TMS of the Supramarginal Gyrus: A WIndow To Spatial Orientation

描述（由申请人提供）：这是一份重新提交的指导患者导向研究职业发展奖（K23）申请。本研究的总体目标是了解我们如何感知与外部环境相关的身体方向，以及这些感知如何对前庭疾病患者产生扭曲和迷失方向。前庭系统提供了相对于重力的头部方向的强大的独立信息来源，并在空间方向中起关键作用。在人类中，大脑皮层的许多区域的功能是未知的，这些区域可以访问和处理来自前庭系统的信息。这个项目是基于一个令人信服的初步发现，即顶叶皮层（SMGp）的一个小区域在准确感知一个人的直立感方面起着核心作用。这一结果表明该区域具有更普遍的功能；从视觉、前庭和本体感觉传感器中获取不同的信息，这些信息在不同的坐标框架中被固有地接收和处理，然后将它们整合到一个连贯的空间方向中。这种机制对于成功地对环境变化的需求做出运动反应是绝对必要的。本研究项目的具体目标是：1)通过系统分析不同的直立知觉知觉方式（即空间定向的功能模型），进一步研究SMGp在空间定向中的功能作用；2)探索左半球相应区域在直立知觉中的功能；3)探讨经颅磁刺激的焦点效应是否可以改变直立感的知觉适应。作为一种潜在的治疗方式。候选人：Amir Kheradmand即将成为约翰霍普金斯医院神经内科和耳鼻喉科的助理教授。他于2003年获得the Tehran University of Medical Sciences的医学博士学位，并于2010年在马萨诸塞大学（University of Massachusetts）完成神经学住院医师培训。作为一名两年的博士后研究员，他一直在研究直立感知的机制，重点研究大脑皮层在处理前庭系统输入中的功能作用。这项工作主要是在Zee博士的指导下进行的，并通过约翰霍普金斯听力与平衡中心和生物医学工程系获得了NIH培训资助。Kheradmand博士的短期研究目标是：1)学习感知心理物理学中的实验设计和数据分析技术；2)学习贝叶斯统计、分析和建模，以应用于空间定向的功能模型；3)获得更多使用经颅磁刺激的实践知识，并在临床中获得临床神经学的神经生理学技术经验。他的长期目标是成为前庭知觉领域的独立研究者和有成就的学术神经学家。环境：本提案中描述的调查将在约翰霍普金斯医院神经内科由Zee博士指导的前庭/眼动实验室进行。来自各部门和机构的导师和顾问团队（David Zee博士、Mark Shelhamer博士、John Carey博士、Pablo Celnik博士和Dora Angelaki博士）将提供指导，并监督本提案中规定目标的及时实现。所有导师都是各自领域的领导者，在指导年轻研究者独立方面有着良好的记录。通过前庭/眼动实验室，Kheradmand博士可以随时获得必要的设备、软件和工程支持。研究：本项目提出的一系列假设和实验提供了一个独特的机会，不仅可以探索大脑如何产生直立的基本感知，还可以为头晕、失衡和空间定向障碍患者的致残症状提供治疗建议。通过这项工作获得的研究经验，强化指导和教学活动，K23职业发展奖将使首席研究员Amir Kheradmand博士成为一名独立的研究者，在前庭生理学领域进行转化研究。

DESCRIPTION (provided by applicant): This is a resubmitted application for Mentored Patient-Oriented Research Career Development Award (K23). The overall goal of this research is to understand how we perceive body orientation relative to our external environment, and how these perceptions become distorted and disorienting to patients with vestibular disease. The vestibular system provides a strong independent source of information about head orientation relative to gravity and plays a key role in spatial orientation. In humans, the function(s) of the many areas of the cerebral cortex that have access to and process information from the vestibular system are largely unknown. This project is based on a compelling preliminary finding that shows a small region of parietal cortex (SMGp) plays a central role in the accurate perception of one's sense of upright. This result suggests a more general function for this area; taking disparate information from visual, vestibular and proprioceptive sensors, which are inherently received and processed in different coordinate frames, and then integrating them into a coherent spatial orientation. Such a mechanism is an absolute requirement for successful motor responses to the changing demands of one's environment. The specific aims of this research project are to 1) study further the functional role of the SMGp in spatial orientation by systematic approach to different sensory modalities that contribute to upright perception ( i.e., using a functional model of spatial orientation) 2) probe the function of the corresponding area within the left hemisphere in upright perception 3) address whether the focal effect of TMS can modify perceptual adaptation of the sense of uprightness, as a potential treatment modality. Candidate: Amir Kheradmand is shortly to be an Assistant Professor in the Departments of Neurology and Otolaryngology at the Johns Hopkins Hospital. He earned an M.D. at the Tehran University of Medical Sciences in 2003 and completed residency training in Neurology at the University of Massachusetts in 2010. As a two-year postdoctoral fellow he has been studying the mechanisms involved in perception of upright with the emphasis on the functional role of the cerebral cortex in processing of inputs from the vestibular system. This work has been primarily under the mentorship of Dr. Zee and it was supported by an NIH training grant through the Johns Hopkins Center for Hearing and Balance and the Department of Biomedical Engineering. Dr. Kheradmand's short term goals in research are to 1) learn techniques for experiment design and data analysis in the psychophysics of perception, 2) learn Bayesian statistics, analysis and modeling to apply to the functional model of spatial orientation, and 3) gain more practical knowledge in using transcranial magnetic stimulation, and in the clinic, to gain experience in the neurophysiological techniques of clinical neurotology. His long term goal is to become an independent investigator in the field of vestibular perception and accomplished academic neurotologist. Environment: The investigations described in this proposal will be performed in the Vestibular/Eye Movement Laboratory, directed by Dr. Zee, in the Neurology Department at Johns Hopkins Hospital. A team of mentors and advisers (Dr. David Zee, Dr. Mark Shelhamer, Dr. John Carey, Dr. Pablo Celnik, and Dr. Dora Angelaki) from across departments and institutions will provide mentorship and oversee timely achievement of the stated goals in this proposal. All mentors are leaders in their respective fields and have a strong track record of mentoring young investigators to independence. Necessary equipment, software and engineering support are readily available to Dr. Kheradmand through the Vestibular/Eye Movement Laboratory. Research: The series of hypotheses and experiments proposed in this project provide a unique opportunity not only to explore how the brain creates the fundamental perception of upright, but also to suggest treatments for the disabling symptoms in patients with dizziness, imbalance and spatial disorientation. Through the research experience acquired by this work, intensive mentoring, and didactic activities, this K23 career development award will allow the primary investigator, Dr. Amir Kheradmand, to become an independent investigator conducting translational research in the field of vestibular physiology.