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论文题名(中文):

 经颅磁声耦合刺激中各物理场对神经电活动调控效果的研究    

姓名:

 马晓旭    

论文语种:

 chi    

学位:

 博士    

学位类型:

 学术学位    

学位授予单位:

 北京协和医学院    

学校:

 北京协和医学院    

院系:

 北京协和医学院生物医学工程研究所    

专业:

 生物医学工程(工)-生物医学工程    

指导教师姓名:

 刘志朋    

论文完成日期:

 2025-05-15    

论文题名(外文):

 Study on the effect of various physical fields in transcranial magnetoacoustic coupled stimulation on the modulation of neural electrical activity    

关键词(中文):

 经颅磁声耦合刺激 经颅超声刺激 神经调控 突触可塑性 神经振荡    

关键词(外文):

 Transcranial Magneto-Acoustic Stimulation (TMAS) Transcranial Ultrasound Stimulation Neuromodulation Synaptic Plasticity Neural Oscillations    

论文文摘(中文):

在无创神经调控技术中,经颅磁声耦合刺激(Transcranial magneto-acoustic coupling stimulation,TMAS)结合经颅超声刺激(Transcranial ultrasound stimulation, TUS)的高穿透性和磁声效应的高空间分辨率优势以实现无创神经调控。TMAS 基 于磁声耦合物理机制,涉及了静磁场(Static magnetic field, SMF)、超声和耦合电场。TMAS中SMF对神经电活动是否发挥调控作用,以及电场和超声在TMAS中各自的作用效果,目前仍存在有待解决的科学问题。本文将以C57BL6小鼠为研究对象,设计SMF、TUS和TMAS组开展实验。 首先探讨TMAS和TUS对海马区短期和长期突触可塑性和神经振荡的调控效果。实验将0.15 MPa和0.3 MPa声压的TMAS和TUS聚焦于C57BL6小鼠的海马区,旨在明确TMAS相较于TUS的神经调控差异,为后续解析多物理场协同机制 建立实验基准。结果显示,不同强度的TUS对比 Control组对长时程抑制(Long Term Depression,LTD)以及gamma频段相干性等指标产生或促进或抑制的调控效 果,而叠加0.2 T正交SMF形成的TMAS在长时程增强(Long-Term Potentiation, LTP)、LTD、 短期突触可塑性、theta 和 high gamma 频段的功率以及 theta-high gamma 的跨频耦合强度对比控制组和TUS组都显著增强,这证明实验条件下, SMF和电场加入的TMAS显著加强了对神经电活动的调控。 其次对SMF的影响进行探究。一方面探究SMF是否会间接影响超声波形或实验温度从而影响整体调控效果,另一方面探究 SMF是否会对神经电活动产生直接影响。结果表明实验条件下SMF并不会影响这些指标。表明TMAS的调控作用并不直接来源于SMF,其对比TUS产生的差异应来自耦合电场。 随后研究了超声和电场的物理参数对 TMAS 调控神经电活动的影响。设置三组不同参数的 TMAS 开展实验,分别比较了超声声压相同但电场强度加倍的TMAS组之间的比较(0.3 MPa+0.2 V/m和0.3 MPa+0.4 V/m),电场强度相同但超声声压加倍(0.3 MPa+0.2 V/m和0.15 MPa+0.2 V/m)的TMAS组之间的比较。结果表明,所有TMAS组对比控制组都在多个指标出现显著性增长,其中TMAS中电场强度和声压的共同提升(0.3 MPa+0.4 V/m)引起了最明显的神经电活动促进效应。其次,电场强度加倍显著引起了LTP、DEP、短期突触可塑性、high-gamma 相对功率以及 theta-highgamma 跨频耦合强度等指标的差异,相较之下声压加倍之间没有产生显著性差异。这表明在 TMAS 中,电场强度的大小可能对神经电活动调控具有更显著的影响。最后,通过行为学实验评估不同物理场刺激对小鼠学习记忆的影响。结果表明,SMF组在行为学指标对比控制组没有显著性差异,0.3 MPa的TUS增强了小鼠的短期记忆,而 TMAS则能进一步提升长期记忆和空间学习能力,其中0.3 MPa+0.4 V/m TMAS的差异最为显著,与上文中神经电活动的实验结果具有一致性。本文在包括长期和短期突触可塑性以及神经振荡的神经电活动层面系统解析了TMAS的神经调控效果来源,初步揭示SMF不直接参与神经调控而通过耦合电场协同超声增强作用效果;建立了基于TMAS耦合机制的电声参数调控解析方式,通过对比声压与电场强度的调控效能差异,表明电场强度对神经电活动调控效果具有更主导的作用。该研究结果为TMAS参数优化提供了实验依据,推进了对TMAS神经调控机制的深入理解,为发展高精度调控技术提供更新的解决方案。

论文文摘(外文):

In non-invasive neuromodulation techniques, Transcranial Magneto-Acoustic Coupling Stimulation (TMAS) utilizes the high penetration and spatial resolution advantages of Transcranial Ultrasound Stimulation (TUS) to achieve non-invasive neural regulation. TMAS is based on magneto-acoustic coupling, involving Static Magnetic Fields (SMF), ultrasound, and coupling electric fields. However, the regulatory effects of SMF on neural electrical activity and the individual contributions of the electric field and ultrasound within TMAS have not been thoroughly investigated. This study uses C57BL6 mice as subjects and conducts experiments with SMF, TUS, and TMAS groups. Firstly, the study investigates the effects of TMAS and TUS on short-term and long-term synaptic plasticity and neural oscillations in the hippocampal region. TMAS and TUS, with ultrasound pressures of 0.15 MPa and 0.3 MPa, were focused on the hippocampus of C57BL6 mice. The aim was to clarify the neuroregulatory gain effect of TMAS compared to TUS, establishing experimental benchmarks for subsequent analysis of multi-physical field synergistic mechanisms. Results indicate that different intensities of TUS, compared to the Control group, promoted or suppressed the modulation effects on Long-Term Depression (LTD) and gamma band Coherence, whereas TMAS, enhanced by a 0.2 T orthogonal SMF, significantly amplified Long-Term Potentiation (LTP), LTD, short-term synaptic plasticity, theta and high gamma power, and theta-high gamma cross-frequency coupling compared to both the Control and TUS groups. This proves that SMF and the electric field together in TMAS significantly strengthen the regulation of neural electrical activity. Next, the study investigates the effects of SMF. On the one hand, it explores whether SMF indirectly affects the ultrasound waveform or experimental temperature, thereby influencing the overall regulatory effect. On the other hand, it examines whether SMF directly influences neural electrical activity. Results show that under the experimental conditions, SMF did not affect these indicators, indicating that the regulatory effect of TMAS is not directly derived from SMF, but rather from the coupling electric field. Subsequently, the study explores the impact of ultrasound and electric field dosages on TMAS’s regulation of neural electrical activity. Three different TMAS parameter groups were set up for comparison: one group with the same ultrasound pressure but doubled electric field intensity (0.3 MPa + 0.2 V/m vs. 0.3 MPa + 0.4 V/m), and another with the same electric field intensity but doubled ultrasound pressure (0.3 MPa + 0.2 V/m vs. 0.15 MPa + 0.2 V/m). The results show that all TMAS groups significantly increased multiple indicators compared to the Control group, with the TMAS group that simultaneously increased both ultrasound pressure and electric field intensity (0.3 MPa + 0.4 V/m) producing the most significant neural electrical activity enhancement. Furthermore, doubling the electric field intensity significantly altered LTP, DEP, short-term synaptic plasticity, high-gamma relative power, and theta-high gamma cross-frequency coupling, while no significant differences were observed with doubled ultrasound pressure. This suggests that the electric field intensity in TMAS has a more significant influence on regulating neural electrical activity. Finally, behavioral experiments were conducted to assess the effects of different physical field stimuli on the learning and memory of mice. The results indicate that the SMF group did not show significant differences compared to the Control group in behavioral indices. TUS at 0.3 MPa enhanced short-term memory, while TMAS further improved long-term memory and spatial learning abilities, with the 0.3 MPa + 0.4 V/m TMAS group showing the most significant difference. These findings are consistent with the neural electrical activity results. This study systematically analyzes the sources of TMAS’s neuroregulatory effects at the level of long-term and short-term synaptic plasticity and neural oscillations. It preliminarily reveals that SMF does not directly participate in neural regulation but rather enhances the effect through the coupling electric field. A TMAS parameter regulation analysis approach based on the coupling mechanism is established. By comparing the regulatory effects of ultrasound pressure and electric field intensity, the study demonstrates that electric field intensity plays a more dominant role in regulating neural electrical activity. The results provide experimental evidence for TMAS parameter optimization, advance the understanding of TMAS’s neural regulation mechanisms, and offer an updated solution for the development of high-precision deep brain modulation techniques.

开放日期:

 2025-06-18    

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