Manipulating Excitation-Inhibition Balance by Temporal Interference Brain Stimulation at Different Frequencies

Temporal interference brain stimulation (TIBS) is a non-invasive technique that can reach deep brain targets by using two kilohertz-frequency currents delivered through scalp electrodes, creating a low-frequency amplitude envelope. Previous research has focused on suppressing targets at 130 Hz, similar to conventional deep brain stimulation, but the specific neurons recruited at different frequencies by TIBS have remained unknown.

To address this question, researchers recorded from genetically defined populations in the mouse hippocampus across envelope frequencies ranging from 10 to 130 Hz. They employed cell-type-specific fiber photometry, retrograde viral labelling, and immunohistochemistry to observe the activity of various neuron types.

Their findings revealed that a 10 Hz envelope drives both glutamatergic pyramidal neurons and GABAergic interneurons. However, at frequencies above 20 Hz, pyramidal activity decreases below baseline, while interneuron activity continues to rise, with both groups reaching their maximum activity at 100 Hz. Retrogradely labelled cortical neurons projecting to CA2 showed weak responses and no frequency dependence, indicating that this switch in activity occurs within the local circuit.

By identifying parvalbumin interneurons as the population recruited at 100 Hz through c-fos co-staining, the researchers concluded that TIBS envelope frequency is a tunable parameter for modulating the excitation-inhibition balance in the brain. These findings could help guide clinical decisions regarding the optimal envelope frequency for TIBS in future research.