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.