切换至 "中华医学电子期刊资源库"
高级检索
中华脑血管病杂志(电子版)

中华脑血管病杂志(电子版) ›› 2025, Vol. 19 ›› Issue (05) : 353 -363. doi: 10.3877/cma.j.issn.1673-9248.2025.05.001

专家论坛

时间干涉刺激的发展：从技术原理到临床应用
黄亮1,2, 徐彬翔3,4, 王凯3,4, 李龙1,2, 何琳5,6, 高强5,6, 赵军3,4,†(), 刘天1,2,†()   
  1. 1　710049　陕西　西安，西安交通大学生命科学与技术学院健康与康复科学研究所与生物医学信息工程教育部重点实验室
    2　710049　陕西　西安，神经功能信息学与康复工程民政部重点实验室
    3　100068　北京，首都医科大学康复医学院
    4　100068　北京，中国康复研究中心
    5　610041　四川　成都，四川大学华西医院康复医学中心与康复医学研究所
    6　610041　四川　成都，四川省康复医学重点实验室
  • 收稿日期:2025-07-03 出版日期:2025-10-01
  • 通信作者: 赵军, 刘天
  • 基金资助:
    国家重大科技专项(2024ZD9528000，2024ZD9528001)

Evolution of temporal interference stimulation: from technical principles to clinical applications

Liang Huang1,2, Binxiang Xu3,4, Kai Wang3,4, Long Li1,2, Lin He5,6, Qiang Gao5,6, Jun Zhao3,4,†(), Tian Liu1,2,†()   

  1. 1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China
    2 The Key Laboratory of Neuro-informatics & Rehabilitation Engineering of Ministry of Civil Affairs, Xi’an 710049, China
    3 The Capital Medical University, School of Rehabilitation Medicine, Beijing 100068, China
    4 The China Rehabilitation Research Center, Beijing 100068, China
    5 The Rehabilitation Medicine Center and Institute of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
    6 The Key Laboratory of Rehabilitation Medicine in Sichuan Province, Chengdu 610041, China
  • Received:2025-07-03 Published:2025-10-01
  • Corresponding author: Jun Zhao, Tian Liu
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

黄亮, 徐彬翔, 王凯, 李龙, 何琳, 高强, 赵军, 刘天. 时间干涉刺激的发展：从技术原理到临床应用[J/OL]. 中华脑血管病杂志(电子版), 2025, 19(05): 353-363.

Liang Huang, Binxiang Xu, Kai Wang, Long Li, Lin He, Qiang Gao, Jun Zhao, Tian Liu. Evolution of temporal interference stimulation: from technical principles to clinical applications[J/OL]. Chinese Journal of Cerebrovascular Diseases(Electronic Edition), 2025, 19(05): 353-363.

时间干涉（TI）刺激是一种新型的无创神经调控技术，其通过两路高频交变电流的干涉效应产生低频包络，可以实现深部脑区的精准靶向调控，突破了传统非侵入神经调控技术无法刺激深部脑区的限制。近年来，TI刺激研究迅速发展，已成为神经调控领域的研究热点，并展现出治疗神经系统疾病的临床潜力，有望成为深部脑区功能异常疾病的一种非侵入性替代疗法。本文系统梳理了近年来TI刺激相关研究进展，从TI刺激技术的原理出发，阐述了其在仿真优化和硬件设备开发等方面的进展，并结合临床应用案例深入探究其治疗神经系统疾病的潜力，为该技术的进一步研究与应用提供参考。

关键词: 时间干涉刺激, 无创神经调控, 仿真优化, 临床应用

Temporal interference (TI) stimulation is a novel non-invasive neuromodulation technology. It generates low-frequency envelopes through the interference effect of two high-frequency alternating currents, enabling precise targeting of deep brain regions. This approach overcomes a major limitation of conventional non-invasive neuromodulation techniques, which are often ineffective in stimulating deeper brain structures. In recent years, research on TI stimulation has progressed rapidly and has become a hotspot in the field of neuromodulation. It demonstrates promising clinical potential for treating neurological disorders and may offer a non-invasive alternative for conditions involving dysfunction in deep brain circuits. This paper systematically reviews the research progress related to TI stimulation in recent years. Beginning with the principles of TI stimulation technology, it elaborates on its progress in simulation optimization and hardware development, and deeply explores its potential for the treatment of neurological diseases by incorporating clinical application cases, providing a reference for the further research and application of this technology.

Key words: Temporal interference stimulation, Non-invasive neuroregulation, Simulation optimization, Clinical application
图1 时间干涉刺激原理示意图
1
Lozano AM, Lipsman N, Bergman H, et al. Deep brain stimulation: current challenges and future directions [J]. Nat Rev Neurol, 2019, 15(3): 148-160.
2
Mattioli F, Maglianella V, D'antonio S, et al. Non-invasive brain stimulation for patients and healthy subjects: current challenges and future perspectives [J]. J Neurol Sci, 2024, 456: 122825.
3
Yavari F, Jamil A, Mosayebi Samani M, et al. Basic and functional effects of transcranial Electrical Stimulation (tES)—An introduction [J]. Neurosci Biobehav Rev, 2018, 85: 81-92.
4
Deng ZD, Lisanby SH, Peterchev AV. Electric field depth–focality tradeoff in transcranial magnetic stimulation: Simulation comparison of 50 coil designs [J]. Brain Stimul, 2013, 6(1): 1-13.
5
Grossman N, Bono D, Dedic N, et al. Noninvasive deep brain stimulation via temporally interfering electric fields [J]. Cell, 2017, 169(6): 1029-1041.e16.
6
Yang C, Xu Y, Feng X, et al. Transcranial temporal interference stimulation of the right globus pallidus in Parkinson's disease [J]. Mov Disord, 2025, 40(6): 1061-1069.
7
Guo W, He Y, Song X, et al. 40-Hz temporally interfering electrical stimulation over the temporal lobe induced antidepressant-like effects in chronic unpredictable mild stress rats [J]. IEEE Trans Neural Syst Rehabil Eng, 2025, 33: 1796-1804.
8
Acerbo E, Jegou A, Luff C, et al. Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers [J]. Front Neurosci, 2022, 16: 945221.
9
Hutcheon B, Yarom Y. Resonance, oscillation and the intrinsic frequency preferences of neurons [J]. Trends Neurosci, 2000, 23(5): 216-222.
10
Li L, Bai H, Wu L, et al. Non-invasive modulation of deep brain nuclei by temporal interference stimulation [J]. Neurosci Bull, 2025, 41(5): 853-865.
11
Liu R, Zhu G, Wu Z, et al. Temporal interference stimulation targets deep primate brain [J]. Neuroimage, 2024, 291: 120581.
12
Violante IR, Alania K, Cassara AM, et al. Non-invasive temporal interference electrical stimulation of the human hippocampus [J]. Nat Neurosci, 2023, 26(11): 1994-2004.
13
Mirzakhalili E, Barra B, Capogrosso M, et al. Biophysics of temporal interference stimulation [J]. Cell Syst, 2020, 11(6): 557-572, e555.
14
Karimi F, Attarpour A, Amirfattahi R, et al. Computational analysis of non-invasive deep brain stimulation based on interfering electric fields [J]. Phys Med Biol, 2019, 64(23): 235010.
15
Plovie T, Schoeters R, Tarnaud T, et al. Nonlinearities and timescales in neural models of temporal interference stimulation [J]. Bioelectromagnetics, 2025, 46(1): e22522.
16
Howell B, Mcintyre CC. Feasibility of interferential and pulsed transcranial electrical stimulation for neuromodulation at the human scale [J]. Neuromodulation, 2021, 24(5): 843-853.
17
Tavakoli AV, Yun K. Transcranial alternating current stimulation (tACS) mechanisms and protocols [J]. Front Cell Neurosci, 2017, 11: 214.
18
Lee S, Lee C, Park J, et al. Individually customized transcranial temporal interference stimulation for focused modulation of deep brain structures: a simulation study with different head models [J]. Sci Rep, 2020, 10(1): 11730.
19
Radman T, Ramos RL, Brumberg JC, et al. Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro [J]. Brain Stimul, 2009, 2(4): 215-228, e213.
20
Rampersad S, Roig-Solvas B, Yarossi M, et al. Prospects for transcranial temporal interference stimulation in humans: a computational study [J]. Neuroimage, 2019, 202: 116124.
21
Vieira PG, Krause MR, Pack CC. Temporal interference stimulation disrupts spike timing in the primate brain [J]. Nat Commun, 2024, 15(1): 4558.
22
Krause MR, Vieira PG, Csorba BA, et al. Transcranial alternating current stimulation entrains single-neuron activity in the primate brain [J]. Proc Natl Acad Sci U S A, 2019, 116(12): 5747-5755.
23
Ahtiainen A, Leydolph L, Tanskanen JMA, et al. Electric field temporal interference stimulation of neurons in vitro [J]. Lab Chip, 2024, 24(16): 3945-3957.
24
Yu H, Wang C, Li K, et al. Resonance dynamics and latent manifolds in cortical neural networks with temporal interference stimulation [C]. Proceedings of the 2022 41st Chinese Control Conference (CCC), 2022.
25
Deans JK, Powell AD, Jefferys JGR. Sensitivity of coherent oscillations in rat hippocampus to AC electric fields [J]. J Physiol, 2007, 583(2): 555-565.
26
Bernardi D, Lindner B. Detecting single-cell stimulation in a large network of integrate-and-fire neurons [J]. Phys Rev E, 2019, 99(3): 032304.
27
Caldas-Martinez S, Goswami C, Forssell M, et al. Cell-specific effects of temporal interference stimulation on cortical function [J]. Commun Biol, 2024, 7(1): 1076.
28
Kwak Y, Lim S, Cho HU, et al. Effect of temporal interference electrical stimulation on phasic dopamine release in the striatum [J]. Brain Stimul, 2023, 16(5): 1377-1383.
29
Qi S, Liu X, Yu J, et al. Temporally interfering electric fields brain stimulation in primary motor cortex of mice promotes motor skill through enhancing neuroplasticity [J]. Brain Stimul, 2024, 17(2): 245-257.
30
Liu X, Qi S, Hou L, et al. Noninvasive deep brain stimulation via temporal interference electric fields enhanced motor performance of mice and its neuroplasticity mechanisms [J]. Mol Neurobiol, 2024, 61(6): 3314-3329.
31
Huang Y, Datta A, Parra LC. Optimization of interferential stimulation of the human brain with electrode arrays [J]. J Neural Eng, 2020, 17(3): 036023.
32
Honarbakhsh B, Mohammadzadeh M. Focusing the temporally interfering electric fields in non-invasive deep brain stimulation [J]. Electron Lett, 2020, 56(25): 1401-1403.
33
Botzanowski B, Acerbo E, Lehmann S, et al. Focal control of non-invasive deep brain stimulation using multipolar temporal interference [J]. Bioelectron Med, 2025, 11(1): 7.
34
Lee S, Park J, Choi DS, et al. Multipair transcranial temporal interference stimulation for improved focalized stimulation of deep brain regions: a simulation study [J]. Comput Biol Med, 2022, 143: 105337.
35
Song X, Zhao X, Li X, et al. Multi-channel transcranial temporally interfering stimulation (tTIS): application to living mice brain [J]. J Neural Eng, 2021, 18(3): 036003.
36
Cao J, Grover P. STIMULUS: noninvasive dynamic patterns of neurostimulation using spatio-temporal interference [J]. IEEE Trans Biomed Eng, 2020, 67(3): 726-737.
37
Ahmadi K, Kok RL, Findeisen R. Surrogate model supported optimization of high-definition temporal interference stimulation [C]. Proceedings of the 2024 IEEE Biomedical Circuits and Systems Conference (BioCAS), 2024.
38
Geng C, Li Y, Li L, et al. Optimized temporal interference stimulation based on convex optimization: a computational study [J]. IEEE Trans Neural Syst Rehabil Eng, 2025, 33: 1400-1410.
39
Stoupis D, Samaras T. Non-invasive stimulation with temporal interference: optimization of the electric field deep in the brain with the use of a genetic algorithm [J]. J Neural Eng, 2022, 19(5): 056018.
40
Zhu X, Li Y, Zheng L, et al. Multi-point temporal interference stimulation by using each electrode to carry different frequency currents [J]. IEEE Access, 2019, 7: 168839-168848.
41
Terasawa Y, Tashiro H, Ueno T, et al. Precise temporal control of interferential neural stimulation via phase modulation [J]. IEEE Trans Biomed Eng, 2022, 69(1): 220-228.
42
Luff CE, Dzialecka P, Acerbo E, et al. Pulse-width modulated temporal interference (PWM-TI) brain stimulation [J]. Brain Stimul, 2024, 17(1): 92-103.
43
Ahsan F, Chi T, Cho R, et al. EMvelop stimulation: minimally invasive deep brain stimulation using temporally interfering electromagnetic waves [J]. J Neural Eng, 2022, 19(4): 046005.
44
Wang H, Shi Z, Sun W, et al. Development of a non-invasive deep brain stimulator with precise positioning and real-time monitoring of bioimpedance [J]. Front Neuroinform, 2020, 14: 574189.
45
Zhang Z, Lin BS, Wu CWG, et al. Designing and pilot testing a novel transcranial temporal interference stimulation device for neuromodulation [J]. IEEE Trans Neural Syst Rehabil Eng, 2022, 30: 1483-1493.
46
Bai JH, Huang SC, Lee PL, et al. A high-frequency temporal-interference alternative current stimulation device using pulse amplitude modulation with push–pull current sources [J]. Bioengineering, 2025, 12(2): 164.
47
Qian R, Cao Z, Li B, et al. A voltage-controlled current source for temporal interference stimulation: analysis, design, and study [J]. Rev Sci Instrum, 2023, 94(8): 084708.
48
Ahsan F, Chi T, Cho R, et al. Non-invasive deep brain stimulation using electromagnetic waves [C]. Proceedings of the 2020 54th Asilomar Conference on Signals, Systems, and Computers, 2020.
49
Gou F, Yu H, Liu X, et al. Simulation and design of a rodent-specific transcranial magnetic stimulation coil based on the principle of temporal interference [J]. IEEE Trans Magn, 2025, 61(5): 1-9.
50
Missey F, Donahue MJ, Weber P, et al. Laser-driven wireless deep brain stimulation using temporal interference and organic electrolytic photocapacitors [J]. Adv Funct Mater, 2022, 32(33): 2200691.
51
Wu CW, Lin BS, Zhang Z, et al. Pilot study of using transcranial temporal interfering theta-burst stimulation for modulating motor excitability in rat [J]. J Neuroeng Rehabil, 2024, 21(1): 147.
52
Ma R, Xia X, Zhang W, et al. High gamma and beta temporal interference stimulation in the human motor cortex improves motor functions [J]. Front Neurosci, 2022, 15: 800436.
53
Zhu Z, Xiong Y, Chen Y, et al. Temporal interference (TI) stimulation boosts functional connectivity in human motor cortex: a comparison study with transcranial direct current stimulation (tDCS) [J]. Neural Plast, 2022, 2022(1): 7605046.
54
Wang Y, Zhu C, Zhou J, et al. 20 Hz temporal interference stimulation can more effectively enhance motor evoked potentials in the primary motor cortex [J]. Front Hum Neurosci, 2025, 19: 1524485.
55
Vassiliadis P, Beanato E, Popa T, et al. Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills [J]. Nat Hum Behav, 2024, 8(8): 1581-1598.
56
Wessel MJ, Beanato E, Popa T, et al. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning [J]. Nat Neurosci, 2023, 26(11): 2005-2016.
57
Zhang Y, Zhou Z, Zhou J, et al. Temporal interference stimulation targeting right frontoparietal areas enhances working memory in healthy individuals [J]. Front Hum Neurosci, 2022, 16: 918470.
58
Zheng S, Zhang Y, Huang K, et al. Temporal interference stimulation boosts working memory performance in the frontoparietal network [J]. Hum Brain Mapp, 2025, 46(3): e70160.
59
Thiele C, Rufener KS, Repplinger S, et al. Transcranial temporal interference stimulation (tTIS) influences event-related alpha activity during mental rotation [J]. Psychophysiology, 2024, 61(11): e14651.
60
Beanato E, Moon HJ, Windel F, et al. Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans [J]. Sci Adv, 2024, 10(44): eado4103.
61
Kurtin DL, Alania K, Rhodes E, et al. Task-related changes in resting state connectivity are affected by temporal interference (TI) stimulation [J]. Brain Stimul, 2025, 18(3): 937-947.
62
Lamoš M, Bočková M, Missey F, et al. Noninvasive temporal interference stimulation of the subthalamic nucleus in Parkinson's disease reduces beta activity [J]. Mov Disord, 2025, 40(6): 1051-1060.
63
Zhou H, Wang M, Qi S, et al. Efficacy and safety of transcranial temporal interference stimulation for treating bipolar disorder with depressive episodes [J]. medRxiv, 2024: 24317540.
64
Yan J, Pang C, Zhou S, et al. 280. Acute temporal interference stimulation of the left dorsolateral prefrontal cortex in patients with depression: first results of a double-blind controlled study [J]. Biol Psychiatry, 2024, 95(10): S214.
65
Demchenko I, Rampersad S, Datta A, et al. Target engagement of the subgenual anterior cingulate cortex with transcranial temporal interference stimulation in major depressive disorder: a protocol for a randomized sham-controlled trial [J]. Front Neurosci, 2024, 18: 1390250.
66
Missey F, Acerbo E, Dickey AS, et al. Non-invasive temporal interference stimulation of the hippocampus suppresses epileptic biomarkers in patients with epilepsy: biophysical differences between kilohertz and amplitude modulated stimulation [J]. medRxiv, 2025: 24303799.
67
Missey F, Rusina E, Acerbo E, et al. Orientation of temporal interference for non-invasive deep brain stimulation in epilepsy [J]. Front Neurosci, 2021, 15: 633988.
68
Mojiri Z, Rouhani E, Akhavan A, et al. Non-invasive temporal interference brain stimulation reduces preference on morphine-induced conditioned place preference in rats [J]. Sci Rep, 2024, 14(1): 21040.
69
Sunshine MD, Cassarà AM, Neufeld E, et al. Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation [J]. Commun Biol, 2021, 4(1): 107.
70
Missey F, Ejneby MS, Ngom I, et al. Obstructive sleep apnea improves with non-invasive hypoglossal nerve stimulation using temporal interference [J]. Bioelectron Med, 2023, 9(1): 18.
71
Botzanowski B, Donahue MJ, Ejneby MS, et al. Noninvasive stimulation of peripheral nerves using temporally-interfering electrical fields [J]. Adv Healthc Mater, 2022, 11(17): 2200075.
72
Von Conta J, Kasten FH, Ćurčić-Blake B, et al. Interindividual variability of electric fields during transcranial temporal interference stimulation (tTIS) [J]. Sci Rep, 2021, 11(1): 20357.
73
Yatsuda K, Fernández-Corazza M, Yu W, et al. Population-optimized electrode montage approximates individualized optimization in transcranial temporal interference stimulation [J]. Comput Biol Med, 2025, 192: 110223.
74
Esmaeilpour Z, Kronberg G, Reato D, et al. Temporal interference stimulation targets deep brain regions by modulating neural oscillations [J]. Brain Stimul, 2021, 14(1): 55-65.
75
Piao Y, Ma R, Weng Y, et al. Safety evaluation of employing temporal interference transcranial alternating current stimulation in human studies [J]. Brain Sci, 2022, 12(9): 1194.
76
Vassiliadis P, Stiennon E, Windel F, et al. Safety, tolerability and blinding efficiency of non-invasive deep transcranial temporal interference stimulation: first experience from more than 250 sessions [J]. J Neural Eng, 2024, 21(2): 024001.
77
Wang Y, Zeng GQ, Wang M, et al. The safety and efficacy of applying a high-current temporal interference electrical stimulation in humans [J]. Front Hum Neurosci, 2024, 18: 1484593.
[1] 许媛媛, 赵悦岐, 李雪, 曲燕. 艾灸在病毒疣中的临床应用及其机制研究进展[J/OL]. 中华实验和临床感染病杂志(电子版), 2023, 17(06): 390-394.
[2] 王淑君, 张楚晗, 唐一阳, 赵雨桐, 李佳伦, 付佳乐. 自粘接树脂水门汀的临床应用及展望[J/OL]. 中华口腔医学研究杂志(电子版), 2024, 18(04): 276-286.
[3] 中华医学会器官移植学分会肝移植学组, 中国医师协会器官移植医师分会. 中国扩大标准供肝移植临床应用指南(2025版)[J/OL]. 中华移植杂志(电子版), 2025, 19(02): 65-75.
[4] 李逸凡, 洪源, 熊茂明. 基于3D Slicer软件的术前规划在腹壁纤维瘤手术中的临床应用价值：一项单中心前瞻性分析[J/OL]. 中华疝和腹壁外科杂志(电子版), 2025, 19(03): 286-291.
[5] 鲁宇青, 李大伟, 邹剑峰, 胡子龙, 李哲, 李琦, 张丽媛, 霍萌, 沈玥, 帅维正. 新型俯卧位翻身辅助装置在急性呼吸窘迫综合征患者中的临床应用[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(05): 757-761.
[6] 中华医学会呼吸病学分会肺功能学组. 成人肺功能检查技术进展及临床应用推荐指南（2025版）[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(02): 197-212.
[7] 林敏杰, 吕艳玲, 姚羽, 王艳泓, 邹如意, 唐成. 支气管镜下钬激光技术在中心气道狭窄中的临床应用[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(02): 315-320.
[8] 陈慧, 田森, 张伟, 董宇超, 白冲, 王琴. 内科胸腔镜检查专用床单在不明原因胸腔积液患者中的临床应用[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(02): 300-303.
[9] 杨柯佳, 孙琦, 瞿伟丰, 翁鸢, 崔启辰, 李金友. Flex-3D 胸腔镜肺叶切除术在非小细胞肺癌中的临床应用[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(01): 62-67.
[10] 马逸夫, 孙芳玲, 刘婷婷, 田欣, 王文. 神经干细胞永生化的机制及其应用进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(04): 251-256.
[11] 戚泽雪, 赵连晖, 王广川, 张春清. 从国内专家共识推荐意见更新探讨经颈静脉肝内门体分流术的临床应用进展[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(03): 193-196.
[12] 王翔, 冯辉斌. 肺部超声在急性呼吸窘迫综合征表型中的应用进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(12): 1155-1160.
[13] 王睿浩, 姜云璐, 田艳君. Apelin/APJ系统生理病理作用的研究进展[J/OL]. 中华诊断学电子杂志, 2024, 12(02): 138-142.
[14] 罗媛元, 曾欣. 无针经皮穴位电刺激治疗胃食管反流病研究进展[J/OL]. 中华胃食管反流病电子杂志, 2024, 11(01): 40-43.
[15] 汪和, 胡梦杰, 王天爱, 梅紫暄, 龚铖, 潘定宇, 李震. 新型减重药物在肥胖治疗中的应用进展[J/OL]. 中华肥胖与代谢病电子杂志, 2025, 11(01): 40-45.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号

AI
小
编
AI小编
你好！我是《中华医学电子期刊资源库》AI小编，有什么可以帮您的吗？