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

描述(由申请人提供)：这是针对NOT-OD-09-058，ARRA呼吁竞争性补充申请的竞争性修订。在过去的十年里，人们越来越意识到精神分裂症患者认知受损的残疾影响，以及开发针对认知缺陷的新疗法的重要性。在同一时期，认知神经科学领域出现了关于认知的神经基础的新知识的爆炸性增长。这一新知识在精神分裂症药物开发中的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。这一担忧导致了认知神经科学研究以改善精神分裂症认知(CNTRICS)倡议，该倡议举办了一系列会议，旨在就认知神经科学的结构和范式达成共识，这些结构和范式适合用于临床试验的翻译。我们最近获得了启动这一翻译过程的资金(认知神经科学任务可靠性和临床应用(CNTRAC)联盟。)行为典范。我们召集了一个协作小组，他们代表了这项努力取得成功所必需的许多领域的重要专业知识。我们关注的是人类认知加工的早期(感知中的增益控制和视觉整合)和更高层次(目标维持、关系编码和提取)的四个结构。如果是这一竞争性修订，我们将朝着一个高度关键和重要的方向扩展这项工作，该方向已被该领域确定为日益增长的需求-开发经过充分验证的、可靠的功能神经成像范例，可以作为预测和评估药物和干预反应的生物标记物，旨在提高认知能力的治疗。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，即用于研究精神疾病的生物材料和生物测量，其中包括“系统地收集和分析生物测量(例如，遗传多态、脑成像指数)，这些测量也可以与临床衍生变量结合使用，以确定结果的预测因素、治疗反应和不良反应的调节因素、或治疗效果的介体和模式。”这些扩展目标的最终目标将是为该领域提供：1)这三种认知功能的易于使用的成像范例：2)针对临床试验环境(高效、可靠、稳健)的使用进行了优化；3)保持它们作为感兴趣的认知和神经过程的具体测量的有效性。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增加的目标是可行的。这套协作的R01提案满足了ARRA刺激计划的目标，为9个新职位提供资金，3个职位将使我们能够保留原本需要解雇的员工，以及1个我们可以从兼职增加到全职的职位。 公共卫生相关性：该项目通过显著提高我们将开发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): 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.