Neural Impact of Positive Mood on Motivation and Reward Networks in Schizophrenia

 描述(申请人提供)：本次K01指导研究科学家发展奖的目的是促进候选人在临床神经科学领域的独立研究人员的发展，重点是了解精神分裂症以及最终在其他严重精神疾病中积极情绪、动机和功能结果之间的神经生物学关系。Subramaniam博士的长期职业目标是为精神分裂症等严重精神疾病患者的大脑-行为关系奠定深厚的知识基础，这些关系是积极情绪-认知互动的基础。最终目标是利用这一知识为成功的治疗和预防干预措施的发展提供信息。为此，K01奖建议调查精神分裂症完整过程的神经基础--体验积极情绪的能力--并检查它是否(以及如何)调节动机行为。这项研究的理由是有证据表明，动机障碍是精神分裂症长期功能受损的主要决定因素之一，而且早在疾病的前驱阶段就出现了。然而，尽管最近的发现表明，在健康的人中，积极的情绪状态会增强动机和随后的目标导向行为，但对精神分裂症患者的这些过程却一无所知。因此，我们将在精神分裂症患者和健康对照个体中研究三个特定的目标，以调查：1)动机网络中的结构连通性；2)积极情绪对连接大脑中对动机行为重要的区域的功能连通性的影响；以及3)积极情绪对支持动机的大脑区域功能激活的影响。这项建议包括通过临床研究方法的课程作业和量身定做的教学方法、先进的多模式结构和功能神经成像分析以及负责任的研究行为进行的正式指导培训。加州大学旧金山分校是拟议培训的理想环境，因为它提供了多模式成像、翻译和临床研究方法以及精神分裂症研究方面的专家和导师，他们在实验室和现场社区环境中工作。成功完成拟议的研究和职业发展活动将为R01提案的制定提供信息，并确保Subramaniam博士成为精神分裂症积极情绪-认知交互作用领域的独立研究员。

 DESCRIPTION (provided by applicant): The purpose of this K01 Mentored Research Scientist Development Award is to promote the candidate's development as an independent researcher in clinical neuroscience, with a focus on understanding the neurobiological relation between positive mood, motivation, and functional outcome in schizophrenia and eventually, in other serious mental illnesses. Dr. Subramaniam's long-term career goal is to develop a deep knowledge base on brain-behavior relationships underlying positive mood-cognition interactions in individuals with serious mental illnesses such as schizophrenia. The ultimate objective is to use this knowledge to inform the development of successful treatments and preventive interventions. Towards this end, this K01 award proposes to investigate the neural underpinnings of an intact process in schizophrenia-- the ability to experience positive moods-and to examine whether (and how) it mediates motivated behavior. The rationale for this study emerges from evidence indicating that motivational impairment is one of the principal determinants of impaired long-term functioning in schizophrenia, and that it is present as early as the prodromal phase of the illness. And yet, while recent findings indicate that motivation and subsequent goal- directed behaviors are enhanced by positive mood states in healthy individuals, nothing is known about these processes in people with schizophrenia. Thus, three specific aims will be studied in participants with schizophrenia and healthy comparison individuals in order to investigate: 1) Structural connectivity within motivation networks; 2) The influence of a positive mood on functional connectivity linking brain regions important for motivated behavior; and 3) The influence of a positive mood on functional activation in brain regions that support motivation. This proposal includes formal mentored training through coursework and tailored didactics in clinical research methodologies, advanced multimodal structural and functional neuroimaging analyses, and responsible conduct of research. The University of California, San Francisco is an ideal environment for the proposed training as it provides access to experts and mentors in multimodal imaging, translational and clinical research methodologies, and schizophrenia research who work in laboratory settings as well as in field-based community settings. Successful completion of the proposed research and career development activities will inform the development of an R01 proposal and ensure Dr. Subramaniam's development as an independent investigator in the field of positive mood-cognition interactions in schizophrenia.