Visualization of Neuro-Molecular Targeting using Distribution-Free, High-Res fMRI

使用无分布的高分辨率 fMRI 实现神经分子靶向的可视化

• 批准号: 8324976
• 负责人: Jin Hyung Lee
• 金额: $ 25.65万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8324976
• 关键词: Address; Animal Model; Animals; Area; Awareness; Brain; Brain Mapping; Complex; Coupling; Development; Disease; Electrical Engineering; Electrodes; Engineering; Ensure; Etiology; Evaluation; Factor Analysis; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Human; Image; Imagery; Imaging problem; Imaging technology; Kinetics; Lead; Maps; Measurement; Measures; Mental Depression; Methods; Modeling; Molecular Target; Monitor; Nature; Neuronal Plasticity; Neurons; Neurosciences; Optical Methods; Optics; Outcome; Pathway interactions; Population; Procedures; Property; Radioactive Tracers; Radiology Specialty; Research; Resolution; Scanning; Scheme; Scientist; Sensory; Signal Transduction; Slice; Structure; System; Techniques; Time; Training; base; blood oxygen level dependent; excitatory neuron; follow-up; hemodynamics; in vivo; inhibitory neuron; innovation; neural stimulation; neuronal circuitry; neuronal patterning; neuropsychiatry; relating to nervous system; research study; response; success; tool

A key in understanding the etiology and interventional outcome of neuropsychiatric diseases is the ability to analyze the brain's functional circuitry through precisely controlled stimulation mechanism, while at the same time non-invasively monitoring changes in neuronal activity. The use of conventional stimulation electrodes is constrained by the lack of its ability to selectively target different neuronal populations. Likewise, electrode-based neural stimulation does not necessarily mimic endogenous neural activity, and a spatial propagation ofthe activity in a biologically realistic fashion cannot always be guaranteed. The monitoring of the resulting brain activity on the other hand includes the use of recording electrodes that wili provide high temporal resolution measurements. However, the lack of "anatomical awareness" of recording electrodes is a limiting factor for the analysis of functional circuitry that involves multiple, and possibly elusive brain areas. Blood oxygenation level dependent (BOLD) functional MRI (fMRI) with Its non-Invasive, whole-brain coverage capability is promising for such large-scale neuronal monitoring. But current fMRI schemes struggle with problems of image distortions and lack of sufficient spatial resolution. The candidate of this K99, Pathway to Independence grant is a superbly trained MR scientist now seeking to bridge the gap between fMRI monitoring and targeted neural stimulation schemes that exist today. In this proposal, the candidate proposes a coordinated development of a highly innovative molecularly targeted neuro-optical stimulation method with a de novo distortion-free, high-resolution functional MRI technique the candidate has developed in recent years. With this new method, specific types of neurons can be molecularly targeted for interrogation, endogenous neuronal activation elicited, and the resulting pattern of neuronal activity monitored at an exceedingly high spatial resolution without distortions. This new capability to non-invasively monitor brain activity at high spatial resolution, while controlling the neuronal activity with high functional precision, will provide a powerful future tool for studying the mechanisms of neuropsychiatric diseases. This will lead to better understanding ofthe disease mechanism as well as the development of new treatments.

理解神经精神疾病的病因和介入结果的关键是能够通过精确控制的刺激机制来分析大脑的功能电路，同时非侵入性地监测神经元活性的变化。常规刺激电极的使用受到其缺乏选择性靶向不同神经元种群的能力的限制。同样，基于电极的神经刺激不一定模仿内源性神经活动，并且空间 以生物学上现实的方式传播活动的传播不能总是得到保证。另一方面，监测所得的大脑活动的方法包括使用Wili提供高时间分辨率测量的记录电极。但是，记录电极缺乏“解剖学意识”是分析涉及多个且可能难以捉摸的大脑区域的功能电路的限制因素。 血液氧合水平取决于（BOLD）功能性MRI（fMRI），其无创，全脑覆盖能力对于这种大规模的神经元监测有望。但是当前的功能磁共振成像方案在图像扭曲问题和缺乏足够的空间分辨率方面挣扎。这项K99的候选人是独立途径，是一位受过良好训练的科学家，现在试图弥合fMRI监测与当今存在的靶向神经刺激方案之间的差距。在此提案中，候选人提出 通过从头无变形，高分辨率的高分辨率功能MRI技术的高度创新性分子靶向神经光刺激方法的协调发展。使用这种新方法，可以将特定类型的神经元靶向询问，内源性神经元激活以及在没有失真的情况下极高的空间分辨率下监测的神经元活性模式。这种新的能力可在高空间分辨率下非侵入性监测大脑活动，同时以高功能精度控制神经元活动，将为研究神经精神疾病的机制提供强大的未来工具。这将使人们更好地了解疾病机制以及新疗法的发展。

项目成果

Frequency-selective control of cortical and subcortical networks by central thalamus.

• DOI: 10.7554/elife.09215
• 发表时间: 2015-12-10
• 期刊: eLife
• 影响因子: 7.7
• 作者: Liu J;Lee HJ;Weitz AJ;Fang Z;Lin P;Choy M;Fisher R;Pinskiy V;Tolpygo A;Mitra P;Schiff N;Lee JH
• 通讯作者: Lee JH