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

描述（由申请人提供）：这是一份响应RFA-MH-08-090的申请，标题为“适应精神分裂症临床评估的基本认知测量”。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致残作用。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，这些治疗方法可能对这些认知缺陷产生积极的影响。在同一时期，认知神经科学领域出现了关于认知神经基础的技术进步和新知识的爆炸式增长。可悲的是，将这些前沿知识和范式发展转化和应用于精神分裂症新药开发，远远落后于认知神经科学领域的整体进展。matrix计划发现，这种转换的主要障碍是缺乏关于认知神经科学中使用的行为任务的测量特性的数据。这种关注催生了认知神经科学研究以改善精神分裂症患者的认知（CNTRICS）倡议，该倡议举办了一系列会议，旨在汇集基础和临床认知神经科学家，就认知神经科学中成熟的翻译结构和范式达成共识，以及在翻译这些任务用于临床试验时的验证和心理测量目标。目前的申请是CNTRICS倡议的一个合乎逻辑且急需的扩展，它将开始范式的翻译过程，这些范式旨在评估在第一次CNTRICS会议上确定为成熟的翻译的四个构念。我们汇集了一个协作的“翻译”团队，代表了这项努力成功所必需的许多领域的重要专业知识，包括基础认知神经科学家、临床认知神经科学家、心理测量学家、统计学家和临床试验专家。我们选择将重点放在四个构念上，这四个构念使我们能够用人类认知加工中早期（例如，感知中的增益控制和视觉整合）和后期（目标维持、关系编码和检索）运作的机制来说明翻译过程。通过研究多种机制，我们将能够在不同层次和类型的认知机制中建立我们提出的翻译方法的通用性。本应用程序的具体目的1是验证（在精神分裂症患者和比较参与者中）评估我们的四个感兴趣的构念（增益控制、视觉整合、目标维持和关系编码/检索）的范式的优化版本。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)最小化任务长度；2)简化跨多个站点的任务管理；3)在评估兴趣的特定认知机制时，最大限度地提高灵敏度和选择性；4)提高可靠性，减少地板和天花板的影响。通过验证，我们的意思是确保这种优化设计，以提高任务的心理测量属性不改变其构念效度。具体目标2将评估和优化在具体目标1中验证的任务版本的重测信度和实践效果。项目说明：该项目通过显著提高我们将范式转化为基础认知神经科学文献的能力，以用于旨在改善精神分裂症认知的临床试验，与公共卫生高度相关。精神分裂症的认知缺陷是这种使人衰弱的疾病的功能结局的主要预测因素。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，以帮助患有这种疾病的人过上更有成效和更充实的生活。

DESCRIPTION (provided by applicant): This is a application in response to RFA-MH-08-090, titled "Adapting Basic Cognitive Measures for Clinical Assessment of Schizophrenia." 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 the overall progress in the cognitive neuroscience field. The MATRICS initiative identified that the major barrier to this translation is a lack of data on the measurement properties of the behavioral 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 bring together basic and clinical cognitive neuroscientists 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 much 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 basic cognitive neuroscientists, clinical cognitive neuroscientists, psychometricians, statisticians, and clinical trials specialists. We have chosen to focus on four constructs that that allow us to illustrate the translation process with mechanisms that operate both early (e.g., gain control and visual integration in perception) and later (goal maintenance, relational encoding and retrieval) in 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 for this application is to validate (in both individuals with schizophrenia and comparison participants) optimized versions of the paradigms that assess our four constructs of interest (gain control, visual integration, goal maintenance and relational encoding/retrieval). 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 interesting; 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.