Development and electrophysiological validation of a temporal interference transcranial magnetic stimulation system for mice_Journal of Biomedical Engineering

Authors：

CUI Chao ^1,2,3 , WANG Tingyu ^1,2,3 , ZHANG Yanqing ^1,2,3 , ZHENG Weiran ^1,2,3 ,  XU Guizhi ^1,2,3

1. School of Electrical Engineering, Hebei University of Technology, Tianjin 300401, P. R. China;
2. State Key Laboratory of Intelligent Power Distribution Equipment and System, Hebei University of Technology, Tianjin 300401, P. R. China;
3. Tianjin Key Laboratory of Bioelectromagnetic Technology and Intelligent Health, Hebei University of Technology, Tianjin 300130 P. R. China;

Corresponding?author：

XU Guizhi, Email: gzxu@hebut.edu.cn

Keywords：

Temporal-interference magnetic stimulation; System design; Electrophysiological validation

DOI：

10.7507/1001-5515.202507008

Video：

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Although transcranial magnetic stimulation (TMS) is widely used in neuromodulation, conventional TMS struggles to achieve both depth and focal specificity. Temporal interference TMS (TI-TMS) offers a promising approach to enhance stimulation depth while reducing the focal area; however, current research remains largely simulation-based, with limited studies on system implementation and experimental validation in rodent deep brain regions. To address this, we developed a TI-TMS system based on a realistic mouse head model using finite element simulation. Electrophysiological recordings of local field potentials (LFPs) in the ventral hippocampal formation (vHPC) were performed to evaluate changes in θ rhythm power spectral density (PSD) and θ-γ phase-amplitude coupling (PAC) following stimulation. The results demonstrated that TI-TMS enhanced θ rhythm power and strengthened θ-γ PAC, indicating effective modulation of deep brain regions. This study establishes a functional TI-TMS system capable of effectively stimulating deep vHPC, providing an experimental basis for its application in precise neuromodulation of subcortical brain areas.

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8.	Grossman N, Okun M S, Boyden E S. Translating temporal interference brain stimulation to treat neurological and psychiatric conditions. JAMA Neurol, 2018, 75(11): 1307-1308.
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26.	Gabriel S, Lau R W, Gabriel C. The dielectric properties of biological tissues: II. Measurements in the frequency range 10 Hz to 20 GHz. Phys Med Biol, 1996, 41(11): 2251.
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28.	Di Matteo S, Viall N M, Kepko L. Power spectral density background estimate and signal detection via the multitaper method. J Geophys Res Space Phys, 2021, 126(2): e2020JA028748.
29.	楊碩, 冀亞坤, 王磊, 等. 基于腦疲勞的Delta-Gamma相位幅值耦合研究. 中國生物醫學工程學報, 2018, 37(4): 445-450.
30.	王龍龍, 李雙燕, 李天翔, 等. 50 Hz電磁場對大鼠工作記憶的影響及其神經機制研究. 生物醫學工程學雜志, 2023, 40(6): 1135-1141.

1. Jannati A, Oberman L M, Rotenberg A, et al. Assessing the mechanisms of brain plasticity by transcranial magnetic stimulation. Neuropsychopharmacology, 2023, 48(1): 191-208.
2. Lu F, Cui Q, Zou Y, et al. Effects of rTMS intervention on functional neuroimaging activities in adolescents with major depressive disorder measured using resting-state fMRI. Bioengineering, 2023, 10(12): 1374.
3. Vucic S, Chen K H S, Kiernan M C, et al. Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee. Clin Neurophysiol, 2023, 150: 131-175.
4. Wang M, Xia R, Shi J, et al. Effect of high-frequency repetitive transcranial magnetic stimulation under different intensities upon rehabilitation of chronic pelvic pain syndrome: protocol for a randomized controlled trial. Trials, 2023, 24(1): 40.
5. Fitzgerald P B. Targeting repetitive transcranial magnetic stimulation in depression: do we really know what we are stimulating and how best to do it?. Brain Stimul, 2021, 14(3): 730-736.
6. 祝凱, 周曉青, 馬任, 等. 基于多物理場復合的新型無創腦深部精準刺激方法探究. 中國生物醫學工程學報, 2024, 43(3): 327-337.
7. Grossman N, Bono D, Dedic N, et al. Noninvasive deep brain stimulation via temporally interfering electric fields. Cell, 2017, 169(6): 1029-1041.
8. Grossman N, Okun M S, Boyden E S. Translating temporal interference brain stimulation to treat neurological and psychiatric conditions. JAMA Neurol, 2018, 75(11): 1307-1308.
9. Zaeimbashi M, Khalifa A, Dong C, et al. Magnetic temporal interference for noninvasive, high-resolution, and localized deep brain stimulation: concept validation. bioRxiv, 2020: 2020.07.20.212845.
10. Sorkhabi M M, Wendt K, Denison T. Temporally interfering TMS: focal and dynamic stimulation location// 2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC). Montreal: IEEE, 2020: 3537-3543.
11. Khalifa A, Abrishami S M, Zaeimbashi M, et al. Magnetic temporal interference for noninvasive and focal brain stimulation. J Neural Eng, 2023, 20(1): 016002.
12. Fang X, Wang S, Luo Y, et al. Deep brain temporally interfering magnetic stimulation via parametric characterized spatial array. AIP Adv, 2024, 14(8): 085201.
13. Wang T, Yan L, Yang X, et al. Optimal design of array coils for multi-target adjustable electromagnetic brain stimulation system. Bioengineering, 2023, 10(5): 568.
14. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington (DC): National Academies Press (US), 2011.
15. Hutcheon B, Yarom Y. Resonance, oscillation and the intrinsic frequency preferences of neurons. Trends Neurosci, 2000, 23(5): 216-222.
16. Mirzakhalili E, Barra B, Capogrosso M, et al. Biophysics of temporal interference stimulation. Cell Syst, 2020, 11(6): 557-572.
17. Wu J, Wang H, Jin J, et al. Influence of coil orientation on the TMS-induced electric field within the clinically recommended brain region for major depressive disorder. Brain Stimul, 2025, 18(2): 109-111.
18. Deng Z D, Lisanby S H, Peterchev A V. Electric field depth–focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimul, 2013, 6(1): 1-13.
19. Deng Z D, Lisanby S H, Peterchev A V. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study. Journal Neural Eng, 2011, 8(1): 016007.
20. Karimi F, Attarpour A, Amirfattahi R, et al. Computational analysis of non-invasive deep brain stimulation based on interfering electric fields. Phys Med Biol, 2019, 64(23): 235010.
21. Yu H, Du B, Guo L, et al. Design of transcranial magnetic stimulation coils for mouse with improved stimulus focus and intensity. IEEE Trans Magn, 2021, 58(2): 1-4.
22. 劉小璽, 于洪麗, 垢福帥, 等. 嚙齒類動物經顱時間干涉電刺激定量分析: 針對電極排列的仿真研究. 生物醫學工程學雜志, 2025, 42(2): 280-287.
23. Deng Z D, Robins P L, Dannhauer M, et al. Optimizing TMS coil placement approaches for targeting the dorsolateral prefrontal cortex in depressed adolescents: an electric field modeling study. Biomedicines, 2023, 11(8): 2320.
24. Chang Y C, Ahmed U, Jayaprakash N, et al. kHz-frequency electrical stimulation selectively activates small, unmyelinated vagus afferents. Brain Stimul, 2022, 15(6): 1389-1404.
25. Barnes W L, Lee W H, Peterchev A V. Approximating transcranial magnetic stimulation with electric stimulation in mouse: a simulation study// 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. Chicago: IEEE, 2014: 6129-6132.
26. Gabriel S, Lau R W, Gabriel C. The dielectric properties of biological tissues: II. Measurements in the frequency range 10 Hz to 20 GHz. Phys Med Biol, 1996, 41(11): 2251.
27. Andreuccetti D, Fossi R, Petrucci C. An Internet resource for the calculation of the dielectric properties of body tissues in the frequency range 10 Hz-100 GHz. Florence: IFAC-CNR, 1997.
28. Di Matteo S, Viall N M, Kepko L. Power spectral density background estimate and signal detection via the multitaper method. J Geophys Res Space Phys, 2021, 126(2): e2020JA028748.
29. 楊碩, 冀亞坤, 王磊, 等. 基于腦疲勞的Delta-Gamma相位幅值耦合研究. 中國生物醫學工程學報, 2018, 37(4): 445-450.
30. 王龍龍, 李雙燕, 李天翔, 等. 50 Hz電磁場對大鼠工作記憶的影響及其神經機制研究. 生物醫學工程學雜志, 2023, 40(6): 1135-1141.

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