Noninvasive Deep Brain Stimulation via Temporal Interference Electric Fields Enhanced Motor Performance of Mice and Its Neuroplasticity Mechanisms

A noninvasive deep brain stimulation via temporal interference (TI) electric fields is a novel neuromodulation technology, but few advances about TI stimulation effectiveness and mechanisms have been reported. One hundred twenty-six mice were selected for the experiment by power analysis. In the present study, TI stimulation was proved to stimulate noninvasively primary motor cortex (M1) of mice, and 7-day TI stimulation with an envelope frequency of 20 Hz (∆f =20 Hz), instead of an envelope frequency of 10 Hz (∆f =10 Hz), could obviously improve mice motor performance. The mechanism of action may be related to enhancing the strength of synaptic connections, improving synaptic transmission efficiency, increasing dendritic spine density, promoting neurotransmitter release, and increasing the expression and activity of synapse-related proteins, such as brain-derived neurotrophic factor (BDNF), postsynaptic density protein-95 (PSD-95), and glutamate receptor protein. Furthermore, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and its upstream BDNF play an important role in the enhancement of locomotor performance in mice by TI stimulation. To our knowledge, it is the first report about TI stimulation promoting multiple motor performances and describing its mechanisms. TI stimulation might serve as a novel promising approach to enhance motor performance and treat dysfunction in deep brain regions.