The effects of priming intermittent theta-burst stimulation on phase-amplitude coupling and its directionality in Alzheimer’s disease rats

Aim Intermittent theta burst stimulation (iTBS) shows promise in alleviating cognitive dysfunction in neurodegenerative diseases. Pre-treatment with iTBS could potentially modulate the threshold of synaptic plasticity, which may enhanc the facilitative effect of subsequent iTBS sessions. This study aims to investigate the effects of priming iTBS on working memory ability and neural oscillations of rats with Alzheimer’s desease (AD).Methods Thirty-six AD rats were randomly divided into one of three groups: priming iTBS, iTBS and sham stimulation. Phase-amplitude coupling (PAC) and its directionality were analyzed using local field potentials recorded during a working memory (WM) task. Additionally, hippocampal Aβ concentrations were analyzed across different stimulation sessions.Results Compared to the AD group, the iTBS group learned the WM behavioral task rules in a shorter period and exhibited increased modulation index values for theta-gamma coupling between the hippocampus (HPC) and prefrontal cortex (PFC). Notably, iTBS reversed the direction of PAC observed in AD rats and significantly reduced hippocampal Aβ concentration. Furthermore, compared to the use of iTBS alone, the iTBS priming stimulus had a significant effect on improving the phase-amplitude coupling between the PFC theta band and the HPC gamma band, although no observable behavioral differences were detected.Conclusion Both priming and non-priming iTBS are both superior to sham stimulation in improving cognitive performance of AD rats by enhancing cross-frequency PAC between the PFC and HPC. Furthermore, these interventions altered the directionality of PAC, suggesting modified network connectivity. While priming iTBS induced unique effects on neural oscillation coupling strength, these differences did not result in significant behavioral changes.