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

描述（由申请人提供）：这是响应NOT-OD-09-058（ARRA对竞争补充申请的要求）的竞争性修订。在过去的十年中，人们越来越意识到精神分裂症患者认知受损的致残作用，以及开发针对认知缺陷的新治疗方法的重要性。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新知识爆炸。这一新知识在精神分裂症药物开发中的应用明显落后于认知神经科学的整体进展，这在很大程度上是由于缺乏认知神经科学中使用的任务测量特性的数据。这种担忧导致了认知神经科学研究以改善精神分裂症的认知（CNTRICS）倡议，该倡议进行了一系列会议，旨在就认知神经科学的结构和范式达成共识，这些结构和范式已经成熟，可以用于临床试验。我们最近获得资助，开始这个翻译过程（认知神经科学任务可靠性和临床应用（CNTRAC）联盟。“）的行为模式。我们汇集了一个合作团队，代表了成功实现这一奋进所需的许多领域的重要专业知识。我们重点关注四个结构，涵盖人类认知处理的早期（感知中的控制和视觉整合）和更高级别（目标维持、关系编码和检索）组件。是这个竞争性的修订，我们将扩展这项工作在一个非常关键和重要的方向，该领域已确定为一个不断增长的需求-发展良好的验证，可靠的功能性神经影像学范式，可以作为生物标志物，用于预测和评估药物和干预治疗的反应，旨在提高认知。这一重点符合NIMH确定的竞争性补充剂的关键主题领域之一，即用于精神疾病研究的生物材料和生物措施，其中包括“系统地收集和分析生物措施（例如，遗传多态性、脑成像指数），其也可以与临床衍生变量组合使用，以鉴定结果的预测因子、治疗反应和副作用的调节因子、或治疗效果的介质和模式。“这些扩展目标的最终目标将是为该领域提供：1）易于使用的这三种认知功能的成像范例：2）已优化用于临床试验背景（有效，可靠，稳健）;同时3）保持其有效性作为感兴趣的认知和神经过程的具体措施。我们认为，鉴于我们已经建立了基础设施，在ARRA宣布的时间框架内完成这一新增目标是可行的。这套合作R 01提案通过为9个新职位提供资金来实现ARRA刺激计划的目标，其中3个职位将使我们能够保留否则需要解雇的员工，1个职位我们可以从兼职增加到全职。 公共卫生相关性：该项目具有高度的公共卫生相关性，显着提高我们的能力，翻译范式开发成基本的认知神经科学文献，用于临床试验，旨在改善精神分裂症的认知。精神分裂症的认知缺陷是这种使人衰弱的疾病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 competitive revision in response to NOT-OD-09-058, the ARRA call for Competitive Supplement Applications. In the past decade there has been a growing awareness of the disabling effects of impaired cognition in individuals with schizophrenia and the importance of developing new treatments that target cognitive deficits. During this same period, the cognitive neuroscience field has seen an explosion of new knowledge regarding the neural basis of cognition. The application of this new knowledge to 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 led to 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 for use in clinical trials contexts. We were recently funded to start this translation process (Cognitive Neuroscience Task Reliability & Clinical Applications (CNTRACs) Consortium.") for behavioral paradigms. We brought together a collaborative team that represents significant expertise from the many fields necessary for the success of this endeavor. We are focusing 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. Is this competitive revision we will extend this work in a highly critical and significant direction that the field has identified as a growing need - the development of well validated, and reliable functional neuroimaging paradigms that can serve as biomarkers for predicting and assessing drug and intervention response to treatments designed to enhance cognition. This focus meets one of the key topic areas for Competitive Supplements identified by the NIMH, namely Biomaterials and Biological Measures for the Study of Mental Disorders, which includes "Systematically collecting and analyzing biological measures (e.g., genetic polymorphisms, brain imaging indexes), which could be used, also in combination with clinically derived variables, to identify predictors of outcome, moderators of treatment response and adverse effects, or mediators and patterns of treatment effects." The end goal for these expanded aims will be to provide the field with: 1) easy to use imaging paradigms of these three cognitive functions that: 2) have been optimized for use in a clinical trials context (efficient, reliable, robust); while 3) maintaining their validity as specific measures of the cognitive and neural processes of interest. We believe that it is feasible to complete this added Aim in the time frame of the ARRA announcement, given that we have an established infrastructure. This set of collaborative R01 proposals meet the goals of the ARRA stimulus by providing for funding for 9 new positions, 3 positions that would allow us to retain staff that would otherwise need to be let go, and 1 position that we can increase from part to full time. PUBLIC HEALTH RELEVANCE: 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.