Cerebellar Anatomic and Functional Connectivity in Autism Spectrum Disorders

描述（由申请人提供）：异常的神经连接越来越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，也是自闭症中最一致的大脑异常部位。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通性。PC减少将解除对兴奋输出的抑制，离开小脑，进入大脑的其他区域。这种异常活动可能反过来导致解剖连接的异常加强以及与边缘、丘脑和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。为了研究自闭症的小脑连通性，我们将采用扩散张量成像（DTI）和功能连通性磁共振成像（FCMRI），前者是一种可以量化白质束结构的MRI方法，后者评估MRI信号变化的区域间一致性，作为功能连通性的指标。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、丘脑和脑皮质部位连接的解剖和功能完整性。连接测量将与特定小脑亚区的体积相关联，以评估解剖异常对连接的影响。我们还将研究这些解剖学和连通性测量与小脑功能独立测量之间的关联。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。这应该会导致更明智的治疗方法，并且应该把重点放在寻找这种常见和破坏性神经发育障碍的病因上。

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.