Research and mentoring on cognitive neuroscience and high-field MRI of the thalamus in schizophrenia

摘要 申请K24以患者为中心的研究(POR)职业中期研究员奖，以：1)增强我的 POR中的能力，包括网络科学和认知神经科学方面的新专业知识 人类丘脑的神经成像；2)应用这些新的专业知识对丘脑进行新的研究 精神障碍的连接性、功能和结构；以及3)增强我的指导技能并提供 指导实习生的时间受到保护。我的研究项目调查精神障碍的神经基础 作为培训POR学员的平台。这包括指导初级教员、博士后研究员、 精神障碍、神经影像和神经心理学专业的研究生和医学博士研究生。 在过去的几年里，我的实验室一直专注于研究大脑丘脑皮质环路的异常 精神错乱。我们是最先证明丘脑功能连接的人之一 精神分裂症的特征是与前额叶皮质(PFC)的连接性降低和 与感觉运动性皮质区域的超连通性。我们的发现与开创性的发现相吻合 丘脑的认知神经科学。然而，基础神经科学的许多最新进展 丘脑的研究尚未转化为对精神病表型机制的更好理解。 这一翻译差距阻碍了在确定认知障碍潜在治疗靶点方面的进展。 传统神经成像方法的局限性进一步阻碍了进展，因为这些方法不能直接 想象一下人类的单个丘脑核团。本提案为解决这些问题提供了基础 挑战。具体地说，我将在网络科学(目标1)和认知方面发展新的研究技能 丘脑神经科学(目标2A)，扩展现有的神经成像专业知识，包括最先进的 活体人类丘脑的成像方法(目标2B)，并应用这些新的专业知识来表征 早期精神分裂症患者丘脑核团结构和功能异常(目标3)。这项建议将：1) 加强我的实验室正在进行的工作，以表征精神病理学和正常认知中的大脑连接 发展；以及2)为我提供未来研究所需的关键专业知识，重点是 精神病表型的丘脑皮质机制。

ABSTRACT A K24 Mid-Career Investigator Award in Patient-Oriented Research (POR) is requested to: 1) augment my capabilities in POR to include new expertise in network science, and the cognitive neuroscience and neuroimaging of the human thalamus; 2) apply these new expertise to perform novel studies of thalamic connectivity, function, and structure in psychotic disorders; and 3) enhance my mentorship skills and provide protected time to mentor trainees. My research program investigating the neural basis of psychotic disorders serves as a platform for training POR trainees. This includes mentoring junior faculty, postdoctoral fellows, graduate students, and MD/PhD medical students in psychotic disorders, neuroimaging, and neuropsychology. For the past several years my lab has focused on investigating thalamocortical circuit abnormalities in psychotic disorders. We were among the first to show that functional connectivity of the thalamus in schizophrenia is characterized by a combination of lower connectivity with the prefrontal cortex (PFC) and hyper-connectivity with sensorimotor cortical areas. Our findings coincided with groundbreaking discoveries in the cognitive neuroscience of the thalamus. However, many recent advances in the fundamental neuroscience of the thalamus have yet to translate to improved understanding of the mechanisms of psychosis phenotypes. This translational gap is impeding progress in identifying potential treatment targets for cognitive impairment. Progress is further hindered by limitations of conventional neuroimaging methods which are unable to directly visualize individual thalamic nuclei in humans. This proposal provides the foundation for addressing these challenges. Specifically, I will develop new research skills in network science (Aim 1) and the cognitive neuroscience of the thalamus (Aim 2A), extend existing expertise in neuroimaging to include state-of-the-art methods for imaging the human thalamus in vivo (Aim 2B), and apply these new expertise to characterize thalamic nuclei structure and function abnormalities in early stage schizophrenia (Aim 3). This proposal will: 1) enhance ongoing work in my lab characterizing brain connectivity in psychopathology and normal cognitive development; and 2) provide me with critical expertise required for future studies focused on informing thalamocortical mechanisms of psychosis phenotypes.