Altered resting-state brain entropy (BEN) by rTMS across the human cortex

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method effective in treating various neuropsychiatric disorders, yet its mechanisms are not fully understood. In general, rTMS protocols are categorized into excitatory protocols including high-frequency rTMS (HF-rTMS) and intermittent theta burst stimulation (iTBS), and inhibitory protocols including low-frequency rTMS (LF-rTMS) and continuous theta burst stimulation (cTBS). Brain entropy (BEN) measures irregularity, disorders, and complexity of brain activity, our previous studies have indicated that BEN affects excitatory rTMS, including HF-rTMS and iTBS. However, two important questions remain whether rTMS is equally sensitive to inhibitory rTMS and whether it can induce opposite brain activities, another question concerns whether rTMS can induce specific changes across brain regions. To address these issues, we utilized our own cTBS targeted on the left dorsal lateral prefrontal cortex (L-DLPFC) dataset and publicly available LF-rTMS dataset with stimulating sites including the L-DLPFC, left temporal parietal junction (L-TPJ), and left occipital cortex (L-OCC), from the OpenNeuro. BEN maps were calculated before and after stimulation. The results showed that L-DLPFC cTBS increased BEN in the MOFC and L-DLPFC LF-rTMS increased BEN in the MOFC, subgenual anterior cingulate cortex (MOFC/sgACC) and putamen, the regions are consistent with our previous findings with HF-rTMS and iTBS. Additionally, L-TPJ LF-rTMS resulted in increased BEN in the right TPJ, while L-OCC LF-rTMS led to decreased BEN in the posterior cingulate cortex (PCC). Our findings suggest that BEN is not only sensitive to excitatory rTMS but also to inhibitory rTMS. Moreover, LF-rTMS induces different effects across brain regions, as detected by BEN.