Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.

Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In this study, 38 healthy adults were recruited to undergo a series of neurological and neuropsychological measurements regarding safety concerns before and after active (2 mA, 20/70 Hz, 30 min) or sham (0 mA, 0 Hz, 30 min) TI-tACS. The neurological and neuropsychological measurements included electroencephalography (EEG), serum neuron-specific enolase (NSE), the Montreal Cognitive Assessment (MoCA), the Purdue Pegboard Test (PPT), an abbreviated version of the California Computerized Assessment Package (A-CalCAP), a revised version of the Visual Analog Mood Scale (VAMS-R), a self-assessment scale (SAS), and a questionnaire about adverse effects (AEs). We found no significant difference between the measurements of the active and sham TI-tACS groups. Meanwhile, no serious or intolerable adverse effects were reported or observed in the active stimulation group of 19 participants. These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use in human brain stimulation studies under typical transcranial electric stimulation (TES) conditions (2 mA, 20/70 Hz, 30 min).

Although previous studies have reported correlations between alpha oscillations and the “retention” subprocess of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain oscillations. Conventional transcranial alternating current stimulation (tACS) is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention subprocess). Here, we developed an online phase-corrected tACS system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits the modulation of brain oscillations at the target stimulation frequency within a short stimulation period and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to participants during the retention subprocess of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. These findings strongly support a causal link between alpha oscillations and WM retention and illustrate the broad application prospects of phase-corrected tACS.

No abstract

Temporal interference (TI) stimulation is a new technique of noninvasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidate. In this study, this issue is investigated in the human primary motor cortex. Participants attended three sessions of TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation. The results indicate that TI stimulation with different envelope frequencies influenced different motor functions. In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential. These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time.