Excitation and Polarization of Isolated Neurons by High-Frequency Sine Waves for Temporal Interference Stimulation

Authors

Iurii Semenov, Old Dominion UniversityFollow
Vitalii Kim, University of California, Irvine
Giedre Silkuniene, Old Dominion UniversityFollow
Andrei G. Pakhomov, Old Dominion UniversityFollow

Document Type

Article

Publication Date

2025

Publication Title

Cell Reports Physical Science

Volume

6

Issue

7

Pages

102660 (15 pp.)

DOI

10.1016/j.xcrp.2025.102660

Abstract

The capacity of temporal interference (TI) stimulation to target deep brain regions without affecting nearby surface electrodes remains uncertain. Using artifact-free optical recording, we compare excitation patterns and thresholds in hippocampal neurons stimulated by “pure” and amplitude-modulated sine waves, representing TI waveforms near electrodes and at the target, respectively. We show that pure 2- and 20-kHz sine waves induce repetitive firing at rates that increase up to 60–90 Hz with stronger electric fields. Beyond this limit, action potentials merge into sustained depolarization, resulting in an excitation block. Modulating the sine waves at 20 Hz aligns firing with amplitude “beats” and prevents the excitation block but does not lower excitation thresholds. Thus, off-target TI effects appear unavoidable, though the patterns of neuronal excitation and downstream effects may differ from those at the target. We further analyze membrane charging and relaxation kinetics at nanoscale resolution and confirm an excitation mechanism independent of envelope extraction.

Rights

© 2025 The Authors

This is an open access article under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.

Data Availability

Article states: "

• Raw images have been deposited at the DANDI Archive (DANDI: 001030, 001031, 001032, 001033, 001034, 001035, 001271, 001272, 001273, and 001274), accessible at https://dandiarchive.org/, and are publicly available as of the date of publication.
• All data reported in this paper will be shared by the lead contact upon request.
• This paper does not report original code.
• Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request."

Original Publication Citation

Semenov, I., Kim, V., Silkuniene, G., & Pakhomov, A. G. (2025). Excitation and polarization of isolated neurons by high-frequency sine waves for temporal interference stimulation. Cell Reports Physical Science, 6(7),102660. https://doi.org/10.1016/j.xcrp.2025.102660

Repository Citation

Semenov, Iurii; Kim, Vitalii; Silkuniene, Giedre; and Pakhomov, Andrei G., "Excitation and Polarization of Isolated Neurons by High-Frequency Sine Waves for Temporal Interference Stimulation" (2025). Bioelectrics Publications. 378.
https://digitalcommons.odu.edu/bioelectrics_pubs/378

ORCID

0000-0002-0302-1355 (Semenov), 0000-0001-8436-9718 (Silkuniene),