Establishing a dose response for ultrasound neuromodulation

建立超声神经调节的剂量反应

• 批准号: 9229212
• 负责人: Charles F Caskey
• 金额: $ 33.65万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-23 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9229212
• 关键词: Acoustics; Affect; Animals; Attention; Behavior; Biological Neural Networks; Brain; Cells; Characteristics; Complement; Coupled; Data; Dose; Electric Capacitance; Electroencephalography; Electrophysiology (science); Event; Event-Related Potentials; Focused Ultrasound; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Goals; Growth; Hippocampus (Brain); Human; Image; In Vitro; Interneurons; Investigation; Ion Channel; Laboratories; Linear Regressions; Location; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Measurement; Measures; Membrane; Membrane Potentials; Methods; Modeling; Monkeys; Motor; Mus; Neurons; Output; Patch-Clamp Techniques; Pattern; Physics; Physiologic pulse; Play; Positioning Attribute; Preparation; Property; Radiation; Research; Research Design; Research Personnel; Rodent; Role; Safety; Scheme; Skin; Slice; Somatosensory Cortex; Stimulus; System; Tactile; Technology; Testing; Tissues; Translating; Ultrasonography; Work; abstracting; base; blood oxygen level dependent; blood oxygenation level dependent response; cranium; density; design; dosage; dosimetry; experience; hippocampal pyramidal neuron; image guided; imaging modality; improved; insight; mathematical model; millimeter; neural stimulation; neuroimaging; neurophysiology; neuroregulation; nonhuman primate; patch clamp; relating to nervous system; research study; response; simulation; somatosensory; tool

Abstract Ultrasound (US) neuromodulation has received increased attention in recent years due to its unique ability to non-invasively activate and inhibit neurons. However, the mechanisms of US neuromodulation are not fully understood, and little is known about the optimal parameters that elicit neuromodulation. In this proposal, we will test a recently proposed model of US neuromodulation at the cellular level using patch clamp methods on pyramidal and interneurons, which have differing characteristics that we hypothesize will cause them to respond differently to US. US pulse parameters will be chosen using a fractional factorial design that will enable us to assess which aspects of the US pulse are most important for eliciting US neuromodulation. We will then translate this work to mice while measuring electrophysiological outputs and blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI). These experiments will allow us to assess whether findings at the cellular level hold in the whole animal and also to test the effects of US neuromodulation in the somatosensory network using BOLD fMRI and electrophysiological readouts. We will characterize the acoustic beam within the skull during these experiments using hydrophones, simulations, and magnetic resonance (MR) methods of imaging US beams, such as MR acoustic radiation force imaging. This quantification is important in interpreting US neuromodulation experiments, particularly in small animals, because their skulls act as reverberation chambers at the frequencies commonly used for neuromodulation. These studies will determine important spatial characteristics and limitations of US neuromodulation when used in the brains of small animals, where increased neuron density and reverberations likely cause proportionally larger effects to occur than in larger animals. In our final aim, we will use an array-based US neuromodulation system that is currently being developed in our lab to evoke activation patterns, and investigate the fine, middle, and long-range circuits in monkeys. This system can generate mm-scale foci through the monkey skull, which will enable exploration of the well-studied somatosensory system that is homologous to that in humans. In these monkeys, we will assess the effects of US neuromodulation over the parameter space identified in the first two aims using electrophysiological readouts and BOLD fMRI to map the S1 subregions of the somatosensory cortex during stimulation and quantify the effect of US parameters on BOLD fMRI to inhibit or excite the skin tactile evoked response. At the completion of the proposed studies, we will have an improved understanding of the cellular interactions of US with neurons, quantitative assessments of electrophysiological and BOLD fMRI activity that occurs at the network level, and an improved understanding of the parameter space that elicits US neuromodulation.

抽象的 超声（US）神经调节近年来因其独特的能力而受到越来越多的关注 非侵入性激活和抑制神经元。但是，美国神经调节的机制尚未完全 理解，对引起神经调节的最佳参数知之甚少。在这个建议中，我们 将使用斑块夹方法在细胞水平上测试最近提出的美国神经调节模型 金字塔和神经元具有不同的特征，我们假设会导致它们 对我们的反应不同。将使用分数阶乘设计选择美国脉冲参数 使我们能够评估美国脉搏的哪些方面对于引起我们神经调节最重要。我们 然后将这项工作转化为小鼠，同时测量电生理产量和血氧水平 依赖性功能磁共振成像（BOLD FMRI）。这些实验将使我们能够评估 在整个动物中，细胞水平的发现是否存在并测试我们的影响 使用大胆的fMRI和电生理读数在体感网络中的神经调节。我们将 在这些实验期间，使用氢，模拟和 成像US梁的磁共振（MR）方法，例如MR声学辐射力成像。这 定量对于解释美国神经调节实验，尤其是在小动物中很重要， 因为它们的头骨在通常用于神经调节的频率下充当混响室。 这些研究将确定美国神经调节的重要空间特征和局限性 在小动物的大脑中使用，神经元的密度和混响可能会导致 比大型动物相比，发生的影响比成比例更大。在我们的最终目标中，我们将使用基于阵列的我们 当前正在我们实验室中开发以唤起激活模式的神经调节系统，并 研究猴子中的细，中和远程电路。该系统可以生成MM级焦点 通过猴子头骨，这将使人们能够探索经过深思熟虑的体感系统 与人类同源。在这些猴子中，我们将评估美国神经调节对 在前两个目的中确定的参数空间使用电生理学读数和粗体fMRI来绘制 刺激过程中体感皮质的S1子区域并量化了美国参数对 大胆的fMRI抑制或激发皮肤触觉反应。拟议的研究完成后，我们 将对我们与神经元的细胞相互作用（定量评估）有了改进的了解 在网络级别发生的电生理和大胆fMRI活动的 了解引起我们神经调节的参数空间。