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  • 1
    Online Resource
    Online Resource
    Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 22 ( 2018-05-29)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 22 ( 2018-05-29)
    Abstract: Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets ( n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1718418115
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
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  • 2
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    Reproducible brain-wide association studies require thousands of individuals
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 603, No. 7902 ( 2022-03-24), p. 654-660
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 603, No. 7902 ( 2022-03-24), p. 654-660
    Abstract: Magnetic resonance imaging (MRI) has transformed our understanding of the human brain through well-replicated mapping of abilities to specific structures (for example, lesion studies) and functions 1–3 (for example, task functional MRI (fMRI)). Mental health research and care have yet to realize similar advances from MRI. A primary challenge has been replicating associations between inter-individual differences in brain structure or function and complex cognitive or mental health phenotypes (brain-wide association studies (BWAS)). Such BWAS have typically relied on sample sizes appropriate for classical brain mapping 4 (the median neuroimaging study sample size is about 25), but potentially too small for capturing reproducible brain–behavioural phenotype associations 5,6 . Here we used three of the largest neuroimaging datasets currently available—with a total sample size of around 50,000 individuals—to quantify BWAS effect sizes and reproducibility as a function of sample size. BWAS associations were smaller than previously thought, resulting in statistically underpowered studies, inflated effect sizes and replication failures at typical sample sizes. As sample sizes grew into the thousands, replication rates began to improve and effect size inflation decreased. More robust BWAS effects were detected for functional MRI (versus structural), cognitive tests (versus mental health questionnaires) and multivariate methods (versus univariate). Smaller than expected brain–phenotype associations and variability across population subsamples can explain widespread BWAS replication failures. In contrast to non-BWAS approaches with larger effects (for example, lesions, interventions and within-person), BWAS reproducibility requires samples with thousands of individuals.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-04492-9
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 3
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    Publisher Correction: Reproducible brain-wide association studies require thousands of individuals
    Springer Science and Business Media LLC ; 2022
    In:  Nature Vol. 605, No. 7911 ( 2022-05-26), p. E11-E11
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 605, No. 7911 ( 2022-05-26), p. E11-E11
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-022-04692-3
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
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  • 4
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    Premotor functional connectivity predicts impulsivity in juvenile offenders
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 27 ( 2011-07-05), p. 11241-11245
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 27 ( 2011-07-05), p. 11241-11245
    Abstract: Teenagers are often impulsive. In some cases this is a phase of normal development; in other cases impulsivity contributes to criminal behavior. Using functional magnetic resonance imaging, we examined resting-state functional connectivity among brain systems and behavioral measures of impulsivity in 107 juveniles incarcerated in a high-security facility. In less-impulsive juveniles and normal controls, motor planning regions were correlated with brain networks associated with spatial attention and executive control. In more-impulsive juveniles, these same regions correlated with the default-mode network, a constellation of brain areas associated with spontaneous, unconstrained, self-referential cognition. The strength of these brain–behavior relationships was sufficient to predict impulsivity scores at the individual level. Our data suggest that increased functional connectivity of motor-planning regions with networks subserving unconstrained, self-referential cognition, rather than those subserving executive control, heightens the predisposition to impulsive behavior in juvenile offenders. To further explore the relationship between impulsivity and neural development, we studied functional connectivity in the same motor-planning regions in 95 typically developing individuals across a wide age span. The change in functional connectivity with age mirrored that of impulsivity: younger subjects tended to exhibit functional connectivity similar to the more-impulsive incarcerated juveniles, whereas older subjects exhibited a less-impulsive pattern. This observation suggests that impulsivity in the offender population is a consequence of a delay in typical development, rather than a distinct abnormality.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1108241108
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
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  • 5
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    A somato-cognitive action network alternates with effector regions in motor cortex
    Springer Science and Business Media LLC ; 2023
    In:  Nature Vol. 617, No. 7960 ( 2023-05-11), p. 351-359
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 617, No. 7960 ( 2023-05-11), p. 351-359
    Abstract: Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations 1,2 , despite evidence for concentric functional zones 3 and maps of complex actions 4 . Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action 5 and physiological control 6 , arousal 7 , errors 8 and pain 9 . This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions 4 and connectivity to internal organs 10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate–isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-023-05964-2
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 120714-3
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  • 6
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    Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD
    Proceedings of the National Academy of Sciences ; 2012
    In:  Proceedings of the National Academy of Sciences Vol. 109, No. 17 ( 2012-04-24), p. 6769-6774
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 17 ( 2012-04-24), p. 6769-6774
    Abstract: Research and clinical investigations in psychiatry largely rely on the de facto assumption that the diagnostic categories identified in the Diagnostic and Statistical Manual (DSM) represent homogeneous syndromes. However, the mechanistic heterogeneity that potentially underlies the existing classification scheme might limit discovery of etiology for most developmental psychiatric disorders. Another, perhaps less palpable, reality may also be interfering with progress—heterogeneity in typically developing populations. In this report we attempt to clarify neuropsychological heterogeneity in a large dataset of typically developing youth and youth with attention deficit/hyperactivity disorder (ADHD), using graph theory and community detection. We sought to determine whether data-driven neuropsychological subtypes could be discerned in children with and without the disorder. Because individual classification is the sine qua non for eventual clinical translation, we also apply support vector machine-based multivariate pattern analysis to identify how well ADHD status in individual children can be identified as defined by the community detection delineated subtypes. The analysis yielded several unique, but similar subtypes across both populations. Just as importantly, comparing typically developing children with ADHD children within each of these distinct subgroups increased diagnostic accuracy. Two important principles were identified that have the potential to advance our understanding of typical development and developmental neuropsychiatric disorders. The first tenet suggests that typically developing children can be classified into distinct neuropsychological subgroups with high precision. The second tenet proposes that some of the heterogeneity in individuals with ADHD might be “nested” in this normal variation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1115365109
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
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  • 7
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    Distinct brain networks for adaptive and stable task control in humans
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 26 ( 2007-06-26), p. 11073-11078
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 26 ( 2007-06-26), p. 11073-11078
    Abstract: Control regions in the brain are thought to provide signals that configure the brain's moment-to-moment information processing. Previously, we identified regions that carried signals related to task-control initiation, maintenance, and adjustment. Here we characterize the interactions of these regions by applying graph theory to resting state functional connectivity MRI data. In contrast to previous, more unitary models of control, this approach suggests the presence of two distinct task-control networks. A frontoparietal network included the dorsolateral prefrontal cortex and intraparietal sulcus. This network emphasized start-cue and error-related activity and may initiate and adapt control on a trial-by-trial basis. The second network included dorsal anterior cingulate/medial superior frontal cortex, anterior insula/frontal operculum, and anterior prefrontal cortex. Among other signals, these regions showed activity sustained across the entire task epoch, suggesting that this network may control goal-directed behavior through the stable maintenance of task sets. These two independent networks appear to operate on different time scales and affect downstream processing via dissociable mechanisms.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0704320104
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
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  • 8
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    Prediction of Individual Brain Maturity Using fMRI
    American Association for the Advancement of Science (AAAS) ; 2010
    In:  Science Vol. 329, No. 5997 ( 2010-09-10), p. 1358-1361
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 329, No. 5997 ( 2010-09-10), p. 1358-1361
    Abstract: Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals’ brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain’s major functional networks.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1194144
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2010
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
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  • 9
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    Development of distinct control networks through segregation and integration
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 33 ( 2007-08-14), p. 13507-13512
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 33 ( 2007-08-14), p. 13507-13512
    Abstract: Human attentional control is unrivaled. We recently proposed that adults depend on distinct frontoparietal and cinguloopercular networks for adaptive online task control versus more stable set control, respectively. During development, both experience-dependent evoked activity and spontaneous waves of synchronized cortical activity are thought to support the formation and maintenance of neural networks. Such mechanisms may encourage tighter “integration” of some regions into networks over time while “segregating” other sets of regions into separate networks. Here we use resting state functional connectivity MRI, which measures correlations in spontaneous blood oxygenation level-dependent signal fluctuations between brain regions to compare previously identified control networks between children and adults. We find that development of the proposed adult control networks involves both segregation (i.e., decreased short-range connections) and integration (i.e., increased long-range connections) of the brain regions that comprise them. Delay/disruption in the developmental processes of segregation and integration may play a role in disorders of control, such as autism, attention deficit hyperactivity disorder, and Tourette's syndrome.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0705843104
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
    detail.hit.zdb_id: 209104-5
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  • 10
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    The maturing architecture of the brain's default network
    Proceedings of the National Academy of Sciences ; 2008
    In:  Proceedings of the National Academy of Sciences Vol. 105, No. 10 ( 2008-03-11), p. 4028-4032
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 10 ( 2008-03-11), p. 4028-4032
    Abstract: In recent years, the brain's “default network,” a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a “default mode” of brain function. In early studies, investigators suggested that, the brain's default mode supports “self-referential” or “introspective” mental activity. Subsequently, regions of the default network have been more specifically related to the “internal narrative,” the “autobiographical self,” “stimulus independent thought,” “mentalizing,” and most recently “self-projection.” However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the network's functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brain's default network. We found that the default regions are only sparsely functionally connected at early school age (7–9 years old); over development, these regions integrate into a cohesive, interconnected network.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0800376105
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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