An fMRI investigation of propagated intrinsic activity in early development and autism

早期发育和自闭症中传播的内在活动的功能磁共振成像研究

• 批准号: 9247037
• 负责人: Anish Mitra
• 金额: $ 4.9万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-04 至 2018-05-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9247037
• 关键词: Adult; Affect; Age; Age-Months; Autistic Disorder; Autopsy; Behavior; Brain; Brain imaging; Brain region; Broca' s area; Child; Clinical; Cognitive; Comorbidity; Data; Databases; Destinations; Development; Diagnosis; Disease; Employee Strikes; Functional Magnetic Resonance Imaging; Future; Genetic Heterogeneity; Heterogeneity; Human; Incidence; Individual; Infant; Investigation; Language; Language Development; Life; Light; Link; Magnetic Resonance Imaging; Maps; Measures; Methods; Motor; National Institute of Mental Health; Neurobiology; Neurodevelopmental Disorder; Neurologic; Neuronal Plasticity; Participant; Pathology; Pattern; Phenotype; Play; Prefrontal Cortex; Recruitment Activity; Reproducibility; Rest; Role; Seeds; Series; Severities; Shapes; Siblings; Signal Transduction; Source; Strategic Planning; Structure; Techniques; Testing; Time; Weight; Work; autism spectrum disorder; base; blood oxygen level dependent; brain abnormalities; developmental disease; early childhood; high risk; imaging study; in utero; in vivo; independent component analysis; interest; motor learning; neural correlate; neuronal circuitry; public health relevance; putamen; relating to nervous system; repetitive behavior; social communication impairment

DESCRIPTION (provided by applicant): Autism spectrum disorders (ASD) constitute a heterogeneous group of neurodevelopmental disorders characterized by impaired social-communication function, repetitive behaviors, and a restricted range of interests. ASD affects approximately 1 in every 88 individuals and the incidence appears to be rising. Within ASD, there exists wide phenotypic heterogeneity in adaptive function, cognitive and language abilities, and neurological comorbidities, leading many to refer to these various disorders as 'the autisms'. Therefore, two key questions emerge: (1) Despite phenotypic and genetic heterogeneity, does ASD have common neurobiological signatures? (2) Can such neurobiological signatures be studied in vivo in humans? Answers to these questions would represent a significant step forward in our understanding of ASD, as well as our ability to diagnose and treat this condition. We have recently developed a new technique for the analysis of resting state fMRI data based on mapping propagated intrinsic brain activity. When applied to fMRI data obtained in high-functioning adults with ASD, the new method appears to be more sensitive than conventional functional connectivity analysis in detecting focal brain abnormalities. The objective of this project is to apply this new technique to fMRI data collected in young, typically developing children, as well as children who develop ASD. Preliminary results indicate that our method detects changes, at the group level, in the temporal structure of intrinsic activity in 6-month-old children who subsequently develop clinical ASD. This finding is consistent with recent post-mortem pathology evidence of disrupted cortical organization in individuals with ASD very early in life, perhaps even in utero. The intimate relationships between the temporal structure of intrinsic activity, neuronal plasticity, and early brain development provide a strong theoretical basis for this investigation. Specific questions to be investigated include: (1) what is the earliest age at which patterns of propagated intrinsic activity in childre with ASD differ, at the group level, from typically developing children? (2) Are different brain regions affected by ASD at different ages? Answers to these questions may illuminate the neurobiological basis of ASD. By investigating the causes and developmental trajectory of ASD, our project is directly in line with the first two objectives of the NIMH strategic plan. We will aso explore how patterns of propagated intrinsic activity change over the course of typical early development to gain a better understanding of the neural correlates of normal developmental milestones. Characterization of normal development could inform future investigations of other neurodevelopmental disorders.

描述（由申请人提供）：自闭症谱系障碍（ASD）构成了一个异质的神经发育障碍群体，其特征是社会通信功能受损，重复行为和受限制的利益范围。 ASD每88个人中大约有1个影响，并且发生率似乎正在上升。在ASD中，自适应功能，认知能力和语言能力以及神经系统合并症中存在广泛的表型异质性，导致许多人将这些各种疾病称为“自闭症”。因此，出现了两个关键问题：（1）尽管表型和遗传异质性，ASD是否具有常见的神经生物学特征？ （2）可以在人类的体内研究这种神经生物学特征吗？这些问题的答案将代表我们对ASD的理解，以及我们诊断和治疗这种情况的能力。我们最近开发了一种基于映射的固有大脑活性的序列fMRI数据分析的新技术。当应用于具有ASD的高功能成年人获得的fMRI数据时，在检测局灶性脑异常时，新方法似乎比常规功能连通性分析更敏感。该项目的目的是将这种新技术应用于年轻的，通常是发展中的儿童以及成长为ASD的儿童的fMRI数据。初步结果表明，我们的方法在群体水平上检测到在6个月大的儿童随后发展临床ASD的固有活性的时间结构中的变化。这一发现与最近验尸的病后病理学证据表明，患有ASD患者的皮质组织干扰了生命早期，甚至可能在子宫内。内在活性，神经元可塑性和早期大脑发育的时间结构之间的亲密关系为这项研究提供了强大的理论基础。要研究的具体问题包括：（1）最早的年龄是哪种与典型成长儿童不同的ChildRe的传播固有活动模式是什么？ （2）不同年龄在不同年龄的ASD影响的不同大脑区域是否受到影响？这些问题的答案可能会阐明ASD的神经生物学基础。通过调查ASD的原因和发展轨迹，我们的项目直接符合NIMH战略计划的前两个目标。我们将探讨在典型的早期发展过程中，繁殖内在活性的模式如何变化，以更好地了解正常发展里程碑的神经相关性。正常发育的表征可以为未来对其他神经发育障碍的研究提供依据。