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  • 1
    Online Resource
    Online Resource
    Mapping the Stability of Human Brain Asymmetry across Five Sex-Chromosome Aneuploidies
    Society for Neuroscience ; 2015
    In:  The Journal of Neuroscience Vol. 35, No. 1 ( 2015-01-07), p. 140-145
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 35, No. 1 ( 2015-01-07), p. 140-145
    Abstract: The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX ( n = 28), XXY ( n = 58), XYY ( n = 26), XXYY ( n = 20), and XXXXY ( n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.3489-14.2015
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2015
    detail.hit.zdb_id: 1475274-8
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  • 2
    Online Resource
    Online Resource
    Topologically Dissociable Patterns of Development of the Human Cerebral Cortex
    Society for Neuroscience ; 2015
    In:  The Journal of Neuroscience Vol. 35, No. 2 ( 2015-01-14), p. 599-609
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 35, No. 2 ( 2015-01-14), p. 599-609
    Abstract: Over 90 years ago, anatomists noted the cortex is thinner in sulci than gyri, suggesting that development may occur on a fine scale driven by local topology. However, studies of brain development in youth have focused on describing how cortical thickness varies over large-scale functional and anatomic regions. How the relationship between thickness and local sulcal topology arises in development is still not well understood. Here, we investigated the spatial relationships between cortical thickness, folding, and underlying white matter organization to elucidate the influence of local topology on human brain development. Our approach included using both T1-weighted imaging and diffusion tensor imaging (DTI) in a cross-sectional sample of 932 youths ages 8–21 studied as part of the Philadelphia Neurodevelopmental Cohort. Principal components analysis revealed separable development-related processes of regionally specific nonlinear cortical thickening (from ages 8–14) and widespread linear cortical thinning that have dissociable relationships with cortical topology. Whereas cortical thinning was most prominent in the depths of the sulci, early cortical thickening was present on the gyri. Furthermore, decline in mean diffusivity calculated from DTI in underlying white matter was correlated with cortical thinning, suggesting that cortical thinning is spatially associated with white matter development. Spatial permutation tests were used to assess the significance of these relationships. Together, these data demonstrate that cortical remodeling during youth occurs on a local topological scale and is associated with changes in white matter beneath the cortical surface.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.3628-14.2015
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2015
    detail.hit.zdb_id: 1475274-8
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  • 3
    Online Resource
    Online Resource
    Development of the Cerebral Cortex across Adolescence: A Multisample Study of Inter-Related Longitudinal Changes in Cortical Volume, Surface Area, and Thickness
    Society for Neuroscience ; 2017
    In:  The Journal of Neuroscience Vol. 37, No. 12 ( 2017-03-22), p. 3402-3412
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 37, No. 12 ( 2017-03-22), p. 3402-3412
    Abstract: Before we can assess and interpret how developmental changes in human brain structure relate to cognition, affect, and motivation, and how these processes are perturbed in clinical or at-risk populations, we must first precisely understand typical brain development and how changes in different structural components relate to each other. We conducted a multisample magnetic resonance imaging study to investigate the development of cortical volume, surface area, and thickness, as well as their inter-relationships, from late childhood to early adulthood (7–29 years) using four separate longitudinal samples including 388 participants and 854 total scans. These independent datasets were processed and quality-controlled using the same methods, but analyzed separately to study the replicability of the results across sample and image-acquisition characteristics. The results consistently showed widespread and regionally variable nonlinear decreases in cortical volume and thickness and comparably smaller steady decreases in surface area. Further, the dominant contributor to cortical volume reductions during adolescence was thinning. Finally, complex regional and topological patterns of associations between changes in surface area and thickness were observed. Positive relationships were seen in sulcal regions in prefrontal and temporal cortices, while negative relationships were seen mainly in gyral regions in more posterior cortices. Collectively, these results help resolve previous inconsistencies regarding the structural development of the cerebral cortex from childhood to adulthood, and provide novel insight into how changes in the different dimensions of the cortex in this period of life are inter-related. SIGNIFICANCE STATEMENT Different measures of brain anatomy develop differently across adolescence. Their precise trajectories and how they relate to each other throughout development are important to know if we are to fully understand both typical development and disorders involving aberrant brain development. However, our understanding of such trajectories and relationships is still incomplete. To provide accurate characterizations of how different measures of cortical structure develop, we performed an MRI investigation across four independent datasets. The most profound anatomical change in the cortex during adolescence was thinning, with the largest decreases observed in the parietal lobe. There were complex regional patterns of associations between changes in surface area and thickness, with positive relationships seen in sulcal regions in prefrontal and temporal cortices, and negative relationships seen mainly in gyral regions in more posterior cortices.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.3302-16.2017
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2017
    detail.hit.zdb_id: 1475274-8
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  • 4
    Online Resource
    Online Resource
    Longitudinally Mapping Childhood Socioeconomic Status Associations with Cortical and Subcortical Morphology
    Society for Neuroscience ; 2019
    In:  The Journal of Neuroscience Vol. 39, No. 8 ( 2019-02-20), p. 1365-1373
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 39, No. 8 ( 2019-02-20), p. 1365-1373
    Abstract: Childhood socioeconomic status (SES) impacts cognitive development and mental health, but its association with human structural brain development is not yet well characterized. Here, we analyzed 1243 longitudinally acquired structural MRI scans from 623 youth (299 female/324 male) to investigate the relation between SES and cortical and subcortical morphology between ages 5 and 25 years. We found positive associations between SES and total volumes of the brain, cortical sheet, and four separate subcortical structures. These associations were stable between ages 5 and 25. Surface-based shape analysis revealed that higher SES is associated with areal expansion of lateral prefrontal, anterior cingulate, lateral temporal, and superior parietal cortices and ventrolateral thalamic, and medial amygdalo-hippocampal subregions. Meta-analyses of functional imaging data indicate that cortical correlates of SES are centered on brain systems subserving sensorimotor functions, language, memory, and emotional processing. We further show that anatomical variation within a subset of these cortical regions partially mediates the positive association between SES and IQ. Finally, we identify neuroanatomical correlates of SES that exist above and beyond accompanying variation in IQ. Although SES is clearly a complex construct that likely relates to development through diverse, nondeterministic processes, our findings elucidate potential neuroanatomical mediators of the association between SES and cognitive outcomes. SIGNIFICANCE STATEMENT Childhood socioeconomic status (SES) has been associated with developmental disparities in mental health, cognitive ability, and academic achievement, but efforts to understand underlying SES–brain relationships are ongoing. Here, we leverage a unique developmental neuroimaging dataset to longitudinally map the associations between SES and regional brain anatomy at high spatiotemporal resolution. We find widespread associations between SES and global cortical and subcortical volumes and surface area and localize these correlations to a distributed set of cortical, thalamic, and amygdalo-hippocampal subregions. Anatomical variation within a subset of these regions partially mediates the positive relationship between SES and IQ. Our findings help to localize cortical and subcortical systems that represent candidate biological substrates for the known relationships between SES and cognition.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.1808-18.2018
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2019
    detail.hit.zdb_id: 1475274-8
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  • 5
    Online Resource
    Online Resource
    Regional White Matter Scaling in the Human Brain
    Society for Neuroscience ; 2021
    In:  The Journal of Neuroscience Vol. 41, No. 33 ( 2021-08-18), p. 7015-7028
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 41, No. 33 ( 2021-08-18), p. 7015-7028
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    URL: Article
    DOI: 10.1523/JNEUROSCI.1193-21.2021
    DOI: 10.1523/JNEUROSCI.1193-21.2021.video.1
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2021
    detail.hit.zdb_id: 1475274-8
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  • 6
    Online Resource
    Online Resource
    Sex-chromosome dosage effects on gene expression in humans
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 28 ( 2018-07-10), p. 7398-7403
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 28 ( 2018-07-10), p. 7398-7403
    Abstract: A fundamental question in the biology of sex differences has eluded direct study in humans: How does sex-chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex-chromosome aneuploidies (XO, XXX, XXY, XYY, and XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity among evolutionarily preserved X-Y homologs and update prevailing theoretical models for SCD compensation by detecting X-linked genes that increase expression with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex-chromosome genes regulate specific coexpression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. These gene coexpression results converge with analysis of transcription factor binding site enrichment and measures of gene expression in murine knockout models to spotlight the dosage-sensitive X-linked transcription factor ZFX as a key mediator of SCD effects on wider genome expression. Our findings characterize the effects of SCD broadly across the genome, with potential implications for human phenotypic variation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1802889115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 7
    Online Resource
    Online Resource
    X-chromosome influences on neuroanatomical variation in humans
    Springer Science and Business Media LLC ; 2021
    In:  Nature Neuroscience Vol. 24, No. 9 ( 2021-09), p. 1216-1224
    Details
    In: Nature Neuroscience, Springer Science and Business Media LLC, Vol. 24, No. 9 ( 2021-09), p. 1216-1224
    Type of Medium: Online Resource
    ISSN: 1097-6256 , 1546-1726
    URL: Article
    DOI: 10.1038/s41593-021-00890-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1494955-6
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  • 8
    Online Resource
    Online Resource
    Longitudinal four-dimensional mapping of subcortical anatomy in human development
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 4 ( 2014-01-28), p. 1592-1597
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 4 ( 2014-01-28), p. 1592-1597
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1316911111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Disrupted sensorimotor and social–cognitive networks underlie symptoms in childhood-onset schizophrenia
    Oxford University Press (OUP) ; 2016
    In:  Brain Vol. 139, No. 1 ( 2016-01), p. 276-291
    Details
    In: Brain, Oxford University Press (OUP), Vol. 139, No. 1 ( 2016-01), p. 276-291
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    URL: Article
    DOI: 10.1093/brain/awv306
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 10
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    Online Resource
    A Comprehensive Quantitative Genetic Analysis of Cerebral Surface Area in Youth
    Society for Neuroscience ; 2019
    In:  The Journal of Neuroscience Vol. 39, No. 16 ( 2019-04-17), p. 3028-3040
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 39, No. 16 ( 2019-04-17), p. 3028-3040
    Abstract: The genetics of cortical arealization in youth is not well understood. In this study, we use a genetically informative sample of 677 typically developing children and adolescents (mean age 12.72 years), high-resolution MRI, and quantitative genetic methodology to address several fundamental questions on the genetics of cerebral surface area. We estimate that 〉 85% of the phenotypic variance in total brain surface area in youth is attributable to additive genetic factors. We also observed pronounced regional variability in the genetic influences on surface area, with the most heritable areas seen in primary visual and visual association cortex. A shared global genetic factor strongly influenced large areas of the frontal and temporal cortex, mirroring regions that are the most evolutionarily novel in humans relative to other primates. In contrast to studies on older populations, we observed statistically significant genetic correlations between measures of surface area and cortical thickness ( r G = 0.63), suggestive of overlapping genetic influences between these endophenotypes early in life. Finally, we identified strong and highly asymmetric genetically mediated associations between Full-Scale Intelligence Quotient and left perisylvian surface area, particularly receptive language centers. Our findings suggest that spatially complex and temporally dynamic genetic factors are influencing cerebral surface area in our species. SIGNIFICANCE STATEMENT Over evolution, the human cortex has undergone massive expansion. In humans, patterns of neurodevelopmental expansion mirror evolutionary changes. However, there is a sparsity of information on how genetics impacts surface area maturation. Here, we present a systematic analysis of the genetics of cerebral surface area in youth. We confirm prior research that implicates genetics as the dominant force influencing individual differences in global surface area. We also find evidence that evolutionarily novel brain regions share common genetics, that overlapping genetic factors influence both area and thickness in youth, and the presence of strong genetically mediated associations between intelligence and surface area in language centers. These findings further elucidate the complex role that genetics plays in brain development and function.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.2248-18.2019
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2019
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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