Manipulating Excitation-Inhibition Balance by Temporal Interference Brain Stimulation at Different Frequencies
- 1National Yang Ming Chiao Tung University
Abstract
Temporal interference brain stimulation (TIBS) is a non-invasive neuromodulation approach that can reach deep brain targets by delivering two kilohertz-frequency currents through scalp electrodes, producing a low-frequency amplitude envelope where the fields intersect. Conventional deep brain stimulation suppresses its targets at 130 Hz, and TIBS studies of epilepsy have adopted the same range. However, which neurons TIBS recruits at different frequencies has never been measured. Here, we recorded from genetically defined populations in the mouse hippocampus across envelope frequencies from 10 to 130 Hz, using cell-type-specific fiber photometry, retrograde viral labelling, and immunohistochemistry. A 10 Hz envelope drives both glutamatergic pyramidal neurons and GABAergic interneurons. From 20 Hz onward pyramidal activity falls below baseline while interneuron activity keeps rising, and the two separate maximally at 100 Hz. Retrogradely labelled cortical neurons projecting to CA2 respond weakly and show no frequency dependence, placing the switch inside the local circuit, and c-fos co-staining identifies parvalbumin interneurons as the population recruited at 100 Hz. Overall, this study provides the first in vivo cell-type-resolved evidence for envelope-frequency-dependent neuromodulation and shows that TIBS envelope frequency is a tunable parameter for excitation-inhibition balance. These findings can guide the choice of envelope frequency in the clinical research of TIBS.
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BibTeX
@misc{fang2026manipulating,
title = {{Manipulating Excitation-Inhibition Balance by Temporal Interference Brain Stimulation at Different Frequencies}},
author = {Y.-C. Fang and L. Chou and Y.-Y. Tseng and P.-H. Chu and Y.-M. Fang and H.-Y. Chen and Y.-T. Liao and C.-H. Huang and P.-H. Chiang},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.748902},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.748902v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Manipulating Excitation-Inhibition Balance by Temporal Interference Brain Stimulation at Different Frequencies
AU - Y.-C. Fang
AU - L. Chou
AU - Y.-Y. Tseng
AU - P.-H. Chu
AU - Y.-M. Fang
AU - H.-Y. Chen
AU - Y.-T. Liao
AU - C.-H. Huang
AU - P.-H. Chiang
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.748902
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.748902v1
AB - Temporal interference brain stimulation (TIBS) is a non-invasive neuromodulation approach that can reach deep brain targets by delivering two kilohertz-frequency currents through scalp electrodes, producing a low-frequency amplitude envelope where the fields intersect. Conventional deep brain stimulation suppresses its targets at 130 Hz, and TIBS studies of epilepsy have adopted the same range. However, which neurons TIBS recruits at different frequencies has never been measured. Here, we recorded from genetically defined populations in the mouse hippocampus across envelope frequencies from 10 to 130 Hz, using cell-type-specific fiber photometry, retrograde viral labelling, and immunohistochemistry. A 10 Hz envelope drives both glutamatergic pyramidal neurons and GABAergic interneurons. From 20 Hz onward pyramidal activity falls below baseline while interneuron activity keeps rising, and the two separate maximally at 100 Hz. Retrogradely labelled cortical neurons projecting to CA2 respond weakly and show no frequency dependence, placing the switch inside the local circuit, and c-fos co-staining identifies parvalbumin interneurons as the population recruited at 100 Hz. Overall, this study provides the first in vivo cell-type-resolved evidence for envelope-frequency-dependent neuromodulation and shows that TIBS envelope frequency is a tunable parameter for excitation-inhibition balance. These findings can guide the choice of envelope frequency in the clinical research of TIBS.
ER -