Translational Research Evaluating Neurocognitive Memory Processes (TREC-MP)

描述（由申请人提供）：本提案为K23指导患者导向研究职业发展奖，将为候选人在转化神经认知研究方面的成功独立职业做好准备。候选人和他在UT西南医学中心（UTSW）和哥伦比亚大学/纽约州立精神病学研究所（CU/NYSPI）的导师设计了一个阶段指导和安排过渡（SMART）的职业发展路径，使他成为一名熟练的独立研究者，在神经认知功能、情绪障碍和神经刺激干预的交叉领域工作。这种独特的研究利基将允许候选人利用他的导师的专业知识，同时建立他的个人身份作为一个独立的调查员。SMART路径形成了一个由专家导师和顾问组成的协作网络。Mustafa M. Husain, Sarah H. Lisanby， C. Munro Cullum, Herb Terrace, Ira Bernstein， George Alexopoulos和Harold A. Pincus)。职业发展计划包括学术教学和研讨会，专家指导，在UTSW和CU/NYSPI的实践经验，以及有形的生产力，包括同行评审的手稿和资助申请。在此奖励期间，候选人的职业道路的独特之处在于预先计划的主要任命从UTSW转移到CU/NYSPI。这将有利于他的过渡目标，并使他顺利过渡到独立地位。他的研究项目的目标是开发和开展评估神经认知记忆过程的转化研究（TREC-MP）。利用模型动物研究神经认知功能已广泛应用于基础科学方法。然而，由此产生的临床人类使用的应用是有限的。TREC-MP是一项转化项目，旨在通过对非人类灵长类动物进行电休克和磁发作治疗的实验计算机化神经认知测量来检测人类的心理测量特性。这项渐进式研究旨在优化健康人群的实验神经认知电池，然后确定抑郁症对测试成绩的影响，最后确定接受电休克治疗（ECT）的抑郁症受试者的神经认知表现。ECT对认知的影响是公认的，具有重要的临床意义，但人们对抑郁症和ECT在认知成分过程中的复杂相互作用知之甚少。因此，需要更新的认知评估方法来阐明物种间相似和不同的认知过程，并确定接受ECT患者记忆障碍的潜在认知成分过程。正如NIMH最近的神经认知转化研究和临床倡议所例证的那样，一个有用的策略是针对特定的神经认知领域和组成过程，发展非人类灵长类动物和人类神经认知的比较措施。基于非人类灵长类动物的基础科学神经认知研究，特定神经认知电池的应用为理解记忆缺陷的认知成分过程提供了一种强大的方法，从而允许未来发展有针对性的治疗干预和有用的临床神经认知措施。[这个项目的目的是：1)开发和验证用于健康人类参与者的实验性神经认知测量，2)确定抑郁对实验性神经认知测量的影响，以及3)确定ECT对实验性神经认知测量的影响。分析将采用经典测试和项目反应理论统计。该项目具有科学创新性和重要性，因为它将为候选人提供一个进行转化神经认知研究的平台，帮助他了解记忆障碍的病因，并最终设计适当的临床神经认知措施和干预措施。候选人的SMART通路和TREC-MP项目为他作为独立的转化神经认知科学家的个性化和系统化发展奠定了基础。

DESCRIPTION (provided by applicant): This proposal is for a K23 Mentored Patient Oriented Research Career Development Award that will prepare the candidate for a successful independent career in translational neurocognitive research. The candidate and his mentors at UT Southwestern Medical Center (UTSW) and Columbia University/New York State Psychiatric Institute (CU/NYSPI) designed a Staged Mentored and Arranged Transition (SMART) career development pathway to enable him to become a proficient, independent investigator working at the intersection of neurocognitive function, mood disorders, and neurostimulation interventions. This unique research niche will allow the candidate to leverage the expertise of his preceptors while establishing his individual identity as an independent investigator. The SMART pathway forms a collaborative network of expert mentors and advisors (Drs. Mustafa M. Husain, Sarah H. Lisanby, C. Munro Cullum, Herb Terrace, Ira Bernstein, George Alexopoulos, and Harold A. Pincus). The career development plan is comprised of scholarly didactics and seminars, expert preceptorship, hands-on experience at UTSW and CU/NYSPI, as well as tangible productivity including peer-reviewed manuscripts and grant applications. Unique to the candidate's career path is the pre- planned shift in primary appointment from UTSW to CU/NYSPI during this award period. This will facilitate his transitional goals as well as smooth his transition to independent status. The goal of his research project is to develop and conduct Translational Research Evaluating Neurocognitive Memory Processes (TREC-MP). The use of model animals to study neurocognitive functions has been employed extensively in basic science methodologies. However, the resulting applications for clinical human use have been limited. TREC-MP is a translational project that examines the psychometric properties in humans of experimental computerized neurocognitive measures developed for nonhuman primates undergoing electroconvulsive shock and magnetic seizure therapy. This incremental research study is designed to optimize the experimental neurocognitive battery in a healthy human cohort, then to determine the effects of depression on test performance, and finally to determine the neurocognitive performance of depressed subjects undergoing electroconvulsive therapy (ECT). The cognitive impact of ECT is well recognized and of considerable clinical significance, but what is less well understood is the complex interaction between depression and ECT on cognitive component processes. As such, newer methods of cognitive assessment are needed to elucidate similar and divergent cognitive processes across species, and identify underlying cognitive component processes of memory impairment in patients receiving ECT. As exemplified in recent NIMH translational neurocognitive research and clinical initiatives, one useful strategy would be the development of comparative nonhuman primate and human neurocognitive measures for specific neurocognitive domains and component processes. The application of a specific neurocognitive battery, predicated on basic science neurocognitive research with nonhuman primates provides a powerful method for understanding the cognitive component processes of memory deficits, thereby permitting the future development of targeted treatment interventions and useful clinical neurocognitive measures. [The aims of this project are: 1) Develop and validate experimental neurocognitive measures for use with healthy human participants, 2) Determine effects of depression on performance on experimental neurocognitive measures, and 3) Determine effects of ECT on performance on experimental neurocognitive measures.] Analyses will be conducted with both classical test and item response theory statistics. This project is scientifically innovative and important because it will provide a platform for the candidate to conduct translational neurocognitive research to help him understand the etiology of memory impairment and ultimately design appropriate clinical neurocognitive measures and interventions. The candidate's SMART pathway and TREC-MP project set the stage for his individualized and systematic development as an independent translational neurocognitive scientist. PUBLIC HEALTH RELEVANCE: Impaired cognitive functions associated with psychiatric treatments of severe depression contribute to poor functional outcomes. The objective of this career development award is for the candidate to become a proficient translational neurocognitive scientist. The long-term goal is for this translational neurocognitive research to provide a clearer understanding of the cognitive component processes that underscore cognitive functional impairments in order to develop psychometrically sound neurocognitive outcome measures and targeted treatment interventions.