Cognitive Effects of Cerebellar Dysfunction in Autism

描述（由申请人提供）：小脑异常可能是自闭症中许多认知和临床症状的基础。虽然自闭症的大脑异常是多种多样的，涉及皮层和皮层下区域，但小脑是最一致报道的损伤部位。在六个独立研究小组进行的定量MRI研究中，在95%的死后自闭症病例和数百名自闭症患者中发现了小脑发育异常。60多项研究发现，自闭症患者的小脑存在分子、代谢、功能或结构异常。越来越多的文献表明，小脑控制或改变了多种认知过程，从而改变了传统的神经学观点，即小脑是一个只支持运动功能的大脑结构。我们实验室的工作不仅将自闭症患者的小脑与认知功能和神经反应联系起来，还将其与正常功能联系起来。我们提出自闭症的一些缺陷可能反映了基本的小脑功能障碍——无法追踪感觉信息、预测未来事件和准备反应。我们现在建议使用功能和结构成像技术来测试这个新兴的自闭症小脑功能障碍模型。

DESCRIPTION (provided by applicant): Cerebellar abnormality may underlie many of the cognitive and clinical symptoms in autism. While brain abnormalities in autism are diverse and involve cortical and subcortical regions, the cerebellum is the most consistently reported site of damage. Developmental abnormality of the cerebellum has been found in 95% of postmortem autism cases and in several hundred individuals with autism on quantitative MRI studies performed by six independent research groups. More than 60 studies have found molecular, metabolic, functional or structural abnormalities of the cerebellum in autism. A rapidly growing body of literature suggests that the cerebellum controls or modifies diverse cognitive processes, thus altering the traditional neurologic view of the cerebellum as a brain structure that supports only motor function. Work in our laboratory has linked the cerebellum to both cognitive function and neural response not only in autism, but also in normal function. We have proposed that some deficits in autism may reflect fundamental cerebellar dysfunction--failure to track sensory information, predict future events and prepare a response. We now propose to test this emerging model of cerebellar dysfunction in autism using functional and structural imaging. We will assess the specificity of cerebellar involvement in these cognitive operations (track, predict, prepare) by comparison of subjects with autism: 1) to patients with cerebellar damage acquired in early childhood; and 2) to those with Asperger syndrome in which the cerebellum may be less affected. We will ground our results from these comparisons by performing fMRI (functional magnetic resonance imaging) studies in normal control subjects to establish that the cerebellum is normally active during these same operations. The fMRI studies of clinical groups will allow us to investigate whether patterns of activation suggest abnormal interaction of the cerebellum and cerebral cortical systems during these important processing operations. Our studies will link both behavioral and neural response (ERP, fMRI) to the underlying neuroanatomy (MRI). These results will help us understand the specific functional deficits associated with developmental or acquired damage to the cerebellum and thereby will contribute to understanding the brain substrates of behavioral dysfunction in autism. Such knowledge may enable more effective treatment and aid the search for the origins of this debilitating disorder.