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.

项目摘要/摘要 Miocinovic博士正在将自己确立为一名医师科学家，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脑刺激（DBS）。这个K23将为Miocinovic博士提供实现以下目标所需的支持：（1）获得高级使用的知识成像技术可视化人脑中的神经途径；（2）精通收购和术中电生理记录的分析；（3）学习翻译新研究所需的技能临床实践的方法；（4）发展独立的研究职业。为了实现这些目标，博士 Miocinovic已经组建了一个由主要导师组成的指导团队：Philip Starr博士（功能性神经外科医生具有人类运动障碍的专业知识电生理学）；两个副官员：吉尔·奥斯特莱姆博士（一种具有DBS管理和临床试验专业知识的运动障碍）和Pratik博士 Mukherjee（具有MRI拖拉学专业知识的神经放射科医生）和两个合作者：Cameron博士 McIntyre（具有DBS计算建模方面具有专业知识的生物医学工程师）和Alastair Martin博士（A MRI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哪些神经途径被DBS应用于患者的丘脑下区域的DB直接激活帕金森氏病。这将通过使用高 - 分辨率下皮质记录条，使用MRI拖拉机和使用三维生物物理计算模型估算刺激效应的传播。主重点放在皮质甲状腺丘脑超直导途径上，因为它在DBS治疗中的潜在重要性直接生理记录的机制和可及性。 AIM 1：Miocinovic博士将确定DBS如何参数调整会使用术中皮质记录影响高直接途径的激活。 AIM 2：Miocinovic博士将验证基于拖拉术的，特定于患者的计算模型的使用预测超直导途径的优先激活。该项目的最终目标是应用鉴定帕金森氏病中丘脑DBS的靶标的融合方法可达到最佳治疗益处。拟议的研究具有创新性，因为它利用电视图来验证用于DBS参数选择的基于拖拉机的患者特异性模型。提议的结果研究将为我们对DBS机制的理解做出重大贡献，并提高方法对于特定于患者的DBS参数选择，因此远离了当前的试用方法用于临床实践。 Miocinovic博士的K23培训将使她准备竞争R01资金并翻译这些新颖的方法进入临床实践。