Non-invasive neuromodulation via targeted delivery of neurotransmitter chemicals

通过神经递质化学物质的靶向递送进行非侵入性神经调节

• 批准号: 9902417
• 负责人: Nicholas E. Todd
• 金额: $ 16.44万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9902417
• 关键词: Affect; Antibodies; Applications Grants; Area; Bayesian Modeling; Behavior; Blood - brain barrier anatomy; Brain; Brain Neoplasms; Brain imaging; Brain region; Chemicals; Clinical; Clinical Treatment; Clinical Trials; Computing Methodologies; Data; Decision Making; Disease; Drug Delivery Systems; Epilepsy; Focused Ultrasound; Foundations; Functional Magnetic Resonance Imaging; Future; Glutamates; Goals; Health; Human; Image; Imaging Techniques; Knowledge; Lead; Liposomes; Magnetic Resonance Imaging; Measures; Mechanics; Mediating; Mentored Research Scientist Development Award; Mentors; Mentorship; Methodology; Methods; Microbubbles; Modeling; Modernization; Molecular; Neurobiology; Neurons; Neurosciences; Neurosciences Research; Neurotransmitters; Nodal; Pain; Parkinson Disease; Pathway interactions; Penetrance; Peripheral; Pharmaceutical Preparations; Process; Rattus; Research; Rest; Rodent; Scientist; Sensory; Site; Somatosensory Cortex; Specificity; Stimulus; System; Tactile; Techniques; Technology; Testing; Thalamic structure; Therapeutic; Training; Training Programs; Translating; United States National Institutes of Health; Work; base; behavior test; behavioral response; career; causal model; chemotherapeutic agent; chronic pain; experience; gamma-Aminobutyric Acid; information processing; macromolecule; millimeter; nerve stem cell; nervous system disorder; neuroimaging; neuroregulation; novel strategies; pain model; painful neuropathy; plasmid DNA; response; sensory cortex; side effect; skills; somatosensory; synaptic function; targeted delivery; tool

Project Summary: Dr. Nicholas Todd is applying for an NIH Mentored Research Scientist Development Award to achieve three interrelated goals: 1) undergo training to gain expertise in two key areas of neuroscience; 2) develop a novel approach to non-invasive neuromodulation based on targeted delivery of neurotransmitter chemicals to the brain; 3) build a strong foundation from which to launch a career as an independent research scientist. The grant proposal has been tailored to achieve these goals by aligning the mentorship expertise, training program, and research aims. Dr. Todd is a magnetic resonance imaging (MRI) physicist by training with particular experience in MR- guided focused ultrasound (FUS) applications and MR neuroimaging. His ambition is to have a long research career as an independent scientist using the tools of FUS and MRI to further our understanding of brain function and advance treatments for neurological diseases. In order to round out his skill set for such a career, he is now seeking training in two key areas of systems level neuroscience, the neurobiology of brain networks and modern computational methods for analyzing neuroimaging data, and also expertise in the specific area of FUS-mediated blood-brain barrier (BBB) opening. Under exceptional mentorship, Dr. Todd will gain a comprehensive understanding of the neurobiology of the pain network (primary mentor, Dr. David Borsook), become proficient in applying Dynamic Causal Modeling for analysis of neuroimaging data (mentor Dr. Lino Becerra and collaborator Dr. Karl Friston), and become an expert in FUS-mediated BBB opening (mentor Dr. Nathan McDannold). The research aims in the proposal build on Dr. Todd’s experience with MR neuroimaging and FUS applications, while providing him with direct experiences in the areas of training. The research work will develop and validate methodology for a novel approach to non-invasive neuromodulation that uses FUS- mediated BBB opening to deliver neurotransmitters to targeted brain regions. The targeted neurotransmitter delivery method will be used to investigate modulation of the rodent pain network. Excitatory (glutamate) and inhibitory (GABA) neurotransmitters will be delivered to nodes of the pain network (thalamus and somatosensory cortex) in healthy and neuropathic pain rats. The effects will be measured throughout the entire pain network using the three complimentary approaches of functional MRI (fMRI), Dynamic Causal Modeling (DCM), and behavioral testing. This work will advance Dr. Todd along his path towards becoming an independent scientist. The training component will provide Dr. Todd with the necessary knowledge of systems level neuroscience to pursue a career using MRI and FUS for brain related research; the research component will develop a new method for non-invasive neuromodulation that will form the basis of future work and grant applications.

项目概要： Nicholas Todd 博士正在申请 NIH 指导研究科学家发展奖，以实现 三个相互关联的目标：1）接受培训以获得神经科学两个关键领域的专业知识；2）发展 一种基于神经递质靶向递送的非侵入性神经调节新方法 大脑化学物质；3）为独立开展职业生涯奠定坚实的基础 研究科学家的资助提案是为了通过协调来实现这些目标而量身定制的。 指导专业知识、培训计划和研究目标。 Todd 博士是一位磁共振成像 (MRI) 物理学家，接受过 MR 方面的培训，拥有丰富的经验 他的野心是引导聚焦超声（FUS）应用和 MR 神经影像。 作为独立科学家的研究生涯，使用 FUS 和 MRI 工具来加深我们的理解 大脑功能和神经系统疾病的先进治疗，以完善他的技能。 为了从事这样的职业，他现在正在寻求系统级神经科学两个关键领域的培训， 脑网络的神经生物学和用于分析神经影像数据的现代计算方法， 以及 FUS 介导的血脑屏障 (BBB) 打开特定领域的专业知识。 杰出的指导，托德博士将获得对神经生物学的全面了解 疼痛网络（主要导师，David Borsook 博士），精通动态因果关系的应用 神经影像数据分析建模（导师 Lino Becerra 博士和合作者 Karl Friston 博士）， 并成为 FUS 介导的 BBB 开放方面的专家（导师 Nathan McDannold 博士）。 该研究旨在以 Todd 博士在 MR 神经影像和 FUS 方面的经验为基础 应用程序，同时为他提供培训领域的直接经验。 开发并验证一种使用 FUS- 的非侵入性神经调节新方法的方法 介导血脑屏障开放，将神经递质输送到目标大脑区域。 神经递质传递方法将用于研究啮齿动物疼痛网络的调节。 兴奋性（谷氨酸）和抑制性（GABA）神经递质将被传递到疼痛的节点 网络（丘脑和体感皮层）对健康和神经性疼痛大鼠的影响将是。 使用三种互补的功能性方法在整个疼痛网络中进行测量 MRI (fMRI)、动态因果模型 (DCM) 和行为测试。 这项工作将推动托德博士走上成为一名独立科学家的道路。 组件将为托德博士提供必要的系统级神经科学知识，以追求 使用 MRI 和 FUS 进行大脑相关研究的职业；研究部分将开发一种新的方法 非侵入性神经调节方法将构成未来工作和拨款申请的基础。