Multi-channel transcranial temporally interfering stimulation (tTIS): application to living mice brain

Abstract

Objective. Transcranial temporally interfering stimulation (tTIS) is a noninvasive neuromodulation method, which has been reported to be able to affect the activity of small neuronal populations. To pinpoint smaller regions of the brain, a multi-channel tTIS strategy is proposed with larger numbers of electrodes and multiple sets of interfering fields. Approach. First, a computational model is adopted to prove the concept of multi-channel tTIS theoretically. Besides, animal experiments are implemented to activate motor cortex neurons in living mice and different frequencies are attempted. Finally, to better understand the envelope modulation properties of the two applied fields, tissue phantom measurement is conducted. Main results. The focality of six-channel (six electrode pairs) tTIS is increased by 46.7% and 70.2% respectively, compared with that of single-channel tTIS when maximal amplitude value drops by 3 dB and 6 dB in a numerical computation experiment. Furthermore, the focality of multi-channel tTIS is less sensitive to the electrode position. Confirmed with the myoelectricity signal, the movement frequencies of the contralateral forepaw are consistent with the corresponding difference frequencies. What is more, compared to single-channel (one electrode pair) tTIS with multi-channel (three electrode pairs) tTIS, the intensity of multi-channel tTIS stimulation is decreased by 28.5% on average in animal experiments. The c-fos-positive neurons of the target region are significantly higher than that of the non-target region. Results of the modulated envelope distribute around the whole region and its amplitude reaches a maximum at the interfering region. Significance. Both computational modeling and animal experiment validate the feasibility of the proposed multi-channel tTIS strategy and confirm that it can enhance focality and reduce scalp sensation.

Multiscale Computational Model Reveals Nerve Response in a Mouse Model for Temporal Interference Brain Stimulation

“…Multiscale modeling was applied to replicate the experiments conducted in Grossman et al (2017), the primary findings of which were: (i) beat frequency does not influence the threshold for the range considered, (ii) the threshold increases with an increase in the carrier frequency, and (iii) the stimulation region changes according to the ratio between the two injection currents. These were also reproduced in another study (Song et al, 2020). Our multiscale modeling replicated the three experiments for the first time using realistically shaped generated current effects on the neuronal model.…”

“…Instead, a small difference in the frequencies of the two injection currents may generate a beat wave (modulation envelope) causing neural stimulation. Previous studies have shown promising results for motor area stimulation in mice ( Grossman et al, 2017 ; Song et al, 2020 ). In addition, various efforts have been made to clarify the mechanism regarding biophysics using neural models ( Karimi et al, 2019 ; Cao and Grover, 2020 ; Howell and McIntyre, 2020 ; Mirzakhalili et al, 2020 ; Esmaeilpour et al, 2021 ).…”

Non-invasive stimulation with Temporal Interference: Optimization of the electric field deep in the brain with the use of a genetic algorithm

“…A multi-channel tTIS study on mice [31] indicated that targeting accuracy significantly improves when considering a six-channel (six electrode pairs) tTIS, performing 70.2% better than the single-channel (one electrode pair) tTIS. Furthermore, in [31], stimulation targeting appeared to be less affected when selecting different electrode pairs. In summary, Song et al [31] showed that more channels make the tTIS method more independent of the exact electrode placement while increasing the focality.…”

“…Considering that we used two electrode pairs in this study, the focality resolution was limited. This problem can be addressed by using more electrode pairs for stimulation [31].…”

Review of Noninvasive or Minimally Invasive Deep Brain Stimulation

“…The characteristics of an envelope may predict the regions of TI stimulation (Gomez-Tames et al, 2021 ). Multichannel array electrodes for TI stimulation enhance focality and reduce scalp sensation in computational modeling and mouse experiments (Song et al, 2020 ). Wang H. et al ( 2020 ) fabricated a TI stimulator that measures bioimpedance in real time and proposed an approach that can easily locate the target position.…”