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致力于单一核心缺陷或局部大脑缺陷，但越来越多的证据表明自闭症是一种“分布式疾病”，涉及许多基因和神经解剖位点，以及许多神经功能和行为系统。由于我们缺乏（i）对自闭症功能连接受损（“连接不足”）意味着什么的精确理解，以及（ii）整合异常局部皮质结构证据的模型，因此阻碍了对网络组织和大脑连接研究的需求有“连接不足”的证据。自闭症儿童（13-17 岁）和匹配的正常发育儿童将在执行两项简单的感官任务（视觉、听觉）和更多任务时参与神经心理学测试、弥散张量成像 (DTI) 和功能性 MRI (fMRI) 实验。复杂的词汇语义语言任务。事件相关的功能磁共振成像设计将使我们能够识别初级视觉和听觉皮层、初级运动皮层和左下额叶皮层的激活峰值。这些激活峰将进一步用于功能连接（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，激活一致性的降低（反映局部皮质组织受损）将与区域间连接性（功能性、解剖性）减少、白质完整性降低以及自闭症神经心理学表现受损相关。四个具体目标将测试自闭症组的假设：（i）核心激活位点（fMRI）活动一致性降低，（ii）功能连接性（fcMRI）和激活一致性之间的相关性，（iii）解剖连接性和白质的相关性完整性（DTI）与局部激活一致性和功能连接性，以及（iv）成像（一致性、连接性）和神经心理学测量之间的相关性。建立认知行为障碍、局部皮质损害、功能连接和解剖连接之间的联系将至少在两个方面具有转化相关性。首先，它有望将目前几个独立的自闭症神经发育研究领域联合起来，这可能成为治疗进展的基础；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：叙事自闭症是一个日益紧迫的儿科健康问题。遗传方法需要识别生物学定义的亚型（内表型），该项目将通过使用几种类型的磁共振成像检查自闭症儿童的局部皮质组织、大脑连接和认知之间的联系来对此做出贡献。