Effect of temporal interference electrical stimulation on phasic dopamine release in the striatum

Background: Temporal interference stimulation (TIS) is a neuromodulation technique that could stimulate deep brain regions by inducing interfering electrical signals based on high-frequency electrical stimulations of multiple electrode pairs from outside the brain. Despite numerous TIS studies, however, there has been limited investigation into the neurochemical effects of TIS. Objective: We performed two experiments to investigate the effect of TIS on the medial forebrain bundle (MFB)evoked phasic dopamine (DA) response. Methods: In the first experiment, we applied TIS next to a carbon fiber microelectrode (CFM) to examine the modulation of the MFB-evoked phasic DA response in the striatum (STr). Beat frequencies and intensities of TIS were 0, 2, 6, 10, 20, 60, 130 Hz and 0, 100, 200, 300, 400, 500 mu A. In the second experiment, we examined the effect of TIS with a 2 Hz beat frequency (based on the first experiment) on MFB-evoked phasic DA release when applied above the cortex (with a simulation-based stimulation site targeting the striatum). We employed 0 Hz and 2 Hz beat frequencies and a control condition without stimulation. Results: In the first experiment, TIS with a beat frequency of 2 Hz and an intensity of 400 mu A or greater decreased MFB-evoked phasic DA release by roughly 40%, which continued until the experiment's end. In contrast, TIS at beat frequencies other than 2 Hz and intensities less than 400 mu A did not affect MFB-evoked phasic DA release. In the second experiment, TIS with a 2 Hz beat frequency decreased only the MFB-evoked phasic DA response, but the reduction in DA release was not sustained. Conclusions: STr-applied and cortex-applied TIS with delta frequency dampens evoked phasic DA release in the STr. These findings demonstrate that TIS could influence the neurochemical modulation of the brain.