Explaining the variability in focused ultrasound neuromodulation

解释聚焦超声神经调节的变异性

• 批准号: 10683935
• 负责人: Jacek Dmochowski
• 金额: $ 17.16万
• 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/10683935
• 关键词: Acceleration; 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; Image; Interneurons; Intervention; Knowledge; Learning; 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; Synaptic Potentials; Techniques; Technology; Testing; Training; Ultrasonics; United States National Institutes of Health; Urethane; Work; awake; cell type; cranium; density; disability; excitatory neuron; extracellular; hippocampal pyramidal neuron; inhibitory neuron; innovation; millimeter; nervous system disorder; neural; neural circuit; neuroregulation; noninvasive brain stimulation; novel; outcome disparities; postsynaptic; preference; 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.

项目概要 虽然非侵入性脑刺激的传统电磁方法在空间上受到限制 分辨率和穿透深度，超声神经调节具有毫米级潜力 无需手术即可刺激大脑深部区域。大量证据表明，低强度 聚焦超声刺激（FUS）调节大脑活动。然而，已有多起报道称 神经对超声波的反应存在很大差异，相同的“剂量”会产生不同的效果。 了解变异性的来源对于利用 FUS 在基础神经科学中的巨大潜力至关重要， 神经病学和精神病学。 这项研究的长期目标是将 FUS 发展成为一种个性化的闭环技术， 可以驱动大脑活动达到理想的状态。作为实现这一目标的第一步，本次会议的总体目标 提议是确定神经元对 FUS 反应变异的主要来源。根据我们组的 根据初步数据，我们的中心假设是对 FUS 的反应很大程度上受大脑状态的影响，并且 通过考虑神经活动的动态，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 依赖于国家的概念 通过探索睡眠和清醒状态下振荡动力学和细胞类型的影响。我们的具体 目标是：(1) 确定基线 LFP 动态与睡眠期间神经元反应之间的关系，(2) 确定细胞类型在睡眠期间响应 FUS 的作用，以及 (3) 确定神经元的决定因素 清醒状态下对 FUS 的反应。我们将使用聚氨酯麻醉和头部固定的清醒大鼠， 并将用 FUS 瞄准海马体，同时捕获电生理活动。 所提出的工作意义重大，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 明确地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 的一个核心问题： 回复。通过描述产生强大效应的条件，这项研究将使 FUS 领域成为第一个 更接近闭环能力，这显然需要可预测的响应。此外，我们将 通过考虑 FUS 的神经生物学底物，对 FUS 的机制有更清晰的了解 本研究中确定的响应状态。例如，如果我们确实确认 FUS 响应与 基线伽玛，这将揭示 FUS 正在调制的（伽玛生成）电路。这 这些知识也将立即为快速发展的 FUS 神经调节研究界提供信息 作为神经病学和精神病学未来的试点研究。