Effect of Intermittent Theta Burst Stimulation on Spatial Working Memory-related Neural Oscillations and Their Synchronicity

Objective Spatial working memory (SWM) is an important function in cognitive behavior, and working memory impairment can seriously affect the patient's life and cause great stress to the patient. Intermittent theta burst stimulation (iTBS) has been shown to regulate working memory function by entrainment of neural oscillations in different frequencies of the brain, but its regulation of working memory-related neural oscillations and their synchronization is not clear. The purpose of this study was to study the effect of iTBS on neural oscillation and synchronization in local and transbrain regions of rats, and to explore the mechanism of iTBS in regulating working memory. Methods Twenty-four rats were randomly divided into four groups according to their age and whether they received iTBS stimulation (AS: adult stimulation group, AC: adult control group, ES: elderly stimulation group, EC: elderly control group). Using the methods of time-frequency distribution, phase synchronization and phase-amplitude coupling analysis, the changes of local field potential signal neural oscillations in the prefrontal and hippocampal brain regions of theta and gamma bands in the process of spatial working memory behavioral tasks in each group of rats were compared and analyzed, and the relationship between the changes of neural oscillations in the two brain regions and the changes in spatial working memory ability of rats was judged based on the Pearson correlation coefficient. Results With the increase of age, the time taken by the elderly rats to learn the spatial working memory task rules increased significantly (P=0.005 P =0.005 6), and the time taken by iTBS stimulation to learn the SWM task rules in adult rats (P=0.001 P =0.001 1) and elderly rats (P=0.009 P =0.009 0) was shortened. At the same time, compared with adult rats, the time-frequency energy of theta and gamma band neural oscillations in the prefrontal and hippocampal brain regions of elderly rats (theta: P <0.000 1; gamma: P <0.000 1) and phase-amplitude coupling across brain regions (PFC-HPC: P =0.000 2; HPC-PFC: P =0.027 7) decreased to a certain extent, and iTBS stimulation could increase the time-frequency energy of neural oscillations of adult rats (theta: P <0.000 1; gamma: P <0.000 1) and elderly rats (theta: P =0.014 4; gamma: P =0.000 6) and the phase-amplitude coupling effect across brain regions in elderly rats (PFC-HPC: P =0.018 0; HPC-PFC: P =0.022 1). In addition, the time-frequency energy and phase-amplitude coupling of signals in each frequency band of the two brain regions were positively correlated with the behavioral accuracy of rats, while the phase synchronization of theta band and gamma band neural oscillations in the two brain regions during working memory was not correlated with the behavioral accuracy. Conclusion iTBS can enhance SWM ability and cognitive function in elderly rats, and this improvement is associated with increased coupling of time-frequency energy and cross-brain phase amplitude of neural oscillations across theta and gamma bands during SWM tasks. Similarly, in adult rats, iTBS enhances SWM ability and cognitive function by increasing the time-frequency energy of theta and gamma band neural oscillations in both brain regions during SWM tasks. Furthermore, in addition to the main findings, this study provides evidence supporting the state-dependent effects of iTBS stimulation to some extent.