Abstract
Temporal interference stimulation (TIS) has been proposed as a non-invasive, focal, and steerable deep brain stimulation method. TIS is hypothesized to activate neurons via the amplitude-modulated envelope of interference generated by two high-frequency (few kHz) sinusoidal electric fields (E-fields). Existing studies, however, oversimplified TIS and have not represent the full spatial dimensions of E-fields and cortical neurons. The response to TIS and other transcranial alternating current stimulation was simulated using detailed models of layer 5 pyramidal neurons adapted from the Blue Brain Project. We examined a wide range of parameter combinations, including the two E-fields’ orientations, frequencies, amplitude ratios, amplitude modulation, and phase difference, and obtained thresholds for both activation and inactivation, when stimulus-induced firing stops due to high stimulation amplitude.
TIS has a unique combination of characteristics. At the target region in the cortex, which is generally considered to be where the two E-fields have similar amplitudes, TIS generates an amplitude-modulated total E-field. The TIS E-field also exhibits rotation where the E-field orientations are not aligned, which generally co-localizes with the target. Outside the target region, the TIS E-field is dominated by the high-frequency carrier, with minimal amplitude modulation and/or rotation, and it is less effective at activation with low amplitudes and more effective at inactivation with high amplitudes. TIS activation thresholds are similar to high-frequency stimulation with or without modulation and/or rotation (75–230 V/m). TIS creates inactivation for some combinations of E-field orientations and amplitude ratios at high amplitudes (>1700 V/m), whereas amplitude modulated single-carrier high-frequency stimulation cannot achieve similar effects, regardless of orientation. All observed effects occurred at E-field strengths that are too high to be delivered tolerably through scalp electrodes, limiting the significance of suprathreshold TIS.
Competing Interest Statement
The authors have declared no competing interest.
