Explaining the variability in focused ultrasound neuromodulation

解释聚焦超声神经调节的变异性

• 批准号: 10411455
• 负责人: Jacek Dmochowski
• 金额: $ 13.99万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10411455
• 关键词: Acoustics; Address; Anesthesia procedures; Brain; Brain region; Cells; Clinical Research; Communities; Data; Deep Brain Stimulation; Device or Instrument Development; Dose; Electromagnetics; Electrophysiology (science); Exhibits; Focused Ultrasound; Frequencies; Future; Goals; Head; Hippocampus (Brain); Image; Interneurons; Intervention; Knowledge; Lead; Learning; Light; Link; Mental disorders; Mission; Modeling; Nature; Neurobiology; Neurology; Neurons; Neurosciences; Operative Surgical Procedures; Organism; Outcome; Penetration; Periodicity; Pilot Projects; Population; Psychiatry; Public Health; Pyramidal Cells; Rattus; Reporting; Research; Resolution; Role; Sleep; Source; Synapses; Techniques; Technology; Testing; Training; Ultrasonics; United States National Institutes of Health; Urethane; Work; awake; base; cell type; cranium; density; disability; excitatory neuron; extracellular; hippocampal pyramidal neuron; inhibitory neuron; innovation; millimeter; nervous system disorder; neural circuit; neuroregulation; noninvasive brain stimulation; novel; postsynaptic; predicting response; preference; relating to nervous system; response; soft tissue; ultrasound

PROJECT SUMMARY While conventional electromagnetic approaches to non-invasive brain stimulation are limited in their spatial resolution and penetration depth, ultrasonic neuromodulation carries the potential of millimeter scale stimulation of deep brain regions without the need for surgery. Abundant evidence shows that low intensity focused ultrasound stimulation (FUS) modulates brain activity. However, there have been several reports of substantial variability in the neural response to ultrasound, with the same "dose" producing disparate effects. Understanding the source of variability is critical to harnessing the vast potential of FUS in basic neuroscience, neurology, and psychiatry. The long term goal of this research is to develop FUS into a personalized, closed loop technology that can drive brain activity towards desirable states. As the first step towards this goal, the overall objective of this proposal is to identify the primary source of the variability in neuronal responses to FUS. Based on our group's preliminary data, our central hypothesis is that response to FUS is greatly influenced by brain state, and that the outcome of stimulation may be accurately predicted by taking into account the dynamics of neural activity leading up to stimulation. In the proposed work, we will thoroughly test the notion that FUS is state dependent by probing the influence of oscillatory dynamics and cell type during both sleep and wake states. Our specific aims are: (1) Identify the relationship between baseline LFP dynamics and neuronal response during sleep, (2) Identify the role of cell type in response to FUS during sleep, and (3) Identify the determinants of neuronal response to FUS in the awake state. We will work with both urethane-anesthetized and head-fixed awake rats, and will target the hippocampus with FUS while simultaneously capturing electrophysiological activity. The proposed work is significant because it addresses the central problem with ultrasonic neuromodulation: how to make its effects more robust and predictable. This research is innovative because it explicitly links neural dynamics leading up to stimulation with the subsequent response to FUS. The products of this research have the potential to solve a central problem in FUS: variability of response. By delineating the conditions that lead to robust effects, this research will bring the FUS field one step closer to closed-loop capabilities, which clearly necessitate predictable responses. Moreover, we will obtain a clearer understanding of the mechanism of FUS by considering the neurobiological substrates of the responsive states identified in this research. For example, if we do confirm a link between FUS response and baseline gamma, this will shed light on the (gamma generating) circuits that FUS is modulating. This knowledge will then immediately inform the rapidly growing FUS neuromodulation research community as well as future pilot studies in neurology and psychiatry.

项目摘要 尽管无创脑刺激的常规电磁方法在其空间上受到限制 分辨率和穿透深度，超声神经调节具有毫米量表的潜力 无需手术的无需手术刺激大脑区域。大量证据表明低强度 聚焦超声刺激（FUS）调节大脑活性。但是，有几份报告 对超声的神经反应的实质性差异，具有相同的“剂量”产生不同的作用。 了解可变性的来源对于利用基本神经科学中的FUS巨大潜力至关重要， 神经病学和精神病学。 这项研究的长期目标是将FUS开发为一种个性化的，封闭的循环技术， 可以将大脑活动推向理想的状态。作为朝着这个目标的第一步，这是总体目标 建议是确定神经元反应的差异的主要来源。根据我们小组的 初步数据，我们的核心假设是，对FUS的反应受到大脑状态的极大影响，并且 通过考虑神经活动的动力学，可以准确预测刺激的结果 导致刺激。在拟议的工作中，我们将彻底测试FUS依赖状态的观念 通过探测睡眠和唤醒状态期间振荡动力学和细胞类型的影响。我们的具体 目的是：（1）确定睡眠过程中基线LFP动力学与神经元反应之间的关系，（2） 确定细胞类型在睡眠过程中响应FUS的作用，（3）确定神经元的决定因素 在清醒状态下对FUS的反应。我们将与氨基氨基 - 麻醉剂和头部固定的醒着老鼠一起工作， 并将用FUS瞄准海马，同时捕获电生理活性。 拟议的工作很重要，因为它解决了超声波的核心问题 神经调节：如何使其效果更加稳健和可预测。这项研究具有创新性，因为它 明确将导致刺激的神经动力学与随后对FUS的反应联系起来。 这项研究的产品有可能解决FUS中的核心问题： 回复。通过描述导致强大效果的条件，这项研究将使FUS领域一个 距离闭环功能更近，这显然需要可预测的响应。而且，我们会的 通过考虑的神经生物学底物，可以更清楚地了解FUS的机制 在这项研究中确定的响应状态。例如，如果我们确实确认了FUS响应和 基线伽玛，这将使FUS正在调节的（伽马生成）电路揭示。这 然后，知识将立即告知快速增长的FUS神经调节研究社区 作为神经和精神病学的未来试点研究。