Understanding Functional Connectivity Abnormalities In Individual Patients with Psychosis

摘要 这是马萨诸塞州综合医院的医学科学家王丹红博士的K01奖申请书 医院和哈佛医学院。王医生正在确立自己作为一名年轻的病人研究者的地位- 精神疾病的神经影像学研究。K01奖将为王博士提供 为实现以下目标提供必要的支持：（1）成为以患者为导向的研究专家， 精神病神经影像学;（2）对患者的神经生物学相关因素进行实验研究 （3）在临床上实施革命性的个人水平功能映射技术 研究;（4）发展独立的临床研究事业。为了实现这些目标，王博士 组建了一个由三位导师组成的指导小组：麦克莱恩医院院长Dost Öngür博士 他领导着一个研究精神病生物学的神经影像实验室; 博士兰迪·巴克纳，哈佛大学心理学和神经科学教授， 马萨诸塞州总医院的精神病学神经影像学，功能性磁共振成像研究的先驱之一; 以及罗切斯特大学药理学和生理学教授Suzanne Haber博士， 神经解剖学领域的科学家此外，香港大学放射科副教授刘和生博士 哈佛医学院和一位在功能成像方面有专长的计算神经科学家， 在这个项目上合作。 博士王女士将参与多种职业发展活动，以扩大她在机械制造领域的发展能力。 关于精神疾病的见解这些措施包括新的培训，以病人为导向的实验研究， 更好地理解精神病的精神病理学，更好地掌握神经解剖学。她还将 接受认知和临床神经科学的高级培训。 确定精神病背后的断开的神经回路已被证明是难以捉摸的。王博士的研究 一个项目旨在揭示电路异常的精神病患者使用特定的主题，交叉诊断 approach.在目标1中，王博士将建立准确表征皮质和皮质下的方法， 个体患者的功能连接网络。在目标2中，利用跨诊断队列， 将使用针对个体水平功能分析优化的方案进行扫描的精神病患者， 以及现有的患者数据集，王博士将识别和验证皮质和皮质下功能 与精神病症状严重程度相关的连接异常。在目标3中，王博士将研究 个体患者连接的时间变化，并揭示动态功能异常 与症状相关的连接。王博士进行的一系列初步研究奠定了基础 每个具体目标的基础。这项研究将构成一项研究的基础，以确定"连接 在个体患者中进行潜在调节的“枢纽”，将在R01赠款申请中提出， K奖结束

Abstract This is an application for a K01 award for Dr. Danhong Wang, a physician-scientist at Massachusetts General Hospital and Harvard Medical School. Dr. Wang is establishing herself as a young investigator in patient- oriented neuroimaging research on psychiatric disorders. This K01 award will provide Dr. Wang with the support necessary to accomplish the following goals: (1) to become an expert in patient-oriented research in psychiatric neuroimaging; (2) to conduct experimental investigations of neurobiological correlates in patients with psychosis; (3) to implement revolutionary individual-level functional mapping techniques in clinical studies; and (4) to develop an independent clinical research career. To achieve these goals, Dr. Wang has assembled a mentoring team comprised of three mentors: Dr. Dost Öngür, Chief of the McLean Hospital Psychotic Disorders Division, who leads a neuroimaging laboratory studying the biology of psychotic illness; Dr. Randy Buckner, Professor of Psychology and Neuroscience at Harvard University and Director of Psychiatric Neuroimaging at Massachusetts General Hospital, one of the pioneers in functional MRI research; and Dr. Suzanne Haber, Professor of Pharmacology and Physiology at the University of Rochester, a leading scientist in the field of neuroanatomy. In addition, Dr. Hesheng Liu, Associate Professor of Radiology at Harvard Medical School and a computational neuroscientist with expertise in functional imaging, will collaborate on this project. Dr. Wang will engage in multiple career development activities to expand her ability to develop mechanistic insights about psychiatric disorders. These include new training in patient-oriented experimental research, a better understanding of the psychopathology of psychosis, and a stronger grasp of neuroanatomy. She will also receive advanced training in cognitive and clinical neuroscience. Determining the disconnected neural circuits underlying psychosis has proved elusive. Dr. Wang's research project aims to reveal circuitry abnormalities in psychotic patients using a subject-specific, cross-diagnostic approach. In Aim 1, Dr. Wang will establish methods for accurately characterizing the cortical and subcortical functional connectivity networks in individual patients. In Aim 2, leveraging a cross-diagnostic cohort of psychotic patients that will be scanned using the protocol optimized for individual-level functional analyses, as well as an existing patient data set, Dr. Wang will identify and validate cortical and subcortical functional connectivity abnormalities related to the severity of psychotic symptoms. In Aim 3, Dr. Wang will investigate the temporal variations of connectivity in individual patients and reveal abnormalities in dynamic functional connectivity related to symptoms. A series of preliminary studies conducted by Dr. Wang have laid the solid foundation for each specific aim. This research will form the basis of a study for identifying the “connectivity hubs” in individual patients for potential modulation, to be proposed in an R01 grant application before the end of the K award.