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.

无创神经刺激（noninvasive neurostimulation）在直接调控神经环路与调节神经元功能中发挥着关键作用。然而，在刺激深部神经元时，难以同时兼顾空间分辨率与穿透深度。本研究设计了一种基于时分、频域与极性的多调制合成（multiple modulation synthesis, MMS）方法，可通过低频包络无创刺激深部神经元。相较于传统经颅电刺激，本研究通过结合有限元分析与霍奇金-赫胥黎动作电位模型的计算模型，证实该方法可在目标放电频率（即拍频）下以更高的空间分辨率刺激深部神经元。此外，本研究通过在生理盐水溶液中测量刺激波形的分布情况，验证了该方法的效果。综上，本研究结果表明，具备更高空间分辨率的MMS刺激具有可调控性，有望成为传统植入式电极的潜在替代方案。