开源超声神经调控预测框架：连接组织弹性力学与神经元放电动力学
An open-source framework for predicting ultrasound neuromodulation: bridging tissue elastomechanics and neuron firing dynamics
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中文总结 AI 辅助
本研究提出开源计算框架，耦合多物理过程与多通路神经元模型，可预测超声神经调控的神经元放电区域，为超声神经调控的机制研究与安全评估提供空间分辨的可验证工具。
中文摘要 AI 辅助
经颅聚焦超声是一种具有毫米级分辨率的非侵入性神经调控方式，但其作用的生物物理机制仍未明确。常规的超声暴露参数由换能器表面或降额焦点压力指定，这些量仅间接关联到治疗的关键因素：哪些神经元放电以及通过何种通路。我们针对这一空白提出了端到端计算框架，可将经颅声场映射到与解剖结构配准的体素级神经元放电图。该流程耦合了异构非线性全波声传播、粘弹性剪切波传播、Pennes生物热扩散、从组织应变到膜张力的双层力学转换，以及多房室Hodgkin-Huxley神经元，该神经元包含机械敏感、空化耦合、钙耦合、热敏、星形胶质细胞-胶质递质、机械敏感-突触等通路。六种候选机制作为可互换组件在共享神经元模型上实现，因此可在同一声场下直接比较其放电预测结果，且所有数值参数均按来源分类并通过敏感性分析界定范围。我们在微CT人类颅骨标本上递送的θ爆发超声刺激（靶向左侧背侧前扣带回皮质）上演示了该框架，预测出焦点热升幅在ITRUSST共识安全包络内时，焦点放电区域体积约为8500 mm³。该框架的主要输出是与驱动其的声学、弹性和热场历史共同解析的体素级放电体积图，提供了空间分辨、可证伪的预测，可通过高密度细胞外记录进行验证，并支持参数估计、细胞类型分辨的机制识别以及超声神经调控的定量安全性评估。
英文摘要
Transcranial focused ultrasound is a non-invasive neuromodulation modality with millimetre-scale resolution, but its biophysical mechanism of action remains unresolved. Exposure is conventionally specified by transducer surface or derated focal pressure, quantities only indirectly related to what matters for therapy: which neurons fire and through which pathway. We address this gap with an end-to-end computational framework that maps a transcranial acoustic field to per-voxel neural firing maps registered to anatomy. The pipeline couples heterogeneous nonlinear full-wave acoustic propagation, viscoelastic shear-wave propagation, Pennes bioheat diffusion, a bilayer-mechanics conversion from tissue strain to membrane tension, and a multi-compartment Hodgkin-Huxley neuron carrying mechanosensitive, cavitation-coupled, calcium-coupled, thermosensitive, astrocytic-gliotransmitter, and mechanosensitive-synaptic pathways. Six candidate mechanisms are implemented as interchangeable components on a shared neuron model, so their firing predictions can be compared directly on the same field, and every numerical parameter is classified by source and bracketed by sensitivity analysis. We demonstrate the framework on a theta-burst sonication delivered through a micro-CT human-skull specimen targeting the left dorsal anterior cingulate cortex, predicting a focal firing zone of approximately 8,500 mm^3 at a focal thermal rise well within ITRUSST consensus safety envelopes. The principal output is a per-voxel firing-volume map resolved jointly with the acoustic, elastic, and thermal field histories that drive it, giving spatially resolved, falsifiable predictions that are testable against high-density extracellular recordings and support parameter estimation, cell-type-resolved mechanism identification, and quantitative safety assessment for ultrasound neuromodulation.
