Responses of Model Cortical Neurons to Temporal Interference Stimulation and Related Transcranial Alternating Current Stimulation Modalities

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 (>1500 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.

Responses of model cortical neurons to temporal interference stimulation and related transcranial alternating current stimulation modalities

“…The data that support the findings of this study are openly available at the following URL/DOI [69]: https://doi.org/10.7924/r4n87d05r.…”

Investigate the therapeutic differences between Temporal Interference Stimulation and Transcranial Alternating Current Stimulation on Post-stroke cognitive dysfunction: A Protocol for Clinical Trial

“…PSCI is a common consequence of stroke that can cause damage not only to the lesion site but also to other cognitive networks, thereby affecting the quality of life, activities of daily living (ADL), and possibly increasing the risk of stroke recurrence [42] .Current treatments for PSCI are limited and have varying effectiveness, making it crucial to explore new therapeutic strategies. In recent years, NIBS technology has rapidly developed and has been applied in research and clinical treatment [43] .Among the various NIBS techniques, tACS and TIS have emerged as two promising approaches [44,45] . Although the application of tACS and TIS in PSCI has not been fully investigated, there is a certain research basis in other neurological diseases [46,47] .…”

Optimized Monophasic Pulses with Equivalent Electric Field for Rapid-Rate Transcranial Magnetic Stimulation

“…The extracellular stimulation was applied using quasi-uniform approximation of the E-field [56]. E-field orientations were sampled in a spherical coordinate system in which the z -axis aligned with the somatodendritic axis [47,57], with 13 polar angles in [0°, 180°] (average spacing of 15°), 18 azimuthal angles in [0°, 360°) (spacing of 20°), and a total of 200 (11×18+2) orientations. For each cell model, amplitude adjustment factors were calculated for all 5000 (200×5×5) combinations of orientations and candidate waveforms.…”

“…The extracellular stimulation was applied using quasi-uniform approximation of the E-field [56]. E-field orientations were sampled in a spherical coordinate system in which the z-axis aligned with the somatodendritic axis [47,57],…”