Skip to main content

Advertisement

SpringerLink
Log in

A review of functional neuromodulation in humans using low-intensity transcranial focused ultrasound

  • Review Article
  • Published:
Biomedical Engineering Letters Aims and scope Submit manuscript

Abstract

Transcranial ultrasonic neuromodulation is a rapidly burgeoning field where low-intensity transcranial focused ultrasound (tFUS), with exquisite spatial resolution and deep tissue penetration, is used to non-invasively activate or suppress neural activity in specific brain regions. Over the past decade, there has been a rapid increase of tFUS neuromodulation studies in healthy humans and subjects with central nervous system (CNS) disease conditions, including a recent surge of clinical investigations in patients. This narrative review summarized the findings of human neuromodulation studies using either tFUS or unfocused transcranial ultrasound (TUS) reported from 2013 to 2023. The studies were categorized into two separate sections: healthy human research and clinical studies. A total of 42 healthy human investigations were reviewed as grouped by targeted brain regions, including various cortical, subcortical, and deep brain areas including the thalamus. For clinical research, a total of 22 articles were reviewed for each studied CNS disease condition, including chronic pain, disorder of consciousness, Alzheimer’s disease, Parkinson’s disease, depression, schizophrenia, anxiety disorders, substance use disorder, drug-resistant epilepsy, and stroke. Detailed information on subjects/cohorts, target brain regions, sonication parameters, outcome readouts, and stimulatory efficacies were tabulated for each study. In later sections, considerations for planning tFUS neuromodulation in humans were also concisely discussed. With an excellent safety profile to date, the rapid growth of human tFUS research underscores the increasing interest and recognition of its significant potential in the field of non-invasive brain stimulation (NIBS), offering theranostic potential for neurological and psychiatric disease conditions and neuroscientific tools for functional brain mapping.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. George MS, Aston-Jones G. Noninvasive techniques for probing neurocircuitry and treating illness: Vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Neuropsychopharmacology. 2010;35(1):301–16. https://doi.org/10.1038/npp.2009.87.

    Article  Google Scholar 

  2. Hoy KE, Fitzgerald PB. Brain stimulation in psychiatry and its effects on cognition. Nat Rev Neurol. 2010;6(5):267–75. https://doi.org/10.1038/nrneurol.2010.30.

    Article  Google Scholar 

  3. Jolesz FA, Hynynen K, McDannold N, Tempany C. MR imaging-controlled focused ultrasound ablation: a noninvasive image-guided surgery. Magn Reson Imaging Clin N Am. 2005;13(3):545–60. https://doi.org/10.1016/j.mric.2005.04.008.

    Article  Google Scholar 

  4. White PJ, Clement GT, Hynynen K. Longitudinal and shear mode ultrasound propagation in human skull bone. Ultrasound Med Biol. 2006;32(7):1085–96. https://doi.org/10.1016/j.ultrasmedbio.2006.03.015.

    Article  Google Scholar 

  5. Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC, Sperling SA, Wylie S, Monteith SJ, et al. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013;369(7):640–8. https://doi.org/10.1056/NEJMoa1300962.

    Article  Google Scholar 

  6. Cammalleri A, Croce P, Lee W, Yoon K, Yoo S-S. Therapeutic potentials of localized blood-brain barrier disruption by noninvasive transcranial focused ultrasound: a technical review. J Clin Neurophysiol. 2020;37(2):104–17. https://doi.org/10.1097/WNP.0000000000000488.

    Article  Google Scholar 

  7. Tyler WJ, Tufail Y, Finsterwald M, Tauchmann ML, Olson EJ, Majestic C. Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound. PLoS ONE. 2008;3(10):e3511. https://doi.org/10.1371/journal.pone.0003511.

    Article  Google Scholar 

  8. Kim H, Chiu A, Lee SD, Fischer K, Yoo S-S. Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters. Brain Stimul. 2014;7(5):748–56. https://doi.org/10.1016/j.brs.2014.06.011.

    Article  Google Scholar 

  9. Lee W, Croce P, Margolin RW, Cammalleri A, Yoon K, Yoo S-S. Transcranial focused ultrasound stimulation of motor cortical areas in freely-moving awake rats. BMC Neurosci. 2018;19:57. https://doi.org/10.1186/s12868-018-0459-3.

    Article  Google Scholar 

  10. Jo Y, Lee S-M, Jung T, Park G, Lee C, Im GH, Lee S, Park JS, Oh C, Kook G, et al. General-purpose ultrasound neuromodulation system for chronic, closed-loop preclinical studies in freely behaving rodents. Adv Sci (Weinh). 2022;9(34):e2202345. https://doi.org/10.1002/advs.202202345.

    Article  Google Scholar 

  11. Kim H, Kim S, Sim NS, Pasquinelli C, Thielscher A, Lee JH, Lee HJ. Miniature ultrasound ring array transducers for transcranial ultrasound neuromodulation of freely-moving small animals. Brain Stimul. 2019;12(2):251–5. https://doi.org/10.1016/j.brs.2018.11.007.

    Article  Google Scholar 

  12. Lee W, Lee SD, Park MY, Foley L, Purcell-Estabrook E, Kim H, Fischer K, Maeng L-S, Yoo S-S. Image-guided focused ultrasound-mediated regional brain stimulation in sheep. Ultrasound Med Biol. 2016c;42(2):459–70. https://doi.org/10.1016/j.ultrasmedbio.2015.10.001.

    Article  Google Scholar 

  13. Gaur P, Casey KM, Kubanek J, Li N, Mohammadjavadi M, Saenz Y, Glover GH, Bouley DM, Pauly KB. Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep. Brain Stimul. 2020;13(3):804–14. https://doi.org/10.1016/j.brs.2020.02.017.

    Article  Google Scholar 

  14. Kubanek J, Brown J, Ye P, Pauly KB, Moore T, Newsome W. Remote, brain region-specific control of choice behavior with ultrasonic waves. Sci Adv. 2020;6(21):eaaz4193. https://doi.org/10.1126/sciadv.aaz4193.

    Article  Google Scholar 

  15. Darmani G, Bergmann TO, Butts Pauly K, Caskey CF, de Lecea L, Fomenko A, Fouragnan E, Legon W, Murphy KR, Nandi T, et al. Non-invasive transcranial ultrasound stimulation for neuromodulation. Clin Neurophysiol. 2022;135:51–73. https://doi.org/10.1016/j.clinph.2021.12.010.

    Article  Google Scholar 

  16. Beisteiner R, Matt E, Fan C, Baldysiak H, Schönfeld M, Philippi Novak T, Amini A, Aslan T, Reinecke R, Lehrner J, et al. Transcranial pulse stimulation with ultrasound in Alzheimer’s disease—A new navigated focal brain therapy. Adv Sci (Weinh). 2020;7(3):1902583. https://doi.org/10.1002/advs.201902583.

    Article  Google Scholar 

  17. Blackmore J, Shrivastava S, Sallet J, Butler CR, Cleveland RO. Ultrasound neuromodulation: a review of results, mechanisms and safety. Ultrasound Med Biol. 2019;45(7):1509–36. https://doi.org/10.1016/j.ultrasmedbio.2018.12.015.

    Article  Google Scholar 

  18. Aubry J-F, Attali D, Schafer M, Fouragnan E, Caskey C, Chen R, et al. ITRUSST consensus on biophysical safety for transcranial ultrasonic stimulation. arXiv. 2023;arXiv:2311.05359v1 [physics.bio-ph]. https://doi.org/10.48550/arXiv.2311.05359.

    Article  Google Scholar 

  19. Fomenko A, Chen K-HS, Nankoo J-F, Saravanamuttu J, Wang Y, El-Baba M, Xia X, Seerala SS, Hynynen K, Lozano AM, Chen R. Systematic examination of low-intensity ultrasound parameters on human motor cortex excitability and behavior. eLife. 2020;9:e54497. https://doi.org/10.7554/eLife.54497.

    Article  Google Scholar 

  20. Legon W, Bansal P, Tyshynsky R, Ai L, Mueller JK. Transcranial focused ultrasound neuromodulation of the human primary motor cortex. Sci Rep. 2018b;8(1):10007. https://doi.org/10.1038/s41598-018-28320-1.

    Article  Google Scholar 

  21. Xia X, Fomenko A, Nankoo J-F, Zeng K, Wang Y, Zhang J, Lozano AM, Chen R. Time course of the effects of low-intensity transcranial ultrasound on the excitability of ipsilateral and contralateral human primary motor cortex. NeuroImage. 2021;243:118557. https://doi.org/10.1016/j.neuroimage.2021.118557.

    Article  Google Scholar 

  22. Nakajima K, Osada T, Ogawa A, Tanaka M, Oka S, Kamagata K, Aoki S, Oshima Y, Tanaka S, Konishi S. A causal role of anterior prefrontal-putamen circuit for response inhibition revealed by transcranial ultrasound stimulation in humans. Cell Rep. 2022;40(7):111197. https://doi.org/10.1016/j.celrep.2022.111197.

    Article  Google Scholar 

  23. Gibson BC, Sanguinetti JL, Badran BW, Yu AB, Klein EP, Abbott CC, Hansberger JT, Clark VP. Increased excitability induced in the primary motor cortex by transcranial ultrasound stimulation. Front Neurol. 2018;9:1007. https://doi.org/10.3389/fneur.2018.01007.

    Article  Google Scholar 

  24. Zhang Y, Ren L, Liu K, Tong S, Yuan T-F, Sun J. Transcranial ultrasound stimulation of the human motor cortex. iScience. 2021;24(12):103429. https://doi.org/10.1016/j.isci.2021.103429.

    Article  Google Scholar 

  25. Ren L, Zhai Z, Xiang Q, Zhuo K, Zhang S, Zhang Y, Jiao X, Tong S, Liu D, Sun J. Transcranial ultrasound stimulation modulates the interhemispheric balance of excitability in human motor cortex. J Neural Eng. 2023;20(1):016043. https://doi.org/10.1088/1741-2552/acb50d.

    Article  Google Scholar 

  26. Zeng K, Darmani G, Fomenko A, Xia X, Tran S, Nankoo J-F, Shamli Oghli Y, Wang Y, Lozano AM, Chen R. Induction of human motor cortex plasticity by theta burst transcranial ultrasound stimulation. Ann Neurol. 2022;91(2):238–52. https://doi.org/10.1002/ana.26294.

    Article  Google Scholar 

  27. Samuel N, Zeng K, Harmsen IE, Ding MYR, Darmani G, Sarica C, Santyr B, Vetkas A, Pancholi A, Fomenko A, et al. Multi-modal investigation of transcranial ultrasound-induced neuroplasticity of the human motor cortex. Brain Stimul. 2022;15(6):1337–47. https://doi.org/10.1016/j.brs.2022.10.001.

    Article  Google Scholar 

  28. Zhang M-F, Chen W-Z, Huang F-B, Peng Z-Y, Quan Y-C, Tang Z-M. Low-intensity transcranial ultrasound stimulation facilitates hand motor function and cortical excitability: a crossover, randomized, double blind study. Front Neurol. 2022;13:926027. https://doi.org/10.3389/fneur.2022.926027.

    Article  Google Scholar 

  29. Zhang T, Guo B, Zuo Z, Long X, Hu S, Li S, Su X, Wang Y, Liu C. Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex. CNS Neurosci Ther. 2023;29(12):3829–41. https://doi.org/10.1111/cns.14303.

    Article  Google Scholar 

  30. Heimbuch IS, Fan TK, Wu AD, Faas GC, Charles AC, Iacoboni M. Ultrasound stimulation of the motor cortex during tonic muscle contraction. PLoS ONE. 2022;17(4):e0267268. https://doi.org/10.1371/journal.pone.0267268.

    Article  Google Scholar 

  31. Ai L, Bansal P, Mueller JK, Legon W. Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI: a pilot study. BMC Neurosci. 2018;19(1):56. https://doi.org/10.1186/s12868-018-0456-6.

    Article  Google Scholar 

  32. Yu K, Liu C, Niu X, He B. Transcranial focused ultrasound neuromodulation of voluntary movement-related cortical activity in humans. IEEE Trans Biomed Eng. 2021;68(6):1923–31. https://doi.org/10.1109/TBME.2020.3030892.

    Article  Google Scholar 

  33. Shamli Oghli Y, Grippe T, Arora T, Hoque T, Darmani G, Chen R. Mechanisms of theta burst transcranial ultrasound induced plasticity in the human motor cortex. Brain Stimul. 2023;16(4):1135–43. https://doi.org/10.1016/j.brs.2023.07.056.

    Article  Google Scholar 

  34. Legon W, Sato TF, Opitz A, Mueller J, Barbour A, Williams A, Tyler WJ. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat Neurosci. 2014;17(2):322–9. https://doi.org/10.1038/nn.3620.

    Article  Google Scholar 

  35. Mueller J, Legon W, Opitz A, Sato TF, Tyler WJ. Transcranial focused ultrasound modulates intrinsic and evoked EEG dynamics. Brain Stimul. 2014;7(6):900–8. https://doi.org/10.1016/j.brs.2014.08.008.

    Article  Google Scholar 

  36. Lee W, Kim H, Jung Y, Song I-U, Chung YA, Yoo S-S. Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex. Sci Rep. 2015;5:8743. https://doi.org/10.1038/srep08743.

    Article  Google Scholar 

  37. Lee W, Chung YA, Jung Y, Song I-U, Yoo S-S. Simultaneous acoustic stimulation of human primary and secondary somatosensory cortices using transcranial focused ultrasound. BMC Neurosci. 2016a;17:68. https://doi.org/10.1186/s12868-016-0303-6.

    Article  Google Scholar 

  38. Lee W, Kim S, Kim B, Lee C, Chung YA, Kim L, Yoo S-S. Non-invasive transmission of sensorimotor information in humans using an EEG/focused ultrasound brain-to-brain interface. PLoS ONE. 2017;12(6):e0178476. https://doi.org/10.1371/journal.pone.0178476.

    Article  Google Scholar 

  39. Liu C, Yu K, Niu X, He B. Transcranial focused ultrasound enhances sensory discrimination capability through somatosensory cortical excitation. Ultrasound Med Biol. 2021;47(5):1356–66. https://doi.org/10.1016/j.ultrasmedbio.2021.01.025.

    Article  Google Scholar 

  40. Kim H-C, Lee W, Weisholtz DS, Yoo S-S. Transcranial focused ultrasound stimulation of cortical and thalamic somatosensory areas in human. PLoS ONE. 2023;18(7):e0288654. https://doi.org/10.1371/journal.pone.0288654.

    Article  Google Scholar 

  41. Lee W, Kim H-C, Jung Y, Chung YA, Song I-U, Lee J-H, Yoo S-S. Transcranial focused ultrasound stimulation of human primary visual cortex. Sci Rep. 2016b;6:34026. https://doi.org/10.1038/srep34026.

    Article  Google Scholar 

  42. Schimek N, Burke-Conte Z, Abernethy J, Schimek M, Burke-Conte C, Bobola M, Stocco A, Mourad PD. Repeated application of transcranial diagnostic ultrasound towards the visual cortex induced illusory visual percepts in healthy participants. Front Hum Neurosci. 2020;14:66. https://doi.org/10.3389/fnhum.2020.00066.

    Article  Google Scholar 

  43. Butler CR, Rhodes E, Blackmore J, Cheng X, Peach RL, Veldsman M, Sheerin F, Cleveland RO. Transcranial ultrasound stimulation to human middle temporal complex improves visual motion detection and modulates electrophysiological responses. Brain Stimul. 2022;15(5):1236–45. https://doi.org/10.1016/j.brs.2022.08.022.

    Article  Google Scholar 

  44. Braun V, Blackmore J, Cleveland RO, Butler CR. Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked. Brain Stimul. 2020;13(6):1527–34. https://doi.org/10.1016/j.brs.2020.08.014.

    Article  Google Scholar 

  45. Nandi T, Johnstone A, Martin E, Zich C, Cooper R, Bestmann S, Bergmann TO, Treeby B, Stagg CJ. Ramped V1 transcranial ultrasonic stimulation modulates but does not evoke visual evoked potentials. Brain Stimul. 2023;16(2):553–5. https://doi.org/10.1016/j.brs.2023.02.004.

    Article  Google Scholar 

  46. Sanguinetti JL, Hameroff S, Smith EE, Sato T, Daft CMW, Tyler WJ, Allen JJB. Transcranial focused ultrasound to the right prefrontal cortex improves mood and alters functional connectivity in humans. Front Hum Neurosci. 2020;14:52. https://doi.org/10.3389/fnhum.2020.00052.

    Article  Google Scholar 

  47. Forster A, Rodrigues J, Ziebell P, Sanguinetti JL, Allen JJ, Hewig J. Investigating the role of the right inferior frontal gyrus in control perception: a double-blind cross-over study using ultrasonic neuromodulation. Neuropsychologia. 2023b;187:108589. https://doi.org/10.1016/j.neuropsychologia.2023.108589.

    Article  Google Scholar 

  48. Forster A, Rodrigues J, Ziebell P, Sanguinetti JL, Allen JJB, Hewig J. Transcranial focused ultrasound modulates the emergence of learned helplessness via midline theta modification. J Affect Disord. 2023a;329:273–84. https://doi.org/10.1016/j.jad.2023.02.032.

    Article  Google Scholar 

  49. Ziebell P, Rodrigues J, Forster A, Sanguinetti JL, Allen JJ, Hewig J. Inhibition of midfrontal theta with transcranial ultrasound explains greater approach versus withdrawal behavior in humans. Brain Stimul. 2023;16(5):1278–88. https://doi.org/10.1016/j.brs.2023.08.011.

    Article  Google Scholar 

  50. Fine JM, Mysore AS, Fini ME, Tyler WJ, Santello M. Transcranial focused ultrasound to human rIFG improves response inhibition through modulation of the P300 onset latency. eLife. 2023;12:e86190. https://doi.org/10.7554/eLife.86190.

    Article  Google Scholar 

  51. Kim YG, Kim SE, Lee J, Hwang S, Yoo S-S, Lee HW. Neuromodulation using transcranial focused ultrasound on the bilateral medial prefrontal cortex. J Clin Med. 2022;11(13):3809. https://doi.org/10.3390/jcm11133809.

    Article  Google Scholar 

  52. Park TY, Jeong JH, Chung YA, Yeo SH, Kim H. Application of subject-specific helmets for the study of human visuomotor behavior using transcranial focused ultrasound: a pilot study. Comput Methods Programs Biomed. 2022;226:107127. https://doi.org/10.1016/j.cmpb.2022.107127.

    Article  Google Scholar 

  53. Yaakub SN, White TA, Roberts J, Martin E, Verhagen L, Stagg CJ, Hall S, Fouragnan EF. Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans. Nat Commun. 2023;14(1):5318. https://doi.org/10.1038/s41467-023-40998-0.

    Article  Google Scholar 

  54. Cain JA, Visagan S, Johnson MA, Crone J, Blades R, Spivak NM, Shattuck DW, Monti MM. Real time and delayed effects of subcortical low intensity focused ultrasound. Sci Rep. 2021b;11(1):6100. https://doi.org/10.1038/s41598-021-85504-y.

    Article  Google Scholar 

  55. Kuhn T, Spivak NM, Dang BH, Becerra S, Halavi SE, Rotstein N, Rosenberg BM, Hiller S, Swenson A, Cvijanovic L, et al. Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans. Front Neural Circuits. 2023;17:1120410. https://doi.org/10.3389/fncir.2023.1120410.

    Article  Google Scholar 

  56. Schafer ME, Spivak NM, Korb AS, Bystritsky A. Design, development, and operation of a low-intensity focused ultrasound pulsation (LIFUP) system for clinical use. IEEE Trans Ultrason Ferroelectr Freq Control. 2021;68(1):54–64. https://doi.org/10.1109/TUFFC.2020.3006781.

    Article  Google Scholar 

  57. Guerra A, Vicenzini E, Cioffi E, Colella D, Cannavacciuolo A, Pozzi S, Caccia B, Paparella G, Di Stefano G, Berardelli A, Bologna M. Effects of transcranial ultrasound stimulation on trigeminal blink reflex excitability. Brain Sci. 2021;11(5):645. https://doi.org/10.3390/brainsci11050645.

    Article  Google Scholar 

  58. Legon W, Ai L, Bansal P, Mueller JK. Neuromodulation with single-element transcranial focused ultrasound in human thalamus. Hum Brain Mapp. 2018a;39(5):1995–2006. https://doi.org/10.1002/hbm.23981.

    Article  Google Scholar 

  59. Badran BW, Caulfield KA, Stomberg-Firestein S, Summers PM, Dowdle LT, Savoca M, Li X, Austelle CW, Short EB, Borckardt JJ, et al. Sonication of the anterior thalamus with MRI-guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: a double-blind, sham-controlled study. Brain Stimul. 2020;13(6):1805–12. https://doi.org/10.1016/j.brs.2020.10.007.

    Article  Google Scholar 

  60. Hameroff S, Trakas M, Duffield C, Annabi E, Gerace MB, Boyle P, Lucas A, Amos Q, Buadu A, Badal JJ. Transcranial ultrasound (TUS) effects on mental states: a pilot study. Brain Stimul. 2013;6(3):409–15. https://doi.org/10.1016/j.brs.2012.05.002.

    Article  Google Scholar 

  61. Shin DH, Son S, Kim EY. Low-energy transcranial navigation-guided focused ultrasound for neuropathic pain: an exploratory study. Brain Sci. 2023;13(10):1433. https://doi.org/10.3390/brainsci13101433.

    Article  Google Scholar 

  62. Yu K, Niu X, He B. Neuromodulation management of chronic neuropathic pain in the central nervous system. Adv Funct Mater. 2020;30(37):1908999. https://doi.org/10.1002/adfm.201908999.

    Article  Google Scholar 

  63. Monti MM, Schnakers C, Korb AS, Bystritsky A, Vespa PM. Non-invasive ultrasonic thalamic stimulation in disorders of consciousness after severe brain injury: a first-in-man report. Brain Stimul. 2016;9(6):940–1. https://doi.org/10.1016/j.brs.2016.07.008.

    Article  Google Scholar 

  64. Cain JA, Spivak NM, Coetzee JP, Crone JS, Johnson MA, Lutkenhoff ES, Real C, Buitrago-Blanco M, Vespa PM, Schnakers C, Monti MM. Ultrasonic thalamic stimulation in chronic disorders of consciousness. Brain Stimul. 2021a;14(2):301–3. https://doi.org/10.1016/j.brs.2021.01.008.

    Article  Google Scholar 

  65. Cain JA, Spivak NM, Coetzee JP, Crone JS, Johnson MA, Lutkenhoff ES, Real C, Buitrago-Blanco M, Vespa PM, Schnakers C, Monti MM. Ultrasonic deep brain neuromodulation in acute disorders of consciousness: a proof-of-concept. Brain Sci. 2022;12(4):428. https://doi.org/10.3390/brainsci12040428.

    Article  Google Scholar 

  66. Nicodemus NE, Becerra S, Kuhn TP, Packham HR, Duncan J, Mahdavi K, Iovine J, Kesari S, Pereles S, Whitney M, et al. Focused transcranial ultrasound for treatment of neurodegenerative dementia. Alzheimers Dement (N Y). 2019;5:374–81. https://doi.org/10.1016/j.trci.2019.06.007.

    Article  Google Scholar 

  67. Jeong H, Im JJ, Park J-S, Na S-H, Lee W, Yoo S-S, Song I-U, Chung Y-A. A pilot clinical study of low-intensity transcranial focused ultrasound in Alzheimer’s disease. Ultrasonography. 2021;40(4):512–9. https://doi.org/10.14366/usg.20138.

    Article  Google Scholar 

  68. Jeong H, Song I-U, Chung Y-A, Park J-S, Na S-H, Im JJ, Bikson M, Lee W, Yoo S-S. Short-term efficacy of transcranial focused ultrasound to the hippocampus in Alzheimer’s disease: a preliminary study. J Pers Med. 2022;12(2):250. https://doi.org/10.3390/jpm12020250.

    Article  Google Scholar 

  69. Shimokawa H, Shindo T, Ishiki A, Tomita N, Ichijyo S, Watanabe T, Nakata T, Eguchi K, Kikuchi Y, Shiroto T, et al. A pilot study of whole-brain low-intensity pulsed ultrasound therapy for early stage of Alzheimer’s disease (LIPUS-AD): a randomized, double-blind, placebo-controlled trial. Tohoku J Exp Med. 2022;258(3):167–75. https://doi.org/10.1620/tjem.2022.J078.

    Article  Google Scholar 

  70. Kovalenko EA, Makhnovich EV, Osinovskaya NA, Bogolepova AN. The therapeutic potential of focused ultrasound in patients with Alzheimer’s disease. Neurosci Behav Physi. 2023;53(5):793–800. https://doi.org/10.1007/s11055-023-01471-z.

    Article  Google Scholar 

  71. Samuel N, Ding MYR, Sarica C, Darmani G, Harmsen IE, Grippe T, Chen X, Yang A, Nasrkhani N, Zeng K, et al. Accelerated transcranial ultrasound neuromodulation in Parkinson’s disease: a pilot study. Mov Disord. 2023;38(12):2209–16. https://doi.org/10.1002/mds.29622.

    Article  Google Scholar 

  72. Zhong Y-X, Liao J-C, Liu X, Tian H, Deng L-R, Long L. Low intensity focused ultrasound: a new prospect for the treatment of Parkinson’s disease. Ann Med. 2023;55(2):2251145. https://doi.org/10.1080/07853890.2023.2251145.

    Article  Google Scholar 

  73. Reznik SJ, Sanguinetti JL, Tyler WJ, Daft C, Allen JJB. A double-blind pilot study of transcranial ultrasound (TUS) as a five-day intervention: TUS mitigates worry among depressed participants. Neurol Psychiatry Brain Res. 2020;37:60–6. https://doi.org/10.1016/j.npbr.2020.06.004.

    Article  Google Scholar 

  74. Riis T, Feldman D, Losser A, Mickey B, Kubanek J. Device for multifocal delivery of ultrasound into deep brain regions in humans. IEEE Trans Biomed Eng. 2024;71(2):660–8. https://doi.org/10.1109/TBME.2023.3313987.

    Article  Google Scholar 

  75. Riis TS, Feldman DA, Vonesh LC, Brown JR, Solzbacher D, Kubanek J, Mickey BJ. Durable effects of deep brain ultrasonic neuromodulation on major depression: a case report. J Med Case Rep. 2023;17(1):449. https://doi.org/10.1186/s13256-023-04194-4.

    Article  Google Scholar 

  76. Zhai Z, Ren L, Song Z, Xiang Q, Zhuo K, Zhang S, Li X, Zhang Y, Jiao X, Tong S, et al. The efficacy of low-intensity transcranial ultrasound stimulation on negative symptoms in schizophrenia: a double-blind, randomized sham-controlled study. Brain Stimul. 2023;16(3):790–2. https://doi.org/10.1016/j.brs.2023.04.021.

    Article  Google Scholar 

  77. Mahdavi KD, Jordan SE, Jordan KG, Rindner ES, Haroon JM, Habelhah B, Becerra SA, Surya JR, Venkatraman V, Zielinski MA, et al. A pilot study of low-intensity focused ultrasound for treatment-resistant generalized anxiety disorder. J Psychiatr Res. 2023;168:125–32. https://doi.org/10.1016/j.jpsychires.2023.10.039.

    Article  Google Scholar 

  78. Mahoney JJ, Haut MW, Carpenter J, Ranjan M, Thompson-Lake DGY, Marton JL, Zheng W, Berry JH, Tirumalai P, Mears A, et al. Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial. Front Psychiatry. 2023b;14:1211566. https://doi.org/10.3389/fpsyt.2023.1211566.

    Article  Google Scholar 

  79. Mahoney JJ, Thompson-Lake DGY, Ranjan M, Marton JL, Carpenter JS, Zheng W, Berry JH, Farmer DL, D’Haese P, Finomore VS, et al. Low-intensity focused ultrasound targeting the bilateral nucleus accumbens as a potential treatment for substance use disorder: a first-in-human report. Biol Psychiatry. 2023a;94(11):E41–3. https://doi.org/10.1016/j.biopsych.2023.06.031.

    Article  Google Scholar 

  80. Brinker ST, Preiswerk F, White PJ, Mariano TY, McDannold NJ, Bubrick EJ. Focused ultrasound platform for investigating therapeutic neuromodulation across the human hippocampus. Ultrasound Med Biol. 2020;46(5):1270–4. https://doi.org/10.1016/j.ultrasmedbio.2020.01.007.

    Article  Google Scholar 

  81. Bubrick EJ, McDannold NJ, Orozco J, Mariano TY, Rigolo L, Golby AJ, Tie Y, White PJ. Transcranial ultrasound neuromodulation for epilepsy: a pilot safety trial. Brain Stimul. 2024;17(1):7–9. https://doi.org/10.1016/j.brs.2023.11.013.

    Article  Google Scholar 

  82. Stern JM, Spivak NM, Becerra SA, Kuhn TP, Korb AS, Kronemyer D, Khanlou N, Reyes SD, Monti MM, Schnakers C, et al. Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy. Brain Stimul. 2021;14(4):1022–31. https://doi.org/10.1016/j.brs.2021.06.003.

    Article  Google Scholar 

  83. Lee C-C, Chou C-C, Hsiao F-J, Chen Y-H, Lin C-F, Chen C-J, Peng S-J, Liu H-L, Yu H-Y. Pilot study of focused ultrasound for drug-resistant epilepsy. Epilepsia. 2022;63(1):162–75. https://doi.org/10.1111/epi.17105.

    Article  Google Scholar 

  84. Wang Y, Li F, He M-J, Chen S-J. The effects and mechanisms of transcranial ultrasound stimulation combined with cognitive rehabilitation on post-stroke cognitive impairment. Neurol Sci. 2022;43(7):4315–21. https://doi.org/10.1007/s10072-022-05906-2.

    Article  Google Scholar 

  85. Yüksel MM, Sun S, Latchoumane C, Boch J, Courtine G, Raffin EE, Hummel FC. Low-intensity focused ultrasound neuromodulation for stroke recovery: a novel deep brain stimulation approach for neurorehabilitation? IEEE Open J Eng Med Biol. 2023;4:300–18. https://doi.org/10.1109/OJEMB.2023.3263690.

    Article  Google Scholar 

  86. Park TY, Koh H, Lee W, Park SH, Chang WS, Kim H. Real-time acoustic simulation framework for tFUS: a feasibility study using navigation system. NeuroImage. 2023;282:120411. https://doi.org/10.1016/j.neuroimage.2023.120411.

    Article  Google Scholar 

  87. Sato T, Shapiro MG, Tsao DY. Ultrasonic neuromodulation causes widespread cortical activation via an indirect auditory mechanism. Neuron. 2018;98(5):1031–1041. https://doi.org/10.1016/j.neuron.2018.05.009.

    Article  Google Scholar 

  88. Johnstone A, Nandi T, Martin E, Bestmann S, Stagg C, Treeby B. A range of pulses commonly used for human transcranial ultrasound stimulation are clearly audible. Brain Stimul. 2021;14(5):1353–5. https://doi.org/10.1016/j.brs.2021.08.015.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by Brain Pool program funded by the Ministry of Science and ICT through the National Research Foundation of Korea (RS-2023-00221187).

Author information

Author notes

  1. Kyuheon Lee and Tae Young Park contributed equally to this work.

Authors and Affiliations

  1. Bionics Research Center, Biomedical Research Division, Korea Institute of Science and Technology, 5 Hwarangro 14-gil, Seongbuk-gu, Seoul, 02792, South Korea

    Kyuheon Lee, Tae Young Park, Wonhye Lee & Hyungmin Kim

  2. Department of Brain and Cognitive Engineering, Korea University, Seoul, South Korea

    Kyuheon Lee

  3. Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul, South Korea

    Tae Young Park & Hyungmin Kim

  4. Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Wonhye Lee

Authors
  1. Kyuheon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tae Young Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wonhye Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hyungmin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wonhye Lee or Hyungmin Kim.

Ethics declarations

Competing interests

The authors have declared that no competing interest exists.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, K., Park, T.Y., Lee, W. et al. A review of functional neuromodulation in humans using low-intensity transcranial focused ultrasound. Biomed. Eng. Lett. 14, 407–438 (2024). https://doi.org/10.1007/s13534-024-00369-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13534-024-00369-0

Keywords

Search

Navigation