Finite-element simulation and experimental investigation of nanosecond transcranial pulsed electric field propagation and distribution in a three-dimensional brain model_Journal of Biomedical Engineering

Authors：

CHEN Yue ,  YAO Chenguo , YAN Fanping , XIAO Pangxin , LU Xiaoyu

State Key Laboratory of Power Transmission Equipment Technology, School of Electrical Engineering, Chongqing University, Chongqing 401331, P. R. China;

Corresponding?author：

YAO Chenguo, Email: yaochenguo@cqu.edu.cn

Keywords：

Alzheimer's disease; Nanosecond transcranial pulsed electric field stimulation; Amyloid-β; Human brain model; Finite-element simulation

DOI：

10.7507/1001-5515.202512068

Video：

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Nanosecond pulsed electric field (nsPEF) exposure can disrupt and disaggregate amyloid-β, indicating its potential to improve symptoms of Alzheimer’s disease. However, the propagation and distribution patterns of nsPEF within brain tissue remain insufficiently understood, making related simulation analysis necessary. In this study, a high-resolution three-dimensional human head model incorporating the scalp, skull, cerebrospinal fluid, gray matter, white matter, and hippocampus was constructed. Based on the spectral characteristics of nsPEF, the dielectric properties of human tissues at different frequency ranges were assigned, and a transient finite-element model of nsPEF exposure in the human brain was established. The simulation analysis identified two optimal electrode-pair positions and characterized the spatial distributions of intracranial electric field strength as well as current density. It further elucidated the dependence of the hippocampal electric field response and current density on pulse parameters. In addition, a physical human brain model was constructed to experimentally validate the finite-element simulation results. The results showed that transcranial nsPEF can reach deep brain regions with extremely narrow pulse widths, and pulsed electric fields with kilovolt-level amplitudes and nanosecond-scale pulse widths can generate electric field strengths of approximately 10³ V/m in the hippocampus. In summary, this work provides a theoretical basis and experimental support for optimizing the electrode configuration and stimulation parameters of transcranial nsPEF, thereby laying a foundation for future research on its application in non-invasive physical interventions for Alzheimer’s disease.

Citation： CHEN Yue, YAO Chenguo, YAN Fanping, XIAO Pangxin, LU Xiaoyu. Finite-element simulation and experimental investigation of nanosecond transcranial pulsed electric field propagation and distribution in a three-dimensional brain model. Journal of Biomedical Engineering, 2026, 43(3): 504-512. doi: 10.7507/1001-5515.202512068 Copy

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31.	胡亞楠, 包家立, 朱金俊, 等. 納秒電脈沖對肝臟組織不可逆電穿孔消融區分布的時域有限差分法仿真. 電工技術學報, 2021, 36(18): 3841-3850.
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35.	Mampre D, Kim M J, Oliver T, et al. Active recharge biphasic stimulation for the intraoperative monopolar review in deep brain stimulation. Front Hum Neurosci, 2024, 18: 1349599.
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39.	Zhang J, Yang B, Li H, et al. A novel 3D-printed head phantom with anatomically realistic geometry and continuously varying skull resistivity distribution for electrical impedance tomography. Sci Rep, 2017, 7(1): 4608.
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2. 徐勇, 王軍, 王虹崢, 等. 2023中國阿爾茨海默病數據與防控策略. 阿爾茨海默病及相關病雜志, 2023, 6(3): 175-192.
3. Zheng Q, Wang X. Alzheimer's disease: insights into pathology, molecular mechanisms, and therapy. Protein Cell, 2025, 16(2): 83-120.
4. 劉芬, 李湘湘, 鄒偉. TGF-β超家族在阿爾茲海默病中的研究進展. 生命的化學, 2023, 43(5): 772-779.
5. Cummings J L, Zhou Y, Lee G, et al. Alzheimer's disease drug development pipeline: 2025. Alzheimers Dement Transl Res Clin Interv, 2025, 11(2): e70098.
6. Karakatsani M E, Ji R, Murillo M F, et al. Focused ultrasound mitigates pathology and improves spatial memory in Alzheimer's mice and patients. Theranostics, 2023, 13(12): 4102-4120.
7. Collins M N, Mesce K A. A review of the bioeffects of low-intensity focused ultrasound and the benefits of a cellular approach. Front Physiol, 2022, 13: 1047324.
8. 燕雨蝶, 張震. 低頻聚焦超聲對阿爾茨海默病治療作用的研究進展. 阿爾茨海默病及相關病雜志, 2022, 5(4): 324-327.
9. Murdock M H, Yang C Y, Sun N, et al. Multisensory gamma stimulation promotes glymphatic clearance of amyloid. Nature, 2024, 627(8002): 149-156.
10. Blanco-Duque C, Chan D, Kahn M C, et al. Audiovisual gamma stimulation for the treatment of neurodegeneration. J Intern Med, 2024, 295(2): 146-170.
11. Shirota Y, Ugawa Y. Transcranial magnetic stimulation. Curr Opin Behav Sci, 2024, 58: 101396.
12. Koch G, Altomare D, Benussi A, et al. The emerging field of non-invasive brain stimulation in Alzheimer's disease. Brain, 2024, 147(12): 4003-4016.
13. Luo Y, Yang W, Li N, et al. Anodal transcranial direct current stimulation can improve spatial learning and memory and attenuate Aβ42 burden at the early stage of Alzheimer's disease in APP/PS1 transgenic mice. Front Aging Neurosci, 2020, 12: 134.
14. Wu L, Cao T, Li S, et al. Long-term gamma transcranial alternating current stimulation improves the memory function of mice with Alzheimer's disease. Front Aging Neurosci, 2022, 14: 980636.
15. De-Paolis M L, Paoletti I, Zaccone C, et al. Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer's disease. Transl Neurodegener, 2024, 13(1): 33.
16. 王濤, 閆少珍, 薛寒笑, 等. 基于磁共振成像三維動脈自旋標記評價經顱交流電刺激對阿爾茨海默病腦灌注的影響. 中華老年心腦血管病雜志, 2024, 26(11): 1315-1319.
17. Peng J, Du Z, Piao Y, et al. Advances in the application of temporal interference stimulation: a scoping review. Front Hum Neurosci, 2025, 19: 1536906.
18. Violante I R, Alania K, Cassarà A M, et al. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci, 2023, 26(11): 1994-2004.
19. Guidetti M, Arlotti M, Bocci T, et al. Electric fields induced in the brain by transcranial electric stimulation: a review of in vivo recordings. Biomedicines, 2022, 10(10): 2333.
20. ?imko P, Pupíková M, Gajdo? M, et al. Exploring the impact of intensified multiple session tDCS over the left DLPFC on brain function in MCI: a randomized control trial. Sci Rep, 2024, 14(1): 1512.
21. Vargas-Rosales P A, D'Addio A, Zhang Y, et al. Disrupting dimeric β-amyloid by electric fields. ACS Phys Chem Au, 2023, 3(5): 456-466.
22. Kalita S, Bergman H, Dubey K D, et al. How can static and oscillating electric fields serve in decomposing Alzheimer's and other senile plaques?. J Am Chem Soc, 2023, 145(6): 3543-3553.
23. Pr??a J, Cifra M. Molecular dynamics simulation of the nanosecond pulsed electric field effect on kinesin nanomotor. Sci Rep, 2019, 9(1): 19721.
24. Wang L, Cheng Y, Wang W, et al. Effects of terahertz radiation on the aggregation of Alzheimer's Aβ42 peptide. Int J Mol Sci, 2023, 24(5): 5039.
25. Makhkamov M, Baev A, Kurganov E, et al. Understanding Osaka mutation polymorphic Aβ fibril response to static and oscillating electric fields: insights from computational modeling. Sci Rep, 2024, 14(1): 22246.
26. Peng W, Zhu Z, Lou J, et al. High-frequency terahertz waves disrupt Alzheimer's β-amyloid fibril formation. eLight, 2023, 3(1): 18.
27. Huang Y, Parra L C, Haufe S. The New York Head-a precise standardized volume conductor model for EEG source localization and tES targeting. NeuroImage, 2016, 140: 150-162.
28. 王耀, 逯邁. 經顱磁刺激和腦電聯合作用時電磁場分布的仿真研究. 中國醫學物理學雜志, 2023, 40(3): 369-377.
29. 逯婭雯, 逯邁. 經顱直流電刺激中陰極參數對電場分布的影響. 中國醫學物理學雜志, 2019, 36(6): 727-731.
30. 李成偉, 李姣, 張璞, 等. 重復經顱磁刺激治療儀的發展與檢測需求分析. 計量科學與技術, 2022, 66(6): 45-48.
31. 胡亞楠, 包家立, 朱金俊, 等. 納秒電脈沖對肝臟組織不可逆電穿孔消融區分布的時域有限差分法仿真. 電工技術學報, 2021, 36(18): 3841-3850.
32. Baumgartner C, Hasgall P A, Di-Gennaro F, et al. IT'IS database for thermal and electromagnetic parameters of biological tissues, version 5.0. (2025-08-21)[2025-12-20]. https://itis.swiss/virtual-population/tissue-properties/database/dielectric-properties.
33. Niemann F, Shahbabaie A, Pa? S, et al. Neuronavigated focalized transcranial direct current stimulation administered during functional magnetic resonance imaging. J Vis Exp, 2024(213): e67155.
34. 王宏利, 于洪麗, 王超, 等. 基于真實頭模型的經顱直流電刺激參數優選研究. 生物醫學工程學雜志, 2021, 38(4): 638-646.
35. Mampre D, Kim M J, Oliver T, et al. Active recharge biphasic stimulation for the intraoperative monopolar review in deep brain stimulation. Front Hum Neurosci, 2024, 18: 1349599.
36. Liebetanz D, Koch R, Mayenfels S, et al. Safety limits of cathodal transcranial direct current stimulation in rats. Clin Neurophysiol, 2009, 120(6): 1161-1167.
37. Besio W, Sharma V, Spaulding J. The effects of concentric ring electrode electrical stimulation on rat skin. Ann Biomed Eng, 2010, 38(3): 1111-1118.
38. Sun Z, Sen P, Hamers J, et al. Optimized conditions for electrical tissue stimulation with biphasic, charge-balanced impulses. Bioengineering, 2025, 12(3): 234.
39. Zhang J, Yang B, Li H, et al. A novel 3D-printed head phantom with anatomically realistic geometry and continuously varying skull resistivity distribution for electrical impedance tomography. Sci Rep, 2017, 7(1): 4608.
40. Saied I, Arslan T, Chandran S, et al. Non-invasive RF technique for detecting different stages of Alzheimer's disease and imaging beta-amyloid plaques and tau tangles in the brain. IEEE Trans Med Imaging, 2020, 39(12): 4060-4070.
41. Uhrhan K, Schwindt E, Witte H. Fabrication and dielectric validation of an arm phantom for electromyostimulation. Bioengineering, 2024, 11(7): 724.

Journal of Biomedical Engineering

Finite-element simulation and experimental investigation of nanosecond transcranial pulsed electric field propagation and distribution in a three-dimensional brain model

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