Nonlinearities and timescales in neural models of temporal interference stimulation.

In temporal interference (TI) stimulation, neuronal cells react to two interfering sinusoidal electric fields with a slightly different frequency ( f 1 ${f}_{1}$ , f 2 ${f}_{2}$ in the range of about 1-4 kHz, ∣ f 1 - f 2 ∣ $| {f}_{1}-{f}_{2}| $ in the range of about 1-100 Hz). It has been previously observed that for the same input intensity, the neurons do not react to a purely sinusoidal signal at f 1 ${f}_{1}$ or f 2 ${f}_{2}$ . This study seeks a better understanding of the largely unknown mechanisms underlying TI neuromodulation. To this end, single-compartment models are used to simulate computationally the response of neurons to the sinusoidal and TI waveform. This study compares five different neuron models: Hodgkin-Huxley (HH), Frankenhaeuser-Huxley (FH), along with leaky, exponential, and adaptive-exponential integrate-and-fire (IF). It was found that IF models do not entirely reflect the experimental behavior while the HH and FH model did qualitatively replicate the observed neural responses. Changing the time constants and steady state values of the ion gates in the FH 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 results show that in the modified (simplified) model, 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 offers insights into neuronal biophysics and computational models of TI stimulation.

Influence of Temporal Interference Stimulation Parameters on Point Neuron Excitability.

Temporal interference (TI) stimulation is a technique in which two high frequency sinusoidal electric fields, oscillating at a slightly different frequency are sent into the brain. The goal is to achieve stimulation at the place where both fields interfere. This study uses a simplified version of the Hodgkin - Huxley model to analyse the different parameters of the TI-waveform and how the neuron reacts to this waveform. In this manner, the underlying mechanism of the reaction of the neuron to a TI -signal is investigated. Clinical relevance- This study shows the importance of the parameter choice of the temporal interference waveform and provides insights into the underlying mechanism of the neuronal response to a beating sine for the application of temporal interference stimulation.