Translational Studies on Cognitive Flexibility

描述（由申请人提供）：认知混乱是一个基本的 精神分裂症的精神病理学方面，有助于整体 发病率的疾病过程和极大地影响结果。电流 抗精神病药物对认知缺陷的有益作用微乎其微 精神分裂症，新的治疗方法的设计取决于 转化研究将有助于更好地了解神经系统 这些赤字的基础。然而，这种转化研究的可行性 主要是因为缺乏认知任务， 实验室动物评估类似的认知结构， 在常规使用的临床测试范例中。一个这样的结构是 “行为灵活性”或注意力转移，这是评估 通常在精神分裂症患者中使用威斯康星州卡片分类测试 （WCST）。虽然实验动物的认知能力有限，但在 特别是啮齿动物，阻碍了认知任务的设计， 被认为完全“类似”于WCST等复杂任务， 可以设计行为范例来评估认知结构， 与许多临床测试范例中测量的那些“相当”。 然而，虽然对实验室动物的研究主要依赖于 验证基于与人类任务的“理论同源性”的任务， 在临床相关的机制研究中，我们认为， “功能同源性”也可以建立。其主要目的是 应用是启动基础和临床之间的合作 研究人员和工作的标准化量化措施，可以 用于建立人类和动物认知任务之间的功能同源性 与精神分裂症有关的这项合作的最初方面 将涉及使用平行的基本和临床定量测量， 建立一个新开发的啮齿动物任务的结构效度， 理论上与WCST一致。具体目标旨在描述 这些任务之间的结构和神经化学同源性。

DESCRIPTION (provided by applicant): Cognitive disorganization is a fundamental aspect of the psychopathology of schizophrenia, contributing to the overall morbidity of the disease process and greatly impacting outcome. Current antipsychotic medications have minimal beneficial effects on cognitive deficits of schizophrenia, and design of novel treatments is contingent upon translational research that will lead to a better understanding of the neural basis of these deficits. However, feasibility of such translational studies has been limited, primarily because of the scarcity of cognitive tasks for laboratory animals that assess similar cognitive constructs as those assessed in the routinely used clinical test paradigms. One such construct is "behavioral flexibility" or attentional set-shifting, which is assessed commonly in patients with schizophrenia using the Wisconsin Card Sort Test (WCST). While the limited cognitive capacity of laboratory animals, in particular rodents, hinders the design of cognitive tasks that would be considered entirely "analogous" to complex tasks such as the WCST, it is possible to design behavioral paradigms that can evaluate cognitive constructs that are "comparable" to those measured in many clinical test paradigms. However, while studies with laboratory animals have primarily relied on validating a task based on "theoretical homology" with human tasks, to carry out clinically relevant mechanistic studies, we believe, it is crucial that "functional homology" also be established. The principal aim of this application is to initiate collaborations between basic and clinical researchers and work toward standardizing quantitative measures that can be used to establish functional homology between human and animal cognitive tasks that are relevant to schizophrenia. The initial aspect of this collaboration will involve the use of parallel basic and clinical quantitative measures to establish the construct validity of a newly developed rodent task that has theoretical homology with WCST. Specific aims are designed to characterize the structural and neurochemical homology between these tasks.