Targeted activation of select neural pathways by deep brain stimulation in patients with Parkinson's disease

通过深部脑刺激靶向激活帕金森病患者的特定神经通路

• 批准号: 9769892
• 负责人: Svjetlana Miocinovic
• 金额: $ 19.24万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769892
• 关键词: 3-Dimensional; Address; Affect; Anatomy; Animals; Area; Axon; Basal Ganglia; Biomedical Engineering; Biophysics; Brain; Cell Nucleus; Clinical; Clinical Trials; Computer Simulation; Consumption; Deep Brain Stimulation; Disease; Electric Stimulation; Electrocorticogram; Electrodes; Electrophysiology (science); Evoked Potentials; Fiber; Frequencies; Funding; Future; Globus Pallidus; Goals; Human; Image; Imaging Techniques; Involuntary Movements; Knowledge; Learning Skill; Location; Magnetic Resonance Imaging; Maps; Measures; Medical; Mentors; Methods; Modeling; Motor; Motor Cortex; Movement Disorders; Neural Pathways; Neurologist; Neurons; Neurosurgeon; Operative Surgical Procedures; Parkinson Disease; Pathway interactions; Patients; Pharmaceutical Preparations; Physicians; Physiologic pulse; Physiological; Physiology; Population; Procedures; Research; Research Methodology; Research Project Grants; Resolution; Scientist; Shapes; Source; Structure of subthalamic nucleus; Technology; Testing; Therapeutic; Time; Tissues; Training; Translating; Width; Work; base; biophysical model; career; clinical imaging; clinical practice; design; electric field; imaging modality; innovation; motor symptom; neuronal cell body; novel; patient oriented; reduce symptoms; relating to nervous system; response; symptomatic improvement; tractography

PROJECT SUMMARY/ABSTRACT Dr. Miocinovic is establishing herself as a physician-scientist conducting patient-centered research in the field of movement disorder electrophysiology and deep brain stimulation (DBS). This K23 will provide Dr. Miocinovic with the support necessary to accomplish the following goals: (1) to gain knowledge in the use of advanced imaging techniques to visualize neural pathways in the human brain; (2) to become proficient in acquisition and analysis of intraoperative electrophysiology recordings; (3) to learn skills necessary to translate novel research methods into clinical practice; and (4) to develop an independent research career. To achieve these goals, Dr. Miocinovic has assembled a mentoring team consisting of a primary mentor: Dr. Philip Starr (a functional neurosurgeon with expertise in human movement disorders electrophysiology); two co-mentors: Dr. Jill Ostrem (a movement disorders neurologist with expertise in DBS management and clinical trials), and Dr. Pratik Mukherjee (a neuroradiologist with expertise in MRI tractography), and two collaborators: Dr. Cameron McIntyre (a biomedical engineer with expertise in computational modeling of DBS), and Dr. Alastair Martin (a medical physicist with expertise in MRI technology). The goal of the proposed research project is to understand which neural pathways are directly activated by DBS applied to the subthalamic area of patients with Parkinson's disease. This will be accomplished by measuring stimulation evoked potentials using a high- resolution subdural cortical recording strip, visualizing specific fiber pathways using MRI tractography and estimating the spread of stimulation effects using 3-dimensional biophysical computational models. The main focus is on the cortico-subthalamic hyperdirect pathway because of its potential importance in DBS therapeutic mechanism and accessibility for direct physiologic recordings. Aim 1: Dr. Miocinovic will determine how DBS parameter adjustments affect activation of the hyperdirect pathway using intraoperative cortical recordings. Aim 2: Dr. Miocinovic will validate the use of tractography-based, patient-specific computational models to predict preferential activation of the hyperdirect pathway. The ultimate goal of this project is to apply convergent methods to identify a target for subthalamic DBS in Parkinson's disease that achieves optimal therapeutic benefit. The proposed research is innovative because it utilizes electrocorticography to validate the use of tractography-based, patient-specific models for DBS parameter selection. Results from the proposed research will make significant contributions to our understanding of DBS mechanisms and advance methods for patient-specific DBS parameter selection, thus moving away from the trial-and-error approach currently used in clinical practice. Dr. Miocinovic's K23 training will prepare her to compete for R01 funding and translate these novel methods into clinical practice.

项目摘要/摘要 米奥西诺维奇博士正在确立自己作为一名内科科学家的地位，在该领域进行以患者为中心的研究 运动障碍、电生理学和脑深部刺激(DBS)。这架K23将为米奥西诺维奇博士提供 在必要的支持下实现以下目标：(1)学习使用先进的 成像技术使人脑中的神经通路可视化；(2)精通获取和 术中电生理记录的分析；(3)学习翻译新研究所需的技能 方法进入临床实践；(4)发展独立的研究事业。为了实现这些目标，Dr。 米奥西诺维奇组建了一个指导团队，由一位主要导师组成：菲利普·斯塔尔博士(一名专业人士 在人类运动障碍电生理学方面有专长的神经外科医生)；两位共同导师：Jill Ostrem博士 (一位在DBS管理和临床试验方面有专长的运动障碍神经科医生)，以及普拉蒂克博士 慕克吉(一位在核磁共振成像方面有专长的神经放射科医生)和两位合作者：卡梅伦博士 McIntyre(生物医学工程师，擅长DBS的计算建模)和Alastair Martin博士( 具有核磁共振技术专业知识的医学物理学家)。拟议的研究项目的目标是了解 DBS应用于患者丘脑底区可直接激活哪些神经通路 帕金森氏症。这将通过测量刺激诱发电位来实现，使用高- 分辨率硬膜下皮质记录条，使用MRI纤维束成像和 使用三维生物物理计算模型估计刺激效应的传播。主 由于皮质-下丘脑超直接通路在DBS治疗中的潜在重要性，人们关注的焦点是它。 直接生理记录的机制和可获得性。目标1：米奥西诺维奇博士将决定星展银行如何 使用术中皮质记录，参数调整会影响超直接通路的激活。 目标2：米奥西诺维奇博士将验证基于气管造影术的、针对患者的计算模型的使用 预测超直接通路的优先激活。这个项目的最终目标是应用 确定帕金森病患者丘脑底核DBS靶点的收敛方法 治疗效果。这项拟议的研究具有创新性，因为它利用皮层脑电图术来验证 使用基于气管造影术的、特定于患者的模型来选择DBS参数。建议的结果 研究将对我们理解DBS的机制和先进的方法做出重大贡献 用于针对患者的DBS参数选择，从而摆脱了目前试错的方法 用于临床实践。米奥西诺维奇博士的K23培训将为她竞争R01资金和翻译做好准备 这些新方法应用于临床实践。