Effects of high-frequency transcranial magnetic stimulation on theta-gamma oscillations and coupling in the prefrontal cortex of rats during working memory task

High-frequency rTMS has been widely used to improve working memory (WM) impairment; however, the underlying neurophysiological mechanisms are unclear. We evaluated the effect of high-frequency rTMS on behaviors relevant to WM as well as coupling between theta and gamma oscillations in the prefrontal cortex (PFC) of rats. Accordingly, Wistar rats received high-frequency rTMS daily for 14 days (5 Hz, 10 Hz, and 15 Hz stimulation; 600 pulses; n = 6 per group), whereas the control group received sham stimulation. Electrophysiological signals were recorded simultaneously to obtain the local field potential (LFP) from the PFC, while the rats performed T-maze tasks for the evaluation of WM. Phase-amplitude coupling (PAC) was utilized to determine the effect of high-frequency rTMS on the theta-gamma coupling of LFPs. We observed that rats in the rTMS groups needed a smaller number of training days to complete the WM task as compared to the control group. High-frequency rTMS reinforced the coupling connection strength in the PFC of rats. Notably, the effect of rTMS at 15 Hz was the most effective among the three frequencies, i.e., 5 Hz, 10 Hz, and 15 Hz. The results suggested that rTMS can improve WM impairment in rats by modulating the coupling of theta and gamma rhythms. Hence, the current study provides a scientific basis for the optimization of TMS models, which would be relevant for clinical application.