Nonlinearities and Timescales in Temporal Interference Stimulation

ABSTRACT In temporal interference (TI) stimulation, neuronal cells react to two interfering sinusoidal electric fields with a slightly different frequency. It was previously seen that for the same input intensity, the neurons do not react to a purely sinusoidal signal. This study aims to get a better understanding of the mechanism underlying TI neuromodulation, which is largely unknown. To this end, single-compartment models are used to simulate computationally the response of neurons to the sinusoidal and TI waveform. This study compares different neuron models to get insight into which models are able to reproduce the experimental observations. It was found that integrate- and-fire models do not entirely reflect the experimental behavior while the Hodgkin-Huxley and Frankenhaeuser-Huxley model do reflect this behavior. Changing the characteristics of the ion gates in the Frankenhaeuser-Huxley model alters the response to both the sinusoidal and TI signal, possibly reducing the firing threshold of the sinusoidal input below that of the TI input. The model results show that TI stimulation is not qualitatively impacted by nonlinearities in the current-voltage relation. In contrast, ion channels have a significant impact on the neuronal response. This paper makes advances both in terms of biophysical insight into the neuron as well as the insight in computational modelling of TI stimulation.