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

基本信息

批准号：
10458233
负责人：
Svjetlana Miocinovic
金额：
$ 12.41万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458233
关键词：
3-Dimensional Address Affect Anatomy Animals Area Axon Basal Ganglia Biomedical Engineering Biophysics Brain Cell Nucleus Clinical Clinical Trials Computer Models 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

项目摘要

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.

项目概要/摘要 Miocinovic 博士正在将自己定位为一名医师科学家，在该领域进行以患者为中心的研究运动障碍电生理学和深部脑刺激（DBS）。这台 K23 将为 Miocinovic 博士提供获得实现以下目标所需的支持：（1）获得使用先进技术的知识可视化人脑神经通路的成像技术； (2) 熟练掌握并掌握术中电生理记录分析； (3) 学习翻译小说研究所需的技能方法应用于临床实践；（4）发展独立的研究事业。为了实现这些目标，博士。 Miocinovic 组建了一个指导团队，其中包括一位主要导师：Philip Starr 博士（一位职能型导师）。具有人体运动障碍电生理学专业知识的神经外科医生）；两位共同导师：Jill Ostrem 博士（一位运动障碍神经科医生，具有 DBS 管理和临床试验方面的专业知识）和 Pratik 博士 Mukherjee（一位神经放射学家，具有 MRI 纤维束成像方面的专业知识）和两位合作者：Cameron 博士 McIntyre（一位生物医学工程师，擅长 DBS 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）。拟议研究项目的目标是了解哪些神经通路是由应用于患者丘脑底区的 DBS 直接激活的帕金森病。这将通过使用高电位测量刺激诱发电位来实现分辨率硬膜下皮质记录带，使用 MRI 纤维束成像可视化特定的纤维通路，使用 3 维生物物理计算模型估计刺激效应的传播。主要重点是皮质-底丘脑超直接通路，因为它在 DBS 治疗中具有潜在的重要性直接生理记录的机制和可访问性。目标 1：Miocinovic 博士将确定星展银行如何参数调整影响使用术中皮质记录的超直接通路的激活。目标 2：Miocinovic 博士将验证基于纤维束成像的、针对患者的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来确定帕金森病的丘脑底脑 DBS 目标，以达到最佳效果治疗益处。拟议的研究具有创新性，因为它利用皮层电图描记术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用于患者特定的 DBS 参数选择，从而摆脱目前的试错方法用于临床实践。 Miocinovic 博士的 K23 培训将为她竞争 R01 资助和翻译做好准备这些新颖的方法进入临床实践。