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

项目概要/摘要 博士Miocinovic正在确立自己作为一名医生科学家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电刺激（DBS）。这辆K23将为米奥辛诺维奇博士 与必要的支持，以实现以下目标：（1）获得知识，在使用先进的 成像技术，以可视化人脑中的神经通路;（2）精通采集和 术中电生理记录的分析;（3）学习翻译新研究所需的技能 方法应用于临床实践;（4）发展独立的研究生涯。为了实现这些目标，博士。 Miocinovic组建了一个由主要导师组成的指导团队：Philip Starr博士（一位功能性的 神经外科医生，具有人体运动障碍电生理学方面的专业知识）;两位共同导师：Jill Ostrem博士 （运动障碍神经学家，擅长DBS管理和临床试验）和Pratik博士 Mukherjee（神经放射学家，擅长MRI纤维束成像）和两名合作者：卡梅隆博士 McIntyre（一位生物医学工程师，擅长DBS的计算建模）和Alastair Martin博士（一位 具有MRI技术专业知识的医学物理学家）。该研究项目的目的是了解 哪些神经通路被施加到患有以下疾病的患者的丘脑底区域的DBS直接激活： 帕金森氏症。这将通过使用高电压测量刺激诱发电位来实现。 分辨率硬膜下皮质记录条，使用MRI纤维束成像可视化特定的纤维通路， 使用三维生物物理计算模型估计刺激效应的扩散。主要 由于皮质-丘脑底核超直接通路在DBS治疗中的潜在重要性， 直接生理记录的机制和可访问性。目标1：Miocinovic博士将确定DBS如何 使用术中皮层记录，参数调整影响超直接通路的激活。 目标2：Miocinovic博士将验证基于纤维束成像的患者特定计算模型的使用， 预测超直接通路的优先激活。该项目的最终目标是应用 收敛方法，以确定帕金森病中丘脑底DBS的目标， 治疗益处。这项研究是创新的，因为它利用了皮层电图来验证 使用基于纤维束成像的患者特定模型进行DBS参数选择。拟议的结果 研究将为我们理解DBS机制和先进方法做出重大贡献 对于患者特定的DBS参数选择，因此摆脱了目前的试错法 用于临床实践。Miocinovic博士的K23培训将为她竞争R 01资金和翻译做好准备 将这些新方法应用于临床实践。

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.