Non-invasive brain stimulation is an important intervention method for brainfunction research in human subjects, it is also a treatment of some psychiatric diseases.The method applying a weak current to the subject's scalp to form an intracranialelectric field and affect the internal nerve activity is called transcranial electricalstimulation. This technology has advantages of simple manipulation, low cost and highportability, but it also faces poor focality and stimulation depth.
For this problem, some researchers have proposed to achieve deeper and morefocused brain stimulation based on the temporally interfering electric fields. Comparedwith traditional transcranial alternating current stimulation (tACS), the temporallyinterfering signals are easier to pass through the scalp and skull with little attenuationand have higher intensity in deep regions. At present, this method has been verified toregulate neuronal activity in anesthetized mice without recruiting neurons of the over-lying cortex, researchers are beginning to care whether it is feasible in human subjectswith larger skulls and more complex anatomical brain structures. Many researchershave predicted that the temporally interference method can achieve effective electricfield strength of 0.2 V/m, which showed subthreshold modulation in traditional tACS,in the human brain based on computational simulation models, but there is still a lackof data support on animal experiments.
In this study, we measured the distribution of temporally interfering stimulation inthe non-human primate brain with implanted electrodes directly, and combined therecordings with simulations to conduct a more comprehensive analysis of the wholebrain intensity distribution. The results show that the distribution of electric field areindeed concentrated in central regions, and the average intensities in these regions arehigher than 0.2 V/m, the maximum can even reach to 0.4～0.5 V/m at a safe current of2 mA used in human, indicating that temporally interfering stimulation meets the basicrequirements of depth and intensity for non-invasive deep brain stimulation in largerskulls. In addition, we built a complete process that can screened out external stimuluscombinations which focus on the specific target and meet the requirements of intensityfor human subjects. These results show the importance of personalized simulation andthe flexibility and focus of temporally interfering stimulation.
Our study fills the data gap of temporally interfering stimulation in large skullsclose to humans, and combines with simulation to verify its potential to be used as non-invasive deep brain stimulation in human subjects. These results provide importantreference for the application and development of this technology in future.
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