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.

摘要 近年来，超声神经调节因其独特的能力而受到越来越多的关注。 非侵入性地激活和抑制神经元。然而，美国神经调节的机制并不完全 了解，但对诱导神经调节的最佳参数知之甚少。在这项提案中，我们 将使用膜片钳方法在细胞水平上测试最近提出的美国神经调节模型 锥体和中间神经元，它们具有不同的特征，我们假设这些特征将导致它们 对美国的反应不同。US脉冲参数将使用部分析因设计进行选择，该设计将 使我们能够评估美国脉搏的哪些方面对引发美国神经调节最重要。我们 然后将这项工作转移到小鼠身上，同时测量电生理输出和血氧水平 依赖功能磁共振成像(BOLD FMRI)。这些实验将使我们能够评估 细胞水平上的发现是否适用于整个动物，并测试US的效果 用BOLD功能磁共振成像和电生理读数研究躯体感觉网络中的神经调节。我们会 在这些实验中，使用水听器、模拟和 磁共振(MR)成像US波束的方法，例如MR声辐射力成像。这 量化对于解释美国的神经调节实验很重要，尤其是在小动物身上。 因为它们的头骨在通常用于神经调节的频率上扮演着混响室的角色。 这些研究将确定美国神经调节的重要空间特征和局限性 用于小动物的大脑，神经元密度增加和回响可能会导致 在比例上比在较大的动物身上发生的影响更大。在我们的最终目标中，我们将使用基于数组的US 我们实验室目前正在开发的神经调节系统，以唤起激活模式，以及 研究猴子的细、中、远距离回路。该系统可以产生毫米级的焦距 通过猴子头骨，这将使探索研究得很好的躯体感觉系统成为可能 与人类的基因同源。在这些猴子身上，我们将评估美国神经调节对 在前两个目标中确定的参数空间使用电生理读数和粗略的fMRI来标测 刺激过程中躯体感觉皮质的S1亚区，并量化US参数对 大胆的功能磁共振成像，以抑制或刺激皮肤触觉诱发反应。在完成建议的研究后，我们 将对US与神经元的细胞相互作用有更好的理解，定量评估 在网络层面上发生的电生理和大胆的fMRI活动，以及改进的 理解引起美国神经调节的参数空间。