Cerebellar Anatomic and Functional Connectivity in Autism Spectrum Disorders

描述(由申请人提供)：异常的神经连接被越来越多地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联系最广泛的结构之一，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，这将极大地影响小脑内以及小脑与其他大脑区域之间的连接。PC的减少将抑制兴奋性输出，将小脑留给其他大脑区域。这种异常活动可能反过来导致解剖连接的异常强化和与边缘、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绪行为的能力，从而导致自闭症的许多缺陷。为了研究自闭症的小脑连通性，我们将使用扩散张量成像(DTI)和功能连通性磁共振成像(FCMRI)，扩散张量成像(DTI)是一种可以量化白质束结构的MRI方法，功能连通性磁共振成像(FCMRI)是评估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组小脑与边缘、丘脑和大脑皮质部位连接的解剖和功能完整性。连通性测量将与特定小脑子区域的体积相关联，以评估解剖异常对连通性的影响。我们还将调查这些解剖学和连接性指标与小脑功能的独立指标之间的关系。与公共健康相关：这项研究的发现将提高我们对自闭症的神经基础的理解。这应该会导致更知情的治疗，并应该集中精力寻找这种常见的和毁灭性的神经发育障碍的病因。

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.