3/5-Cognitive Neuroscience Task Reliability & Clinical Applications Consortium

描述(由申请人提供)：在过去的十年里，人们越来越意识到精神分裂症患者认知障碍的残疾影响。随着这种新的认识，人们越来越强调开发新的治疗方法的重要性，这些治疗方法可能会对这些认知缺陷产生积极影响。在同一时期，认知神经科学领域出现了关于认知的神经基础的技术进步和新知识的爆炸性增长。可悲的是，这种尖端知识和范式开发在精神分裂症新药开发中的转化和应用远远落后于认知神经科学的整体进展，这在很大程度上是因为缺乏关于认知神经科学中使用的任务的测量特性的数据。这种担忧催生了认知神经科学研究以改善精神分裂症中的认知(CNTRICS)倡议，该倡议举办了一系列会议，旨在就认知神经科学中成熟的翻译概念和范例，以及在翻译此类任务用于临床试验环境时的验证和心理测量目标达成共识。目前的应用是对CNTRICS倡议的合乎逻辑和必要的扩展，该倡议将开始范型的翻译进程，这些范型旨在评估CNTRICS第一次会议确定的已成熟翻译的四个结构。我们汇集了一个协作的“翻译”团队，他们代表了这项工作成功所必需的许多领域的重要专业知识，包括基础和临床认知神经科学家、心理测量学家和临床试验专家。我们选择关注四个结构，这四个结构既包括人类认知加工的早期(感知中的增益控制和视觉整合)和更高水平(目标维持、关系编码和提取)组成部分。通过考察多种机制，我们将能够确定我们提出的翻译方法在不同层次和类型的认知机制中的普遍性。具体目标1是验证(在精神分裂症患者和对照参与者中)评估我们感兴趣的四个结构的范式的优化版本，以及检查精神分裂症患者的任务表现与临床和功能结果的关系。通过优化，我们指的是检查对已经验证的范例的修改，这些范例旨在：1)最大限度地减少任务长度；2)简化跨多个站点的任务管理；3)在评估感兴趣的特定认知机制时最大限度地提高灵敏度和选择性；以及4)提高可靠性并最大限度地减少底限和天花板影响。通过验证，我们的意思是确保这种旨在增强任务的心理测量学特性的优化不会改变其结构效度。具体目标2将评估和优化在特定目标1中验证的任务版本的重测可靠性和练习效果。项目叙述这个项目通过显著提高我们将发展成基本认知神经科学文献的范例转化为临床试验以改善精神分裂症认知的能力，对公共卫生具有很高的相关性。精神分裂症的认知缺陷是这种衰弱疾病功能结果的主要预测因素。因此，我们需要改进检测和增强精神分裂症患者认知功能的方法，以帮助这种疾病患者过上更有成效和更有成就感的生活。

DESCRIPTION (provided by applicant): Over the past decade there has been a growing awareness of the disabling effects of impaired cognition in individuals with schizophrenia. Along with this new awareness has come an increasing emphasis on the importance of developing new treatments that may positively impact these cognitive deficits. During this same period, the cognitive neuroscience field has seen an explosion of technical advances and new knowledge regarding the neural basis of cognition. Sadly, the translation and application of this cutting edge knowledge and paradigm development to new drug development in schizophrenia has lagged significantly behind overall progress in cognitive neuroscience, in large part due to the lack of data on the measurement properties of tasks used in cognitive neuroscience. This concern spawned the Cognitive Neuroscience Research To Improve Cognition in Schizophrenia (CNTRICS) initiative, which conducted a series of conferences designed to develop consensus on the constructs and paradigms from cognitive neuroscience that are ripe for translation, and the validation and psychometric goals when translating such tasks for use in clinical trials contexts. The current application is a logical and needed extension of the CNTRICS initiative that will begin the translation process for paradigms designed to assess four of the constructs identified as being ripe for translation in the first CNTRICS meeting. We have brought together a collaborative "translation" team that represents significant expertise from the many fields necessary for the success of this endeavor, including both basic and clinical cognitive neuroscientists, psychometricians, and clinical trials specialists. We have chosen to focus on four constructs that span both early (gain control and visual integration in perception) and higher-level (goal maintenance, relational encoding and retrieval) components of human cognitive processing. By examining multiple mechanisms, we will be able to establish the generality of the translational approach we propose across different levels and types of cognitive mechanisms. Specific Aim 1 is to validate (in both individuals with schizophrenia and comparison participants) optimized versions of the paradigms that assess our four constructs of interest, as well as to examine the relationship of task performance to clinical and functional outcomes in schizophrenia. By optimization, we mean examining modifications on already validated paradigms that are designed to: 1) minimize task length; 2) simplify task administration across multiple sites; 3) maximize sensitivity and selectivity in assessing the specific cognitive mechanisms of interest; and 4) enhance reliability and minimize floor and ceiling effects. By validation, we mean ensuring that such optimizations designed to enhance the psychometric properties of the task do not alter its construct validity. Specific Aim 2 will be to assess and optimize test-retest reliability and practice effects for the task versions validated in Specific Aim 1. PROJECT NARRATIVE This project has high relevance for public health by significantly improving our ability to translate paradigms developed into the basic cognitive neuroscience literature for use in clinical trials aimed at improving cognition in schizophrenia. Cognitive deficits in schizophrenia are a major predictor of functional outcome in this debilitating illness. Thus, we need to improve our methods for detecting and enhancing cognitive function in schizophrenia in order to help individuals with this illness lead more productive and fulfilling lives.