The same biophysical mechanism is involved in both temporal interference and direct kHz stimulation of peripheral nerves

Temporal interference stimulation (TIS) is a promising noninvasive method for neurostimulation, yet its mechanism remains debated. TIS is often described as delivering low-frequency stimulation via the amplitude modulation (beat frequency) of interfering kHz carriers. However, this view overlooks known biophysical responses to kHz stimuli. Here, we test modulated (TIS) and unmodulated kHz waveforms on peripheral nerves in Locusta migratoria and in human sensory and motor pathways. We find that stimulation thresholds and strength-frequency relationships are governed by the kHz carrier itself, with minimal dependence on amplitude modulation. Across 0.5-12.5 kHz in humans and up to 100 kHz in locusts, all waveforms show overlapping excitation behavior, indicating a shared underlying mechanism. Our results support the hypothesis that suprathreshold TIS acts through kHz rectification, rather than envelope-specific effects. We further explore modulation frequency resonance, tonic vs. phasic effects, and suggest that two-electrode premodulated kHz may offer advantages over multielectrode TIS approaches.

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Publication Details

Journal
Nature Communications
Published
2025-10-09
DOI
https://doi.org/10.1038/s41467-025-64059-w
Citations
4
Primary Topic
Muscle activation and electromyography studies
Type
article
Field-Weighted Citation Impact
2.70

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article

The same biophysical mechanism is involved in both temporal interference and direct kHz stimulation of peripheral nerves

Aleksandar Opančar, Eric Daniel Głowacki, Vedran Đerek, Jan Trajlínek et al.
4 citations
Nature Communications
Muscle activation and electromyography studies
2.70
article

The same biophysical mechanism is involved in both temporal interference and direct kHz stimulation of peripheral nerves

Aleksandar Opančar, Eric Daniel Głowacki, Vedran Đerek, Jan Trajlínek, Petra Ondráčková, David Rose
article en
4 citations

Abstract

Temporal interference stimulation (TIS) is a promising noninvasive method for neurostimulation, yet its mechanism remains debated. TIS is often described as delivering low-frequency stimulation via the amplitude modulation (beat frequency) of interfering kHz carriers. However, this view overlooks known biophysical responses to kHz stimuli. Here, we test modulated (TIS) and unmodulated kHz waveforms on peripheral nerves in Locusta migratoria and in human sensory and motor pathways. We find that stimulation thresholds and strength-frequency relationships are governed by the kHz carrier itself, with minimal dependence on amplitude modulation. Across 0.5-12.5 kHz in humans and up to 100 kHz in locusts, all waveforms show overlapping excitation behavior, indicating a shared underlying mechanism. Our results support the hypothesis that suprathreshold TIS acts through kHz rectification, rather than envelope-specific effects. We further explore modulation frequency resonance, tonic vs. phasic effects, and suggest that two-electrode premodulated kHz may offer advantages over multielectrode TIS approaches.

Nature CommunicationsVol. 16(1)
Central European Institute of Technology (CZ), University of Zagreb (HR), University Hospital Brno (CZ), Czech Academy of Sciences, Institute of Scientific Instruments (CZ), St. Anne's University Hospital Brno (CZ), Brno University of Technology (CZ)
European Commission, Ministerstvo Školství, Mládeže a Tělovýchovy, Grantová Agentura České Republiky, Hrvatska Zaklada za Znanost, European Regional Development Fund
Openalex Percentile: Top 9%
Muscle activation and electromyography studies
2.70
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