Temporal interference stimulation for human brain: Opportunities and challenges

Temporal interference (TI) stimulation is a non-invasive technique for electrically stimulating neurons at depth.1 It leverages the low-pass filtering properties of neural membranes, which render neurons more sensitive to low-frequency oscillating fields compared with high-frequency fields (e.g., ≥1 kHz). This approach generates a low-frequency modulated electric field—termed envelope modulation—by superimposing high-frequency currents with slightly different frequencies, applied via scalp electrodes. The characteristics of the envelope modulation are determined by the vector sum of the applied field vectors at a given point. By adjusting electrode positions and current ratios, the amplitude of the envelope modulation can be maximized at a point distant from the scalp, potentially reaching deep brain regions.

Non-invasive deep brain stimulation via TI in mice

Several years ago, Grossman et al. explored the concept of TI and proposed that the application of two or more high-frequency electric fields on the scalp, differing by a low frequency within the dynamic range of neural firing, could enable focal stimulation of deep brain neurons.1 They demonstrated that TI stimulation with a 10 Hz envelope modulation, was capable of selectively activating the hippocampus while sparing superficial neurons in the living mouse brain. This success positions TI as a promising strategy for non-invasive deep brain stimulation (DBS) in humans. However, physiological differences between humans and rodents, such as skull and cortical thickness, raise uncertainties regarding the feasibility of translating this approach to human applications when maintaining its original efficacy and precision.