Neuron selective modulation of brain circuitry in non-human primates

非人类灵长类动物脑回路的神经元选择性调节

• 批准号: 9148240
• 负责人: Charles F Caskey
• 金额: $ 45.63万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-23 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9148240
• 关键词: Acoustics; Action Potentials; Address; Animal Model; Animals; Architecture; Area; Behavioral; Biological Neural Networks; Brain; Brain Mapping; Cell membrane; Cells; Charge; Coupled; Couples; Development; Devices; Electric Capacitance; Electroconvulsive Therapy; Electrodes; Electroencephalography; Electrophysiology (science); Event; Focused Ultrasound Therapy; Foundations; Functional Magnetic Resonance Imaging; Generations; Goals; Hodgkin-Huxley model; Human; Image; Investigation; Ion Channel; Macaca; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mechanics; Membrane; Metabolic; Methods; Modeling; Monoclonal Antibody R24; Neurons; Pattern; Performance; Physiologic pulse; Procedures; Property; Resolution; Safety; Scheme; Signal Transduction; Skin; Spottings; Stimulus; System; Tactile; Technology; Testing; Thalamic structure; Transcranial magnetic stimulation; Transducers; Translating; Translations; Ultrasonic Transducer; Ultrasonics; Ultrasonography; Visual; Visual Cortex; Visual system structure; Work; base; behavior measurement; behavioral response; blood oxygen level dependent; brain circuitry; brain volume; design; image guided; imaging system; improved; mathematical model; model design; neural circuit; neural stimulation; neuroimaging; neurophysiology; neuroregulation; next generation; nonhuman primate; novel; novel strategies; optogenetics; public health relevance; relating to nervous system; research study; response; somatosensory; tool

 DESCRIPTION (provided by applicant): All presently available neural stimulation methods are either invasive or can only be moderately localized, and a neurostimulation method that could overcome these limitations would be invaluable for brain circuit investigation. Neural stimulation with magnetic resonance guided high intensity focused ultrasound (MRgHIFU) is a promising technology that can noninvasively excite or inhibit neural activity in well-defined discrete volumes of the brain, subsequently enabling investigation of brain circuits with magnetic resonance imaging (MRI). We seek to explore this brain stimulation method in the somatosensory and visual systems of non- human primates with the goal of quantifying and expanding the capabilities of MRgHIFU as a tool for understanding neural circuits. The significance of this proposal results from the potential for ultrasound to be used as an investigative tool for neural stimulation that can address the shortcomings of other available methods. The mechanism of action of ultrasound on neurons suggests that different acoustic pulses can selectively activate neurons based on their ion channel types, allowing for cells to be differentially stimulated. In our preliminary work, we have developed methods for measuring and subsequently optimizing acoustic beams using MRI and designed a transducer array that is optimized for stimulation of the macaque cortex. We will integrate this into a high-field (7T) human magnet and implement novel methods for transcranially focusing a small burst of ultrasound within the macaque cortex in a controlled manner. With this technology in place, we will leverage our background in behavioral and neurophysiological measurements in macaques to quantify effects at the macro-, meso-, and microscale in behaving animals. We will then use blood oxygen level dependent functional MRI (BOLD fMRI) to map the S1 subregions of the brain during stimulation. Specifically, we will quantify the effect of acoustic parameters on BOLD fMRI and use ultrasound to inhibit or excite the skin tactile evoked response, while imaging the subsequent change in the BOLD signal. We will also use ultrasound to evoke activation patterns, and investigate the fine, middle, and long range circuits of the brain. Acoustic pulses will be designed to excite or inhibit neurons based on a newly validated model of the interaction of ultrasound with neurons. This model couples acoustically induced oscillation of cell membranes to the Hodgkin-Huxley model of action potential generation and may provide a method to differentially stimulate neurons based on their ion channels, which would be a very powerful and unprecedented neurostimulation technology. We propose simple experiments in a highly relevant animal that would test the utility of this model to design ultrasonic stimulation (either exciting or inhibiting) in localized regions and examine the BOLD fMRI signals resulting from such stimulation. The completion of these aims will expand the capabilities of MRgHIFU in conjunction with fMRI for investigating neural circuits, paving this way for this potentially important new approach to the assessment of brain function.

 描述（由申请人提供）：目前所有可用的神经刺激方法要么是侵入性的，要么只能是适度局部的，并且能够克服这些限制的神经刺激方法对于磁共振引导的高强度聚焦超声的神经刺激来说是非常有价值的。 （MRgHIFU）是一项有前景的技术，可以无创地刺激或抑制明确的离散大脑体积中的神经活动，从而能够通过磁共振成像（MRI）研究大脑回路。我们寻求探索这种大脑刺激方法。研究非人类灵长类动物的体感和视觉系统，目标是量化和扩展 MRgHIFU 作为理解神经回路工具的能力。该提案的重要性源于超声作为神经刺激研究工具的潜力。超声波对神经元的作用机制表明，不同的声脉冲可以根据其离子通道类型选择性地激活神经元，从而使细胞受到差异性刺激。开发了使用 MRI 测量和随后优化声束的方法，并设计了一种针对猕猴皮层刺激进行优化的换能器阵列，我们将其集成到高场 (7T) 人体磁铁中，并实施经颅聚焦小型物体的新方法。有了这项技术，我们将利用我们在猕猴行为和神经生理学测量方面的背景来量化宏观、中观和微观行为的影响。然后，我们将使用血氧水平依赖性功能 MRI (BOLD fMRI) 来绘制刺激过程中大脑的 S1 分区图。具体来说，我们将量化声学参数对 BOLD fMRI 的影响，并使用超声波抑制或刺激皮肤触觉。诱发反应，同时对 BOLD 信号的后续变化进行成像，我们还将使用超声波诱发激活模式，并研究大脑的精细、中程和长程电路，声脉冲将被设计为基于神经元的兴奋或抑制。该模型将声学诱导的细胞膜振荡与动作电位生成的霍奇金-赫胥黎模型耦合起来，并可能提供一种基于离子通道差异刺激神经元的方法。我们提出了一种非常强大且前所未有的神经刺激技术，在高度相关的动物中进行简单的实验，以测试该模型在局部区域设计超声波刺激（刺激或抑制）的实用性，并检查由此产生的 BOLD fMRI 信号。这些目标的完成将扩展 MRgHIFU 与 fMRI 结合研究神经回路的能力，为这种潜在重要的大脑功能评估新方法铺平道路。