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The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development. This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and Year 1. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.

Author(s): Herting, Megan M; Uban, Kristina A; Gonzalez, Marybel Robledo; Baker, Fiona C; Kan, Eric C; Thompson, Wesley K; Granger, Douglas A; Albaugh, Matthew D; Anokhin, Andrey P; Bagot, Kara S; Banich, Marie T; Barch, Deanna M; Baskin-Sommers, Arielle; Breslin, Florence J; Casey, BJ; Chaarani, Bader; Chang, Linda; Clark, Duncan B; Cloak, Christine C; Constable, R Todd; Cottler, Linda B; Dagher, Rada K; Dapretto, Mirella; Dick, Anthony S; Dosenbach, Nico; Dowling, Gayathri J; Dumas, Julie A; Edwards, Sarah; Ernst, Thomas; Fair, Damien A; Feldstein-Ewing, Sarah W; Freedman, Edward G; Fuemmeler, Bernard F; Garavan, Hugh; Gee, Dylan G; Giedd, Jay N; Glaser, Paul EA; Goldstone, Aimee; Gray, Kevin M; Hawes, Samuel W; Heath, Andrew C; Heitzeg, Mary M; Hewitt, John K; Heyser, Charles J; Hoffman, Elizabeth A; Huber, Rebekah S; Huestis, Marilyn A; Hyde, Luke W; Infante, M Alejandra; Ivanova, Masha Y; Jacobus, Joanna; Jernigan, Terry L; Karcher, Nicole R; Laird, Angela R; LeBlanc, Kimberly H; Lisdahl, Krista; Luciana, Monica; Luna, Beatriz; Maes, Hermine H; Marshall, Andrew T; Mason, Michael J; McGlade, Erin C; Morris, Amanda S; Nagel, Bonnie J; Neigh, Gretchen N; Palmer, Clare E; Paulus, Martin P; Potter, Alexandra S; Puttler, Leon I; Rajapakse, Nishadi; Rapuano, Kristina; Reeves, Gloria; Renshaw, Perry F; Schirda, Claudiu; Sher, Kenneth J; Sheth, Chandni; Shilling, Paul D; Squeglia, Lindsay M; Sutherland, Matthew T; Tapert, Susan F; Tomko, Rachel L; Yurgelun-Todd, Deborah; Wade, Natasha E; Weiss, Susan RB; Zucker, Robert A | Abstract: AimTo examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.MethodsCross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.ResultsPDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.ConclusionsSociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.

The growing amount of screen time among adolescents has raised concerns about the effects it may have on their physical and psychological health. Although the literature is divided on whether the effects are mostly positive, neutral, or mostly negative, it is likely that the impacts will be highly individualized with a mixture of good and bad consequences for each person. Understanding behavioral and neurobiological phenomena of adolescence may help to guide research and interventions to optimize the benefits and minimize the risks. Particular aspects of adolescent development relevant to the issue include: (i) hunger for human connectedness; (ii) appetite for adventure; and (iii) desire for data. .La creciente cantidad de tiempo que pasan los adolescentes frente a la pantalla ha generado preocupaciones acerca de los efectos que esto puede producir en su salud física y psicológica. Aunque la literatura está dividida entre efectos mayormente positivos, neutros o mayormente negativos, es probable que las consecuencias sean altamente individualizadas con una combinación de buenos y malos resultados para cada persona. La comprensión de los fenómenos conductuales y neurobiológicos de la adolescencia puede ayudar a guiar la investigación y las intervenciones para optimizar los beneficios y minimizar los riesgos. Los aspectos particulares del desarrollo adolescente relevantes para el tema incluyen: (1) hambre de conectividad humana, (2) apetito por la aventura y (3) deseo de datos.Les adolescents passant de plus en plus de temps sur les écrans, des questions se posent quant aux effets possibles sur leur santé physique et psychologique. Dans la littérature, les avis sont partagés entre effets surtout positifs, neutres ou surtout négatifs, mais en réalité les répercussions sont propres à chaque individu, avec un mélange de conséquences positives et négatives. Afin d'optimiser les avantages et de minimiser les risques, la recherche et les traitements pourraient bénéficier de la compréhension des phénomènes comportementaux et neurobiologiques de l'adolescence, en particulier la soif de contacts humains, le désir d'aventure et l’intérêt pour les données qui sont autant d’aspects qui comptent dans ce cadre.

The neural substrates of intelligence represent a fundamental but largely uncharted topic in human developmental neuroscience. Prior neuroimaging studies have identified modest but highly dynamic associations between intelligence and cortical thickness (CT) in childhood and adolescence. In a separate thread of research, quantitative genetic studies have repeatedly demonstrated that most measures of intelligence are highly heritable, as are many brain regions associated with intelligence. In the current study, we integrate these 2 streams of prior work by examining the genetic contributions to CT–intelligence relationships using a genetically informative longitudinal sample of 813 typically developing youth, imaged with high-resolution MRI and assessed with Wechsler Intelligence Scales (IQ). In addition to replicating the phenotypic association between multimodal association cortex and language centers with IQ, we find that CT–IQ covariance is nearly entirely genetically mediated. Moreover, shared genetic factors drive the rapidly evolving landscape of CT–IQ relationships in the developing brain.

Recent advances in human neuroimaging research have revealed that white-matter connectivity can be described in terms of an integrated network, which is the basis of the human connectome. However, the developmental changes of this connectome in childhood are not well understood. This study made use of two independent longitudinal diffusion-weighted imaging data sets to characterize developmental changes in the connectome by estimating age-related changes in fractional anisotropy (FA) for reconstructed fibers (edges) between 68 cortical regions. The first sample included 237 diffusion-weighted scans of 146 typically developing children (4-13 years old, 74 females) derived from the Pediatric Longitudinal Imaging, Neurocognition, and Genetics (PLING) study. The second sample included 141 scans of 97 individuals (8-13 years old, 62 females) derived from the BrainTime project. In both data sets, we compared edges that had the most substantial age-related change in FA to edges that showed little change in FA. This allowed us to investigate if developmental changes in white matter reorganize network topology. We observed substantial increases in edges connecting peripheral and a set of highly connected hub regions, referred to as the rich club. Together with the observed topological differences between regions connecting to edges showing the smallest and largest changes in FA, this indicates that changes in white matter affect network organization, such that highly connected regions become even more strongly imbedded in the network. These findings suggest that an important process in brain development involves organizing patterns of inter-regional interactions. Hum Brain Mapp 39:157-170, 2018. © 2017 Wiley Periodicals, Inc.

Although social-communication difficulties and repetitive behaviors are hallmark features of autism spectrum disorder (ASD) and persist across the lifespan, very few studies have compared age-related differences in these behaviors between youth with ASD and same-age typically developing (TD) peers. We examined this issue using SRS-2 (Social Responsiveness Scale-Second Edition) measures of social-communicative functioning and repetitive behaviors in a stratified cross-sectional sample of 324 youth with ASD in the absence of intellectual disability, and 438 TD youth (aged 4-29 years). An age-by-group interaction emerged indicating that TD youth exhibited age-related improvements in social-communication scores while the ASD group demonstrated age-related declines in these scores. This suggests that adolescents/adults with ASD may fall increasingly behind their same-age peers in social-communicative skills.

Structural magnetic resonance imaging (MRI) scans at high spatial resolution can detect potential foci of early brain dysmaturation in children with autism spectrum disorders (ASD). In addition, comparison between MRI and behavior measures over time can identify patterns of brain change accompanying specific outcomes. We report structural MRI data from two time points for a total of 84 scans in children with ASD and 30 scans in typical controls (mean age time one = 4.1 years, mean age at time two = 6.6 years). Surface-based cortical morphometry and linear mixed effects models were used to link changes in cortical anatomy to both diagnostic status and individual differences in changes in language and autism severity. Compared with controls, children with ASD showed accelerated gray matter volume gain with age, which was driven by a lack of typical age-related cortical thickness (CT) decrease within 10 cortical regions involved in language, social cognition, and behavioral control. Greater expressive communication gains with age in children with ASD were associated with greater CT gains in a set of right hemisphere homologues to dominant language cortices, potentially identifying a compensatory system for closer translational study. Hum Brain Mapp 37:2616-2629, 2016. © 2016 Wiley Periodicals, Inc.

While the potential for small amounts of motion in functional magnetic resonance imaging (fMRI) scans to bias the results of functional neuroimaging studies is well appreciated, the impact of in-scanner motion on morphological analysis of structural MRI is relatively under-studied. Even among "good quality" structural scans, there may be systematic effects of motion on measures of brain morphometry. In the present study, the subjects' tendency to move during fMRI scans, acquired in the same scanning sessions as their structural scans, yielded a reliable, continuous estimate of in-scanner motion. Using this approach within a sample of 127 children, adolescents, and young adults, significant relationships were found between this measure and estimates of cortical gray matter volume and mean curvature, as well as trend-level relationships with cortical thickness. Specifically, cortical volume and thickness decreased with greater motion, and mean curvature increased. These effects of subtle motion were anatomically heterogeneous, were present across different automated imaging pipelines, showed convergent validity with effects of frank motion assessed in a separate sample of 274 scans, and could be demonstrated in both pediatric and adult populations. Thus, using different motion assays in two large non-overlapping sets of structural MRI scans, convergent evidence showed that in-scanner motion-even at levels which do not manifest in visible motion artifact-can lead to systematic and regionally specific biases in anatomical estimation. These findings have special relevance to structural neuroimaging in developmental and clinical datasets, and inform ongoing efforts to optimize neuroanatomical analysis of existing and future structural MRI datasets in non-sedated humans. Hum Brain Mapp 37:2385-2397, 2016. © 2016 Wiley Periodicals, Inc.

© 2015 Studies suggest marijuana impacts gray and white matter neural tissue development, however few prospective studies have determined the relationship between cortical thickness and cannabis use spanning adolescence to young adulthood. This study aimed to understand how heavy marijuana use influences cortical thickness trajectories across adolescence. Subjects were adolescents with heavy marijuana use and concomitant alcohol use (MJ + ALC, n = 30) and controls (CON, n = 38) with limited substance use histories. Participants underwent magnetic resonance imaging and comprehensive substance use assessment at three independent time points. Repeated measures analysis of covariance was used to look at main effects of group, time, and Group × Time interactions on cortical thickness. MJ + ALC showed thicker cortical estimates across the brain (23 regions), particularly in frontal and parietal lobes (ps

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.HighlightsAn overview of the MRI processing pipeline for the ABCD StudyA discussion on the challenges of large, multisite population studiesA methodological reference for users of publicly shared data from the ABCD Study

Objectives: Past research suggests that youth with sex chromosome aneuploidies (SCAs) present with verbal fluency deficits. However, most studies have focused on sex chromosome trisomies. Far less is known about sex chromosome tetrasomies and pentasomies. Thus, the current research sought to characterize verbal fluency performance among youth with sex chromosome trisomies, tetrasomies, and pentasomies by contrasting how performance varies as a function of extra X number and X versus Y status. Methods: Participants included 79 youth with SCAs and 42 typically developing controls matched on age, maternal education, and racial/ethnic background. Participants completed the phonemic and semantic conditions of a verbal fluency task and an abbreviated intelligence test. Results: Both supernumerary X and Y chromosomes were associated with verbal fluency deficits relative to controls. These impairments increased as a function of the number of extra X chromosomes, and the pattern of impairments on phonemic and semantic fluency differed for those with a supernumerary X versus Y chromosome. Whereas one supernumerary Y chromosome was associated with similar performance across fluency conditions, one supernumerary X chromosome was associated with relatively stronger semantic than phonemic fluency skills. Conclusions: Verbal fluency skills in youth with supernumerary X and Y chromosomes are impaired relative to controls. However, the degree of impairment varies across groups and task condition. Further research into the cognitive underpinnings of verbal fluency in youth with SCAs may provide insights into their verbal fluency deficits and help guide future treatments. (JINS, 2018, 24, 917–927)

The phenotype of 48, XXYY syndrome (referred to as XXYY) is associated with characteristic but variable developmental, cognitive, behavioral and physical abnormalities. To discern the neuroanatomical phenotype of the syndrome, we conducted quantitative and qualitative analyses on MRI brain scans from 25 males with XXYY and 92 age and SES matched typically developing XY males. Quantitatively, males in the XXYY group had smaller gray and white matter volumes of the frontal and temporal lobes. Conversely, both gray and white matter volumes of the parietal lobe as well as lateral ventricular volume were larger in the XXYY group. Qualitatively, males in the XXYY group had a higher incidence of colpocephaly (84% vs. 34%, p ≤ 0.001), white matter lesions (25% vs. 5%, p = 0.007), and thin posterior body of the corpus callosum (28% vs. 3%, p = 0.001). The specificity of these findings may shed light on the role of the X and Y chromosomes in typical and atypical brain development and help provide direction for future studies of brain–behavior relationships in males with XXYY syndrome., Highlights • GM and WM of the frontal and temporal lobe are smaller. • GM and WM of the parietal lobe, as well as lateral ventricular volumes are larger. • Colpocephaly, WM lesions and abnormalities of the corpus callosum were increased.

There are varying, often conflicting, reports with respect to altered striatal volume and morphometry in the major psychoses due to the influences of antipsychotic medications on striatal volume. Thus, disassociating disease effects from those of medication become exceedingly difficult. For the first time, using a longitudinally studied sample of structural magnetic resonance images from patients with childhood onset schizophrenia (COS; neurobiologically contiguous with the adult onset form of schizophrenia), their nonpsychotic siblings (COSSIBs), and novel shape mapping algorithms that are volume independent, we report the familial contribution of striatal morphology in schizophrenia. The results of our volumetric analyses demonstrate age-related increases in overall striatal volumes specific only to COS. However, both COS and COSSIBs showed overlapping shape differences in the striatal head, which normalized in COSSIBs by late adolescence. These results mirror previous studies from our group, demonstrating cortical thickness deficits in COS and COSSIBs as these deficits normalize in COSSIBs in the same age range as our striatal findings. Finally, there is a single region of nonoverlapping outward displacement in the dorsal aspect of the caudate body, potentially indicative of a response to medication. Striatal shape may be considered complimentary to volume as an endophenotype, and, in some cases may provide information that is not detectable using standard volumetric techniques. Our striatal shape findings demonstrate the striking localization of abnormalities in striatal the head. The neuroanatomical localization of these findings suggest the presence of abnormalities in the striatal-prefrontal circuits in schizophrenia and resilience mechanisms in COSSIBs with age dependent normalization.

Understanding how brain development normally proceeds is a premise of understanding neurodevelopmental disorders. This has sparked a wealth of magnetic resonance imaging (MRI) studies. Unfortunately, they are in marked disagreement on how the cerebral cortex matures. While cortical thickness increases for the first 8–9 years of life have repeatedly been reported, others find continuous cortical thinning from early childhood, at least from age 3 or 4 years. We review these inconsistencies, and discuss possible reasons, including the use of different scanners, recording parameters and analysis tools, and possible effects of variables such as head motion. When tested on the same subsample, 2 popular thickness estimation methods (CIVET and FreeSurfer) both yielded a continuous thickness decrease from 3 years. Importantly, MRI-derived measures of cortical development are merely our best current approximations, hence the term “apparent cortical thickness” may be preferable. We recommend strategies for reaching consensus in the field, including multimodal neuroimaging to measure phenomena using different techniques, for example, the use of T1 / T2 ratio, and data sharing to allow replication across analysis methods. As neurodevelopmental origins of early- and late-onset disease are increasingly recognized, resolving inconsistencies in brain maturation trajectories is important.

Background Schizophrenia is a disorder of brain connectivity and altered neurodevelopmental processes. Cross-sectional case-control studies in different age groups have suggested that deficits in cortical thickness in childhood-onset schizophrenia may normalize over time, suggesting a disorder-related difference in cortical growth trajectories. Methods We acquired magnetic resonance imaging scans repeated over several years for each subject, in a sample of 106 patients with childhood-onset schizophrenia and 102 age-matched healthy volunteers. Using semiparametric regression, we modeled the effect of schizophrenia on the growth curve of cortical thickness in ~80,000 locations across the cortex, in the age range 8 to 30 years. In addition, we derived normative developmental modules composed of cortical regions with similar maturational trajectories for cortical thickness in typical brain development. Results We found abnormal nonlinear growth processes in prefrontal and temporal areas that have previously been implicated in schizophrenia, distinguishing for the first time between cortical areas with age-constant deficits in cortical thickness and areas whose maturational trajectories are altered in schizophrenia. In addition, we showed that when the brain is divided into five normative developmental modules, the areas with abnormal cortical growth overlap significantly only with the cingulo-fronto-temporal module. Conclusions These findings suggest that abnormal cortical development in schizophrenia may be modularized or constrained by the normal community structure of developmental modules of the human brain connectome.

Growing access to large-scale longitudinal structural neuroimaging data has fundamentally altered our understanding of cortical development en route to human adulthood, with consequences for basic science, medicine, and public policy. In striking contrast, basic anatomical development of subcortical structures such as the striatum, pallidum, and thalamus has remained poorly described--despite these evolutionarily ancient structures being both intimate working partners of the cortical sheet and critical to diverse developmentally emergent skills and disorders. Here, to begin addressing this disparity, we apply methods for the measurement of subcortical volume and shape to 1,171 longitudinally acquired structural magnetic resonance imaging brain scans from 618 typically developing males and females aged 5-25 y. We show that the striatum, pallidum, and thalamus each follow curvilinear trajectories of volume change, which, for the striatum and thalamus, peak after cortical volume has already begun to decline and show a relative delay in males. Four-dimensional mapping of subcortical shape reveals that (i) striatal, pallidal, and thalamic domains linked to specific fronto-parietal association cortices contract with age whereas other subcortical territories expand, and (ii) each structure harbors hotspots of sexually dimorphic change over adolescence--with relevance for sex-biased mental disorders emerging in youth. By establishing the developmental dynamism, spatial heterochonicity, and sexual dimorphism of human subcortical maturation, these data bring our spatiotemporal understanding of subcortical development closer to that of the cortex--allowing evolutionary, basic, and clinical neuroscience to be conducted within a more comprehensive developmental framework.

Regions of the human brain develop at different rates across the first two decades of life, with some maturing before others. It has been hypothesized that a mismatch in the timing of maturation between subcortical regions (involved in affect and reward processing) and prefrontal regions (involved in cognitive control) underlies the increase in risk-taking and sensation-seeking behaviors observed during adolescence. Most support for this ‘dual systems' hypothesis relies on cross-sectional data, and it is not known whether this pattern is present at an individual level. The current study utilizes longitudinal structural magnetic resonance imaging (MRI) data to describe the developmental trajectories of regions associated with risk-taking and sensation-seeking behaviors, namely, the amygdala, nucleus accumbens (NAcc) and prefrontal cortex (PFC). Structural trajectories of gray matter volumes were analyzed using FreeSurfer in 33 participants aged 7-30 years, each of whom had at least three high-quality MRI scans spanning three developmental periods: late childhood, adolescence and early adulthood (total 152 scans). The majority of individuals in our sample showed relatively earlier maturation in the amygdala and/or NAcc compared to the PFC, providing evidence for a mismatch in the timing of structural maturation between these structures. We then related individual developmental trajectories to retrospectively assessed self-reported risk-taking and sensation-seeking behaviors during adolescence in a subsample of 24 participants. Analysis of this smaller sample failed to find a relationship between the presence of a mismatch in brain maturation and risk-taking and sensation-seeking behaviors during adolescence. Taken together, it appears that the developmental mismatch in structural brain maturation is present in neurotypically developing individuals. This pattern of development did not directly relate to self-reported behaviors at an individual level in our sample, highlighting the need for prospective studies combining anatomical and behavioral measures.

Although prior studies have demonstrated that genetic factors play the dominant role in the patterning of the pediatric brain, it remains unclear how these patterns change over time. Using 1748 longitudinal anatomic MRI scans from 792 healthy twins and siblings, we quantified how genetically mediated inter-regional associations change over time via multivariate longitudinal structural equation modeling. These analyses found that genetic correlations for both lobar volumes and cortical thickness are dynamic, with relatively static effects on surface area. While genetic correlations for lobar volumes decrease over childhood and adolescence, in general they increase for cortical thickness in the second decade of life. Quantification of how genetic factors influence maturational coupling improves our understanding of typical neurodevelopment and informs future molecular genetic analyses.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9–10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.

Patient lesion and functional magnetic resonance imaging (fMRI) studies have provided convincing evidence that a distributed brain network subserves word knowledge. However, little is known about the structural correlates of this network within the context of typical development and whether anatomical coupling in linguistically relevant regions of cortex varies as a function of vocabulary skill. Here we investigate the association between vocabulary and anatomical coupling in 235 typically developing youth (ages 6–19 years) using structural MRI. The study's primary aim was to evaluate whether higher vocabulary performance was associated with greater vertex-level cortical thickness covariation in distributed regions of cortex known to be associated with word knowledge. Results indicate that better vocabulary skills are associated with greater anatomical coupling in several linguistically relevant regions of cortex, including the left inferior parietal (temporal-parietal junction), inferior temporal, middle frontal, and superior frontal gyri and the right inferior frontal and precentral gyri. Furthermore, in high vocabulary scorers, stronger coupling is found among these regions. Thus, complementing patient and fMRI studies, this is the first investigation to highlight the relevance of anatomical covariance within the cortex to vocabulary skills in typically developing youth, further elucidating the distributed nature of neural systems subserving word knowledge. Hum Brain Mapp 35:1885–1895, 2014. © 2013 Wiley Periodicals, Inc.

Autism spectrum disorders are associated with atypically excessive early brain growth. Recent studies suggest that later cortical development, specifically cortical thickness, during adolescence and young adulthood is also aberrant. Nevertheless, previous studies of other surface-based metrics (e.g. surface area and gyrification) at high-resolution in autism spectrum disorders are limited. Forty-one males with autism spectrum disorders and 39 typically developing males matched on age (mean ∼17; range = 12–24 years) and IQ (mean ∼113; range = 85–143) provided high-resolution 3 T anatomical magnetic resonance imaging scans. The FreeSurfer image analysis suite quantified vertex-level surface area and gyrification. There were gyrification increases in the autism spectrum disorders group (relative to typically developing subjects) localized to bilateral posterior cortices (cluster corrected P < 0.01). Furthermore, the association between vocabulary knowledge and gyrification in left inferior parietal cortex (typically developing group: positive correlation; autism spectrum disorders group: no association) differed between groups. Finally, there were no group differences in surface area, and there was no interaction between age and group for either surface area or gyrification (both groups showed decreasing gyrification with increasing age). The present study complements and extends previous work by providing the first evidence of increased gyrification (though no differences in surface area) at high resolution among adolescents and young adults with autism spectrum disorders and by showing a dissociation in the relationship between vocabulary and gyrification in autism spectrum disorders versus typically developing subjects. In contrast with previous findings of age-related cortical thinning in this same autism spectrum disorders sample, here we find that increases in gyrification are maintained across adolescence and young adulthood, implicating developmentally dissociable cortical atypicalities in autism spectrum disorders.

Neuroimaging studies have implicated the corpus callosum (CC) in the pathophysiology of obsessive-compulsive disorder (OCD). Putative dysfunctions in prefrontal cortical regions suggest anomalies in anterior segments of the CC. However, recent studies have also implicated the middle and posterior CC. The present study soughts to examine the CC using parcellation scheme informed by diffusion tensor imaging. Anatomic brain magnetic resonance scans were obtained from 21 OCD subjects (mean age=26.9 ± 9.93) and 42 healthy age- and sex-matched controls (mean age=26.6 ± 9.46) between the ages of 14 and 49. Area and volume measures of five subregions of the CC were obtained via manual tracings. A multivariate analysis of variance (after correcting for multiple comparisons) identified smaller area and volume in the mid-anterior region of the CC in OCD patients relative to controls. These findings implicate medio-frontal regions of the cortex in the pathophysiology of OCD.

Age-related changes in social attribution skills were assessed using the “Triangles Playing Tricks” task in 7–17 year old high functioning children with ASDs (n = 41) and in typically developing (TD) children (n = 58) matched on age, IQ, and sex ratio. Children with ASDs gave responses that received lower intentionality and appropriateness ratings than did TD children in both the goal-directed and theory of mind (ToM) conditions. Results remained unchanged when the effects of verbal output (i.e., number of clause produced) and verbal IQ were included as covariates in the analyses. Whereas age was highly associated with ToM performance in the TD children, this relationship was not as strong among children with ASDs. These results indicate not only a diminished tendency among high functioning children with ASDs to attribute social meaning and intentionality to ambiguous visual displays of interactive forms but also an aberrant developmental trajectory. That is, children with ASDs may fall further behind their typically developing peers in social attribution abilities as they get older.

Gyrification is a fundamental property of the human cortex that is increasingly studied by basic and clinical neuroscience. However, it remains unclear if and how the global architecture of cortical folding varies with 3 interwoven sources of anatomical variation: brain size, sex, and sex chromosome dosage (SCD). Here, for 375 individuals spanning 7 karyotype groups (XX, XY, XXX, XYY, XXY, XXYY, XXXXY), we use structural neuroimaging to measure a global sulcation index (SI, total sulcal/cortical hull area) and both determinants of sulcal area: total sulcal length and mean sulcal depth. We detail large and patterned effects of sex and SCD across all folding metrics, but show that these effects are in fact largely consistent with the normative scaling of cortical folding in health: larger human brains have disproportionately high SI due to a relative expansion of sulcal area versus hull area, which arises because disproportionate sulcal lengthening overcomes a lack of proportionate sulcal deepening. Accounting for these normative allometries reveals 1) brain size-independent sulcal lengthening in males versus females, and 2) insensitivity of overall folding architecture to SCD. Our methodology and findings provide a novel context for future studies of human cortical folding in health and disease.

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings.SIGNIFICANCE STATEMENTSex and sex-chromosome dosage (SCD) are known to modulate human brain size and cortical anatomy, but very little is known regarding their impact on subcortical structures that work with the cortex to subserve a range of behaviors in health and disease. Moreover, regional brain allometry (nonlinear scaling) poses largely unaddressed methodological and theoretical challenges for such research. We build the first set of allometric norms for global and regional subcortical anatomy, and use these to dissect out the complex, distributed and topologically organized patterns of areal contraction and expansion, which characterize sex and SCD effects on subcortical anatomy. Our data inform basic research into the patterning of neuroanatomical variation, and the clinical neuroscience of sex-chromosome aneuploidy.

Owing to their unique evolutionary history, modern mammalian X- and Y-chromosomes have highly divergent gene contents counterbalanced by regulatory features, which preferentially restrict expression of X- and Y-specific genes. These 2 characteristics make opposing predictions regarding the expected dissimilarity of X- vs. Y-chromosome influences on biological structure and function. Here, we quantify this dissimilarity using in vivo neuroimaging within a rare cohort of humans with diverse sex chromosome aneuploidies (SCAs). We show that X- and Y-chromosomes have opposing effects on overall brain size but exert highly convergent influences on local brain anatomy, which manifest across biologically distinct dimensions of the cerebral cortex. Large-scale online meta-analysis of functional neuroimaging data indicates that convergent sex chromosome dosage effects preferentially impact centers for social perception, communication, and decision-making. Thus, despite an almost complete lack of sequence homology, and opposing effects on overall brain size, X- and Y-chromosomes exert congruent effects on the proportional size of cortical systems involved in adaptive social functioning. These convergent X–Y effects (i) track the dosage of those few genes that are still shared by X- and Y-chromosomes, and (ii) may provide a biological substrate for the link between SCA and increased rates of psychopathology.

Social cognition provides humans with the necessary skills to understand and interact with one another. One aspect of social cognition, mentalizing ,i s associated with a network of brain regions often referred to as thesocial brain.� These consist of medial prefrontal cortex (medial Brodmann Area 10 (mBA10)), temporoparietal junction (TPJ), posterior superior temporal sulcus (pSTS) and anterior temporal cortex (ATC). How these specific regions develop structurally across late childhood and adolescence is not well established. This study examined the structural developmental trajectorie so f social brain regions in the longest ongoing longitudinal neuroimaging study of human brain maturation. Structural trajectories of grey matter volume, cortical thickness and surface area were analyzed using surface-based cortical reconstruction software and mixed modeling in a longitudinal sampl eo f 288 participants (ages 7-30 years, 857 total scans). Grey matter volume and cortical thickness in mBA10, TPJ and pSTS decreased from childhood into the early twenties. The ATC increased in grey matter volume until adolescence and in cortical thickness until early adulthood. Surface area for each region followed a cubic trajectory, peaking in early or pre-adolescence before decreasing into the early twenties. These results are discussed in the context of developmental changes in social cognition across adolescence.

MET receptor tyrosine kinase (MET) has been proposed as a candidate risk gene for autism spectrum disorder (ASD) based on associations between MET polymorphisms and ASD diagnosis, as well as evidence from animal studies that MET protein may regulate early development of cortical regions implicated in the neurobiology of ASD. The relevance of differences in MET signaling for human cortical development remains unexamined, however. We sought to address this issue by relating genotype at a functional single nucleotide polymorphism within the MET promoter (rs1858830, G→C), to in vivo measures of cortical thickness development derived from 222 healthy children and adolescents with 514 longitudinally acquired structural MRI brain scans between ages 9 and 22 years. We identified a statistically significant, developmentally fixed, and stepwise CT reduction with increasing C allele dose in superior and middle temporal gyri, ventral pre- and post-central gyri, and anterior cingulate bilaterally, and in the right fronto-polar cortex. We were also able to demonstrate that mean CT within these cortical regions showed a statistically significant reduction with increasing scores on a continuous measure of autistic traits (the Social Responsiveness Scale). The cortical regions highlighted by our analyses are not only established areas of MET expression during prenatal life, but are also key components of the “social brain” which have frequently shown structural and functional abnormalities in autism. Our results suggest that genetic differences in the MET gene may influence the development of cortical systems implicated in the neurobiology of ASD

Background Several lines of evidence suggest that autism may be associated with abnormalities in white matter development. However, inconsistencies remain in the literature regarding the nature and extent of these abnormalities, partly because of the limited types of measurements that have been used. Here, we used magnetization transfer imaging to provide insight into the myelination of the corpus callosum in children with autism. Methods Magnetization transfer imaging scans were obtained in 101 children with autism and 35 typically developing children who did not significantly differ with regard to gender or age. The midsagittal area of the corpus callosum was manually traced and the magnetization transfer ratio (MTR) was calculated for each voxel within the corpus callosum. Mean MTR and height and location of the MTR histogram peak were analyzed. Results Mean MTR and MTR histogram peak height and location were significantly higher in children with autism than in typically developing children, suggesting abnormal myelination of the corpus callosum in autism. Conclusions The differences in callosal myelination suggested by these results may reflect an alteration in the normally well-regulated process of myelination of the brain, with broad implications for neuropathology, diagnosis, and treatment of autism.

Remarkable advances in technologies that enable the distribution and use of information encoded as digital sequences of 1s or 0s have dramatically changed our way of life. Adolescents, old enough to master the technologies and young enough to welcome their novelty, are at the forefront of this “digital revolution.” Underlying the adolescent’s eager embracement of these sweeping changes is a neurobiology forged by the fires of evolution to be extremely adept at adaptation. The consequences of the brain’s adaptation to the demands and opportunities of the digital age have enormous implications for adolescent health professionals. 2012 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. IMPLICATIONS AND CONTRIBUTION Adolescents tend to be early adopters of the latest digital technologies. Insights from adolescent neurodevelopment are key to understanding why and how young people use these technologies.

Supernumerary sex chromosome aneuploidies (referred to here as X/Y-aneuploidies), the presence of extra X- and/or Y-chromosomes, occur at a collective rate of ~1/475 births (Nielsen & Wohlert, 1990). Sex chromosome trisomies (e.g., XXX, XXY, XYY) occur most frequently, each with rates of ~1/900 births, while tetra- and pentasomies (e.g., XXXX, XXXXX, XXXY, XXXXY) are considerably rarer, each with rates of ~1/85,000 births or fewer (Linden, Bender, & Robinson, 1995). There is longstanding evidence that children with X/Y-aneuploidies have language-learning difficulties. However, only recently, attention also has been drawn to social difficulties, including autism spectrum disorder (ASD) symptomatology, in these groups (for reviews, see Leggett, Jacobs, Nation, Scerif, & Bishop, 2010; Lee, Lopez, Adeyemi, & Giedd, 2011). Given the close connection between idiopathic language impairments and ASDs and the fact no prior studies have examined language and/or social functioning in children with the X/Y tri-, tetra-, and pentasomies, the current study sought to examine both of these domains of functioning in a sample of children with XXX, XXXX, XXXXX, XYY, XXY, XXXY, and XXXXY and typically developing (TD) controls. In particular, we aimed to evaluate dosage effects of X- and Y-chromosomes on language and social functioning in order to shed light not only on the nature of language and social difficulties in children with X/Y aneuploidies, but also on the possible contributions of the X- and Y-chromosomes to idiopathic language impairments and ASDs. Prospective newborn screening studies of X/Y-aneuploidies (Walzer, Bashir, & Silbert, 1990; Ratcliffe et al., 1982, Bender et al., 1983; Netley & Rovet, 1982) and more recent reports (Bishop et al., 2011; Ross, Zeger, Kushner, Zinn, & Roeltgen, 2009) have noted increased rates of language-based learning disorders, including speech, semantic and syntactic deficits (which we refer to as ‘structural language’ or non-social language deficits) and depressed Verbal IQ scores in XXY and XXX. While these children often have lower nonverbal IQ scores than siblings, significant nonverbal learning difficulties are not commonly reported (Bender, Linden, & Robinson, 1991). For males with an additional Y-chromosome (XYY), cognitive findings are inconsistent. Some prospective studies reported about a one standard deviation decrease in general cognitive functioning (Ratcliffe et al., 1982; Walzer et al., 1990). However, when data were pooled across early studies, no significant depression in overall cognitive abilities was found (Netley, 1986). Nevertheless, more recent research suggests that at a minimum, males with XYY have depressed verbal cognitive and structural language skills relative to TD peers (Bishop et al., 2011; Ross et al., 2009). Research on children with X-chromosome tetra- and pentasomies (XXXX, XXXXX, XXXY, XXXXY) suggests decreases in verbal and nonverbal intellectual abilities with each additional X-chromosome (Linden et al., 1995), such that many of these individuals have cognitive abilities in the borderline to intellectually disabled range (Visootsak, Rosner, Dykens, Tartaglia, & Graham, 2007; though Gropman et al., 2010 suggests that nonverbal cognition is relatively preserved in XXXXY despite profound language deficits). Furthermore, studies suggest significant structural language impairments in these groups (Visootsak et al., 2007), including severe dyspraxia resulting in limited to no speech in XXXXY (Gropman et al., 2010). In summary, there appears to be strong evidence for structural language impairments in X/Y-aneuploidies. However, less is known about pragmatic or more social aspects of language, including discourse, understanding of metaphor and humor, and nonverbal communication. The few studies that have been completed converge in implicating pragmatic language difficulties in X/Y trisomies using standardized (Ross et al., 2009) and experimental cognitive tasks (van Rijn et al., 2007) as well as parent report (Bishop et al., 2011). However, no study has examined pragmatic language skills in X/Y tetra- and pentasomies, or pragmatic language vis-a-vis structural language functioning in any X/Y-aneuploidy. Even less is known about the social phenotype associated with X/Y-aneuploidies. Recent studies suggest that the addition of one X-chromosome in males (XXY) is associated with heightened rates of ASDs and social-cognitive impairments (Bishop et al., 2011; Bruining, Swaab, Kas, & van Engeland, 2009; van Rijn, Swaab, Aleman, & Kahn, 2006). In contrast, reports of females with XXX and males with XXXY and XXXXY are not indicative of increased ASD risk (Bishop et al., 2011; Visootsak et al., 2007). Reports of males with XYY indicate that an additional Y-chromosome may be associated with social difficulties, as these males appear to have increased rates of ASDs and ASD symptomatology (Bishop et al., 2011; Geerts, Steyaert, & Fryns, 2003). Thus, the current research sought to examine verbal and nonverbal intellectual skills, structural and pragmatic language abilities, and ASD symptomatology in a large sample of children with sex chromosome tri-, tetra-, and pentasomies and TD controls in order to examine X- and Y-chromosome dosage effects on these phenotypes. Unlike previous studies investigating genotype-specific profiles, we focused on quantity of supernumerary sex chromosomes. Therefore, we collapsed across genotypes (e.g., +0X=XX, XY; +1X=XXX, XXY), and in the case of tetra- and pentasomies, limited sample size necessitated combining these groups (i.e., +2/3X=XXXX, XXXXX, XXXY, XXXXY; consistent with prior work by Visootsak et al., 2007) in order to answer study questions regarding X and Y dosage effects. We predict that: 1- Increased X- and Y-chromosome number will be associated with increased intellectual impairments with a discrepantly stronger impact on verbal relative to nonverbal intelligence. 2-Supernumerary X- and Y-chromosomes will be associated with impairments in both structural and pragmatic language; however, a supernumerary Y-chromosome will be associated with more pronounced pragmatic than structural language deficits. 3-Elevated ASD symptomatology will be associated with X/Y-aneuploidy, but supernumerary X-chromosome dosage effects will not be present.

Prenatal life encompasses a critical phase of human brain development, but neurodevelopmental consequences of normative differences in prenatal growth among full-term pregnancies remain largely uncharted. Here, we combine the power of a within-monozygotic twin study design with longitudinal neuroimaging methods that parse dissociable components of structural brain development between ages 3 and 30 y, to show that subtle variations of the in utero environment, as indexed by mild birth weight (BW) variation within monozygotic pairs, are accompanied by statistically significant ( i ) differences in postnatal intelligence quotient (IQ) and ( ii ) alterations of brain anatomy that persist at least into late adolescence. Greater BW within the normal range confers a sustained and generalized increase in brain volume, which in the cortical sheet, is specifically driven by altered surface area rather than cortical thickness. Surface area is maximally sensitive to BW variation within cortical regions implicated in the biology of several mental disorders, the risk for which is modified by normative BW variation. We complement this near-experimental test of prenatal environmental influences on human brain development by replicating anatomical findings in dizygotic twins and unrelated singletons. Thus, using over 1,000 brain scans, across three independent samples, we link subtle differences in prenatal growth, within ranges seen among the majority of human pregnancies, to protracted surface area alterations, that preferentially impact later-maturing associative cortices important for higher cognition. By mapping the sensitivity of postnatal human brain development to prenatal influences, our findings underline the potency of in utero life in shaping postnatal outcomes of neuroscientific and public health importance.

Human brain functional networks are embedded in anatomical space and have topological properties—small-worldness, modularity, fat-tailed degree distributions—that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas.

SummaryUnderstanding of human structural brain development has rapidly advanced in recent years, but remains fundamentally “localizational” in nature. Here, we use 376 longitudinally acquired structural brain scans from 108 typically developing adolescents to conduct the first study of coordinated anatomical change within the developing cortex. Correlation in rates of anatomical change was regionally heterogeneous, with fronto-temporal association cortices showing the strongest and most widespread maturational coupling with other cortical areas, and lower-order sensory cortices showing the least. Canonical cortical systems with rich structural and functional interconnectivity showed significantly elevated maturational coupling. Evidence for sexually dimorphic maturational coupling was found within a frontopolar-centered prefrontal system involved in complex decision-making. By providing the first link between cortical connectivity and the coordination of cortical development, we reveal a hitherto unseen property of healthy brain maturation, which may represent a target for neurodevelopmental disease processes, and a substrate for sexually dimorphic behavior in adolescence.

Background It was recently found that the development of typical patterns of prefrontal, but not posterior, cortical asymmetry is disrupted in right-handed youth with attention-deficit/hyperactivity disorder (ADHD). Using longitudinal data, we tested the hypothesis that there would be a congruent disruption in the growth of the anterior corpus callosum, which contains white matter tracts connecting prefrontal cortical regions. Methods Areas of five subregions of the corpus callosum were quantified using a semiautomated method from 828 neuroanatomic magnetic resonance scans acquired from 236 children and adolescents with ADHD (429 scans) and 230 typically developing youth (399 scans), most of whom had repeated neuroimaging. Growth rates of each diagnostic group were defined using mixed-model linear regression. Results Right-handed participants with ADHD showed a significantly higher rate of growth in the anterior-most region of the corpus callosum (estimated annual increase in area of .97%, SEM .12%) than their typically developing peers (annual increase in area of .32% SEM .13%; t = 3.64, p = .0003). No significant diagnostic differences in growth rates were found in any other regions in right-handed participants, and no significant diagnostic differences were found in non-right-handed participants. Conclusions As hypothesized, we found anomalous growth trajectories in the anterior corpus callosum in ADHD. This disrupted anterior callosal growth may reflect, or even drive, the previously reported disruption in the development of prefrontal cortex asymmetry. The finding documents the dynamic, age-dependent nature of callosal and congruent prefrontal cortical abnormalities characterizing ADHD.

We investigated repetitive and stereotyped behavior (RSB) and its relationship to morphometric measures of the basal ganglia and thalami in 3- to 4-year-old children with autism spectrum disorder (ASD; n = 77) and developmental delay without autism (DD; n = 34). Children were assessed through clinical evaluation and parent report using RSB-specific scales extracted from the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview, and the Aberrant Behavior Checklist. A subset of children with ASD (n = 45), DD (n = 14), and a group of children with typical development (TD; n = 25) were also assessed by magnetic resonance imaging. Children with ASD demonstrated elevated RSB across all measures compared to children with DD. Enlargement of the left and right striatum, more specifically the left and right putamen, and left caudate, was observed in the ASD compared to the TD group. However, nuclei were not significantly enlarged after controlling for cerebral volume. The DD group, in comparison to the ASD group, demonstrated smaller thalami and basal ganglia regions even when scaled for cerebral volume, with the exception of the left striatum, left putamen, and right putamen. Elevated RSB, as measured by the ADOS, was associated with decreased volumes in several brain regions: left thalamus, right globus pallidus, left and right putamen, right striatum and a trend for left globus pallidus and left striatum within the ASD group. These results confirm earlier reports that RSB is common early in the clinical course of ASD and, furthermore, demonstrate that such behaviors may be associated with decreased volumes of the basal ganglia and thalamus.

Deficits in executive function (EF) are reported to occur in individuals with Klinefelter syndrome (XXY). The degree of impairment, if any, is variable and the nature of these deficits has not been clearly elucidated in young males. In this report, we (a) examine EF skills using multiple tasks in a non-clinic referred group of youth with XXY, (b) describe the extent of EF weaknesses in XXY when this group is compared with typical males of a similar SES or typical males with similar verbal abilities, and (c) evaluate the contribution of comorbid attention-deficit/hyperactivity disorder (ADHD) to EF skills. The sample included 27 males with XXY (ages 9–25), 27 typically developing age- and vocabulary-matched males, and 22 age- and socioeconomic status-matched males. EF tasks included Verbal Fluency, the Trail Making Test, and the CANTAB Spatial Working Memory and Stockings of Cambridge tasks. Mixed model analysis of variance was used to compare the groups on EF tasks and revealed a main effect of group but no group by task interaction. Overall, the XXY group performed less well than both control groups, but performance did not differ significantly as a function of task. ADHD comorbidity in males with XXY was related to poorer EF skills. (JINS, 2011, 17, 522–530)

Biological development is driven by a complex dance between nurture and nature, determined not only by the specific features of the interacting genetic and environmental influences but also by the timing of their rendezvous. The initiation of large-scale longitudinal studies, ever-expanding knowledge of genetics, and increasing availability of neuroimaging data to provide endophenotypic bridges between molecules and behavior are beginning to provide some insight into interactions of developmental stage, genes, and the environment, although daunting challenges remain. Prominent amongst these challenges are difficulties in identifying and quantifying relevant environmental factors, discerning the relative contributions to multiply determined outcomes, and the likelihood that brain development is a non-linear dynamic process in which small initial differences may yield large later effects. Age-sensitive mechanisms include developmental changes in gene expression, epigenetic modifications, synaptic arborization/pruning, and maturational improvements in our capacity to seek out environments of our choosing. Greater understanding of how genetic and environmental factors interact differently across ages is an important step toward elucidating the mechanisms by which phenotypes are created – and how they may differ in health and disease. This knowledge may also provide clues to guide the type and timing of interventions to maximize outcomes.

The adolescent brain is more “plastic” than it will ever be again, capable of remarkable adaptability in light of the many social, physical, sexual, and intellectual challenges that this developmental phase brings. This is also a peak time for clinical onset of most mental illnesses (see the chart) ( 1 ). One in five adolescents have a mental illness that will persist into adulthood ( 2 ). Mental illnesses that emerge before adulthood impose a 10-fold higher cost than those that emerge later in life ( 3 ). Mental health costs are the highest single source of global economic burden in the world ( 4 ).

Studies of head size and brain volume in autism spectrum disorders have suggested that early cortical overgrowth may be followed by prematurely arrested growth. However, the few investigations quantifying cortical thickness have yielded inconsistent results, probably due to variable ages and/or small sample sizes. We assessed differences in cortical thickness between high-functioning adolescent and young adult males with autism spectrum disorders (n = 41) and matched typically developing males (n = 40). We hypothesized thinner cortex, particularly in frontal, parietal and temporal regions, for individuals with autism spectrum disorders in comparison with typically developing controls. Furthermore, we expected to find an age × diagnosis interaction: with increasing age, more pronounced cortical thinning would be observed in autism spectrum disorders than typically developing participants. T(1)-weighted magnetization prepared rapid gradient echo 3 T magnetic resonance imaging scans were acquired from high-functioning males with autism spectrum disorders and from typically developing males matched group-wise on age (range 12-24 years), intelligence quotient (≥ 85) and handedness. Both gyral-level and vertex-based analyses revealed significantly thinner cortex in the autism spectrum disorders group that was located predominantly in left temporal and parietal regions (i.e. the superior temporal sulcus, inferior temporal, postcentral/superior parietal and supramarginal gyri). These findings remained largely unchanged after controlling for intelligence quotient and after accounting for psychotropic medication usage and comorbid psychopathology. Furthermore, a significant age × diagnosis interaction was found in the left fusiform/inferior temporal cortex: participants with autism spectrum disorders had thinner cortex in this region with increasing age to a greater degree than did typically developing participants. Follow-up within group comparisons revealed significant age-related thinning in the autism spectrum disorders group but not in the typically developing group. Both thinner temporal and parietal cortices during adolescence and young adulthood and discrepantly accelerated age-related cortical thinning in autism spectrum disorders suggest that a second period of abnormal cortical growth (i.e. greater thinning) may be characteristic of these disorders.

Humans have systematic sex differences in brain-related behavior, cognition, and pattern of mental illness risk. Many of these differences emerge during adolescence, a developmental period of intense neurostructural and endocrine change. Here, by creating “movies” of sexually dimorphic brain development using longitudinal in vivo structural neuroimaging, we show regionally specific sex differences in development of the cerebral cortex during adolescence. Within cortical subsystems known to underpin domains of cognitive behavioral sex difference, structural change is faster in the sex that tends to perform less well within the domain in question. By stratifying participants through molecular analysis of the androgen receptor gene, we show that possession of an allele conferring more efficient functioning of this sex steroid receptor is associated with “masculinization” of adolescent cortical maturation. Our findings extend models first established in rodents, and suggest that in humans too, sex and sex steroids shape brain development in a spatiotemporally specific manner, within neural systems known to underpin sexually dimorphic behaviors.

Magnetic resonance imaging (MRI) allows unprecedented access to the anatomy and physiology of the developing brain without the use of ionizing radiation. Over the past two decades, thousands of brain MRI scans from healthy youth and those with neuropsychiatric illness have been acquired and analyzed with respect to diagnosis, sex, genetics, and/or psychological variables such as IQ. Initial reports comparing size differences of various brain components averaged across large age spans have given rise to longitudinal studies examining trajectories of development over time and evaluations of neural circuitry as opposed to structures in isolation. Although MRI is still not of routine diagnostic utility for evaluation of pediatric neuropsychiatric disorders, patterns of typical versus atypical development have emerged that may elucidate pathologic mechanisms and suggest targets for intervention. In this review we summarize general contributions of structural MRI to our understanding of neurodevelopment in health and illness.

Adolescence is a time of increased divergence between males and females in physical characteristics, behavior, and risk for psychopathology. Here we will review data regarding sex differences in brain structure and function during this period of the lifespan. The most consistent sex difference in brain morphometry is the 9-12% larger brain size that has been reported in males. Individual brain regions that have most consistently been reported as different in males and females include the basal ganglia, hippocampus, and amygdala. Diffusion tensor imaging and magnetization transfer imaging studies have also shown sex differences in white matter development during adolescence. Functional imaging studies have shown different patterns of activation without differences in performance, suggesting male and female brains may use slightly different strategies for achieving similar cognitive abilities. Longitudinal studies have shown sex differences in the trajectory of brain development, with females reaching peak values of brain volumes earlier than males. Although compelling, these sex differences are present as group averages and should not be taken as indicative of relative capacities of males or females.

Turner syndrome (TS) is a model for X chromosome influences on neurodevelopment because it is most commonly caused by absence of one X chromosome and associated with altered brain structure and function. However, all prior in vivo magnetic resonance imaging studies of the brain in TS have either used manual approaches or voxel-based morphometry (VBM) to measure cortical volume (CV). These methods, unlike surface-based morphometry (SBM), cannot measure the two neurobiologically distinct determinants of CV- cortical thickness (CT) and surface area (SA) - which have differing genetic determinants and may be independently altered. Therefore, in 24 adults with X monosomy and 19 healthy female controls, we used SBM to compare (i) lobar CV, CT and SA; (ii) an index of hemispheric gyrification; (iii) CT throughout the cortical sheet; and (iv) CT correlation between cortical regions. Compared to controls, females with TS had (i) significantly increased CT and decreased SA in parietal and occipital lobes (resulting in no significant difference in lobar CV); (ii) reduced hemispheric gyrification bilaterally; (iii) foci of significantly increased CT involving inferior temporal, lateral occipital, intraparietal sulcus (IPS), cingulate and orbitofrontal cortices; and (iv) significantly reduced CT correlation between the left IPS and cortical regions including supramarginal and lateral occipital gyri. Our findings suggest that females with TS have complex, sometimes "opposing", abnormalities in SA/gyrification (decreased) and CT (increased), which can result in no overall detectable differences in CV. Thus, haploinsufficiency of X chromosome genes, may differentially impact the distinct mechanisms shaping SA (e.g. cortical folding) and CT (e.g. dendritic arborization/pruning). CT disruptions are maximal within and between cortical regions previously implicated in the TS cognitive phenotype.