A multiple modulation synthesis method with high spatial resolution for noninvasive neurostimulation.

Noninvasive neurostimulation plays a pivotal role in the direct control of neural circuits and the modulation of neuronal function. However, it is difficult to balance both spatial resolution and penetration depth when stimulating deep neurons. Here, we designed a multiple (time-division, frequency and polarity) modulation synthesis (MMS) method for noninvasively stimulating deep neurons with low-frequency envelopes. Compared to conventional transcranial electrical stimulation, we demonstrated that it can stimulate deep neurons at the desired firing rate (beat frequency) with higher spatial resolution via a computational model combining finite element analysis and Hodgkin-Huxley action potential model. Additionally, we measured the distribution of stimulus waveforms in saline solution to validate its effect. Taken together, the results of this study indicate that MMS stimulation with higher spatial resolution is steerable and might be a potential alternative to traditional implanted electrodes.