Kilohertz electrical stimulation drives widespread neuronal activation and temporal interference imposes focal rhythmic modulation
Abstract
Temporal interference (TI) stimulation has attracted attention as a non-invasive approach that can target deep brain structures through interacting kilohertz-frequency electric fields. Its basic premise is that TI stimulation evokes neuronal responses through low-frequency amplitude modulation (AM), while the underlying kilohertz-frequency stimulation is ineffective to induce activity, the latter of which has not been tested rigorously at the cellular level. Here, we combined two-photon imaging in mouse models with immunohistochemistry and computational modeling to characterize spatiotemporal patterns of neuronal responses during TI stimulation. We found that kilohertz-frequency stimulation was sufficient to evoke activity without AM. In contrast, AM organized neuronal activity into rhythmic responses at AM frequency, with the strongest entrainment near the center of interference. Thus, kilohertz-frequency stimulation can drive widespread neuronal activation, upon which TI imposes focal rhythmic modulation. Our results provide a framework for refining TI stimulation and highlight the potential of kilohertz-frequency stimulation for brain stimulation.
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BibTeX
@misc{yoshimoto2026kilohertz,
title = {{Kilohertz electrical stimulation drives widespread neuronal activation and temporal interference imposes focal rhythmic modulation}},
author = {Ryohei Yoshimoto and Matthew A. Stern and Thomas Eggers and Emma Acerbo and Nealen Laxpati and Ken Berglund and Claire-Anne Gutekunst},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.15.759497},
url = {https://www.biorxiv.org/content/10.64898/2026.10.15.759497v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Kilohertz electrical stimulation drives widespread neuronal activation and temporal interference imposes focal rhythmic modulation
AU - Ryohei Yoshimoto
AU - Matthew A. Stern
AU - Thomas Eggers
AU - Emma Acerbo
AU - Nealen Laxpati
AU - Ken Berglund
AU - Claire-Anne Gutekunst
PY - 2026
DA - 2026/10/15
PB - bioRxiv
DO - 10.64898/2026.10.15.759497
UR - https://www.biorxiv.org/content/10.64898/2026.10.15.759497v1
AB - Temporal interference (TI) stimulation has attracted attention as a non-invasive approach that can target deep brain structures through interacting kilohertz-frequency electric fields. Its basic premise is that TI stimulation evokes neuronal responses through low-frequency amplitude modulation (AM), while the underlying kilohertz-frequency stimulation is ineffective to induce activity, the latter of which has not been tested rigorously at the cellular level. Here, we combined two-photon imaging in mouse models with immunohistochemistry and computational modeling to characterize spatiotemporal patterns of neuronal responses during TI stimulation. We found that kilohertz-frequency stimulation was sufficient to evoke activity without AM. In contrast, AM organized neuronal activity into rhythmic responses at AM frequency, with the strongest entrainment near the center of interference. Thus, kilohertz-frequency stimulation can drive widespread neuronal activation, upon which TI imposes focal rhythmic modulation. Our results provide a framework for refining TI stimulation and highlight the potential of kilohertz-frequency stimulation for brain stimulation.
SN - 2692-8205
ER -