Pediatric Brain Imaging

我们的工作中出现了一个统一的主题，即在神经成像中，就像在生活中一样，过程通常与目的地一样重要。与时间快照相比，脑形态测量的轨迹与认知参数的相关性更高，是临床结果的更好预测指标，并且更有力地区分了按基因型分类的群体。为了捕捉发展的路径，我们在人们的整个发展过程中跟踪他们，让他们大约每两年回来参加一次。在访问NIH期间，参与者将在三个领域进行评估-脑成像，神经心理学和遗传学。(1)脑成像。磁共振成像（MRI）结合了强大的磁铁、无线电波和复杂的计算机技术，以创造出精确的大脑解剖和生理图像。它不使用电离辐射，因此对所有年龄段的人都是安全的。扫描结果通过一系列不断改进的图像分析工具进行处理，这些工具是由世界各地的合作者开发的。分析工具的输出使我们能够比较不同群体之间或同一个人随时间变化的大脑解剖学和生理学。通过在不同年龄获得的图像之间变换，我们可以制作大脑发育的电影，可以在http://www.nimh.nih.gov/videos/press/prbrainmaturing.mpeg上看到。(2)神经心理学。对于典型发育的研究，我们首先进行电话筛选，然后将问卷邮寄给家长和老师，然后亲自前往NIH。一旦被纳入研究，参与者将接受一系列心理测试，包括标准的智商测试。测试的具体内容因诊断组而异，但一般涵盖语言、执行和社会功能领域。(3)基因。我们要求参与者通过抽血提供DNA样本（其中淋巴细胞可以永生，为未来的分析提供基因检测），或者如果他们不希望通过唾液抽血。通过结合这三个领域的数据，我们希望深入了解大脑、基因和发育中的大脑行为之间的动态相互作用。

A unifying theme emerging from our work is that in neuroimaging, as in life, the journey is often as important as the destination. Trajectories of brain morphometry, as opposed to snapshots in time, are more highly correlated with cognitive parameters, are better predictors of clinical outcome, and more robustly distinguish groups classified by genotype. To capture the path of development we follow people throughout their development by having them return for participation at approximately two-year intervals. During their visit to the NIH participants are assessed in three realms - Brain Imaging, Neuropsychology, and Genetics. (1) Brain imaging. Magnetic resonance imaging (MRI) combines a powerful magnet, radio waves, and sophisticated computer technology to create exquisitely accurate pictures of the anatomy and physiology of the brain. It does this without the use of ionizing radiation making it safe for people of all ages. The scans are processed through a series of ever improving image analysis tools developed by collaborators throughout the world. The output of the analytic tools allows us to compare the anatomy and physiology of brains between groups or within an individual over time. By morphing between images acquired at different ages we can create movies of brain development as can be seen at http://www.nimh.nih.gov/videos/press/prbrainmaturing.mpeg. (2) Neuropsychology. For our studies of typical development we begin with an initial phone screening followed by questionnaires mailed to parents and teachers and then the in-person visit to the NIH. Once accepted into the study participants undergo a collection of psychological tests, including a standard IQ test. The specifics of the testing vary by diagnostic group but in general cover domains of language, executive, and social functions. (3) Genetics. We request that participants provide a DNA sample via a blood draw (in which lymphoblasts can be immortalized to provide genetic testing for ongoing future analysis) or if they prefer not to have blood drawn via saliva. By combining data from these three realms we hope to gain insight into the dynamic interplay between brains, genes, and behavior in the developing brain. Key Findings and Recent Results from Project 1 - Mapping Developmental Trajectories of Brain and Behavior in Health and Illness. Prior work from our group has shown that brain developmental is characterized by increases in white matter volumes and inverted U shaped trajectories for cortical and subcortical gray matter structures with relatively late maturation of higher association areas such as superior temporal lobe and the prefrontal cortex. Prior investigations have also elucidated deviations from typical developmental trajectories for several clinical populations. Several publications related to Project 1 in the past year utilized graph theory approaches to characterize the network properties of how different regions of the brain relate to each other (REFS 1, 2). Differences in brain anatomy and network properties were characterized for several clinical populations including Autism Spectrum Disorder (REFS 11), and Obsessive Compulsive Disorder (REF 5). Additional publications examined: (1) how cortical expansion relates to folding patterns on the surface of the brain (REF 9); (2) introduced a novel method of quantifying the corpus collosum the main connection between the left and right halves of the brain (REF 10); (3) reviewed the literature and methodology of early brain overgrowth in autism (REF 8); and (4) quantified improvement in social attribution skills in children with high functioning autism spectrum disorder (REF 3). Key Findings and Recent Results from Project 2 - Male/Female Differences in Brain Development; Sexual dimorphism of the developing brain is especially pertinent for child psychiatry because nearly all neuropsychiatric disorders of childhood demonstrate male/female differences with respect to age of onset, prevalence, and symptom patterns. Prior work from our lab characterizing male/female differences in typical pediatric brain development has been amongst the most cited in the field. Publications within the past year related to Project 2 characterized brain development differences in people with 49,XXXXY Syndrome (i.e. three extra X chromosomes) (REF 4) and used high resolution imaging to show similar brain changes in mice and humans with XO (missing an X chromosome) (REF 7). Key Findings and Recent Results from Project 3 - Genetic and Environmental Influences on Brain Development; By comparing how alike identical twins (monozygotic) are to how alike fraternal twins (dizygotic) are we can begin to quantify the extent to which differences are due to genetic or environmental factors. Current sample size from the ongoing longitudinal study is approximately 300 twin pairs. Studies of specific genes and environmental factors allow exploration of the mechanisms and influences on brain development. Understanding influences on trajectories of brain development may shed light on the emergence of psychopathology during childhood and adolescence and ultimately may guide therapeutic interventions. Prior work from our group established that: (1) heritability is high and shared environmental effects low for most brain morphometric measures; (2) the cerebellum has a distinct heritability profile; (3) genetic and environmental factors contribute to the development of the cortex in a regional and age specific manner; and (4) shared genetic effects account for more of the variance than structure specific effects. Multivariate analyses indicate that 60 percent of cortical thickness variance is accounted for by a single genetic factor and that five distinct groups of brain measures are influenced by shared genetic and environmental factors. Publications in the past year related to Project 3 have characterized the impact on brain development of specific gene variants, specifically Autism Risk Gene MET Variation (REF 12), DUF1220-Domain Copy Number (REF 18), and Homeobox A1 (REF 24). Impact: The project has generated over 250 papers and 30,000 citations since its inception in 1989. Results of the studies, particularly regarding adolescent brain development, have generated wide spread public interest and discussion affecting social, educational, and judicial realms. The findings have helped spawn other research initiatives, both nationally and internationally, to replicate and extend the findings. Data from the typically developing children and adolescents have been widely used as a comparison group for clinical populations. Collaborative studies have been published with over 400 different investigators representing over 50 universities. The long term nature of the study, the emphasis on typical development, and extensive data sharing/collaboration make the Brain Imaging projects well-suited for the Intramural program.