Effect of transcranial magneto-acousto-electrical stimulation on the plasticity of the prefrontal cortex network in mice

doi:10.12307/2025.306

Abstract

Abstract:
BACKGROUND: Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system. However, the mechanism by which it affects synaptic plasticity in the brain is still not enough.
OBJECTIVE: To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice.
METHODS: (1) Animal experiment: Twenty-four C57 mice were equally and randomly divided into four groups: the control group receiving pseudo-stimulation, the 6.35 W/cm2 stimulation group receiving coupled stimulation of 0.3 T, 6.35 W/cm2, the 17.36 W/cm2 stimulation group receiving coupled stimulation of 0.3 T, 17.36 W/cm2, and the 56.25 W/cm2 stimulation group receiving coupled stimulation of 0.3 T, 56.25 W/cm2. The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice. (2) Modeling and simulation experiments: A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities.
RESULTS AND CONCLUSION: Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time, improve the working memory ability of mice (P < 0.05), and continue to stimulate the frontal lobe of mice after learning behavior. There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups (P > 0.1). Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β and γ rhythms. As the stimulation intensity increased, there was an asynchronous decrease in β and γ rhythms. Through β-γ phase amplitude coupling, it was found that stimuli could enhance the neural network’s ability to adapt to new information and task requirements. Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network, increase the long-term synaptic weight level, and decrease the short-term synaptic weight level only when the stimulation intensity was high. To conclude, there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks. This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.

Key words: transcranial magneto-acoustic-electrical stimulation, working memory, synaptic plasticity, cortical network, LIF neuron model

CLC Number:

Zhang Shuai, Li Zichun, Xu Yihao, Xie Xiaofeng, Guo Zhongsheng, Zhao Qingyang. Effect of transcranial magneto-acousto-electrical stimulation on the plasticity of the prefrontal cortex network in mice [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(6): 1108-1117.

Figures/Tables 8

通过对小鼠工作记忆过程中前额叶的局部场电位信号进行相位幅值耦合分析，计算低频β相位对高频γ幅值的耦合值，对比分析对照组、刺激6.35 W/cm2组、刺激17.36 W/cm2组、刺激56.25 W/cm2组小鼠β节律与γ节律的耦合强度，研究经颅磁声电刺激对小鼠工作记忆过程中神经节律耦合特征的影响。如图5所示为不同组别小鼠工作记忆过程中前额叶β-γ相位幅值耦合分布。对照组相位幅值耦合主要分布在12-13 Hz与75-80 Hz。刺激6.35 W/cm2组与对照组比较，其β-γ相位幅值耦合分布更为集中，主要分布在12-14 Hz。刺激17.36 W/cm2组相位幅值耦合强度没有明显增强，但β高频带与γ低频带相位幅值耦合明显增强。而刺激56.25 W/cm2组相位幅值耦合程度明显增强，β高节律与γ低节律相位幅值耦合程度进一步增强。 Pearson相关性分析反映了脑区之间的线性相关性，描述了它们的同步性和功能连接。对照组、刺激6.35 W/cm2组、刺激17.36 W/cm2组和刺激56.25 W/cm2组的Pearson相关性r值分别为0.666 8±0.209 0，0.590 9±0.272 4，0.386 1±0.385 6，0.692 0± 0.119 2。经颅磁声刺激处理的小鼠前额叶皮质导致局部场电位的Pearson相关系数降低。感应电流促使不同脑区的活动解耦，促进大脑网络的结构重组和动态变化。随着刺激强度的增加，相关系数逐渐增加，网络同步性逐渐改善。不同脑区之间的功能连接强度增加。脑区之间的信号传输趋向于呈现同步和相关的状态，表明抑制性连接增强，网络的动态稳定性得到改善。脑网络的全局效率结果如图6所示。感应电流刺激改变了前额叶网络的全局效率 (P < 0.001)。各刺激组前额叶全局效率要高于对照组，但随刺激增强，全局效率明显降低，局部效率增大。经颅磁声电刺激增强了小鼠脑网络的局部聚类程度，有效重塑了网络的信息传输结构。随着刺激强度的增加，全局效率降低，减少了前额叶网络的信息处理能耗，神经网络稳定性增强。但不同脑区之间的信息传输效率降低，不同脑区之间的信息整合和协调受到阻碍，这可能影响认知任务。 2.2 仿真实验结果分析不同感应电流刺激强度下，皮质网络在工作记忆形成过程中的平均放电率变化，采用滑动平均窗方法确定的神经元集群平均放电率，其中滑动时间窗取10 ms，如图7所示；神经网络平均放电率变化趋势如图8所示。由皮质网络在工作记忆形成过程中的平均放电率变化的仿真结果可以看出，随着刺激强度的增加，神经网络过渡到工作记忆延迟期的过程显著加快，但延迟期后恢复静息态所需的时间增加。当刺激强度超过20 μA/cm2时，神经网络平均放电率直到仿真结束仍未恢复到预提示期放电水平，且随着刺激强度的逐渐增加，神经网络在恢复静息态后，其稳定平均放电率逐渐增加。刺激强度对恢复静息态平均放电率具有显著影响(P < 0.001)。而当刺激强度超过70 μA/cm2时，神经网络在预提示期内的平均放电率出现明显增加。此次仿真结果与课题组之前实验结果一致[50]。突触权重变化，如图9A所示，LTP反映了第一次工作记忆形成过程中突触权重的变化。只有在较低的刺激强度下，神经网络权重才会有一定程度的降低。然而，当刺激强度超过40 μA/cm2时，神经网络的平均权重值会增加。如图9B所示，在0-70 μA/cm2的刺激强度范围内，STP没有显著变化，但超过该范围，短时程突触权重水平性减小。"

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