Evidence map›Paper›PMID 41167554›Full record

SynthesisBrain stimulation

Human applications of transcranial temporal interference stimulation: A systematic review.

Ilya Demchenko, Ishaan Tailor, Sina Chegini, Haochen Yu, Fatemeh Gholamali Nezhad, Alice Rueda, Anne Kever, Sridhar Krishnan, Abhishek Datta, Jed A Meltzer and 8 more

Abstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Review
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  6. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Ilya DemchenkoInterventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, 193 Yonge Street, Toronto, ON, M5B 1M4, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent, Toronto, ON, M5S 3H2, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), Keenan Research Centre for Biomedical Science, St. Michael's Hospital - Unity Health Toronto, 209 Victoria Street, Toronto, ON, M5B 1X3, Canada. Electronic address: ilya.demchenko@unityhealth.to.
Ishaan TailorInterventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, 193 Yonge Street, Toronto, ON, M5B 1M4, Canada. Electronic address: ishaan.tailor@rutgers.edu.
Sina CheginiInterventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, 193 Yonge Street, Toronto, ON, M5B 1M4, Canada. Electronic address: schegin@uwo.ca.
Haochen YuInterventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, 193 Yonge Street, Toronto, ON, M5B 1M4, Canada. Electronic address: Haochen.Yu@unityhealth.to.
Fatemeh Gholamali NezhadInterventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, 193 Yonge Street, Toronto, ON, M5B 1M4, Canada. Electronic address: Fatemeh.Gholamalinezhad@unityhealth.to.
Alice RuedaInterventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, 193 Yonge Street, Toronto, ON, M5B 1M4, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), Keenan Research Centre for Biomedical Science, St. Michael's Hospital - Unity Health Toronto, 209 Victoria Street, Toronto, ON, M5B 1X3, Canada. Electronic address: Alice.Rueda@unityhealth.to.
Anne KeverBARLO Multiple Sclerosis Centre and Division of Neurology, St. Michael's Hospital - Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada; Department of Psychology, Faculty of Arts & Science, University of Toronto, 100 St. George Street, Toronto, ON, M5S 3G3, Canada. Electronic address: Anne.Kever@unityhealth.to.
Sridhar KrishnanInstitute for Biomedical Engineering, Science and Technology (iBEST), Keenan Research Centre for Biomedical Science, St. Michael's Hospital - Unity Health Toronto, 209 Victoria Street, Toronto, ON, M5B 1X3, Canada; Department of Electrical, Computer, and Biomedical Engineering, Toronto Metropolitan University, 350 Victoria Street, ON, Toronto, M5B 2K3, Canada. Electronic address: krishnan@torontomu.ca.
Abhishek DattaResearch and Development, Soterix Medical, Inc., 1480 U.S. Highway 9 North, Woodbridge, NJ, 07095, United States; Department of Biomedical Engineering, City College of New York, 160 Convent Avenue, New York, NY, 10031, United States. Electronic address: adatta@soterixmedical.com.
Jed A MeltzerInstitute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent, Toronto, ON, M5S 3H2, Canada; Department of Psychology, Faculty of Arts & Science, University of Toronto, 100 St. George Street, Toronto, ON, M5S 3G3, Canada; Rotman Research Institute, Baycrest Hospital, 3560 Bathurst Street, Toronto, ON, M6A 1W1, Canada. Electronic address: jmeltzer@research.baycrest.org.
Simon J GrahamInstitute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent, Toronto, ON, M5S 3H2, Canada; Physical Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada; Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, 101 College Street, Toronto, ON, M5G 2C4, Canada. Electronic address: sgraham@sri.utoronto.ca.
Tom A SchweizerInstitute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent, Toronto, ON, M5S 3H2, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital - Unity Health Toronto, 209 Victoria Street, Toronto, ON, M5B 1X3, Canada; Neuroscience Research Program, St. Michael's Hospital - Unity Health Toronto, 209 Victoria Street, Toronto, ON, M5B 1X3, Canada; Division of Neurosurgery, Department of Surgery, Temerty Faculty of Medicine, University of Toronto, 149 College Street, Toronto, ON, M5T 1P5, Canada. Electronic address: Tom.Schweizer@unityhealth.to.
Sumientra RampersadDepartment of Physics, University of Massachusetts Boston, 100 William T Morrissey Boulevard, Boston, MA, 02125, United States; Department of Electrical and Computer Engineering, Northeastern University, 100 Forsyth Street, Boston, MA, 02115, United States. Electronic address: s.rampersad@northeastern.edu.
Edward S BoydenDepartment of Brain and Cognitive Sciences, Media Arts and Sciences, and Biological Engineering, McGovern Institute for Brain Research and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, United States; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD, 20815, United States. Electronic address: edboyden@mit.edu.
Ines R ViolanteSchool of Biomedical Engineering & Imaging Sciences, King's College London, Strand, London, WC2R 2LS, United Kingdom; School of Psychology, Faculty of Health and Medical Sciences, University of Surrey, 30 Priestley Road, Guildford, GU2 7YH, United Kingdom. Electronic address: ines.violante@kcl.ac.uk.
Robert ChenInstitute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent, Toronto, ON, M5S 3H2, Canada; Krembil Brain Institute, Toronto Western Hospital - University Health Network, 135 Nassau Street, Toronto, ON, M5T 1M8, Canada; Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital - University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S6, Canada; Division of Neurology, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent West, Toronto, ON, M5S 3H2, Canada. Electronic address: robert.chen@uhn.ca.
Andres M LozanoInstitute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent, Toronto, ON, M5S 3H2, Canada; Division of Neurosurgery, Department of Surgery, Temerty Faculty of Medicine, University of Toronto, 149 College Street, Toronto, ON, M5T 1P5, Canada; Krembil Brain Institute, Toronto Western Hospital - University Health Network, 135 Nassau Street, Toronto, ON, M5T 1M8, Canada. Electronic address: Andres.Lozano@uhn.ca.
Venkat BhatInterventional Psychiatry Program, St. Michael's Hospital - Unity Health Toronto, 193 Yonge Street, Toronto, ON, M5B 1M4, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, 6 Queen's Park Crescent, Toronto, ON, M5S 3H2, Canada; Institute for Biomedical Engineering, Science and Technology (iBEST), Keenan Research Centre for Biomedical Science, St. Michael's Hospital - Unity Health Toronto, 209 Victoria Street, Toronto, ON, M5B 1X3, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital - Unity Health Toronto, 209 Victoria Street, Toronto, ON, M5B 1X3, Canada; Neuroscience Research Program, St. Michael's Hospital - Unity Health Toronto, 209 Victoria Street, Toronto, ON, M5B 1X3, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada. Electronic address: venkat.bhat@utoronto.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMany neurological and psychiatric disorders involve dysregulation of subcortical structures. Transcranial temporal interference stimulation (tTIS) is a novel, non-invasive method developed to selectively modulate deep brain regions and associated neural circuits.

methodsA systematic review was conducted to evaluate human applications of tTIS (PROSPERO ID: CRD42024559678). MEDLINE, Embase, APA PsycINFO, CENTRAL, ClinicalTrials.gov, and WHO ICTRP were searched up to December 12, 2024. Studies involving human applications of tTIS were eligible. Methodological quality was appraised using the National Institutes of Health and modified Oxford Centre for Evidence-Based Medicine tools.

resultsForty-eight records were reviewed (20 published studies, 28 ongoing trials). Of published studies, 16 single-session and 4 multi-session studies assessed safety, mechanistic outcomes, or therapeutic effects of tTIS in 820 participants. Stimulation was most commonly delivered at beta (20 Hz) or gamma (30-130 Hz) envelope frequencies. Neuroimaging studies support target engagement of the motor cortex, basal ganglia, and hippocampus in humans, particularly when stimulation is paired with behavioural tasks. Preliminary clinical findings in small samples demonstrated acute symptom improvements in bradykinesia and tremor within 60 min following a single tTIS session in Parkinson's disease and essential tremor. Reported adverse events across studies were mild (e.g., tingling, itching). Emerging trials increasingly utilize multi-session protocols (2-40 sessions) and are extending tTIS to patients with neurological and psychiatric disorders, particularly epilepsy and depression.

conclusionsPhase 1 studies demonstrate that tTIS is safe, well-tolerated, and capable of engaging deep brain targets in humans. Well-controlled Phase 2 trials are needed to assess its therapeutic potential in patient populations.

Indexed as

Transcranial Direct Current StimulationHumansMental DisordersTranscranial Magnetic StimulationBrainClinical studyDeep brain stimulationElectric stimulationHumansSystematic reviewTemporal interference

Identifiers

PMID41167554

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.