Neuromodulation therapy for phantom limb pain: A review of the current status and future perspectives

Abstract

Background: Phantom Limb Pain (PLP) is a common and intractable neuropathic pain condition that occurs following limb amputation, significantly impacting patients’ quality of life. The prevalence of PLP ranges from 45% to 85%. Traditional pharmacological treatments have limited efficacy and are frequently accompanied by significant side effects.
Objective: This review aims to provide a comprehensive overview of the multi-level pathophysiological mechanisms underlying PLP, synthesize clinical evidence on both invasive and non-invasive neuromodulation techniques, analyze differences in therapeutic outcomes and targets, and offer insights for clinical practice and future research.
Methods: This is a narrative review that integrates the existing evidence and current clinical applications of various treatment approaches for PLP.
Results: The mechanisms of PLP involve peripheral nerve ectopic discharges, cortical reorganization, and the interaction of various psychological factors. The short-term efficacy of invasive treatments, such as spinal cord stimulation (SCS) and dorsal root ganglion (DRG) stimulation, ranges from 14% to 80%. DRG stimulation shows more promise in terms of long-term stability. Non-invasive techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), when combined with mirror therapy, can enhance therapeutic outcomes. Emerging technologies, such as brain-computer interfaces (BCI) and temporally interfering stimulation (TIS), remain in the preclinical phase of investigation.
Conclusion: Neuromodulation techniques offer a multi-dimensional treatment strategy for PLP, with potential improvements through parameter standardization, individualized treatment optimization, validation in multi-center randomized controlled trials, and an overall enhancement of clinical efficacy.

Keywords

Phantom limb pain / Chronic pain / Stimulation / Neuromodulation technology / Invasive stimulation / Non-invasive stimulation

CRediT authorship contribution statement

Jingming Hou: Writing – review & editing, Supervision, Project administration, Methodology, Funding acquisition, Conceptualization. Rubing Yan: Resources, Project administration. Han Chen: Project administration, Methodology. Zhou Feng: Visualization, Software, Methodology. Peng Tang: Writing – review & editing. Lijuan Xie: Writing – review & editing. Xiaoyan Duan: Writing – review & editing, Writing – original draft, Visualization, Software, Investigation, Data curation. All the authors have read and approved the final version of this manuscript.

Ethics approval

Not applicable.

Funding information

This work was supported by the National Natural Science Foundation of China (Grant No. 82301569; Grant No. 82472607), Chongqing Young and Middle Aged Medical High-end Talent Project (grant number YXGD202460), and Chongqing Medical Youth Outstanding Talent Project (grant number YXQN2022417).

Data Availability

Not applicable.

Declaration of Competing Interest

Jingming Hou is an editorial board member of Healthcare and Rehabilitation but has not been involved in the journal’s review or decisions related to this manuscript. The authors declare that they have no known competing financial interests or personal relationships related to this work.

Declaration of Generative AI and AI-assisted technologies in the writing process

During the preparation of this study, the authors used ChatGPT-4 and DeepSeek (latest version) to optimize the language expression and improve the readability of the manuscript. All content generated by these AI tools was carefully reviewed, revised, and verified by the authors. The authors take full responsibility for the scientific content, accuracy, and integrity of the final published article.

Acknowledgments

The authors would like to express our gratitude for the drawing materials provided by BioRender.

References

[1] Flor H. Phantom-limb pain: characteristics, causes, and treatment. Lancet Neurol. 2002; 1(3):182-189. https://doi.org/10.1016/s1474-4422(02)00074-1

[2] Kuffler DP. Origins of Phantom Limb Pain. Mol Neurobiol. 2018; 55(1):60-69. https://doi.org/10.1007/s12035-017-0717-x

[3] Collins KL, Russell HG, Schumacher PJ, et al. A review of current theories and treatments for phantom limb pain. J Clin Invest. 2018; 128(6):2168-2176. https://doi.org/10.1172/jci94003

[4] Kuffler DP.Coping with phantom limb pain. Mol Neurobiol. 2018; 55(1):70-84. https://doi.org/10.1007/s12035-017-0718-9

[5] Limakatso K, Parker R. Treatment recommendations for phantom limb pain in people with amputations: an expert consensus Delphi study. PM R. 2021; 13(11):1216-1226. https://doi.org/10.1002/pmrj.12556

[6] Pacheco-Barrios K, Meng X, Fregni F. Neuromodulation techniques in phantom limb pain: a systematic review and meta-analysis. Pain Med. 2020; 21(10):2310-2322. https://doi.org/10.1093/pm/pnaa039

[7] Schone HR, Baker CI, Katz J, et al. Making sense of phantom limb pain. J Neurol Neurosurg Psychiatry. 2022; 93(8):833-843. https://doi.org/10.1136/jnnp-2021-328428

[8] Hill A. Phantom limb pain: a review of the literature on attributes and potential mechanisms. J Pain Symptom Manag. 1999; 17(2):125-142. https://doi.org/10.1016/s0885-3924(98)00136-5

[9] Greenwald JD, Shafritz KM. An integrative neuroscience framework for the treatment of chronic pain: from cellular alterations to behavior. Front Integr Neurosci. 2018; 12:18. https://doi.org/10.3389/fnint.2018.00018

[10] Subedi B, Grossberg GT. Phantom limb pain: mechanisms and treatment approaches. Pain Res Treat. 2011; 2011(1): 864605. https://doi.org/10.1155/2011/864605

[11] Petersen BA, Nanivadekar AC, Chandrasekaran S, Fisher LE. Phantom limb pain: peripheral neuromodulatory and neuroprosthetic approaches to treatment. Muscle Nerve. 2019; 59(2):154-167. https://doi.org/10.1002/mus.26294

[12] Erlenwein J, Diers M, Ernst J, Schulz F, Petzke F. Klinisches Update zu Phantomschmerz: Deutsche Fassung [Clinical updates on phantom limb pain: German version]. Schmerz. 2023; 37(3):195-214. https://doi.org/10.1007/s00482-022-00629-x

[13] Vasylyev DV, Zhao P, Schulman BR, Waxman SG. Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain. J Gen Physiol. 2024; 156(11):e202413596. https://doi.org/10.1085/jgp.202413596

[14] Münger M, Pinto CB, Pacheco-Barrios K, et al. Protective and risk factors for phantom limb pain and residual limb pain severity. Pain Pract. 2020; 20(6):578-587. https://doi.org/10.1111/papr.12881

[15] Makin TR, Flor H. Brain (re)organisation following amputation: implications for phantom limb pain. Neuroimage. 2020; 218:116943. https://doi.org/10.1016/j.neuroimage.2020.116943

[16] MacIver K, Lloyd DM, Kelly S, Roberts N, Nurmikko T. Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery. Brain. 2008; 131(8):2181-2191. https://doi.org/10.1093/brain/awn124

[17] Zhao J, Guo X, Xia X, et al. Functional reorganization of the primary somatosensory cortex of a phantom limb pain patient. Pain Physician. 2016; 19(5):E781-E786.

[18] Raffin E, Richard N, Giraux P, Reilly KT. Primary motor cortex changes after amputation correlate with phantom limb pain and the ability to move the phantom limb. Neuroimage. 2016; 130:134-144. https://doi.org/10.1016/j.neuroimage.2016.01.063

[19] Zheng BX, Yin Y, Xiao H, et al. Altered cortical reorganization and brain functional connectivity in phantom limb pain: a functional MRI Study. Pain Pract. 2021; 21(4):394-403. https://doi.org/10.1111/papr.12966

[20] Katz J.Psychophysiological contributions to phantom limbs. Can J Psychiatry. 1992; 37(5):282-298. https://doi.org/10.1177/070674379203700502

[21] Zvolensky MJ, Goodie JL, McNeil DW, Sperry JA, Sorrell JT. Anxiety sensitivity in the prediction of pain-related fear and anxiety in a heterogeneous chronic pain population. Behav Res Ther. 2001; 39(6):683-696. https://doi.org/10.1016/s0005-7967(00)00049-8

[22] Yang C, Tian S, Liu M, et al. Alterations in white matter microstructure and structural network topology associated with cortisol level in major depressive disorder patients. Brain Res Bull. 2025; 232:111586. https://doi.org/10.1016/j.brainresbull.2025.111586

[23] Fuchs X, Flor H, Bekrater-Bodmann R. Psychological factors associated with phantom limb pain: a review of recent findings. Pain Res Manag. 2018; 2018(1): 5080123. https://doi.org/10.1155/2018/5080123

[24] Giray E, Akyuz GD. Noninvasive neuromodulation for the management of phantom limb pain: a systematic review. Ann Phys Rehabil Med. 2018; 61:e371-e372. https://doi.org/10.1016/j.rehab.2018.05.861

[25] Culp CJ, Abdi S. Current Understanding of phantom pain and its treatment. Pain Physician. 2022; 25(7):E941-E957.

[26] Pang D, Ashkan K. Deep brain stimulation for phantom limb pain. Eur J Paediatr Neurol. 2022; 39:96-102. https://doi.org/10.1016/j.ejpn.2022.05.009

[27] Alamri A, Pereira EAC. Deep brain stimulation for chronic pain. Neurosurg Clin N Am. 2022; 33(3):311-321. https://doi.org/10.1016/j.nec.2022.02.013

[28] Boccard SGJ, Prangnell SJ, Pycroft L, et al. Long-term results of deep brain stimulation of the anterior cingulate cortex for neuropathic pain. World Neurosurg. 2017; 106:625-637. https://doi.org/10.1016/j.wneu.2017.06.173

[29] Deng Z, Li D, Zhan S, et al. Spinal Cord Stimulation Combined with Anterior Cingulotomy to Manage Refractory Phantom Limb Pain. Stereo Funct Neurosurg. 2018; 96(3):204-208. https://doi.org/10.1159/000489946

[30] Vetkas A, Germann J, Elias G, et al. Identifying the neural network for neuromodulation in epilepsy through connectomics and graphs. Brain Commun. 2022; 4(3):fcac092. https://doi.org/10.1093/braincomms/fcac092

[31] Tan H, Yamamoto EA, Elkholy MA, Raslan AM. Treating chronic pain with deep brain stimulation. Curr Pain Headache Rep. 2023; 27(1):11-17. https://doi.org/10.1007/s11916-022-01099-7

[32] Ahmed S, Vanneste S. 132 the underlying effect of burst stimulation on chronic pain using multimodal neuroimaging-EEG, fMRI and PET. Neurosurgery. 2017; 64(CN__1):230. https://doi.org/10.1093/neuros/nyx417.132

[33] Chitneni A, Jain E, Sahni S, Mavrocordatos P, Abd-Elsayed A. Spinal cord stimulation waveforms for the treatment of chronic pain. Curr Pain Headache Rep. 2024; 28(7):595-605. https://doi.org/10.1007/s11916-024-01247-1

[34] McAuley J, van Gröningen R, Green C. Spinal cord stimulation for intractable pain following limb amputation. Neuromodulation. 2013; 16(6):530-536. https://doi.org/10.1111/j.1525-1403.2012.00513.x

[35] D'Souza RS, Her YF. Stimulation holiday rescues analgesia after habituation and loss of efficacy from 10-kilohertz dorsal column spinal cord stimulation. Reg Anesth Pain Med. 2022; 47(12):722-727. https://doi.org/10.1136/rapm-2022-103881

[36] Knotkova H, Hamani C, Sivanesan E, et al.Neuromodulation for chronic pain. Lancet. 2021; 397(10289):2111-2124. https://doi.org/10.1016/S0140-6736(21)00794-7

[37] Raut R, Shams S, Rasheed M, Niaz A, Mehdi W, Chaurasia B. Spinal cord stimulation in the treatment of phantom limb pain: a case report and review of literature. Neurol India. 2021; 69(1):157-160. https://doi.org/10.4103/0028-3886.310092

[38] Heijmans L, Joosten EA. Mechanisms and mode of action of spinal cord stimulation in chronic neuropathic pain. Post Med. 2020; 132(sup3):17-21. https://doi.org/10.1080/00325481.2020.1769393

[39] Abd-Elsayed A, Vardhan S, Aggarwal A, Vardhan M, Diwan SA. Mechanisms of action of dorsal root ganglion stimulation. Int J Mol Sci. 2024; 25(7):3591. https://doi.org/10.3390/ijms25073591

[40] Eldabe S, Burger K, Moser H, et al. Dorsal Root Ganglion (DRG) Stimulation in the Treatment of Phantom Limb Pain (PLP). Neuromodulation. 2015; 18(7):610-616. https://doi.org/10.1111/ner.12338

[41] Deer TR, Grigsby E, Weiner RL, Wilcosky B, Kramer JM. A prospective study of dorsal root ganglion stimulation for the relief of chronic pain. Neuromodulation. 2013; 16(1):67-72. https://doi.org/10.1111/ner.12013

[42] Vaso A, Adahan HM, Gjika A, et al. Peripheral nervous system origin of phantom limb pain. Pain. 2014; 155(7):1384-1391. https://doi.org/10.1016/j.pain.2014.04.018

[43] Hagedorn JM, Romero J, Ha CT, D'Souza RS. Patient satisfaction with spinal cord stimulation and dorsal root ganglion stimulation for chronic intractable pain: a systematic review and meta-analysis. Neuromodulatio. 2022; 25(7):947-955. https://doi.org/10.1016/j.neurom.2022.04.043

[44] Yang A, Hunter CW. Dorsal root ganglion stimulation as a salvage treatment for complex regional pain syndrome refractory to dorsal column spinal cord stimulation: a case series. Neuromodulation. 2017; 20(7):703-707. https://doi.org/10.1111/ner.12622

[45] Skaribas IM, Peccora C, Skaribas E. Single S 1 Dorsal Root Ganglia stimulation for intractable complex regional pain syndrome foot pain after lumbar spine surgery: a case series. Neuromodulation. 2019; 22(1):101-107. https://doi.org/10.1111/ner.12780

[46] Srinivasan N, Zhou B, Park E. Dorsal root ganglion stimulation for the management of phantom limb pain: a scoping review. Pain Physician. 2022; 25(8) E1174-e1182.

[47] Gozani SN. Remote analgesic effects of conventional transcutaneous electrical nerve stimulation: a scientific and clinical review with a focus on chronic pain. J Pain Res. 2019; 12:3185-3201. https://doi.org/10.2147/jpr.S226600

[48] Stagg CJ, Antal A, Nitsche MA. Physiology of transcranial direct current stimulation. J ECT. 2018; 34(3):144-152. https://doi.org/10.1097/yct.0000000000000510

[49] Bocci T, De Carolis G, Ferrucci R, et al. Cerebellar Transcranial Direct Current Stimulation (ctDCS) Ameliorates Phantom Limb Pain and Non-painful Phantom Limb Sensations. Cerebellum. 2019; 18(3):527-535. https://doi.org/10.1007/s12311-019-01020-w

[50] Santos Ferreira I, Teixeira Costa B, Lima Ramos C, Lucena P, Thibaut A, Fregni F. Searching for the optimal tDCS target for motor rehabilitation. J Neuroeng Rehabil. 2019; 16(1):90. https://doi.org/10.1186/s12984-019-0561-5

[51] Bolognini N, Spandri V, Ferraro F, et al. Immediate and sustained effects of 5-Day transcranial direct current stimulation of the motor cortex in phantom limb pain. J Pain. 2015; 16(7):657-665. https://doi.org/10.1016/j.jpain.2015.03.013

[52] Boone A, Frey S. Combined use of transcranial direct current stimulation (tDCS) and mirror therapy for reduction of phantom limb pain: a case study. 7311520404p 1 Am J Occup Ther. 2019; 73(4_ement_1) https://doi.org/10.5014/ajot.2019.73s1-po3018

[53] Gunduz ME, Pacheco-Barrios K, Bonin Pinto C, et al. Effects of combined and alone transcranial motor cortex stimulation and mirror therapy in phantom limb pain: a randomized factorial trial. Neurorehabil Neural Repair. 2021; 35(8):704-716. https://doi.org/10.1177/15459683211017509

[54] Pinto CB, Saleh Velez FG, Bolognini N, Crandell D, Merabet LB, Fregni F. Optimizing rehabilitation for phantom limb pain using mirror therapy and transcranial direct current stimulation: a randomized, double-blind clinical trial study protocol. JMIR Res Protoc. 2016; 5(3):e138. https://doi.org/10.2196/resprot.5645

[55] Segal N, Pud D, Amir H, et al. Additive analgesic effect of transcranial direct current stimulation together with mirror therapy for the treatment of phantom pain. Pain Med. 2021; 22(2):255-265. https://doi.org/10.1093/pm/pnaa388

[56] Damercheli S, Ramne M, Ortiz-Catalan M. transcranial Direct Current Stimulation (tDCS) for the treatment and investigation of Phantom Limb Pain (PLP). Psychoradiology. 2022; 2(1):23-31. https://doi.org/10.1093/psyrad/kkac004

[57] Fitzgerald PB. An update on the clinical use of repetitive transcranial magnetic stimulation in the treatment of depression. J Affect Disord. 2020; 276:90-103. https://doi.org/10.1016/j.jad.2020.06.067

[58] Di Rollo A, Pallanti S. Phantom limb pain: low frequency repetitive transcranial magnetic stimulation in unaffected hemisphere. Case Rep Med. 2011; 2011(1): 130751. https://doi.org/10.1155/2011/130751

[59] Lee JH, Byun JH, Choe YR, Lim SK, Lee KY, Choi IS. Successful treatment of phantom limb pain by 1 Hz repetitive transcranial magnetic stimulation over affected supplementary motor complex: a case report. Ann Rehabil Med. 2015; 39(4):630-633. https://doi.org/10.5535/arm.2015.39.4.630

[60] Malavera A, Silva FA, Fregni F, Carrillo S, Garcia RG. Repetitive transcranial magnetic stimulation for phantom limb pain in land mine victims: a double-blinded, randomized, sham-controlled trial. J Pain. 2016; 17(8):911-918. https://doi.org/10.1016/j.jpain.2016.05.003

[61] Ahmed MA, Mohamed SA, Sayed D. Long-term antalgic effects of repetitive transcranial magnetic stimulation of motor cortex and serum beta-endorphin in patients with phantom pain. Neurol Res. 2011; 33(9):953-958. https://doi.org/10.1179/1743132811y.0000000045

[62] Töpper R, Foltys H, Meister IG, Sparing R, Boroojerdi B. Repetitive transcranial magnetic stimulation of the parietal cortex transiently ameliorates phantom limb pain-like syndrome. Clin Neurophysiol. 2003; 114(8):1521-1530. https://doi.org/10.1016/s1388-2457(03)00117-2

[63] Bolognini N, Olgiati E, Maravita A, Ferraro F, Fregni F. Motor and parietal cortex stimulation for phantom limb pain and sensations. Pain. 2013; 154(8):1274-1280. https://doi.org/10.1016/j.pain.2013.03.040

[64] Vats D, Bhatia R, Fatima S, et al. Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex for phantom limb pain. Pain Physician. 2024; 27(5):E589-E595.

[65] Johnson MI, Mulvey MR, Bagnall A-M. Transcutaneous electrical nerve stimulation (TENS) for phantom pain and stump pain following amputation in adults. Cochrane Database Syst Rev. 2015(8): CD007264. https://doi.org/10.1002/14651858.cd007264.pub3

[66] DeSantana JM, Walsh DM, Vance C, Rakel BA, Sluka KA. Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain. Curr Rheuma Rep. 2008; 10(6):492-499. https://doi.org/10.1007/s11926-008-0080-z

[67] Grimmer K. A controlled double blind study comparing the effects of strong Burst Mode TENS and High Rate TENS on painful osteoarthritic knees. Aust J Physiother. 1992; 38(1):49-56. https://doi.org/10.1016/s0004-9514(14)60551-1

[68] Bi Y, Wei Z, Kong Y, Hu L. Supraspinal neural mechanisms of the analgesic effect produced by transcutaneous electrical nerve stimulation. Brain Struct Funct. 2021; 226(1):151-162. https://doi.org/10.1007/s00429-020-02173-9

[69] Hu X, Trevelyan E, Yang G, et al. The effectiveness of acupuncture/TENS for phantom limb syndrome. I: A systematic review of controlled clinical trials. Eur J Integr Med. 2014; 6(3):355-364. https://doi.org/10.1016/j.eujim.2014.01.003

[70] Limakatso K. Managing acute phantom limb pain with transcutaneous electrical nerve stimulation: a case report. J Med Case Rep. 2023; 17(1):209. https://doi.org/10.1186/s13256-023-03915-z

[71] Tilak M, Isaac SA, Fletcher J, et al. Mirror Therapy and Transcutaneous Electrical Nerve Stimulation for Management of Phantom Limb Pain in Amputees — A Single Blinded Randomized Controlled Trial. Physiother Res Int. 2016; 21(2):109-115. https://doi.org/10.1002/pri.1626

[72] Takiguchi N, Shomoto K. Contralateral segmental transcutaneous electrical nerve stimulation inhibits nociceptive flexion reflex in healthy participants. Eur J Pain. 2019; 23(6):1098-1107. https://doi.org/10.1002/ejp.1373

[73] Mulvey MR, Radford HE, Fawkner HJ, Hirst L, Neumann V, Johnson MI. Transcutaneous electrical nerve stimulation for phantom pain and stump pain in adult amputees. Pain Pract. 2013; 13(4):289-296. https://doi.org/10.1111/j.1533-2500.2012.00593.x

[74] Wolf SL, Gersh MR, Rao VR. Examination of electrode placements and stimulating parameters in treating chronic pain with conventional transcutaneous electrical nerve stimulation (TENS). Pain. 1981; 11(1):37-47. https://doi.org/10.1016/0304-3959(81)90137-8

[75] Mulvey MR, Bagnall A-M, Marchant PR, Johnson M. Transcutaneous electrical nerve stimulation (TENS) for phantom pain and stump pain following amputation in adults: an extended analysis of excluded studies from a Cochrane systematic review. Phys Ther Rev. 2014; 19(4):234-244. https://doi.org/10.1179/1743288x13y.0000000128

[76] Chen CC, Johnson MI. An investigation into the hypoalgesic effects of high- and low-frequency transcutaneous electrical nerve stimulation (TENS) on experimentally-induced blunt pressure pain in healthy human participants. J Pain. 2010; 11(1):53-61. https://doi.org/10.1016/j.jpain.2009.05.008

[77] Faghani Jadidi A, Stevenson AJT, Zarei AA, Jensen W, Lontis R. Effect of modulated TENS on corticospinal excitability in healthy subjects. Neuroscience. 2022; 485:53-64. https://doi.org/10.1016/j.neuroscience.2022.01.004

[78] Faghani Jadidi A, Jensen W, Zarei AA, Lontis ER. Alteration in cortical activity and perceived sensation following modulated TENS. Modul Tens IEEE Trans Neural Syst Rehabil Eng. 2023; 31:875-883. https://doi.org/10.1109/tnsre.2023.3236038

[79] Raffin E. Les différentes formes de réorganisations cérébrales après amputation et leurs liens avec les thérapies antalgiques. Rev Neurol (Paris). 2021; 177:S142. https://doi.org/10.1016/j.neurol.2021.02.032

[80] Yanagisawa T, Fukuma R, Seymour B, et al. S109 Magnetoencephalographic-based brain-machine interface robotic hand for controlling sensorimotor cortical plasticity and phantom limb pain. Clin Neurophysiol. 2017; 128(9):e124. https://doi.org/10.1016/j.clinph.2017.07.120

[81] Yanagisawa T, Fukuma R, Seymour B, et al. BCI training to move a virtual hand reduces phantom limb pain: a randomized crossover trial. Neurology. 2020; 95(4):e417-e426. https://doi.org/10.1212/wnl.0000000000009858

[82] Yanagisawa T, Fukuma R, Seymour B, et al. MEG-BMI to Control Phantom Limb Pain. Neurol Med Chir (Tokyo). 2018; 58(8):327-333. https://doi.org/10.2176/nmc.st.2018-0099

[83] Cao T-A, Zhou H, Chen Z, et al. A novel hand motion intention recognition method that decodes EMG signals based on an improved LSTM. Symmetry (Basel). 2025; 17(10):1587. https://doi.org/10.3390/sym17101587

[84] Lendaro E, Van der Sluis CK, Hermansson L, et al. Extended reality used in the treatment of phantom limb pain: a multicenter, double-blind, randomized controlled trial. Pain. 2025; 166(3):571-586. https://doi.org/10.1097/j.pain.0000000000003384

[85] Qi S, Liu X, Yu J, Liang Z, Liu Y, Wang X. Temporally interfering electric fields brain stimulation in primary motor cortex of mice promotes motor skill through enhancing neuroplasticity. Brain Stimul. 2024; 17(2):245-257. https://doi.org/10.1016/j.brs.2024.02.014

[86] Xu S, Cui H, Xiao X, Manshaii F, Hong G, Chen J. Precision at deep brain: non-invasive temporal interference stimulation. ACS Nano. 2025; 19(46):39589-39614. https://doi.org/10.1021/acsnano.5c15238

[87] 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). Neural Plast. 2022; 2022(1): 7605046. https://doi.org/10.1155/2022/7605046

[88] Guo W, He Y, Zhang W, et al. A novel non-invasive brain stimulation technique: “Temporally interfering electrical stimulation. Front Neurosci. 2023; 17:1092539. https://doi.org/10.3389/fnins.2023.1092539

[89] Song X, Zhao X, Li X, Liu S, Ming D. Multi-channel transcranial temporally interfering stimulation (tTIS): application to living mice brain. J Neural Eng. 2021; 18(3):036003. https://doi.org/10.1088/1741-2552/abd2c9

[90] Violante IR, Alania K, Cassarà AM, et al. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023; 26(11):1994-2004. https://doi.org/10.1038/s41593-023-01456-8

[91] Missey F, Rusina E, Acerbo E, et al. Orientation of Temporal Interference for Non-Invasive Deep Brain Stimulation in Epilepsy. Front Neurosci. 2021; 15:633988. https://doi.org/10.3389/fnins.2021.633988

[92] Acerbo E, Jegou A, Luff C, et al. Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers. Front Neurosci. 2022; 16:945221. https://doi.org/10.3389/fnins.2022.945221

[93] di Biase L, Falato E, Di Lazzaro V. Transcranial Focused Ultrasound (tFUS) and Transcranial Unfocused Ultrasound (tUS) Neuromodulation: From Theoretical Principles to Stimulation Practices. Front Neurol. 2019; 10:549. https://doi.org/10.3389/fneur.2019.00549

[94] Kubanek J.Neuromodulation with transcranial focused ultrasound. Neurosurg Focus. 2018; 44(2):E41. https://doi.org/10.3171/2017.11.focus17621

[95] Beisteiner R, Matt E, Fan C, et al. Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. Adv Sci (Weinh). 2019; 7(3):1902583. https://doi.org/10.1002/advs.201902583

[96] Bubrick E, White PJ, Mariano T, Orozco J, Purandare M, McDannold N.Transcranial focused ultrasound for epilepsy. Brain Stimul. 2021; 14(6):1747. https://doi.org/10.1016/j.brs.2021.10.533

[97] Habelhah B, Mahdavi KD, Zielinski MA, et al. Comparing therapeutic-focused ultrasound (TFUS) in conjunction with bosutinib versus independent TFUS administration among Alzheimer’s patients. Alzheimers Dement. 2021; 17(S9):e054631. https://doi.org/10.1002/alz.054631

[98] Jeanmonod D, Werner B, Morel A, et al. Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg Focus. 2012; 32(1):E1. https://doi.org/10.3171/2011.10.focus11248

[99] Martínez-Fernández R, Rodríguez-Rojas R, del Álamo M, et al. Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study. Lancet Neurol. 2018; 17(1):54-63. https://doi.org/10.1016/s1474-4422(17)30403-9

[100] Hsieh TH, Chu PC, Nguyen TXD, et al. Neuromodulatory responses elicited by intermittent versus continuous transcranial focused ultrasound stimulation of the motor cortex in rats. Int J Mol Sci. 2024; 25(11):5687. https://doi.org/10.3390/ijms25115687

[101] Zhang T, Guo B, Zuo Z, et al. Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex. CNS Neurosci Ther. 2023; 29(12):3829-3841. https://doi.org/10.1111/cns.14303

[102] Lim L. Traumatic brain injury recovery with photobiomodulation: cellular mechanisms, clinical evidence, and future potential. Cells. 2024; 13(5):385. https://doi.org/10.3390/cells13050385

[103] Ma H, Du Y, Xie D, Wei ZZ, Pan Y, Zhang Y. Recent advances in light energy therapeutic strategies with photobiomodulation on central nervous system disorders. Brain Res. 2024; 1822:148615. https://doi.org/10.1016/j.brainres.2023.148615

[104] Gaggi NL, Iosifescu DV. Transcranial photobiomodulation: an emerging therapeutic method to enhance brain bioenergetics. Neuropsychopharmacology. 2024; 50:314-315. https://doi.org/10.1038/s41386-024-01929-9

[105] Li S, Wong TWL, Ng SSM. Potential and challenges of transcranial photobiomodulation for the treatment of stroke. CNS Neurosci Ther. 2024; 30(12):e70142. https://doi.org/10.1111/cns.70142

[106] Papi S, Allahverdipour H, Jahan A, Dianat I, Jafarabadi MA, Salimi MM. The effect of transcranial photobiomodulation on cognitive function and attentional performance of older women with mild cognitive impairment: a randomized controlled trial. Prz Menopauzalny. 2022; 21(3):157-164. https://doi.org/10.5114/pm.2022.119794

[107] 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. https://doi.org/10.1093/brain/awae292

[108] Estrada-Rojas K, Cedeño Ortiz NP. Increased improvement in speech-language skills after transcranial photobiomodulation plus speech-language therapy, compared to speech-language therapy alone: case report with Aphasia. Photobiomodul Photomed Laser Surg. 2023; 41(5):234-240. https://doi.org/10.1089/photob.2022.0024

[109] Stevens AR, Hadis M, Phillips A, et al. Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury. Bioeng Transl Med. 2024; 9(6):e10674. https://doi.org/10.1002/btm2.10674

[110] Browne JD, Fraiser R, Cai Y, Leung D, Leung A, Vaninetti M. Unveiling the phantom: what neuroimaging has taught us about phantom limb pain. Brain Behav. 2022; 12(3):e2509. https://doi.org/10.1002/brb3.2509

[111] Marullo G, Innocente C, Ulrich L, et al. Home-based mirror therapy in phantom limb pain treatment: the augmented humans framework. Multimed Tools Appl. 2025; 84(28):34145-34177. https://doi.org/10.1007/s11042-025-20628-1