权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Ultrasonic Neuromodulation: From Mechanism To Optimal Application

超声神经调节：从机制到最佳应用

基本信息

批准号：
10186833
负责人：
Jan Kubanek
金额：
$ 23.31万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10186833
关键词：
Animals Award Brain Brain region Caenorhabditis elegans Clinic Collaborations Data Deep Brain Stimulation Disease Effectiveness Electric Stimulation Electrophysiology (science)Engineering Event Evoked Potentials Faculty Focused Ultrasound Frequencies Future Genetic Heating Human Invertebrates Investigation Ion Channel Knowledge Lateral Geniculate Body Learning Libraries Macaca Magnetic Resonance Imaging Major Depressive Disorder Mammals Mechanics Mental Depression Mentors Methods Migraine Modality Modeling Monkeys Nature Neurons Neurophysiology - biologic function Neurosciences Pathway interactions Patients Pharmacology Phase Physiologic pulse Primates Principal Investigator Protocols documentation Research Research Personnel Role Safety Sensory Sheep Sodium Channel Specificity Stimulus Structure Students Testing Tissues Training Transcranial magnetic stimulation Transgenic Animals Ultrasonics Ultrasonography Universities Visual Cortex Work awake behavioral response clinical application cranium epithelial Na+ channel experimental study frontier indexing innovation insight mechanical force member mutant nervous system disorder neural circuit neuroregulation painful neuropathy relating to nervous system response side effect skills tool

项目摘要

Entirely noninvasive neuromodulation achieved using low-intensity focused ultrasound (US) is one of the most exciting frontiers in neuroscience today. US is emerging as a new way of stimulating specific regions of the brain noninvasively through the skull of animals and humans. In comparison to other noninvasive alternatives such as transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (tDCS, tACS), US propagates deep into the brain while also retaining a sharp spatial focus. TMS is currently used to treat neuropathic pain and major depressive disorder. US will provide a much more focused alternative, with fewer side effects, to treat these disorders. The method may also be used as a noninvasive and focused alternative to deep brain stimulation (DBS). However, it is unknown how US stimulates neurons and what stimulus parameters researchers and clinicians should use to achieve optimal stimulation. The principal investigator (PI) has a background in neural engineering, including pharmacological neuromodulation and electrophysiology. To elucidate the mechanism of US neuromodulation and to work toward optimal stimulation, the PI will pursue training through the K99 Pathway to Independence Award mechanism at Stanford University. He has three faculty members with expertise in diverse aspects of US neuromodulation as mentors. In the mentored phase, the PI and colleagues will identify which neurons and ion channels are activated by US using a small invertebrate (C. elegans) as a model. Using this animal, the PI will also rapidly establish the set of optimal stimulation parameters. In a translational part of the training, the PI, within an interdisciplinary team at Stanford, will build on these findings to determine optimal stimulus parameters in a large mammal (sheep). To do so, they will ultrasonically stimulate a deep brain structure, verify the US focus using MR imaging, and record EEG responses. This work will also establish safety threshold at which there is no detectable tissue damage. The training will teach the PI five skills essential to attain independence. He will learn how to i) conduct mechanistic investigations at the circuit level ii) perform US stimulation in large animals iii) mentor a student to conduct US experiments iv) establish collaborations and v) present findings. In the independent phase, the PI and his students will apply this training. They will build on the optimal stimulus and safety data to devise optimal stimulation protocols in species with which the PI worked previously: macaque monkeys and humans. The monkey will serve to optimize the effectiveness and validate the safety of the approach before it will be advanced to humans. Together, this research will elucidate how US activates neurons, and provide a set of US parameters that activates neurons efficiently. It is expected that this knowledge will provide a new tool to study the function of neural circuits and open doors for clinical applications to alleviate neurological disorders.

使用低强度聚焦超声（US）实现的非侵入性神经调节是当今神经科学最令人兴奋的前沿领域。美国正在成为刺激特定地区的新方式通过动物和人类的头骨进行非侵入性的大脑扫描。与其他非侵入性替代方案，例如经颅磁刺激（TMS）或经颅电刺激（tDCS，tACS）， US传播到大脑深处，同时也保留了清晰的空间焦点。TMS目前用于治疗神经性疼痛和重度抑郁症。美国将提供一个更有针对性的替代方案，副作用来治疗这些疾病。该方法也可以作为一种非侵入性和集中的替代方法脑深部电刺激（DBS）然而，US如何刺激神经元以及什么刺激是未知的。研究人员和临床医生应该使用的参数来实现最佳刺激。主要研究者（PI）具有神经工程背景，包括药理学神经调节和电生理学。阐明超声神经调节的机制，为了获得最佳刺激，PI将通过K99独立之路奖进行培训斯坦福大学的一项研究。他有三名教师，他们在美国的各个方面都有专业知识。神经调节作为导师在指导阶段，PI和同事将识别哪些神经元和离子通道通过使用小无脊椎动物（C. Elegans）作为一个模型。利用这种动物，PI也将迅速建立最佳刺激参数的集合。在训练的翻译部分中，PI在斯坦福大学的一个跨学科小组将在这些发现的基础上，大型哺乳动物（绵羊）。为此，他们将用超声波刺激大脑深层结构，使用磁共振成像，并记录脑电图反应。这项工作还将建立安全阈值，没有可检测到的组织损伤培训将教授PI获得独立所必需的五项技能。他将学习如何i）在电路级进行机械研究ii）在大型动物中进行US刺激 iii）指导学生进行美国实验iv）建立合作和v）呈现结果。在独立阶段，PI及其学生将应用此培训。他们将建立在最佳的刺激和安全性数据，以在PI之前工作的物种中设计最佳刺激方案：猕猴和人类。猴子将用于优化有效性并验证在它被应用于人类之前。总之，本研究将阐明US如何激活神经元，并提供一组US参数能有效激活神经元期望这些知识能为研究该函数提供新的工具为临床应用打开大门，以减轻神经系统疾病。