Evidence map›Paper›PMID 42079128›Full record

ArticlebioRxiv : the preprint server for biology2026

Temporal Interference Stimulation of the Motor Cortex Produces Frequency-Dependent Analgesia.

Amin Dehghani, David M Gantz, Ethan K Murphy, Ryan J Halter, Tor D Wager

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Amin DehghaniDepartment of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.ORCID 0000-0002-5638-3624
David M GantzDepartment of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.ORCID 0009-0007-5622-7086
Ethan K MurphyThayer School of Engineering and Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.ORCID 0000-0002-4635-3384
Ryan J HalterThayer School of Engineering and Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
Tor D WagerDepartment of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.ORCID 0000-0002-1936-5574

Funding

The neural bases of placebo effects and their relation to regulatory processesR37MH076136 · NIMH · DARTMOUTH COLLEGE · PI TOR D. WAGER · 2024 to 2026
$2.4M
NIMH NIH HHS R37 MH076136
6 · The paper itself

Abstract

Background: Transcranial temporal interference stimulation (tTIS) is an emerging noninvasive neuromodulation approach that enables focal, frequency-specific modulation of deep brain regions, offering a novel method for investigating therapeutic mechanisms underlying brain and mental health disorders. Pain is a key target because it is a feature of multiple disorders and is increasingly understood to depend on brain circuits. Here, we tested the effects of tTIS on bilateral evoked pain, capitalizing on converging evidence from human and animal studies indicating that the primary motor cortex (M1) contains body-wide inter-effector regions and has descending projections to regions implicated in nociceptive, motivational, and autonomic processing, making it a key cortical target for pain modulation. Methods: We conducted a pre-registered, triple-blind, randomized crossover study (N = 32, 160 study sessions), investigating frequency-dependent effects of tTIS applied to the left M1 on experimentally evoked thermal pain in healthy adults. We tested four stimulation frequencies (10 Hz, 20 Hz, 70 Hz, and sham) on separate days (>10,000 pain trials total). Noxious heat was applied to both the right and left forearms using individually calibrated temperatures both pre- and post-stimulation. Results: Active tTIS produced significant analgesia at all stimulation frequencies (10 Hz, 20 Hz, and 70 Hz) relative to sham (Cohen's d = 0.46-0.82, all p < 0.05). 10 Hz produced the greatest reduction (d = 0.82), and both 10 Hz and 20 Hz produced more analgesia than 70 Hz (d = 0.44 and 0.38, respectively; p < 0.05). Stimulation-related sensations were equivalent across frequencies, and participants were blind to condition. Pain reductions remained stable over a ~40-min post-stimulation period and were bilateral, consistent with stimulation of body-wide inter-effector regions. Conclusions: These results provide the first evidence that tTIS can reliably reduce experimental pain perception in humans in a frequency-dependent manner, providing a foundation for noninvasive pain modulation with tTIS.

Indexed as

analgesiaexperimental painfrequency-dependentinter-effector regionsipsilateral–contralateralneuromodulationNoxious heatpain modulationprimary motor cortex (M1)Temporal interference stimulation (tTIS)

Identifiers

PMID42079128
PMCPMC13131613

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Registered trials

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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.