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许多认知和临床症状的基础。虽然自闭症的大脑异常是多样的，涉及皮层和皮层下区域，小脑是最一致的报告损伤部位。在六个独立的研究小组进行的定量MRI研究中，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。超过60项研究发现自闭症患者小脑的分子、代谢、功能或结构异常。越来越多的文献表明，小脑控制或修改不同的认知过程，从而改变了小脑作为一个大脑结构，只支持运动功能的传统神经学观点。我们实验室的工作已经将小脑与认知功能和神经反应联系起来，不仅在自闭症中，而且在正常功能中。我们提出，自闭症的某些缺陷可能反映了小脑的基本功能障碍--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来测试这种新兴的自闭症小脑功能障碍模型。 我们将通过比较自闭症受试者来评估小脑参与这些认知操作（跟踪，预测，准备）的特异性：1）在儿童早期获得小脑损伤的患者; 2）小脑可能受影响较小的Bogger综合征患者。我们将通过对正常对照受试者进行fMRI（功能性磁共振成像）研究，以确定小脑在这些相同的操作过程中通常是活跃的，从而从这些比较中得出我们的结果。临床组的功能磁共振成像研究将使我们能够调查激活模式是否表明在这些重要的处理操作中小脑和大脑皮层系统的异常相互作用。 我们的研究将把行为和神经反应（ERP，fMRI）与潜在的神经解剖学（MRI）联系起来。这些结果将帮助我们了解与小脑发育或获得性损伤相关的特定功能缺陷，从而有助于理解自闭症行为功能障碍的大脑基底。这样的知识可以使更有效的治疗和帮助寻找这种衰弱性疾病的起源。

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.