Brain Imaging in Major Psychoses: Functional Imaging

描述(申请人提供)：本申请使用功能成像检查精神分裂症患者的小脑功能障碍。它建立在我们之前的工作的基础上，一直表明精神分裂症患者在许多类型的认知任务中存在分布回路(包括皮质区域、丘脑和小脑)的局部脑血流量(RCBF)的功能异常。我们将由此产生的行为/认知异常描述为“认知障碍”。在本申请中，基于我们在过去四年中的工作，我们建议主要关注小脑。在此期间，我们研究了各种任务，从“经典小脑”(眨眼条件作用)到“高级”认知和情感任务。所有类型的任务都显示出正常人的小脑激活和精神分裂症患者的流量减少。因此，在目前的应用中，我们计划通过检测正常大脑中三种不同的小脑功能模型来扩展这项工作：联想学习、时间和精神运动整合以及多用途微复合体。我们将在健康的正常志愿者身上使用八种不同的PET方案来检查这三种模型。这些模型是分层次的，因为模型1和模型2包含在模型3中。我们假设我们将确认所有三个模型，并且模型3对小脑在认知中的作用提供了最好的表征。这八项方案包括对“经典小脑”功能(如联想学习和精神运动整合)和“高级大脑皮层”功能(如工作记忆、情绪和社会认知)的研究。我们将使用这些方案来研究八组不同的精神分裂症患者的这些功能。我们假设患者将在所有八组任务中表现出小脑血流减少(与健康志愿者相比)，从而证实精神分裂症患者在广泛的任务范围内小脑功能障碍，并表明小脑在正常精神功能和精神分裂症中的重要性被低估。

DESCRIPTION (provided by applicant): This application uses functional imaging to examine cerebellar dysfunction in schizophrenia. It builds on our previous work, which has consistently shown that patients with schizophrenia have functional abnormalities in regional cerebral blood flow (rCBF) in distributed circuits (including cortical regions, thalamus, and cerebellum) in many types of cognitive tasks. We have described the resulting behavioral/cognitive abnormality as "cognitive dysmetria." In this application we propose to focus primarily on the cerebellum, based on our work during the past four years. During this time we examined a variety of tasks, which ranged from "classic cerebellar" (eyeblink conditioning) to "higher" cognitive and emotional tasks. All types of tasks showed cerebellar activations in normals and decreased flow in schizophrenia. Therefore, in the present application we plan to extend this work by examining three different models of cerebellar function in the normal brain: associative learning, timing and psychomotor integration, and multipurpose microcomplexes. We will examine these three models by using eight different PET protocols in healthy normal volunteers. These models are hierarchical, in that models 1 and 2 are encompassed in model 3. We hypothesize that we will confirm all three models, and that model 3 provides the best characterization of the role of the cerebellum in cognition. The eight protocols include studies of "classic cerebellar" functions (e.g., associative learning and psychomotor integration) and "higher cortical" functions (e.g., working memory, emotion, and social cognition). We will use these protocols to study these functions in eight different groups of patients suffering from schizophrenia. We hypothesize that the patients will show decreased cerebellar blood flow in all eight groups of tasks (as compared to the healthy volunteers), thereby confirming that the cerebellum is dysfunctional in schizophrenia in a broad range of tasks and suggesting that the importance of the cerebellum in both normal mental function and in schizophrenia has been underestimated.