Cerebellar Anatomic and Functional Connectivity in Autism Spectrum Disorders

自闭症谱系障碍的小脑解剖和功能连接

• 批准号: 7870253
• 负责人: GREG ALLEN
• 金额: $ 24.62万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7870253
• 关键词: Address; Affect; Affective; Anatomy; Anterior; Autistic Disorder; Autopsy; Behavior; Brain; Brain region; Cell Count; Cell Nucleus; Cereals; Cerebellar Nuclei; Cerebellar cortex structure; Cerebellar vermis structure; Cerebellum; Cerebral cortex; Cerebrum; Characteristics; Cognitive; Data; Defect; Deformity; Dentate nucleus; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Etiology; Functional Magnetic Resonance Imaging; Hemisphere of the Cerebellum; Impairment; Individual; Investigation; Lead; Left; Limbic System; Magnetic Resonance Imaging; Manuals; Measurement; Measures; Medial; Neuraxis; Neurobiology; Neurodevelopmental Disorder; Neurons; Neuropsychological Tests; Neurosciences; Nucleus Emboliformis; Nucleus fastigii; Output; Parietal Lobe; Participant; Pathology; Pattern; Play; Procedures; Purkinje Cells; Reporting; Resolution; Role; Signal Transduction; Site; Source; Structure; Symptoms; System; Testing; Thalamic structure; autism spectrum disorder; base; cognitive function; data integration; design; gray matter; imaging modality; improved; indexing; neurobehavioral; neurochemistry; neuroimaging; neuropathology; neuropsychological; public health relevance; relating to nervous system; white matter

DESCRIPTION (provided by applicant): Abnormal neural connectivity is increasingly thought to be key contributor to the neurobiology of autism. The cerebellum is one of the most widely connected structures in the central nervous system, and it is also the most consistent site of brain abnormality in autism. The most common defect is a reduced number of Purkinje cells (PC), which will drastically impact connectivity within the cerebellum and between the cerebellum and other brain regions. PC reduction will disinhibit excitatory output leaving the cerebellum for other brain regions. Such aberrant activity may in turn lead to the abnormal strengthening of anatomic connections and the emergence of aberrant functional connectivity with limbic, thalamic, and cerebrocortical sites. This will disrupt the cerebellum's ability to coordinate cognitive and socioemotional behaviors, thereby contributing to many of the deficits characteristic of autism. To investigate cerebellar connectivity in autism, we will employ diffusion tensor imaging (DTI), an MRI method that allows the quantification of white matter tract structure, and functional connectivity magnetic resonance imaging (FCMRI), which assesses interregional coherence of MRI signal change as an index of functional connectivity. DTI and FCMRI will be used to examine the anatomic and functional integrity of cerebellar connections with limbic, thalamic, and cerebrocortical sites in individuals with autism spectrum disorders and in healthy controls. Connectivity measures will be correlated with volumes of specific cerebellar sub-regions to assess the impact of anatomic abnormality on connectivity. We will also investigate associations between these anatomic and connectivity measures and independent measures of cerebellar function. PUBLIC HEALTH RELEVANCE: Findings from this study will improve our understanding of the neural basis of autism. Such should lead to better-informed treatments, and it should focus the search for the etiology of this common and devastating neurodevelopmental disorder.

描述（由申请人提供）：异常神经连接越来越多地被认为是自闭症神经生物学的关键因素。小脑是中枢神经系统中连接最广泛的结构之一，也是自闭症患者大脑异常最一致的部位。最常见的缺陷是浦肯野细胞（PC）数量减少，这将严重影响小脑内部以及小脑与其他大脑区域之间的连接。PC减少将解除抑制兴奋性输出，离开小脑到其他大脑区域。这种异常的活动可能反过来导致解剖连接的异常加强，以及与边缘系统、丘脑和大脑皮质部位的异常功能连接的出现。这将破坏小脑协调认知和社会情感行为的能力，从而导致自闭症的许多缺陷特征。为了研究自闭症小脑的连通性，我们将采用扩散张量成像（DTI），一种MRI方法，可以量化的白色物质束结构，和功能连接磁共振成像（FCMRI），评估区域间的一致性MRI信号变化作为功能连接的指标。DTI和FCMRI将用于检查自闭症谱系障碍患者和健康对照者小脑与边缘系统、丘脑和大脑皮质部位连接的解剖和功能完整性。连接性测量将与特定小脑子区域的体积相关，以评估解剖异常对连接性的影响。我们还将调查这些解剖和连接措施和小脑功能的独立措施之间的关联。公共卫生相关性：这项研究的发现将提高我们对自闭症神经基础的理解。这应该会导致更好的知情治疗，它应该集中在寻找这种常见的和破坏性的神经发育障碍的病因。