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Temporal Interference Brain Stimulation

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Temporal Interference Brain Stimulation
TIS modelled on a bust of the human head – an electric current oscillating at 2010Hz is delivered to the right side of the head and another oscillating at 2000Hz is delivered to the left side. The stimulation target is the right visual cortex, where there is maximal temporal interference between both oscillations; the interfering waveform is visualised on the monitor.

Temporal interference brain stimulation (TI) is a non-invasive form of deep brain stimulation (DBS). External electrodes apply high-frequency alternating currents of slightly different frequencies to the brain, and the superposition of the two waves produces a low-frequency envelope. As neurones are responsive to low-frequency electrical signals but not high-frequency signals[1], TI can use this envelope to focally stimulate deep brain tissues without impacting the overlying and surrounding ones. Since the stimulation strength depends not only on the absolute amplitude but also on the relative amplitude and orientation of the applied fields, this enables precise three-dimensional targeting of deep brain regions[2].

Technical Details

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TI stimulation is delivered by using two current sources, which both operate at high frequency with a defined difference in frequency between them. This frequency difference creates an envelope which modulates the target region. Frequencies of operation are typically in the kHz range.[3] The currents are delivered to the scalp using carbon-rubber or silver-silver chloride electrodes. Due to the high frequency and low amplitude of the currents (1-2 mA), there is typically little sensation on the skin compared to other methods, like tACS.

The target region will be dependent on the current densities (the size of the electrodes for a given current amplitude) and the physical location of the electrodes on the scalp. This can be modelled in software such as Sim4Life or SimNIBS.

Potential Applications

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DBS via implanted electrodes is already used worldwide to treat patients with severe neurological and psychiatric disorders such as Parkinson's disease and Obsessive–compulsive disorder (OCD)[4][5], and has been investigated as a treatment option for Alzheimer's disease[6][7] and depression[8][9], but its invasiveness makes widespread clinical use and deployment in research impractical.[10] TI is posited as an alternative treatment to invasive implants for epilepsy patients who are ineligible for resective surgery, or for whom such surgery was unsuccessful.[11]

Manufacturers

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  • TI Solutions
  • Soterix Medical
  • neuroConnea

Safety

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Compared to other non-invasive stimulation methods, experiments suggest that adverse effects are generally rare, with just a few incidences of mild common stimulation side effects such as tingling or fatigue.[10] Below certain frequency thresholds, exposure conditions appear to be equivalent to those known to be safe in other stimulation methods.[12]

History

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The first TI stimulator, built in 2017

Low intensity electrical stimulation is believed to have originated in the studies of galvanic currents in humans and animals as conducted by Giovanni Aldini, Alessandro Volta and others in the 18th century. Aldini had experimented with galvanic head current as early as 1794 (upon himself) and reported the successful treatment of patients with melancholia using direct low-intensity currents in 1804.[13]

Due to the rise of pharmaceutical treatments for depression, anxiety and insomnia, such as Prozac in the 1980s and Ambien in the 1990s, electrostimulation was not a well-known treatment for doctors and patients. During the mid-2000s, the combination of pharmaceutical brands becoming generic and Internet advertising caused CES devices to gain popularity.

In 2017, TI methods were validated in rodents and posited as an alternative electric stimulation option. More recent tests have showed that patients are just as likely to think the machine is switched on as switched off, given the minimal sensation on the skin.

Limitations

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  1. ^ Hutcheon, B.; Yarom, Y. (2000-05). "Resonance, oscillation and the intrinsic frequency preferences of neurons". Trends in Neurosciences. 23 (5): 216–222. doi:10.1016/s0166-2236(00)01547-2. ISSN 0166-2236. PMID 10782127. {{cite journal}}: Check date values in: |date= (help)
  2. ^ Grossman, Nir; Bono, David; Dedic, Nina; Kodandaramaiah, Suhasa B.; Rudenko, Andrii; Suk, Ho-Jun; Cassara, Antonino M.; Neufeld, Esra; Kuster, Niels; Tsai, Li-Huei; Pascual-Leone, Alvaro; Boyden, Edward S. (2017-06-01). "Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields". Cell. 169 (6): 1029–1041.e16. doi:10.1016/j.cell.2017.05.024. ISSN 1097-4172. PMC 5520675. PMID 28575667.
  3. ^ Grossman, Nir (2023-01-01). "Principles, preclinical validation, and mechanism of TI brain stimulation". Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 16 (1): 122–123. doi:10.1016/j.brs.2023.01.032. ISSN 1935-861X.
  4. ^ Benabid, Alim Louis; Chabardes, Stephan; Mitrofanis, John; Pollak, Pierre (2009-01-01). "Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease". The Lancet Neurology. 8 (1): 67–81. doi:10.1016/S1474-4422(08)70291-6. ISSN 1474-4422.
  5. ^ Greenberg, B. D.; Gabriels, L. A.; Malone, D. A.; Rezai, A. R.; Friehs, G. M.; Okun, M. S.; Shapira, N. A.; Foote, K. D.; Cosyns, P. R.; Kubu, C. S.; Malloy, P. F.; Salloway, S. P.; Giftakis, J. E.; Rise, M. T.; Machado, A. G. (2010-01). "Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience". Molecular Psychiatry. 15 (1): 64–79. doi:10.1038/mp.2008.55. ISSN 1476-5578. {{cite journal}}: Check date values in: |date= (help)
  6. ^ Kuhn, J.; Hardenacke, K.; Lenartz, D.; Gruendler, T.; Ullsperger, M.; Bartsch, C.; Mai, J. K.; Zilles, K.; Bauer, A.; Matusch, A.; Schulz, R.-J.; Noreik, M.; Bührle, C. P.; Maintz, D.; Woopen, C. (2015-03). "Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia". Molecular Psychiatry. 20 (3): 353–360. doi:10.1038/mp.2014.32. ISSN 1476-5578. {{cite journal}}: Check date values in: |date= (help)
  7. ^ Lozano, Andres M.; Fosdick, Lisa; Chakravarty, M. Mallar; Leoutsakos, Jeannie-Marie; Munro, Cynthia; Oh, Esther; Drake, Kristen E.; Lyman, Christopher H.; Rosenberg, Paul B.; Anderson, William S.; Tang-Wai, David F.; Pendergrass, Jo Cara; Salloway, Stephen; Asaad, Wael F.; Ponce, Francisco A. (2016-09-06). "A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease". Journal of Alzheimer’s Disease. 54 (2): 777–787. doi:10.3233/JAD-160017. ISSN 1387-2877. PMC 5026133. PMID 27567810.{{cite journal}}: CS1 maint: PMC format (link)
  8. ^ Scangos, Katherine W.; Khambhati, Ankit N.; Daly, Patrick M.; Makhoul, Ghassan S.; Sugrue, Leo P.; Zamanian, Hashem; Liu, Tony X.; Rao, Vikram R.; Sellers, Kristin K.; Dawes, Heather E.; Starr, Philip A.; Krystal, Andrew D.; Chang, Edward F. (2021-10). "Closed-loop neuromodulation in an individual with treatment-resistant depression". Nature Medicine. 27 (10): 1696–1700. doi:10.1038/s41591-021-01480-w. ISSN 1546-170X. PMC 11219029. PMID 34608328. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  9. ^ Mayberg, Helen S.; Lozano, Andres M.; Voon, Valerie; McNeely, Heather E.; Seminowicz, David; Hamani, Clement; Schwalb, Jason M.; Kennedy, Sidney H. (2005-03-03). "Deep Brain Stimulation for Treatment-Resistant Depression". Neuron. 45 (5): 651–660. doi:10.1016/j.neuron.2005.02.014. ISSN 0896-6273. PMID 15748841.
  10. ^ a b Violante, Ines R.; Alania, Ketevan; Cassarà, Antonino M.; Neufeld, Esra; Acerbo, Emma; Carron, Romain; Williamson, Adam; Kurtin, Danielle L.; Rhodes, Edward; Hampshire, Adam; Kuster, Niels; Boyden, Edward S.; Pascual-Leone, Alvaro; Grossman, Nir (2023-11). "Non-invasive temporal interference electrical stimulation of the human hippocampus". Nature Neuroscience. 26 (11): 1994–2004. doi:10.1038/s41593-023-01456-8. ISSN 1546-1726. {{cite journal}}: Check date values in: |date= (help)
  11. ^ Acerbo, Emma; Jegou, Aude; Luff, Charlotte; Dzialecka, Patrycja; Botzanowski, Boris; Missey, Florian; Ngom, Ibrahima; Lagarde, Stanislas; Bartolomei, Fabrice; Cassara, Antonino; Neufeld, Esra; Jirsa, Viktor; Carron, Romain; Grossman, Nir; Williamson, Adam (2022-08-17). "Focal non-invasive deep-brain stimulation with temporal interference for the suppression of epileptic biomarkers". Frontiers in Neuroscience. 16. doi:10.3389/fnins.2022.945221. ISSN 1662-453X.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ^ Cassarà, Antonino M.; Newton, Taylor H.; Zhuang, Katie; Regel, Sabine J.; Achermann, Peter; Pascual-Leone, Alvaro; Kuster, Niels; Neufeld, Esra (2025). "Recommendations for the Safe Application of Temporal Interference Stimulation in the Human Brain Part II: Biophysics, Dosimetry, and Safety Recommendations". Bioelectromagnetics. 46 (1): e22536. doi:10.1002/bem.22536. ISSN 1521-186X. PMC 11733664. PMID 39810626.{{cite journal}}: CS1 maint: PMC format (link)
  13. ^ Zaghi, Soroush; Acar, Mariana; Hultgren, Brittney; Boggio, Paulo S.; Fregni, Felipe (2010-06). "Noninvasive Brain Stimulation with Low-Intensity Electrical Currents: Putative Mechanisms of Action for Direct and Alternating Current Stimulation". The Neuroscientist. 16 (3): 285–307. doi:10.1177/1073858409336227. ISSN 1073-8584. {{cite journal}}: Check date values in: |date= (help)
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