio-demographic, psychological and genetic factors. For this, we leveraged the unique power of the large-scale, longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study (n ~ 11 k) and combined MRI data across modalities (task-fMRI from three tasks: resting-state fMRI, structural MRI and DTI) using machine-learning. Our brain-based, predictive models for cognitive abilities were stable across 2 years during young adolescence and generalisable to different sites, partially predicting childhood cognition at around 20% of the variance. Moreover, our use of ‘opportunistic stacking’ allowed the model to handle missing values, reducing the exclusion from around 80% to around 5% of the data. We found fronto-parietal networks during a working-memory task to drive childhood-cognition prediction. The brain-based, predictive models significantly, albeit partially, accounted for variance in childhood cognition due to (1) key socio-demographic and psychological factors (proportion mediated = 18.65% [17.29%–20.12%]) and (2) genetic variation, as reflected by the polygenic score of cognition (proportion mediated = 15.6% [11%–20.7%]). Thus, our brain-based predictive models for cognitive abilities facilitate the development of a robust, transdiagnostic research tool for cognition at the neural level in keeping with the RDoC's integrative framework. | 9724/11878 | Secondary Analysis | Shared |
| Prevalence of anhedonia and related risk and protective factors in the general population: results from UK Biobank and ABCD study | Background
Anhedonia (defined as the capacity to experience pleasure) is present in healthy people and in mental disorders but its prevalence and predictors are largely unknown in the general population. We aimed to estimate the prevalence of anhedonia and identify risk and protective factors within two large population-based samples, UK Biobank (UKB) and the US Adolescent Brain and Cognitive Development (ABCD) study.
Methods
A total of 487,631 adults from UKB (mean age = 56.56 years, 54.39% female) and 9,829 early adolescents from ABCD (mean age = 9.9 years, 47.64% female) were included. The prevalence of anhedonia and common mental disorders were estimated at baseline in both cohorts separately. Multiple factors were assessed, including demographics, family history, early life factors, lifestyle, physical factors, mental health conditions, and family, school and social environments. We conducted bivariate analyses, multinomial logistic regression, Poisson regression and logistic regression in subsamples with complete data to identify factors associated with current or future anhedonia.
Results
In UKB, 21.47% [95% CI, 21.36-21.59%] had state anhedonia during the preceding two weeks and 36.92% [95% CI, 36.68-37.15%] endorsed lifetime severe anhedonia. Risk factors associated with state anhedonia and lifetime severe anhedonia included parental depression history, sleeplessness, poor overall health, any lifetime mental disorders, childhood trauma, and adulthood traumatic life events, whereas social support was a protective factor. In ABCD, youth report and parent report revealed a prevalence of 10.11% (95% CI, 9.44-10.82%) for state anhedonia and 8.70% (95% CI, 8.07-9.37%) for lifetime severe anhedonia. Contributing risk factors included Black and Hispanic race/ethnicity, high family conflict, any lifetime mental disorders, high school disengagement and high impact of adverse life experiences. High parent acceptance and higher parental educational degree were protective.
Conclusions
Anhedonia is common in the general population and multiple risk factors are implicated during early adolescence and rom middle to later adulthood. These risk factors are largely consistent with previous findings for diagnoses such as depression and bipolar disorder and may represent promising prevention targets for addressing anhedonia in the general population.
| 10059/11876 | Primary Analysis | Shared |
| Neuroanatomical correlates of impulsive traits in children aged 9 to 10 | Impulsivity refers to a set of traits that are generally negatively related to critical domains of adaptive functioning and are core features of numerous psychiatric disorders. The current study examined the gray and white matter correlates of five impulsive traits measured using an abbreviated version of the UPPS-P (Urgency, (lack of) Premeditation, (lack of) Perseverance, Sensation-Seeking, Positive Urgency) impulsivity scale in children aged 9 to 10 (N = 11,052) from the Adolescent Brain and Cognitive Development (ABCD) study. Linear mixed effect models and elastic net regression were used to examine features of regional gray matter and white matter tractography most associated with each UPPS-P scale; intraclass correlations were computed to examine the similarity of the neuroanatomical correlates among the scales. Positive Urgency showed the most robust association with neuroanatomy, with similar but less robust associations found for Negative Urgency. Perseverance showed little association with neuroanatomy. Premeditation and Sensation Seeking showed intermediate associations with neuroanatomy. Critical regions across measures include the dorsolateral prefrontal cortex, lateral temporal cortex, and orbitofrontal cortex; critical tracts included the superior longitudinal fasciculus and inferior fronto-occipital fasciculus. Negative Urgency and Positive Urgency showed the greatest neuroanatomical similarity. Some UPPS-P traits share neuroanatomical correlates, while others have distinct correlates or essentially no relation to neuroanatomy. Neuroanatomy tended to account for relatively little variance in UPPS-P traits (i.e., Model R2 < 1%) and effects were spread throughout the brain, highlighting the importance of well powered samples. | 9595/11051 | Secondary Analysis | Shared |
| Association of Mental Health Burden With Prenatal Cannabis Exposure From Childhood to Early Adolescence: Longitudinal Findings From the Adolescent Brain Cognitive Development (ABCD) Study | Dramatic increases in cannabis use during pregnancy are alarming because of evidence that prenatal exposure may be associated with a host of adverse outcomes.1 We previously found that prenatal cannabis exposure (PCE) following maternal knowledge of pregnancy is associated with increased psychopathology during middle childhood using baseline data from the Adolescent Brain Cognitive Development (ABCD) study.2 Here, leveraging longitudinal ABCD study data (data release 4.0), we examined whether associations with psychopathology persist into early adolescence. | 9043/10640 | Secondary Analysis | Shared |
| Effect of exposure to maternal diabetes during pregnancy on offspring’s brain cortical thickness and neurocognitive functioning | OBJECTIVE: Maternal diabetes may affect the developing brain of the fetus, which may adversely affect the neurocognitive functioning (NCF) of diabetes-exposed children. We examined the effect of prenatal exposure to maternal diabetes (DP) on brain structure and neurocognition in preadolescent children, ages 9-10.
RESEARCH DESIGN AND METHODS: This secondary data analysis study used cross-sectional structural neuroimaging and NCF data from the Adolescent Brain and Cognitive Development (ABCD) study (N=9,963). Differences in brain cortical thickness (CTh) and five cognitive abilities (executive function, working and episodic memory, processing speed, and language abilities) between diabetes-exposed and unexposed children were examined. Generalized linear models were used to adjust for the effect of confounding variables. Indirect effect of CTh into the relationship between maternal DP and NCF were also examined.
RESULTS: The average age of the children was 9.9 years (SD 7.5); half of them were male and non-Hispanic White. Diabetes-exposed children (n=714) had lower CTh of the whole-brain (2.744mm VS 2.756mm; p 0.008) and lower scores in processing speed task (85.97 VS 87.28; p=0.021 compared to unexposed children (n=9249) after adjusting for demographic and other confounding variables. Diabetes-exposed children also had lower score in fluid intelligence [β (95%CI): -0.837 (-1.604, -0.171)]) and total cognition [β (95%CI): -0.728 (-1.338,-0.119)]. CTh partially mediated [Direct effect=β (95%CI): -3.239 (-5.834, -0.644); indirect effect=β (95%CI): -3.239 (-5.834, -0.644)] the effect of maternal DP on offspring’s processing speed.
CONCLUSION: Diabetes-exposed children have reduced CTh and NCF during preadolescence age, which may have implications for psychomotor development during later life. Prospective studies are needed to confirm our findings | 8372/10218 | Secondary Analysis | Shared |
| Effect of maternal hypertensive disorder on their children’s neurocognitive functioning | Objective: The aim of the study was to examine the effect of prenatal exposure to maternal HDP on brain structure and NCF in singleton children aged between 9-10 years the baseline wave of the Adolescent Brain and Cognitive Development (ABCD) Study.
Methods: The ABCD Study® interviewed each child (and their parents), measured NCF, and performed neuroimaging. Exposure to maternal high blood pressure (HBP) and preeclampsia or eclampsia (PE/EL) were extracted from the developmental history questionnaire. Differences in cortical thickness (CTh) and five cognitive abilities (executive function, working and episodic memory, processing speed, and language abilities) between exposed and unexposed children were examined using generalized linear models. The mediating effects of CTh, birthweight, and BMI on the relationship between maternal HDP on NCF were also examined.
Result: A total of 584-children exposed to HBP, 387-children exposed to PE/EL, and 5,877 unexposed children were included in the analysis. Neither CTh nor NCF differed between the exposed and unexposed children with or without adjusting for the confounders including the child’s age, sex, race, education, and birth histories. The whole-brain CTh did not mediate any of the relationships between HDP and NCF. However, the relationship between HDP and most of the NCF was mediated by birthweight and BMI.
Conclusions: Our results do not support maternal HDP, in comparison to other perinatal risk factors, as a direct risk factor for later-life cognitive functions. Prospective longitudinal studies, following up from infancy, are needed to further delineate the effect of HDP on children’s cognitive abilities. | 8619/10183 | Secondary Analysis | Shared |
| Polygenic risk scores for alcohol involvement relate to brain structure in substance‐naïve children: results from the ABCD Study | Brain imaging-derived structural correlates of alcohol involvement have largely been speculated to arise as a consequence of alcohol exposure. However, they may also reflect predispositional risk. In substance naïve children of European ancestry who completed the baseline session of the Adolescent Brain Cognitive Development (ABCD) Study (n = 3013), mixed-effects models estimated whether polygenic risk scores (PRS) for problematic alcohol use (PAU-PRS) and drinks per week (DPW-PRS) are associated with magnetic resonance imaging-derived brain structure phenotypes (i.e., total and regional: cortical thickness, surface area and volume; subcortical volume; white matter volume, fractional anisotropy, mean diffusivity). Follow-up analyses evaluated whether any identified regions were also associated with polygenic risk among substance naïve children of African ancestry (n = 898). After adjustment for multiple testing correction, polygenic risk for PAU was associated with lower volume of the left frontal pole and greater cortical thickness of the right supramarginal gyrus (|βs| > 0.009; ps < 0.001; psfdr < 0.046; r2s < 0.004). PAU PRS and DPW PRS showed nominally significant associations with a host of other regional brain structure phenotypes (e.g., insula surface area and volume). None of these regions showed any, even nominal association among children of African ancestry. Genomic liability to alcohol involvement may manifest as variability in brain structure during middle childhood prior to alcohol use initiation. Broadly, alcohol-related variability in brain morphometry may partially reflect predisposing genomic influence. Larger discovery genome-wide association studies and target samples of diverse ancestries are needed to determine whether observed associations may generalize across ancestral origins. | 8413/10054 | Secondary Analysis | Shared |
| BrainGB: A Benchmark for Brain Network Analysis with Graph Neural Networks | 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 established performance in other 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. | 9748/9748 | Secondary Analysis | Shared |
| Differentiating distinct and converging neural correlates of types of systemic environmental exposures | Background: Systemic environmental disadvantage relates to a host of health and functional outcomes. Specific structural factors have seldom been linked to neural structure, however, clouding understanding of putative mechanisms. Examining relations during childhood/preadolescence, a dynamic period of neurodevelopment, could aid bridge this gap.
Methods: A total of 10,213 youth were recruited from the Adolescent Brain and Cognitive Development study. Self-report and objective measures (Census and Federal bureau of investigation metrics extracted using geocoding) of environmental exposures were used, including stimulation indexing lack of safety and high attentional demands, discrepancy indexing social exclusion/lack of belonging, and deprivation indexing lack of environmental enrichment. Environmental measures were related to cortical thickness, surface area and subcortical volume regions, controlling for other environmental exposures and accounting for other brain regions.
Results: Self-report (|β|=0.04-0.09) and objective (|β|=0.02-0.06) environmental domains related to area/thickness in overlapping (e.g. insula, caudal anterior cingulate), and unique regions (e.g. for discrepancy, rostral anterior and isthmus cingulate, implicated in socioemotional functions; for stimulation, precuneus, critical for cue reactivity and integration of environmental cues, and for deprivation, superior frontal, integral to executive functioning). For stimulation and discrepancy exposures, self-report and objective measures showed similarities in correlate regions, while deprivation exposures evidenced distinct correlates for self-report and objective measures.
Conclusions: Results represent a necessary step toward broader work aimed at establishing mechanisms and correlates of structural disadvantage, highlighting the relevance of going beyond aggregate models by considering types of environmental factors, and the need to incorporate both subjective and objective measurements in these efforts. | 7824/9043 | Primary Analysis | Shared |
| A multi-cohort study of resting-state connectivity alterations in attention-deficit/hyperactivity disorder | Most studies examining connectomic abnormalities associated with ADHD have used small, underpowered samples and thus produced inconsistent findings. Here we combined data from the Adolescent Brain Cognitive Development (ABCD) and Lifespan Human Connectome Project Development (HCP-D) cohorts (NDAR collections #2573, #2846 and #3165), as well as datasets from non-NDAR sources including the ADHD-200, Healthy Brain Network (HBN), National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) and Neurobehavioral Clinical Research (NCR) cohorts. We aimed to identify network-level resting-state features associated ADHD diagnosis and traits in this large multi-cohort sample. We applied the same 36-parameter+despiking pipeline to subjects from all datasets, and combined data using mega-analytic mixed models, which included nested random intercepts for study, site and family ID. In the group comparison, we compared 1301 subjects with diagnosed ADHD against 1301 unaffected controls (total N=2,602; 1710 males (65.72%); mean age=10.86 years, sd=2.05). Patients and controls were 1:1 nearest neighbor matched on in-scanner motion and key demographic variables. Associations between ADHD-traits and resting-state connectivity were assessed in a large multi-cohort sample (N=10,113). ADHD diagnosis was associated with less anticorrelation between the default mode and salience/ventral attention (B=0.009, t=3.45, p-FDR=0.004, d=0.14, 95% CI=0.004, 0.014), somatomotor (B=0.008, t=3.49, p-FDR=0.004, d=0.14, 95% CI=0.004, 0.013), and dorsal attention networks (B=0.01, t=4.28, p-FDR<0.001, d=0.17, 95% CI=0.006, 0.015). These results were robust to sensitivity analyses considering comorbid internalizing problems, externalizing problems and psychostimulant medication. Similar findings were observed when examining ADHD traits. Finding associations between ADHD and connectivity of the default mode to task-positive networks is consistent with default mode network models of disorder, although all effect sizes were small. | 7283/8817 | Secondary Analysis | Shared |
| Multimethod investigation of the neurobiological basis of ADHD symptomatology in children aged 9-10: baseline data from the ABCD study | Attention deficit/hyperactivity disorder is associated with numerous neurocognitive deficits, including poor working memory and difficulty inhibiting undesirable behaviors that cause academic and behavioral problems in children. Prior work has attempted to determine how these differences are instantiated in the structure and function of the brain, but much of that work has been done in small samples, focused on older adolescents or adults, and used statistical approaches that were not robust to model overfitting. The current study used cross-validated elastic net regression to predict a continuous measure of ADHD symptomatology using brain morphometry and activation during tasks of working memory, inhibitory control, and reward processing, with separate models for each MRI measure. The best model using activation during the working memory task to predict ADHD symptomatology had an out-of-sample R2 = 2% and was robust to residualizing the effects of age, sex, race, parental income and education, handedness, pubertal status, and internalizing symptoms from ADHD symptomatology. This model used reduced activation in task positive regions and reduced deactivation in task negative regions to predict ADHD symptomatology. The best model with morphometry alone predicted ADHD symptomatology with an R2 = 1% but this effect dissipated when including covariates. The inhibitory control and reward tasks did not yield generalizable models. In summary, these analyses show, with a large and well-characterized sample, that the brain correlates of ADHD symptomatology are modest in effect size and captured best by brain morphometry and activation during a working memory task. | 6708/7999 | Secondary Analysis | Shared |
| Human cortex development is shaped by molecular and cellular brain systems | Human brain morphology undergoes complex developmental changes with diverse regional trajectories. Various biological factors influence cortical thickness development, but human data are scarce. Building on methodological advances in neuroimaging of large cohorts, we show that population-based developmental trajectories of cortical thickness unfold along patterns of molecular and cellular brain organization. During childhood and adolescence, distributions of dopaminergic receptors, inhibitory neurons, glial cell populations as well as features of brain metabolism explain up to 50% of variance associated with regional cortical thickness trajectories. Cortical maturation patterns in later life are best explained by distributions of cholinergic and glutamatergic systems. These observations are validated in longitudinal data from over 8,000 adolescents, explaining up to 59% of developmental change at population- and 18% at single-subject level. Integrating multilevel brain atlases with normative modeling and population neuroimaging provides a biologically and clinically meaningful path to understand typical and atypical brain development in living humans. | 5827/7209 | Secondary Analysis | Shared |
| Stability of polygenic scores across discovery genome-wide association studies | Polygenic scores (PGS) are commonly evaluated in terms of their predictive accuracy at the population level by the proportion of phenotypic variance they explain. To be useful for precision medicine applications, they also need to be evaluated at the individual level when phenotypes are not necessarily already known. We investigated the stability of PGS in European American (EUR) and African American (AFR)-ancestry individuals from the Philadelphia Neurodevelopmental Cohort and the Adolescent Brain Cognitive Development study using different discovery genome-wide association study (GWAS) results for post-traumatic stress disorder (PTSD), type 2 diabetes (T2D), and height. We found that pairs of EUR-ancestry GWAS for the same trait had genetic correlations >0.92. However, PGS calculated from pairs of same-ancestry and different-ancestry GWAS had correlations that ranged from <0.01 to 0.74. PGS stability was greater for height than for PTSD or T2D. A series of height GWAS in the UK Biobank suggested that correlation between PGS is strongly dependent on the extent of sample overlap between the discovery GWAS. Focusing on the upper end of the PGS distribution, different discovery GWAS do not consistently identify the same individuals in the upper quantiles, with the best case being 60% of individuals above the 80th percentile of PGS overlapping from one height GWAS to another. The degree of overlap decreases sharply as higher quantiles, less heritable traits, and different-ancestry GWAS are considered. PGS computed from different discovery GWAS have only modest correlation at the individual level, underscoring the need to proceed cautiously with integrating PGS into precision medicine applications. | 4701/5962 | Secondary Analysis | Shared |
| A Phenome-Wide Association Study (PheWAS) of Late Onset Alzheimer Disease Genetic Risk in Children of European Ancestry at Middle Childhood: Results from the ABCD Study | Genetic risk for Late Onset Alzheimer Disease (AD) has been associated with lower cognition and smaller hippocampal volume in healthy young adults. However, whether these and other associations are present during childhood remains unclear. Using data from 5556 genomically-confirmed European ancestry youth who completed the baseline session of the ongoing the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®), our phenome-wide association study estimating associations between four indices of genetic risk for late-onset AD (i.e., AD polygenic risk scores (PRS), APOE rs429358 genotype, AD PRS with the APOE region removed (ADPRS-APOE), and an interaction between ADPRS-APOE and APOE genotype) and 1687 psychosocial, behavioral, and neural phenotypes revealed no significant associations after correction for multiple testing (all ps > 0.0002; all pfdr > 0.07). These data suggest that AD genetic risk may not phenotypically manifest during middle-childhood or that effects are smaller than this sample is powered to detect. | 4914/5556 | Secondary Analysis | Shared |
| Changes in patterns of age-related network connectivity are associated with risk for schizophrenia | Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied an average of three fMRI scans per individual. To identify potential familial risk-related FNC changes, we compared age-related FNC in unaffected siblings (SIB) and first-degree relatives (FHR) of SCZ patients with neurotypical controls (NC) at the same age-stage. Then, we examined how polygenic risk scores for SCZ influenced risk-related FNC patterns. Finally, we investigated the same risk-related FNC patterns in adult SCZ patients (oSCZ) and young individuals with subclinical psychotic symptoms (PSY). Age-sensitive risk-related FNC patterns emerge during adolescence and early adulthood, but not before. Young SIB always followed older NC patterns, with decreased FNC in a cerebellar-occipitoparietal circuit and increased FNC in two prefrontal-sensorimotor circuits when compared to young NC. Some of these FNC alterations were also found in oSCZ, with one exhibiting reversed pattern. All were linked to polygenic risk for SCZ in unrelated individuals (R2 varied from 0.02 to 0.09). Young PSY showed FNC alterations in the same direction as SIB when compared to NC. These results suggest that age-related neurotypical FNC correlate with genetic risk for SCZ and are detectable with MRI in young participants. | 4280/4936 | Secondary Analysis | Shared |
| Overlapping brain correlates of superior cognition among children at genetic risk for Alzheimer’s disease and/ or major depressive disorder | 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. | 3969/4499 | Secondary Analysis | Shared |
| Shared heritability of human face and brain shape | Evidence from model organisms and clinical genetics suggests coordination between the developing brain and face, but the role of this link in common genetic variation remains unknown. We performed a multivariate genome-wide association study of cortical surface morphology in 19,644 individuals of European ancestry, identifying 472 genomic loci influencing brain shape, of which 76 are also linked to face shape. Shared loci include transcription factors involved in craniofacial development, as well as members of signaling pathways implicated in brain-face cross-talk. Brain shape heritability is equivalently enriched near regulatory regions active in either forebrain organoids or facial progenitors. However, we do not detect significant overlap between shared brain-face genome-wide association study signals and variants affecting behavioral-cognitive traits. These results suggest that early in embryogenesis, the face and brain mutually shape each other through both structural effects and paracrine signaling, but this interplay may not impact later brain development associated with cognitive function. | 3938/4470 | Secondary Analysis | Shared |
| Associations among household and neighborhood socioeconomic disadvantages, resting-state frontoamygdala connectivity, and internalizing symptoms in youth | Exposure to socioeconomic disadvantages (SED) can have negative impacts on mental health, yet SED is a multifaceted construct and the precise processes by which SED confer deleterious effects are less clear. Using a large and diverse sample of preadolescents (ages 9-10 at baseline; N = 4,038; 49% female) from the Adolescent Brain Cognitive Development Study, we examined associations among SED at both household (i.e., income-to-needs and material hardship) and neighborhood (i.e., area deprivation and neighborhood unsafety) levels, frontoamygdala resting-state functional connectivity, and internalizing symptoms at baseline and 1-year follow-up. SED were positively associated with internalizing symptoms at baseline, and indirectly predicted symptoms one year later through elevated symptoms at baseline. At the household level, youth in households characterized by higher disadvantage (i.e., lower income-to-needs ratio) exhibited more strongly negative frontoamygdala coupling, particularly between the bilateral amygdala and medial orbitofrontal (mOFC) regions within the Frontoparietal Network. While more strongly positive amygdala-mOFC coupling was associated with higher levels of internalizing symptoms at baseline and 1-year follow-up, it did not mediate the association between income-to-needs ratio and internalizing symptoms. However, at the neighborhood level, amygdala-mOFC functional coupling moderated the effect of neighborhood deprivation on internalizing symptoms. Specifically, higher neighborhood deprivation was associated with higher internalizing symptoms for youth with more strongly positive connectivity, but not for youth with more strongly negative connectivity, suggesting a potential buffering effect. Findings highlight the importance of capturing multileveled socioecological contexts in which youth develop to identify youth who are most likely to benefit from early interventions. Exposure to socioeconomic disadvantages (SED) can have negative impacts on mental health, yet SED is a multifaceted construct and the precise processes by which SED confer deleterious effects are less clear. Using a large and diverse sample of preadolescents (ages 9-10 at baseline; N = 4,038; 49% female) from the Adolescent Brain Cognitive Development Study, we examined associations among SED at both household (i.e., income-to-needs and material hardship) and neighborhood (i.e., area deprivation and neighborhood unsafety) levels, frontoamygdala resting-state functional connectivity, and internalizing symptoms at baseline and 1-year follow-up. SED were positively associated with internalizing symptoms at baseline, and indirectly predicted symptoms one year later through elevated symptoms at baseline. At the household level, youth in households characterized by higher disadvantage (i.e., lower income-to-needs ratio) exhibited more strongly negative frontoamygdala coupling, particularly between the bilateral amygdala and medial orbitofrontal (mOFC) regions within the Frontoparietal Network. While more strongly positive amygdala-mOFC coupling was associated with higher levels of internalizing symptoms at baseline and 1-year follow-up, it did not mediate the association between income-to-needs ratio and internalizing symptoms. However, at the neighborhood level, amygdala-mOFC functional coupling moderated the effect of neighborhood deprivation on internalizing symptoms. Specifically, higher neighborhood deprivation was associated with higher internalizing symptoms for youth with more strongly positive connectivity, but not for youth with more strongly negative connectivity, suggesting a potential buffering effect. Findings highlight the importance of capturing multileveled socioecological contexts in which youth develop to identify youth who are most likely to benefit from early interventions. | 4000/4163 | Secondary Analysis | Shared |
| Neuroanatomical correlates of genetic risk for obesity in children | 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. | 3709/4157 | Secondary Analysis | Shared |
| Relating neighborhood deprivation to childhood obesity in the ABCD Study®: evidence for theories of neuroinflammation and neuronal stress | Objective: We evaluated whether relationships between area deprivation (ADI), body mass index (BMI) and brain structure (e.g., cortical thickness, subcortical volume) during pre-adolescence 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.
Methods: Data were gathered from the Adolescent Brain Cognitive DevelopmentSM Study® (9-12-years-old; n=3,087, 51% male). Linear mixed-effects models identified brain regions that were associated with both ADI and BMI; longitudinal associations were evaluated with mediation models. The NI model included ADI and BMI at 9/10-years-old and brain data at 11/12-years-old. The NS model included ADI and brain data at 9/10-years-old and BMI at 11/12-years-old.
Results: BMI at 9/10-years-old partially mediated the relationship between ADI and Ventral DC volume at 11/12-years-old. Additionally, the Ventral DC at 9/10-years-old partially mediated the relationship between ADI and BMI at 11/12-years-old, even in youth who at baseline, were of a healthy weight. Results were unchanged when controlling for differences in brain structure and weight across the two-years.
Conclusion: Greater area deprivation may indicate fewer access to resources that support healthy development, like nutritious food and nonstressful environments. Our findings provide evidence in support of the NI and NS theories of overeating, specifically, with greater ADI influencing health outcomes of obesity via brain structure alterations.
| 2732/3087 | Secondary Analysis | Shared |
| What Is the Link Between Attention-Deficit/Hyperactivity Disorder and Sleep Disturbance? A Multimodal Examination of Longitudinal Relationships and Brain Structure Using Large-Scale Population-Based Cohorts | Background: Attention-deficit/hyperactivity disorder (ADHD) comorbid with sleep disturbances can produce profound disruption in daily life and negatively impact quality of life of both the child and the family. However, the temporal relationship between ADHD and sleep impairment is unclear, as are underlying common brain mechanisms.
Methods: This study used data from the Quebec Longitudinal Study of Child Development (n = 1601, 52% female) and the Adolescent Brain Cognitive Development Study (n = 3515, 48% female). Longitudinal relationships between symptoms were examined using cross-lagged panel models. Gray matter volume neural correlates were identified using linear regression. The transcriptomic signature of the identified brain-ADHD-sleep relationship was characterized by gene enrichment analysis. Confounding factors, such as stimulant drugs for ADHD and socioeconomic status, were controlled for.
Results: ADHD symptoms contributed to sleep disturbances at one or more subsequent time points in both cohorts. Lower gray matter volumes in the middle frontal gyrus and inferior frontal gyrus, amygdala, striatum, and insula were associated with both ADHD symptoms and sleep disturbances. ADHD symptoms significantly mediated the link between these structural brain abnormalities and sleep dysregulation, and genes were differentially expressed in the implicated brain regions, including those involved in neurotransmission and circadian entrainment.
Conclusions: This study indicates that ADHD symptoms and sleep disturbances have common neural correlates, including structural changes of the ventral attention system and frontostriatal circuitry. Leveraging data from large datasets, these results offer new mechanistic insights into this clinically important relationship between ADHD and sleep impairment, with potential implications for neurobiological models and future therapeutic directions. | 2948/3075 | Secondary Analysis | Shared |
| Investigation of Psychiatric and Neuropsychological Correlates of Default Mode Network and Dorsal Attention Network Anticorrelation in Children. | The default mode network (DMN) and dorsal attention network (DAN) demonstrate an intrinsic "anticorrelation" in healthy adults, which is thought to represent the functional segregation between internally and externally directed thought. Reduced segregation of these networks has been proposed as a mechanism for cognitive deficits that occurs in many psychiatric disorders, but this association has rarely been tested in pre-adolescent children. The current analysis used data from the Adolescent Brain Cognitive Development study to examine the relationship between the strength of DMN/DAN anticorrelation and psychiatric symptoms in the largest sample to date of 9- to 10-year-old children (N = 6543). The relationship of DMN/DAN anticorrelation to a battery of neuropsychological tests was also assessed. DMN/DAN anticorrelation was robustly linked to attention problems, as well as age, sex, and socioeconomic factors. Other psychiatric correlates identified in prior reports were not robustly linked to DMN/DAN anticorrelation after controlling for demographic covariates. Among neuropsychological measures, the clearest correlates of DMN/DAN anticorrelation were the Card Sort task of executive function and cognitive flexibility and the NIH Toolbox Total Cognitive Score, although these did not survive correction for socioeconomic factors. These findings indicate a complicated relationship between DMN/DAN anticorrelation and demographics, neuropsychological function, and psychiatric problems. | 2558/3004 | Secondary Analysis | Shared |
| Different patterns of intrinsic functional connectivity at the default mode and attentional networks predict crystallized and fluid abilities in childhood | Crystallized abilities are skills used to solve problems based on experience, while fluid abilities are linked to reasoning without prior knowledge. To what extent crystallized and fluid abilities involve dissociated or overlapping neural systems is debatable. Due to often deployed small sample sizes or different study settings in prior work, the neural basis of crystallized and fluid abilities in childhood remains largely unknown. Here we analyzed within and between network connectivity patterns from resting-state functional MRI of 2707 children from the ABCD study. We hypothesized that differences in functional connectivity at the default mode network (DMN) and ventral and dorsal attentional networks (VAN, DAN) explain differences in fluid and crystallized abilities. We found that stronger between-network connectivity of the DMN and VAN, DMN and DAN, and VAN and DAN predicted crystallized abilities. Within-network connectivity of the DAN predicted both crystallized and fluid abilities. Our findings reveal that crystallized abilities rely on the functional coupling between attentional networks and the DMN, whereas fluid abilities are associated with a focal connectivity configuration at the DAN. Our study provides new evidence into the neural basis of child intelligence and calls for future comparative research in adulthood during neuropsychiatric diseases. | 2417/2707 | Secondary Analysis | Shared |
| A pattern of cognitive resource disruptions in childhood psychopathology | The Hurst exponent ( H ) isolated in fractal analyses of neuroimaging time-series is
implicated broadly in cognition. Within this literature, H is associated with multiple
mental disorders, suggesting that H is transdimensionally associated with
psychopathology. Here, we unify these results and demonstrate a pattern of decreased
H with increased general psychopathology and attention-deficit/hyperactivity factor
scores during a working memory task in 1,839 children. This pattern predicts current
and future cognitive performance in children and some psychopathology in 703 adults.
This pattern also defines psychological and functional axes associating
psychopathology with an imbalance in resource allocation between fronto-parietal and
sensory-motor regions, driven by reduced resource allocation to fronto-parietal regions.
This suggests the hypothesis that impaired working memory function in
psychopathology follows from a reduced cognitive resource pool and a reduction in
resources allocated to the task at hand. | 1667/1839 | Secondary Analysis | Shared |
| Comparison Between Gradients and Parcellations for Functional Connectivity Prediction of Behavior | 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. | 1333/1476 | Secondary Analysis | Shared |
| A morphometrics approach for inclusion of localised characteristics from medical imaging studies into genome-wide association studies | Medical images, such as magnetic resonance or computed tomography, are increasingly being used to investigate the genetic architecture of neurological diseases like Alzheimer's disease, or psychiatric disorders like attention-deficit hyperactivity disorder. The quantified global or regional brain imaging measures are commonly known as imaging-specific or -derived phenotypes (IDPs) when conducting genotype-phenotype association studies. Inclusion of whole medical images rather than derived tabular data as IDPs has been done by either a voxel-wise approach or a global approach of whole medical images via principal component analysis. Limitations with multiple testing and inability to isolate high variation regions within the principal components arise with either of these approaches. This work proposes a principal component analysis-like localised approach of dimensionality reduction using diffeomorphic morphometry allowing for the selection of distances to model more regional effects.The main benefit of the proposed method is that it can can reduce the dimensionality of the problem considerably in comparison to the medical image's variability it is describing while grouping spatial information potentially lost in dimensionality reduction techniques like principal component analyses. Moreover, the approach not only allows to include locality in the analysis but can also be used as a generative model to explore the morphometric changes across an axis of particular components of interest. To demonstrate the feasibility of this pipeline for inclusion in a multivariate genome-wide association study, it was applied to 1,359 subjects from the Adolescent Brain Cognitive Development Study for traits related to attention-deficit disorder. The results show that the proposed method can identify more specific morphometric features associated with genome regions. | 1207/1359 | Secondary Analysis | Shared |
| Predicting multilingual effects on executive function and individual connectomes in children: An ABCD study | While there is a substantial amount of work studying multilingualism’s effect on cognitive functions, little is known about how the multilingual experience modulates the brain as a whole. In this study, we analyzed data of over 1,000 children from the Adolescent Brain Cognitive Development (ABCD) Study to examine whether monolinguals and multilinguals differ in executive function, functional brain connectivity, and brain–behavior associations. We observed significantly better performance from multilingual children than monolinguals in working-memory tasks. In one finding, we were able to classify multilinguals from monolinguals using only their whole-brain functional connectome at rest and during an emotional n-back task. Compared to monolinguals, the multilingual group had different functional connectivity mainly in the occipital lobe and subcortical areas during the emotional n-back task and in the occipital lobe and prefrontal cortex at rest. In contrast, we did not find any differences in behavioral performance and functional connectivity when performing a stop-signal task. As a second finding, we investigated the degree to which behavior is reflected in the brain by implementing a connectome-based behavior prediction approach. The multilingual group showed a significant correlation between observed and connectome-predicted individual working-memory performance scores, while the monolingual group did not show any correlations. Overall, our observations suggest that multilingualism enhances executive function and reliably modulates the corresponding brain functional connectome, distinguishing multilinguals from monolinguals even at the developmental stage. | 1024/1075 | Secondary Analysis | Shared |
| Tuber locations associated with infantile spasms map to a common brain network | Objective: Approximately 50% of patients with Tuberous Sclerosis Complex develop infantile spasms, a
sudden-onset epilepsy syndrome associated with poor neurological outcomes. While an increased burden of tubers confers an elevated risk of infantile spasms, it remains unknown whether some tuber locations confer higher risk than others. Here, we test whether tuber location and connectivity are associated with infantile spasms.
Methods: We segmented tubers from 123 children with (n=74) and without (n=49) infantile spasms from a prospective observational cohort. We used voxel-wise lesion symptom mapping to test for an association between spasms and tuber location. We then used lesion network mapping to test for an association between spasms and connectivity with tuber locations. Finally, we tested the discriminability of identified associations with logistic regression and cross validation as well as statistical mediation.
Results: Tuber locations associated with infantile spasms were heterogenous, and no single location was significantly associated with spasms. However, >95% of tuber locations associated with spasms were functionally connected to the globus pallidi and cerebellar vermis. These connections were specific compared to tubers in patients without spasms. Logistic regression found that globus pallidus connectivity was a stronger predictor of spasms (OR 1.96, 95%CI [1.10, 3.50], p=0.02) than tuber burden (OR 1.65, 95%CI [0.90, 3.04], p=0.11), with a mean ROC area under the curve of 0.73 (+/-0.1) during repeated cross validation.
Interpretation: Connectivity between tuber locations and the bilateral globus pallidus is associated with infantile spasms. Our findings lend insight into spasm pathophysiology and may identify patients at risk. | 1000/1000 | Secondary Analysis | Shared |
| Brain structural associations with depression in a large early adolescent sample (the ABCD Study) | Background: Depression is the leading cause of disability worldwide with >50% of cases emerging before the age of 25 years. Large-scale neuroimaging studies in depression implicate robust structural brain differences in the disorder. However most studies have been conducted in adults and therefore, the temporal origins of depression-related imaging features remain largely unknown. This has important implications for understanding aetiology and informing timings of potential intervention.
Methods: Here, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample of early adolescents from the Adolescent Brain and Cognitive Development (ABCD) Study (N=9981, 9-11-year-olds).
Findings: We report significantly decreased global cortical and white matter metrics, and regionally in frontal, limbic and temporal areas in adolescent depression (Cohen’s d = -0.018 to -0041, β = -0·019 to -0.057). Further, we report consistently stronger imaging associations for caregiver-reported compared to child-reported depression ratings. Divergences between reports (caregiver vs child) were found to significantly relate to negative socio-environmental factors (e.g., family conflict, absolute β=0.048 to 0.169).
Interpretation: Depression ratings in early adolescence were associated with similar imaging findings to those seen in adult depression samples, suggesting neuroanatomical abnormalities may be present early in the disease course, arguing for the importance of early intervention. Associations between socio-environmental factors and reporter discrepancy warrant further consideration, both in the wider context of the assessment of adolescent psychopathology, and in relation to their role in aetiology.
Funding: Wellcome Trust, Mental Health Research UK.
| 855/999 | Secondary Analysis | Shared |
| Lifestyle Factors Counteract the Neurodevelopmental Impact of Genetic Risk for Accelerated Brain Aging in Adolescence | Background
The transition from childhood to adolescence is characterised by enhanced neural plasticity and a consequent susceptibility to both beneficial and adverse aspects of one’s milieu.
Methods
To understand the implications of the interplay between protective and risk-enhancing factors, we analysed longitudinal data from the Adolescent Brain and Cognitive Development study (N = 834; 394 female). We probed the maturational correlates of positive lifestyle variables (friendships, parental warmth, school engagement, physical exercise, healthy nutrition) and of genetic vulnerability to neuropsychiatric disorders (Major Depressive Disorder, Alzheimer’s Disease, Anxiety Disorders, Bipolar Disorder, Schizophrenia), and further sought to elucidate their implications for psychological well-being.
Results
Genetic risk factors and lifestyle buffers showed divergent relationships with later attentional and interpersonal problems. These effects were mediated by distinguishable functional neurodevelopmental deviations spanning the limbic, default mode, visual and control systems. Specifically, greater genetic vulnerability was associated with alterations in the normative maturation of areas rich in dopamine (D2), glutamate and serotonin receptors, and of areas with stronger expression of astrocytic and microglial genes, a molecular signature implicated in the brain disorders discussed here. Greater availability of lifestyle buffers predicted deviations in the normative functional development of higher density GABA-ergic receptor regions. The two profiles of neurodevelopmental alterations showed complementary roles in protection against psychopathology, which varied with environmental stress levels.
Conclusions
Our results underscore the importance of educational involvement and healthy nutrition in attenuating the neurodevelopmental sequelae of genetic risk factors. They also underscore the importance of characterising early life biomarkers associated with adult-onset pathologies. | 810/843 | Secondary Analysis | Shared |
| Longitudinal assessment of brain structure and behavior in youth with rapid weight gain: Potential contributing causes and consequences | Objective: Independent of weight status, rapid weight gain has been associated with underlying brain structure variation in regions associated with food intake and impulsivity among pre-adolescents. Yet, we lack clarity on how developmental maturation coincides with rapid weight gain and weight stability.
Methods: We identified brain predictors of two-year rapid weight gain and its longitudinal effects on brain structure and impulsivity in the Adolescent Brain Cognitive DevelopmentSM Study®. Youth were categorized as Healthy Weight/Weight Stable (WSHW, n=527) or Weight Gainers (WG, n=221, >38lbs); 63% of the WG group were healthy weight at 9-to-10-years-old.
Results: A five-fold cross-validated logistic elastic-net regression revealed that rapid weight gain was associated with structural variation amongst 39 brain features at 9-to-10-years-old in regions involved with executive functioning, appetitive control, and reward sensitivity. Two years later, WG youth showed differences in change over time in several of these regions and performed worse on measures of impulsivity.
Conclusions: These findings suggest that brain structure in pre-adolescence may predispose some to rapid weight gain and that weight gain itself may alter maturational brain change in regions important for food intake and impulsivity. Behavioral interventions that target inhibitory control may improve trajectories of brain maturation and facilitate healthier behaviors.
| 696/748 | Secondary Analysis | Shared |
