Linking Local Activity and Functional Connectivity in Autism

将自闭症患者的局部活动与功能连接联系起来

• 批准号: 8489812
• 负责人: Ralph-Axel Mueller
• 金额: $ 9.25万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8489812
• 关键词: Affect; Age; Anatomy; Anisotropy; Architecture; Auditory; Auditory area; Autistic Disorder; Behavioral; Biochemical; Brain; Cerebral cortex; Cerebrum; Child; Childhood; Cognition; Cognitive; Complex; Consensus; Data; Defect; Development; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Event; Fiber; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Genes; Genetic; Genetic Risk; Growth; Health; Image; Impairment; Individual; Inferior; Language; Left; Link; Literature; Magnetic Resonance Imaging; Measures; Modeling; Motor; Motor Cortex; Neurocognitive; Neurodevelopmental Disorder; Neuropsychological Tests; Noise; Participant; Pathogenesis; Pathologic Processes; Pathology; Pathway interactions; Performance; Phenotype; Physiological; Play; Population; Process; Process Measure; Property; Public Health; Radial; Research; Role; Sampling; Semantics; Sensory; Series; Site; System; Techniques; Testing; Therapeutic; Time; Variant; Visual; area striata; autism spectrum disorder; behavioral impairment; design; endophenotype; frontal lobe; insight; neuropathology; neuropsychological; relating to nervous system; research study; white matter

DESCRIPTION (provided by applicant): While in the past autism research has often been dedicated to a single core deficit or localized brain defect, growing evidence suggests that autism is a "distributed disorder" involving many genes and neuroanatomical loci, and many neurofunctional and behavioral systems. The resulting need for studies of network organization and brain connectivity is hampered by our lack of (i) a precise understanding of what impaired functional connectivity ("underconnectivity") in autism means, and (ii) a model integrating evidence of abnormal local cortical architecture with evidence of "underconnectivity". Children with autism (ages 13-17 years) and matched typically developing children will participate in neuropsychological testing, diffusion tensor imaging (DTI), and functional MRI (fMRI) experiments during performance on two simple sensory tasks (visual, auditory) and a more complex lexico-semantic language task. Event-related fMRI designs will allow us to identify activation peaks in primary visual and auditory cortices, primary motor cortex, and left inferior frontal cortex. These activation peaks will be further used for functional connectivity (fcMRI) analyses, testing for time series correlations across the brain. According to our overarching hypothesis, reduced activation concordance (reflecting compromised local cortical organization) will be associated with reduced interregional connectivity (functional, anatomical), reduced white matter integrity, and with impaired neuropsychological performance in autism. Four specific aims will test hypotheses for the autism group of (i) reduced concordance of activity in core activation sites (fMRI), (ii) correlation between functional connectivity (fcMRI) and activation concordance, (iii) correlations of anatomical connectivity and white matter integrity (DTI) with local activation concordance and functional connectivity, and (iv) correlations between imaging (concordance, connectivity) and neuropsychological measures. Establishing links between cognitive-behavioral impairment, local cortical compromise, functional connectivity, and anatomical connectivity will have translational relevance in at least two respects. First, it promises to unite several currently separate lines of neurodevelopmental research in autism that may be the foundation for therapeutic advances; and second, it will provide an approach to characterizing neurofunctionally defined endophenotypes of autism, in support of identifying subtypes of genetic risk within the population. PUBLIC HEALTH RELEVANCE: Narrative Autism is a pediatric health issue of growing urgency. Genetic approaches require the identification of biologically defined subtypes (endophenotypes), to which this project will contribute by examining links between local cortical organization, brain connectivity, and cognition in children with autism, using several types of magnetic resonance imaging.

描述（由申请人提供）：虽然过去的自闭症研究通常专门用于单个核心缺陷或局部脑缺陷，但越来越多的证据表明自闭症是一种涉及许多基因和神经解剖基因座的“分布障碍”，以及许多神经功能和行为系统。由于缺乏（i）对自闭症手段中的功能连通性（“连接性不足”）的确切理解，以及（ii）整合异常的局部皮质体系结构证据的模型，与“不融合性”的证据相结合，因此对网络组织和大脑连通性进行研究的需求受到了阻碍。自闭症儿童（13-17岁）并匹配通常发展的儿童的儿童将参加神经心理学测试，扩散量张量成像（DTI）和功能性MRI（FMRI）实验在两个简单的感觉任务（视觉，听觉）和更复杂的Lexico-Lixico-Ementicalmenticalmentical语言任务上进行性能。与事件相关的FMRI设计将使我们能够识别主要视觉和听觉皮层，主运动皮层和左下额叶皮质中的激活峰。这些激活峰将进一步用于功能连通性（FCMRI）分析，测试整个大脑的时间序列相关性。根据我们的总体假设，减少的激活一致性（反映局部皮质组织受损）将与区域间连通性降低（功能，解剖学），白质完整性降低以及自闭症中神经心理学表现受损有关。 Four specific aims will test hypotheses for the autism group of (i) reduced concordance of activity in core activation sites (fMRI), (ii) correlation between functional connectivity (fcMRI) and activation concordance, (iii) correlations of anatomical connectivity and white matter integrity (DTI) with local activation concordance and functional connectivity, and (iv) correlations between imaging (concordance,连通性）和神经心理学措施。建立认知行为障碍，局部皮质折衷，功能连通性和解剖连通性之间的联系将在至少两个方面具有转化相关性。首先，它有望在自闭症中结合几条目前的神经发育研究，这可能是治疗进展的基础。其次，它将提供一种表征自闭症神经功能定义的内表型的方法，以支持识别人群中遗传风险的亚型。公共卫生相关性：叙事自闭症是越来越紧迫的儿科健康问题。遗传方法需要鉴定生物定义的亚型（内型），该项目将使用几种类型的磁共振成像来检查自闭症儿童的局部皮质组织，大脑连通性和认知的联系，从而对此做出贡献。