Intermittent theta burst stimulation is superior to 10 Hz-repetitive transcranial magnetic stimulation in promoting episodic-like memory in healthy male rats by enhancing low γ oscillation and glutamate neuronal activities of the anterior cingulate cortex.

Intermittent theta-burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (rTMS) produce beneficial after-effects on memory performance. The two modalities have modulatory after-effects on the prefrontal neuronal oscillations and neurotransmitters, which are critically involved in episodic memory processing. However, whether iTBS exerts better cognitive effects than high-frequency rTMS through modulating neuronal oscillations and neurotransmitter levels in the prefrontal cortex has not been determined. Thus, iTBS and 10 Hz-rTMS modalities were applied to healthy male rats respectively, and behavior tests, electrophysiological experiments and microdialysis and neurochemistry were performed. We found that iTBS and 10 Hz-rTMS promoted episodic memory in healthy male rats, and iTBS exerted better cognitive effects than 10 Hz-rTMS. Intriguingly, iTBS induced greater effects than 10 Hz-rTMS in enhancing low γ oscillation in the anterior cingulate cortex (ACC) which is a subregion of the prefrontal cortex. Further, compared to sham stimuli, iTBS suppressed δ oscillation and enhanced θ oscillation, while 10 Hz-rTMS did not, suggesting that iTBS induces higher cortical excitability in the ACC than 10 Hz-rTMS. This is supported by a higher increase in glutamate neuronal activities in the ACC following iTBS than 10 Hz-rTMS. Finally, we found that iTBS and 10 Hz-rTMS decreased extracellular gamma-aminobutyric acid levels and increased extracellular glutamate levels in the ACC, thus leading to the activation of ACC glutamate neurons after the two modalities. These findings suggest that iTBS produces better cognitive effects in healthy male rats, which may be attributed to enhanced low γ oscillation and activated glutamatergic neurons in the ACC.