| Objective:By generating a low frequency envelope without impacting the superficial cortex,the new non-invasive electrical stimulation approach known as"temporal interference"(TI)stimulation modulates the activity of neurons in deeper regions.The majority of current research focuses on electric field simulation and animal studies.Due to functional and anatomical differences,above results cannot be directly applied to humans and TI stimulation in humans is still in the exploratory stage.This study intends to examine the effects of frontoparietal TI stimulation protocol on working memory in healthy adults in order to further confirm the safety and efficacy of TI stimulation.It also aims to give some theoretical support for the use of TI stimulation in future human studies.Methods:In this randomized,cross-over,double-blind controlled study,twenty-six healthy adults(22.24±1.53 years)were received TI stimulation and Sham stimulation at a random order with a 1-week washout period.The N-back task was completed before,during(online)and after(offline)stimulation.Also,the Lee version of the Fatigue Visual Analogue Scale(VAS-F)and Digit Span Test(DST)were completed by the participants immediately after stimulation.At the end of each visit,participants were required to complete questionnaires to assess the blinding efficacy and side effects.The stimulation target of this study was the middle frontal gyrus and inferior parietal lobule(i.e.,F4 and P4 of the EEG 10/20 system).The frequency of the currents was set at 2,000 Hz for two channels and 2,006 Hz for the other two channels.The peak-to-peak amplitude of the current was 2 m A for each pair of electrodes.The duration of the stimulation was20 minutes.The montages of Sham stimulation were the same as those in TI but the Sham stimulation only lasted 30s.Two-way repeated measures ANOVA was used to analyse the effects of different stimulation groups on the online and offline effects of working memory,as well as on the VAS-F scores.The paired T-tests were used to analyse the effects of different stimulation groups on DST scores.In addition,the side effects questionnaire was analysed using a one-way ordered R x C contingency table.Results:The results of this study showed that no serious adverse effects were reported after TI stimulation.Blinding was effective with an overall correct rate of 46.15%when speculating the type of stimulation.The results showed that participants received TI stimulation had significantly higher scores on the DST compared to participants received Sham stimulation(p<0.05).Online effect results showed there was no interaction effect for accuracy or reaction time in 1-back and3-back.Offline effect results showed that there was an interaction effect for accuracy in 3-back(F=5.581,p=0.022,ηp~2=0.100).After TI stimulation,accuracy for 3-back was significantly increased(p=0.001)and participants with poorer baseline performance had greater improvement.Furthermore,there was no interaction effect for accuracy or reaction time in 1-back,as well as reaction time in 3-back.Conclusion:This study demonstrates that TI stimulation can be safely and tolerably applied in humans as a new non-invasive electrical stimulation technique.TI stimulation was effective in improving working memory performance in healthy adults under high cognitive load,especially participants with poorer working memory performance. |