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Developmental Cognitive Neuroscience

Elsevier BV

All preprints, ranked by how well they match Developmental Cognitive Neuroscience's content profile, based on 14 papers previously published here. The average preprint has a 0.05% match score for this journal, so anything above that is already an above-average fit. Older preprints may already have been published elsewhere.

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Preterm birth, socioeconomic status, and white matter development across childhood

Mckinnon, K.; Blesa, M.; Thye, M.; Abel, S.; Smikle, R.; Skelton, J.; Jimenez Sanchez, L.; Vaher, K.; Sullivan, G.; Corrigan, A.; Barclay, G.; Jardine, C.; Gerrish, I.; McIntyre, D.; Chua, Y. W.; Amir, R.; Quigley, A. J.; Battersby, C.; Tsanas, A.; Batty, G. D.; Reynolds, R. M.; Cox, S. R.; Whalley, H. C.; Thrippleton, M. J.; Bastin, M. E.; Richardson, H.; Boardman, J. P.

2025-06-11 pediatrics 10.1101/2025.06.10.25328994
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BackgroundPreterm birth and socioeconomic status (SES) are associated with brain development in early life, but the contribution of each over time is uncertain. We examined the effects of gestational age (GA) and SES on white matter microstructure in the neonatal period and at five years. MethodsParticipants included preterm and term children. Diffusion MRI was collected at term-equivalent age (n=153 preterm, n=90 term [127/243 female]) and from a subset at five years (n=26 preterm, n=32 term [22/58 female]). We assessed linear associations of GA, SES (Scottish Index of Multiple Deprivation [SIMD] and maternal education), and GAxSES interactions on fractional anisotropy (FA) using tract-based spatial statistics. We compared the proportion of voxels with significant associations between timepoints. ResultsIn preterm neonates, higher GA and higher maternal education, but not SIMD, were associated with higher FA (p corrected for family-wise error rate, pFWER<0.05). GA-FA associations depended on maternal education and SIMD ({beta}=|0.001-0.005|, p<0.001). At five years, the strength and direction of GA-FA associations depended on SIMD ({beta}=|0.013-0.028|, p<0.001), but not maternal education. In term infants, lower SES was associated with higher FA at the neonatal timepoint only (pFWER<0.05). ConclusionsPreterm birth and SES both shape brain development at birth and continue to do so at five years. The SES measure most strongly associated with FA in preterm infants switches from a family-level (i.e. maternal education) to neighborhood-level (i.e. SIMD) measure between birth and five years, which suggests strategies to mitigate adverse effects of social inequalities on development may require adaptation as children grow.

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Cardiometabolic risk and structural brain development in a large community-based U.S. cohort

Beck, D.; Westlye, L. T.; Tamnes, C. K.

2025-10-24 pediatrics 10.1101/2025.10.23.25338683
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ObjectiveCardiometabolic risk factors are already detectable in childhood and adolescence, but their relations to the developing brain remains unclear. The current study tested whether poorer cardiometabolic health is associated with brain structure and microstructure development in 10-17-year-old youth. MethodsUsing the Adolescent Brain Cognitive Development Study, we analysed data from 3,527 participants with 4,433 observations across three waves. We related anthropometric (body-mass index, waist circumference), cardiovascular (systolic and diastolic blood pressure, resting heart rate), and metabolic (haemoglobin A1c, high-density lipoprotein cholesterol) indices to global cortical thickness and surface area, and to white matter fractional anisotropy and mean diffusivity. Bayesian multilevel models were fitted to estimate main and time-interaction effects, and sensitivity analyses tested within-person change, prospective prediction to the next wave, and replaced chronological age with puberty status. ResultsHigher body-mass index was associated with thinner cortex, and higher resting heart rate was associated with higher mean diffusivity, an association that strengthened over time. Other cardiometabolic measures favoured the null, and sensitivity analyses provided little evidence that wave-to-wave changes in cardiometabolic health tracked contemporaneous brain change or predicted subsequent brain structure. ConclusionAcross late childhood and adolescence, brain architecture appears largely insensitive to variation in cardiometabolic risk indices.

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Associations between prenatal alcohol and tobacco exposure and cortical and subcortical brain measures in South African children: a pilot study

Uban, K. K. A.; Jonker, D. D.; Donald, K. K. A.; Brooks, S. S. J.; Bodison, S. S. C.; Kan, E. E.; Butler-Kruger, L. L.; Roos, A. A.; Steigelmann, B. B.; Melly, B. B.; Adise, S. S.; Marshall, A. A.; Narr, K. K. L.; Joshi, S. S.; Odendaal, H. H. J.; Sowell, E. E. R.; Stein, D. D. J.

2022-06-08 pediatrics 10.1101/2022.06.07.22276078
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ObjectiveThe aim of this pilot study was to assess associations of prenatal alcohol exposure (PAE), prenatal tobacco exposure (PTE), and their interaction and quantity on subsequent cortical and subcortical measures at age 6 years. MethodsMothers with varying levels of alcohol and tobacco exposure at different trimesters during pregnancy were approached when their children (born participating in the Safe Passage Study) were approximately 6 years old. 72 mothers agreed to participate, and 51 children completed brain magnetic resonance imaging (MRI). Brain regions of interest (ROIs) that were significantly associated prior to multiple comparison testing, were examined for associations related to exposure quantity, frequency, and timing (QFT), to explore how patterns of PAE and PTE influence brain outcomes in children. Linear regression was used to identify associations between PAE, PTE, and their interaction with cortical (n = 68 ROIs) and subcortical (n = 40 ROIs) measures. ResultsPrior to correction for multiple comparison testing, both PAE and PTE, as well as their interaction, were associated with a range of cortical and subcortical measures. However, none of these findings survived correction for multiple comparisons. Nevertheless, when exploring quantity of PAE, the total amount of standard drinks consumed during pregnancy and the average number of drinks per drinking day were positively associated with cortical volume in the right fusiform gyrus. ConclusionThese trend results in this pilot study provide preliminary evidence that PAE impacts brain development in unique ways from PTE, and their interactive co-exposure is not a straight forward synergistic or additive effect on the brain.

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Orbito-frontal cortex functional connectivity mediates the relationship between fetal growth and childhood impulsivity

Maires Hoppe, J. P.; Ruge, O.; Dalle Molle, R.; Elgbeili, G.; Xia, Q.; Silveira, P. P.

2025-09-17 pediatrics 10.1101/2025.09.16.25335932
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The prenatal period is critical for a healthy development, and exposure to adversity during it may provoke alterations of several biological tissues and systems, resulting in health outcomes that may take place into childhood and adulthood. The orbito-frontal cortex (OFC), central in cognitive processes, is sensitive to negative environmental effects in the intrauterine environment. We investigated the association between OFC function and decision-making behavior in response to a poor-quality prenatal environment. We evaluated a subsample of the MAVAN longitudinal Canadian birth cohort gathering data on anthropometric measurements at birth, and resting-state functional MRI (rsfMRI) and decision-making (using the Information Sampling Task from the CANTAB battery) measured later in life. We performed a mediation analysis to investigate the direct and indirect effect of being born small for gestational age (SGA) on the Information Sampling Task performance, through OFC-related functional connectivity. Being born SGA is associated with decreased functional connectivity between the left hemisphere OFC and the middle frontal gyrus (OFC-MFG). Additionally, increased OFC-MFG connectivity is linked to better IST performance. Thus, SGA individuals have an altered OFC- MFG functional connectivity, which impacts on their performance on a decision-making task. Lower OFC-MFG functional connectivity and impulsive decision-making were associated to the SGA condition, reflecting a poor-quality prenatal environment. These findings highlight the importance of the prenatal period for a healthy development and suggest that neuroimaging focusing on the affected areas may identify individuals at higher risk of developing psychopathologies, and direct for proper interventions.

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Mindfulness-based intervention in preterm young adolescents: benefits on neurobehavioural functioning and its association with white-matter microstructural changes

Siffredi, V.; Liverani, M. C.; Van De Ville, D.; Freitas, L. G. A.; Borradori Tolsa, C.; Huppi, P.; Ha-Vinh Leuchter, R.

2021-10-23 pediatrics 10.1101/2021.10.20.21265246
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Very preterm (VPT) young adolescents are at high risk of executive, behavioural and socio-emotional difficulties. Previous research has shown significant evidence of the benefits of mindfulness-based intervention (MBI) on these abilities. This study aims to assess the association between the effects of MBI on neurobehavioral functioning and changes in white-matter microstructure in VPT young adolescents who completed an 8-week MBI program. Neurobehavioural assessments and multi-shell diffusion MRI were performed before and after MBI in 32 VPT young adolescents. Combined diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) measures were extracted on well-defined white matter tracts (TractSeg). A multivariate data-driven approach (partial least squares correlation) was used to explore associations between MBI-related changes on neurobehavioural measures and microstructural changes. Our finding showed an enhancement of global executive functioning after MBI that was associated with a general pattern of significant increase in fractional anisotropy (FA) and decrease in axonal dispersion (ODI) in white-matter tracts involved in executive processes. Young VPT adolescents with lower gestational age at birth showed the greatest gain in white-matter microstructural changes after MBI. HighlightsO_LIVery preterm adolescents (VPT) completed an 8-week mindfulness-based intervention (MBI) C_LIO_LIImprovement in overall executive functioning was observed after MBI C_LIO_LIExecutive gain was associate with white-matter microstructural changes C_LIO_LIThe increase in microstructural properties was in tracts involved in executive processes C_LIO_LIVPT with lower gestational age show bigger gains in microstructural changes C_LI CRediT rolesVanessa Siffredi: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Software; Visualization; Writing - original draft; Writing - review & editing - Maria Chiara Liverani: Conceptualization; Data curation; Investigation; Methodology; Project administration; Writing - review & editing. - Dimitri Van De Ville: Methodology; Resources; Software; Supervision; Writing - review & editing. - Lorena Freitas: Data curation; Investigation; Writing - review & editing. - Cristina Borradori Tolsa: Conceptualization; Funding acquisition; Investigation; Project administration; Resources; Supervision; Validation; Writing - review & editing. - Petra Susan Huppi: Conceptualization; Funding acquisition; Methodology; Project administration; Resources; Supervision; Validation; Writing - review & editing. -Russia Ha-Vinh Leuchter: Conceptualization; Funding acquisition; Investigation; Methodology; Project administration; Resources; Supervision; Validation; Writing - review & editing.

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Puberty Timing and Cognitive Functioning: Insights from the Adolescent Brain Cognitive Development (ABCD) Study and Mendelian Randomization

Dinkelbach, L.; Serio, B.; Valk, S.; Weisner, F. E.; Bläschke, L.; Peters, T.; Hinney, A.; Schmidt, B.; Hirtz, R.

2025-07-11 pediatrics 10.1101/2025.07.10.25331286
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PurposeEarly puberty timing is associated with altered neurodevelopment and adverse mental health. Its association with cognitive functioning remains unclear. We investigated the effects of puberty timing on various cognitive abilities. MethodsIn 10,174 participants from the Adolescent Brain and Cognitive Development (ABCD) Study, we assessed associations between puberty timing at baseline (age 9.9{+/-}0.6 years) and performance on six cognitive tasks at baseline, 2-year, and 4-year follow-ups. Linear-mixed-regression models were calculated separately by sex, adjusting for bodyweight, birthweight, parental income, and race/ethnicity. To probe causal relationships, we performed Mendelian randomization utilizing external Genome Wide Association Study (GWAS) data on age at menarche (N=632,955), male puberty timing (N=205,354), and executive functioning (N=427,037). ResultsIn the ABCD study, earlier puberty timing was associated with poorer performance pooled across timepoints on the NIH Toolbox(R) Picture Sequence Memory Task (girls: standardized {beta}=-0.04, 95%-CI [-0.06, -0.01]; boys: {beta}=-0.03, 95%-CI [-0.05, -0.01]), the List Sorting Working Memory Test (girls: {beta}=-0.03, 95%-CI [-0.06, -0.01]; boys: {beta}=-0.04, 95%-CI [-0.06, -0.01]), and both the learning of a word list (girls: {beta}=-0.05, 95%-CI [-0.07, -0.02]; boys: {beta}=-0.04, 95%-CI [-0.06, -0.01]) and its recall (girls: {beta}=-0.03, 95%-CI [-0.06, -0.01]; boys: {beta}=-0.03, 95%-CI [-0.06, -0.01]). Mendelian randomization indicated better executive functioning with later age at menarche (b=0.005/year, 95%-CI [0.000, 0.011]); the association with male puberty timing was directionally consistent but remained non-significant (b=0.012/year, 95%-CI [-0.004, 0.028]). DiscussionThese findings support a causal link between earlier puberty timing and poorer cognitive performance. However, effect sizes were small, indicating negligible clinical relevance.

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The Impact of Early Life Stress on the Genetic Influence on Brain and Cognitive Development in Children

Wang, H.-H.; Moon, S.-Y.; Kim, K.; Kim, H.-J.; Ahn, W.-Y.; Joo, Y. Y.; Cha, J.

2021-12-30 pediatrics 10.1101/2021.12.27.21268445
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Early life stress (ELS), such as abuse, neglect, and maltreatment, is a well-known risk factor for mental illness. However, it is unclear how ELS affects the brain and cognitive development. Identifying specific relationships of ELS with the genetic and brain-related underpinnings of cognitive development may reveal biological mechanisms responsible for the negative impact of ELS and those that lead to individual differences in sensitivity (or resilience) to ELS. In this study, to investigate the interlinked processes of cognitive development, we analyzed the multimodal data of DNA genotypes, brain imaging (MRI), and neuropsychological assessment (NIH Toolbox) outcomes of 4,276 children (ages 9 to 10 years, European ancestry) from the Adolescent Brain Cognitive Development (ABCD) study. We estimated the genetic influence on cognitive capacity using genome-wide polygenic scores (GPSs). Our regression and mediation analyses revealed significant causal relationships for the gene-brain-cognition pathway: Brain structural development significantly mediated the genetic influence on cognitive development (partial mediation effect = 0.016, PFWE<0.001). Interestingly, within the triangular relationship, we found a significant moderation effect of abuse only on the gene-to-brain pathway (Index of Moderated Mediation = -0.007; 95% CI= -0.012 [~] -0.002; PFWE<0.05). These findings indicate the negative modulatory effects of ELS on the genetic influence on brain structural development that lead to disadvantageous neurocognitive development in prepubertal children.

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Pre-pandemic mental health and brain characteristics predict adolescent stress and emotions during the COVID-19 pandemic

Risner, M.; Hu, L.; Stamoulis, C.

2025-05-13 pediatrics 10.1101/2025.05.12.25327434
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BackgroundThe COVID-19 pandemic had profound effects on developing adolescents that, to date, remain incompletely understood. Youth with preexisting mental health problems and associated brain alterations were at increased risk for higher stress and poor mental health. This study investigated impacts of adolescent pre-pandemic mental health problems and their neural correlates on stress, negative emotions and poor mental health during the first [~]15 months of the COVID-19 pandemic. MethodsN=2,641 adolescents (median age=12.0 years) from the Adolescent Brain Cognitive Development (ABCD) cohort, with pre-pandemic data on anxiety, depression, and behavioral (attention, aggression, social withdrawal, internalizing, externalizing) problems, longitudinal survey data on mental health, stress and emotions during the first [~]15 months following the outbreak, structural MRI, and resting-state fMRI. Data were analyzed using mixed effects mediation and moderation models. ResultsPreexisting mental health and behavioral problems predicted higher stress, negative affect and negative emotions ({beta}=0.09-0.21, CI=[0.03,0.32]), and lower positive affect ({beta}=-0.21 to -0.09, CI=[-0.31,-0.01]) during the first [~]6 months of the outbreak. Pre-pandemic structural characteristics of brain regions supporting social function and emotional processing (insula, superior temporal gyrus, orbitofrontal cortex, and the cerebellum) mediated some of these relationships ({beta}=0.10-0.15, CI=[0.01,0.24]). Pre-pandemic brain circuit organization moderated (attenuated) relationships between preexisting mental health and pandemic stress and negative emotions ({beta}=-0.17 to -0.06, CI=[-0.27,-0.01]). ConclusionsPreexisting mental health problems and their structural brain correlates were risk factors for youth stress and emotions during the early months of the outbreak. In addition, the organization of some brain circuits was protective and attenuated the effects of preexisting mental health issues on youth responses to the pandemics stressors.

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The effect of sleep-corrected social jetlag on crystalized intelligence, school performance, and functional connectome in early adolescence

Yang, F. N.; Picchioni, D.; Duyn, J. H.

2023-07-23 pediatrics 10.1101/2023.07.18.23292833
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Approximately half of adolescents encounter a mismatch between their sleep patterns on school days and free days, also referred to as "social jetlag". This condition has been linked to various adverse outcomes, such as poor sleep, cognitive deficits, and mental disorders. However, prior research was unsuccessful in accounting for other variables that are correlated with social jetlag, including sleep duration and quality. To address this limitation, we applied a propensity score matching method on a sample of 8853 11-12-year-olds from the two-year follow-up (FL2) data of the Adolescent Brain Cognitive Development (ABCD) study. We identified 3366 pairs of participants with high sleep-corrected social jetlag (SJLsc, over 1 hour) and low SJLsc (<= 1 hour) at FL2, as well as 1277 pairs at three-year follow-up (FL3), after matching based on 11 covariates including socioeconomic status, demographics, and sleep duration and quality. Our results showed that high SJLsc, as measured by the Munich Chronotype Questionnaire, was linked to reduced crystallized intelligence, lower school performance - grades, and decreased functional connectivity between cortical networks and subcortical regions, specifically between cingulo-opercular network and right hippocampus (cerc-hprh). Further mediation and longitudinal mediation analyses revealed that cerc-hprh connection mediated the associations between SJLsc and crystallized intelligence at FL2, and between SJLsc and grades at both FL2 and FL3. We validated these findings by replicating these results using objective SJLsc measurements obtained via Fitbit watches. Overall, our study highlights the negative association between social jetlag and crystallized intelligence during early adolescence.

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Relations between near-term white matter tract microstructure, medical complications, and 2-year language outcomes after preterm birth

Dubner, S. E.; Rose, J.; Feldman, H. M.; Travis, K. E.

2019-11-08 pediatrics 10.1101/19011361
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AimTo determine whether variability in diffusion MRI (dMRI) white matter tract metrics, obtained in a cohort of preterm infants prior to neonatal hospital discharge, would be associated with language outcomes at age 2 years, after consideration of age at scan and number of major neonatal complications. Method: 30 children, gestational age 28.9 (2.4) weeks, underwent dMRI at mean post menstrual age 36.4 (1.4) weeks and language assessment with the Bayley Scales of Infant Development-III at mean age 22.2 (1.7) months chronological age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for 5 white matter tracts. Hierarchical linear regression assessed associations between tract FA, moderating variables, and language outcomes. Results: FA of the left inferior longitudinal fasciculus accounted for 17% (p = 0.03) of the variance in composite language and FA of the posterior corpus callosum accounted for 19% (p = 0.02) of the variance in composite language, beyond that accounted for by post menstrual age at scan and neonatal medical complications. The number of neonatal medical complications moderated the relationship between language and posterior corpus callosum FA but did not moderate the association in the other tract. Conclusion: Language at 2 is associated with white matter metrics in early infancy in preterm children. The different pattern of associations by fiber group may relate to the stage of brain maturation and/or the nature and timing of medical complications related to preterm birth. Future studies should replicate these findings with a larger sample size to assure reliability of the findings.

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Synchrony between brain age maturation and internalising and externalising symptoms across adolescence

Beck, D.; Carrick, C.; Aksnes, E.; MacSweeney, N.; Westlye, L. T.; Fuhrmann, D.; Tamnes, C. K.

2026-01-02 psychiatry and clinical psychology 10.64898/2025.12.31.25343265
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BackgroundAdolescence is a period of rapid neurobiological and behavioural change, yet it remains unclear how deviations from normative brain maturation relate to the development of internalising and externalising symptoms. MethodsUsing data from the Adolescent Brain Cognitive Development (ABCD) Study, we combined brain age prediction with bivariate latent growth curve (BLGC) models to test whether deviations in brain maturation - indexed by the brain age gap (BAG) - relate to mental health development across late childhood and adolescence. Brain age was estimated using T1-weighted, diffusion (dMRI), resting-state fMRI, and multimodal MRI data across four waves (ages [~]8.3-17.5). Internalising and externalising symptoms were assessed across ten waves with the self-report Brief Problem Monitor (BPM). ResultsAcross T1, dMRI, and multimodal models, deviations from age-expected brain maturation and internalising and externalising symptoms showed coordinated nonlinear development across adolescence. Adolescents whose brains increasingly diverged from age-expected maturation over time also showed increasing symptom trajectories. These associations were small to moderate in magnitude and were most consistent for internalising symptoms in females (r = .15-.23), whereas externalising symptoms showed broader but less selective nonlinear associations across modalities in both males and females (r = .15-.23). Intercept-level associations were weaker and modality-specific (r = .06-.11). Formal tests provided no evidence for robust sex differences in these associations after correction for multiple comparisons. ConclusionThese results indicate that adolescent development of mental health problems is more strongly linked to nonlinear changes in how individuals diverge from age-expected brain trajectories, rather than to fixed differences in brain age. Shifts in brain maturational tempo may therefore be a key feature underlying vulnerability to psychopathology in youth.

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Assessing sustained attention processes and related cerebral activations in typically developing adolescents using the gradual-onset continuous performance task (gradCPT)

Awada, J.; Fernandez, N. B.; Siffredi, V.; Liverani, M. C.; Miehlbradt, J.; Borradori Tolsa, C.; Ha-Vinh Leuchter, R.

2024-10-01 pediatrics 10.1101/2024.10.01.24314449
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IntroductionSustained attention and inhibition processes are fundamental components of attention that mature during adolescence, a transitive period between childhood and adulthood characterized by a rapid behavioral and cognitive development. The current study aimed to provide a better understanding of sustained attention and inhibition processes in typically developing adolescents (n = 26) aged 11-18. MethodsFunctional magnetic resonance images (fMRI) were acquired during two different modalities (the face and the scene) from a previously validated gradual{square}onset continuous (gradCPT) paradigm to evaluate sustained attention performances. In addition, we performed linear regression analyses to investigate how cerebral activation varied as a function of covariates of interest. ResultsWe showed a bilateral fronto-parieto-occipito brain activation during response inhibition regardless the type of task. Participants demonstrated better behavioral performances during the scene gradCPT. We observed a mainly left-lateralized pattern of activation in a fronto-cingulo-cerebellum area during the face gradCPT and an extended bilateral fronto-temporo-parieto-occipital activation during the scene gradCPT. Finally, we found associations between brain activity and behavioral attentional responses. ConclusionThis study gives a better understanding of the neural correlates of sustained attention and inhibition in a typically developing adolescent population.

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Long-term development of white matter fibre density and morphology up to 13 years after preterm birth

Kelly, C. E.; Thompson, D. K.; Genc, S.; Chen, J.; Yang, J. Y.; Adamson, C.; Beare, R.; Seal, M. L.; Doyle, L. W.; Cheong, J. L.; Anderson, P. J.

2020-04-06 pediatrics 10.1101/2020.04.01.20049585
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BackgroundIt is well documented that infants born very preterm (VP) are at risk of brain injury and altered brain development in the neonatal period, however there is a lack of long-term, longitudinal studies on the effects of VP birth on white matter development over childhood. Most previous studies were based on voxel-averaged, non-fibre-specific diffusion magnetic resonance imaging (MRI) measures, such as fractional anisotropy. In contrast, the novel diffusion MRI analysis framework, fixel-based analysis (FBA), enables whole-brain analysis of microstructural and macrostructural properties of individual fibre populations at a sub-voxel level. We applied FBA to investigate the long-term implications of VP birth and associated perinatal risk factors on fibre development in childhood and adolescence. MethodsDiffusion images were acquired for a cohort of VP (born <30 weeks gestation) and full-term (FT, [&ge;]37 weeks gestation) children at two ages: mean (SD) 7.6 (0.2) years (n=138 VP and 32 FT children) and 13.3 (0.4) years (n=130 VP and 45 FT children). 103 VP and 21 FT children had images at both ages for longitudinal analysis. At every fixel (individual fibre population within an image voxel) across the white matter, we compared FBA metrics (fibre density (FD), cross-section (FC) and a combination of these properties (FDC)) between VP and FT groups cross-sectionally at each age, and longitudinally between ages. We also examined associations between perinatal risk factors and FBA metrics in the VP group. ResultsCompared with FT children, VP children had lower FD, FC and FDC throughout the white matter, particularly in the corpus callosum, tapetum, inferior fronto-occipital fasciculus, fornix and cingulum at ages 7 and 13 years, as well as the motor pathways at age 13 years. VP children also had slower FDC development in the corpus callosum and corticospinal tract between ages 7 and 13 years compared with FT children. Within VP children, earlier gestational age at birth, lower birth weight z-score, and neonatal brain abnormalities were associated with lower FD, FC and FDC throughout the white matter at both ages. ConclusionsVP birth and concomitant perinatal risk factors are associated with fibre tract-specific alterations to axonal development in childhood and adolescence.

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Multivariate patterns between brain network properties, polygenic scores, phenotypes, and environment in preadolescents

Seo, J.; Lee, E.; Kim, B.-G.; Kim, G.; Joo, Y. Y.; Cha, J.

2023-07-24 pediatrics 10.1101/2023.07.24.23293075
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Brain development in childhood is shaped by complex interactions between genetic predispositions, environmental influences, and neural connectivity, yet how these factors jointly contribute to cognitive and mental health outcomes remains unclear. Structural brain networks, quantified through graph-theoretic measures, have been linked to cognition and psychiatric risk, but the extent to which genetic architecture and environmental exposures shape these networks, and whether brain networks mediate these influences, is not well understood. Here we show that genetic predispositions related to cognitive ability and socioeconomic status (SES) exhibit the strongest covariation with structural brain network topology in children. Using sparse canonical correlation analysis (SCCA) on ABCD Study data (N = 10,343), we identified robust associations between brain network properties, polygenic scores for cognition, SES indicators, and cognitive-psychopathological phenotypes. Mediation analysis further demonstrated that structural brain networks partially mediate the influence of genetic and environmental factors on cognitive performance and mental health outcomes, suggesting that neurodevelopmental trajectories may be shaped by both genetic liability and modifiable environmental conditions. These findings provide empirical support for a multivariate, systems-level perspective on brain development and cognitive-psychopathological variation in youth. By elucidating shared neural substrates underlying genetic and environmental influences, this work advances our understanding of brain network development and highlights potential pathways for individualized interventions and predictive modeling in developmental psychiatry and neuroscience.

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Screen Time and Puberty Timing: Findings from the Adolescent Brain Cognitive Development Study

Bläschke, L. M.; Weisner, F. E.; Hinney, A.; Peters, T.; Hirtz, R.; Schmidt, B.; Dinkelbach, L.

2026-01-28 pediatrics 10.64898/2026.01.26.26344850
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ObjectiveTo examine whether screen time predicts interindividual variability regarding pubertal development across adolescence. Study designThis longitudinal cohort study included 10786 participants (47.9% female) from the Adolescent Brain Cognitive Development (ABCD) study. First, associations were examined between average daily screen time (hours/day, parent-reported Screen Time Survey) at baseline (mean age = 9.91 {+/-} 0.63 years) and pubertal timing, derived from Pubertal Development Scale (PDS) scores through 4-year follow-up (mean age = 14.08 {+/-} 0.68 years) and standardized by age and sex. Second, associations were examined between screen time groups (very low: 0-1.29 h/day; low: 1.29-2.07 h/day; moderate: 2.07-2.86 h/day; high: 2.86-4.0 h/day; very high: 4.00-12.43 h/day) and age at mid-puberty, defined as the age at first parent report of Pubertal Development Scale (PDS) category at least 3. ResultsIn linear mixed models adjusting for age, sex, race/ethnicity, socioeconomic status, BMI, and physical activity, higher log-transformed screen time at baseline was associated with more advanced pubertal timing at 1-, 2- and 3- year follow-ups, with the strongest effect observed at year 2 (standardized {beta}=0.07 [95%-CI, 0.05 to 0.10]). The associations were more pronounced in girls. The group of participants with very high screen time reached mid-puberty 2.47 months earlier [adjusted effect size, 95%-CI, -3.38 to -1.56) than participants with very low screen time. ConclusionThese findings suggest that screen time in late childhood is linked with earlier pubertal development and highlight its relevance for parental guidance on preadolescents screen media use.

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Associations between prenatal adversity and neonatal white matter microstructure on language outcomes at age 2 years

Bjork, J. R.; Kenley, J. K.; Gardner, C.; Latham, A.; Smyser, T. A.; Miller, J. P.; Shimony, J. J.; Neil, J. J.; Warner, B.; Luby, J.; Barch, D. M.; Rogers, C. E.; Smyser, C. D.; Lean, R. E.

2024-08-05 pediatrics 10.1101/2024.08.02.24311434
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BackgroundEarly life adversity is associated with microstructural alterations in white matter regions that subserve language. However, the mediating and moderating pathways between adversities experienced in utero and key neonatal white matter tracts including the corpus callosum (CC), superior longitudinal fasciculus (SLF), arcuate fasciculus (AF), inferior fronto- occipital fasciculus (IFOF), and uncinate on early language outcomes remains unknown. MethodsThis longitudinal study includes 160 neonates, oversampled for prenatal exposure to adversity, who underwent diffusion MRI (dMRI) in the first weeks of life. dMRI parameters were obtained using probabilistic tractography in FSL. Maternal Social Disadvantage and Psychosocial Stress was assessed throughout pregnancy. At age 2 years, the Bayley Scales of Infant and Toddler Development-III evaluated language outcomes. Linear regression, mediation, and moderation assessed associations between prenatal adversities and neonatal white matter on language outcomes. ResultsPrenatal exposure to Social Disadvantage (p<.001) and Maternal Psychosocial Stress (p<.001) were correlated with poorer language outcomes. When Social Disadvantage and maternal Psychosocial Stress were modeled simultaneously in relation to language outcomes, only Social Disadvantage was significant (p<.001). Independent of Social Disadvantage (p<.001), lower neonatal CC fractional anisotropy (FA) was related to poorer global (p=.02) and receptive (p=.02) language outcomes. CC FA did not mediate the association between Social Disadvantage and language outcomes (indirect effect 95% CIs -0.96-0.15), and there was no interaction between Social Disadvantage and CC FA on language outcomes (p>.05). Bilateral SLF/AF, IFOF, and uncinate were not significant (p>.05). ConclusionsPrenatal exposure to Social Disadvantage and neonatal CC FA were independently related to language problems by age 2, with no evidence of mediating or moderating associations with language outcomes. These findings elucidate the early neural underpinnings of language development and suggest that the prenatal period may be an important time to provide poverty- reducing support to expectant mothers to promote offspring neurodevelopmental outcomes.

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Adherence to 24h movement recommendations and health indicators in the ABCD study: Cross-sectional and longitudinal associations with cognition, psychosocial health, BMI and brain structure

Fung, H.; Yeo, B. T. T.; Chen, C.; Lo, J. C.; Chee, M. W. L.; Ong, J. L.

2022-03-24 pediatrics 10.1101/2022.03.23.22272692
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Adherence to 24h movement guidelines of [&ge;]60min of physical activity, [&le;]2h of screen time, and 9-11h of sleep has been shown to benefit cognition, physical and psychosocial health in children aged 5-13y. However, these findings are largely based on cross-sectional studies or small samples. Here we utilize data from the Adolescent Brain Cognitive Development (ABCD) study of 10000+ children aged 9-11y to examine whether adherence to 24h movement guidelines benefit cognition, BMI, psychosocial health and brain morphometric measures at baseline (T1) and 2 years later (T2). After adjustment for sociodemographic confounders in multivariable linear mixed models, we observed better cognitive scores, fewer behavioural problems, lower adiposity levels and greater gray matter volumes in children who met both sleep and screen time recommendations compared to those who met none. Longitudinal follow up further supports these findings; participants who met both recommendations at T1 and T2 evidenced better outcome measures than those who met none, even after controlling for T1 measures. These findings support consideration of integrated rather than isolated movement recommendations across the day for better cognitive, physical, psychosocial and brain health.

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Multimodal Neuroimaging Signature of Sleep Problems Predicts Preadolescent Mental Health Trajectories

Wang, Y.; Tahmasian, M.; Genon, S.; Samea, F.; He, Z.; Liu, X.; Lei, X.; Eickhoff, S. B.; Dong, D.

2025-09-23 pediatrics 10.1101/2025.09.22.25336312
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Sleep-related problems (SRP) in childhood are common and clinically relevant yet their underlying neural mechanisms and links to future mental health outcomes remain poorly understood. Here, we investigated how distinct dimensions of SRP relate to multimodal brain structure and function in preadolescents, and whether these neural signatures predict trajectories of mental health difficulties. We employed multivariate mapping to investigate the relationship between structural and functional brain network patterns and various dimensions of SRP in the Adolescent Brain Cognitive Development (ABCD) dataset. Moreover, we explored whether and how the identified multimodal brain signatures could predict the trajectory of internalizing and externalizing behavior difficulties over a two-year follow-up. Our multivariate analysis revealed two robust dimensions of SRP: a general sleep disturbance dimension and a hypersomnolence and parasomnia dimension. Each was associated with partially distinct patterns of brain morphology and functional connectivity, consistent with their differential alignment along the hierarchical organization of cortical neurodevelopment maps. However, both dimensions shared common disruptions in the somatosensory, attention, and default mode networks. We further observed that only these neural patterns associated with the general sleep disturbance dimension predict the longitudinal trajectories of internalizing/externalizing symptoms. Our findings enhance the understanding of the neurobiological mechanisms underlying dimensions of SRP in preadolescence and could inform brain-based intervention and treatment programs to improve sleep-related and mental health-related outcomes across development.

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Antenatal Maternal Anaemia and Infant Brain Structure: 3T and 64mT MRI Findings from South Africa

Ringshaw, J. E.; Zieff, M. R.; Bourke, N. J.; Casella, C.; Bradford, L. E.; Williams, S. R.; Herr, D.; Miles, M.; Bennallick, C.; Khula South Africa Data Collection Team, ; Deoni, S.; O'Muircheartaigh, J.; Stein, D. J.; Alexander, D. C.; Jones, D. K.; Williams, S. C. R.; Donald, K. A.

2025-12-02 pediatrics 10.64898/2025.11.28.25341220
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With the evolution of ultra-low-field MRI and the recognition of antenatal maternal anaemia as an important driver of altered neurodevelopment in toddlers and children, it is critical to determine whether these effects are detectable at 64mT in infancy. The aim of this study was to assess the impact of antenatal maternal anaemia on infant brain structure across the first two years of life, using conventional high-field (3T) and ultra-low-field (64mT) MRI. This neuroimaging sub-study was embedded within Khula, an observational population-based birth cohort in South Africa. Pregnant women were enrolled antenatally and postnatally. Mother-child dyads (n=394) were followed prospectively with a subsample attending neuroimaging at approximately 3, 6, 12, 18, and 24 months of age. Anaemia was classified using WHO thresholds and neuroimaging data was processed using MiniMORPH. Linear mixed effects models were used to investigate associations between antenatal maternal anaemia status and absolute regional infant brain volumes using high-field and ultra-low-field MRI. In repeated measures high-field (n=195) and ultra-low-field (n=341) infant neuroimaging subsamples, the prevalence of antenatal maternal anaemia was 28.24% (37/131) and 29.76% (61/205), respectively. Maternal anaemia in pregnancy was associated with altered child brain structure across both MRI systems, with group differences becoming detectable at approximately 12 months. In the ultra-low-field subsample, infants born to anaemic mothers had 3.77% smaller ICV ({beta}=-0.24, p=0.004) and 3.32% smaller putamen volumes ({beta}=-0.18, p=0.04) across the first 2 years of life. The interaction between antenatal maternal anaemia and age was significant for the caudate nucleus ({beta}=-0.13, p=0.038) and the corpus callosum ({beta}=-0.13, p=0.037). Maternal anaemia in pregnancy was associated with 3.70% and 4.29% smaller caudate nucleus at 18 and 24 months of age, respectively. Similarly, infants born to anaemic mothers had 4.18% smaller corpus callosum volumes by 12 months and 7.10% smaller corpus callosum volumes by 24 months. Postnatal child anaemia and antenatal maternal iron deficiency status were not associated with total or regional child brain volumes in the ultra-low-field subsample from this cohort. Maternal anaemia remained a robust predictor of volume differences in sensitivity analyses. This study is the first to demonstrate that the impact of maternal anaemia in pregnancy on child brain structure is detectable as early as infancy. The implications of this research are two-fold; (1) informing the feasibility of ultra-low-field MRI for use in low- and middle-income countries, as well as (2) the timing and optimisation of targeted recommendations for anaemia management in both practice and policy.

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Associations of reading skills and properties of cerebral white matter pathways in 8-year-old children born preterm

Dubner, S. E.; Ben-Shachar, M.; Mezer, A.; Feldman, H. M.; Travis, K. E.

2020-12-14 pediatrics 10.1101/2020.12.11.20247965
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AIMChildren born preterm (PT) experience perinatal white matter injury and later reading deficits at school age. We used two complementary neuroimaging modalities to determine if reading skills would be associated with contemporaneous white matter properties in school-aged PT children. METHODIn 8-year-old PT children (N=29), we measured diffusivity (fractional anisotropy, FA), from diffusion MRI, and myelin content (relaxation rate, R1) from quantitative relaxometry. We assessed reading (Grays Oral Reading Test, Fifth Edition) in each child. Whole-brain deterministic tractography coupled with automatic segmentation and quantification were applied to extract FA and R1 along four tracts and assess their statistical association with reading scores. RESULTSReading-FA correlations were not significant along the four analyzed tracts. Reading-R1 correlations were significantly positive in portions of the left superior longitudinal fasciculus, right uncinate fasciculus, and left inferior longitudinal fasciculus. FA positively correlated with R1 in limited areas of reading-R1 associations, but did not contribute to the variance in reading scores. INTERPRETATIONCombining complementary neuroimaging approaches identified relations between reading and white matter properties not found using a single MRI measure. Associations of reading skills and white matter properties may vary across white matter tracts and metrics in PT children. What this paper adds{blacksquare} Preterm childrens reading was associated with white matter myelin content. {blacksquare}Preterm childrens reading was not associated with white matter diffusivity.