Intermittent theta burst stimulation (iTBS)-induced changes of resting-state brain entropy (BEN)

Abstract Intermittent theta burst stimulation (iTBS) is a novel protocol of repetitive transcranial magnetic stimulation (rTMS). While iTBS has shown better therapeutic effects for depression than conventional high-frequency rTMS (HF-rTMS), its underlying neuronal mechanism remains elusive. Brain entropy (BEN), a measure of irregularity of brain activity, has recently emerged as a novel marker of regional brain activity. Our previous studies have shown the sensitivity of BEN to depression and HF-rTMS, suggesting BEN as a sensitive tool for understanding the brain mechanism of iTBS. To assess this possibility, we calculated BEN using resting state fMRI data provided by an open dataset in OpenNeuro. Sixteen healthy participants underwent 600 pulses of iTBS applied over the left dorsolateral prefrontal cortex (L-DLPFC) at two intensities (90% and 120% of individual resting motor threshold (rMT)) on separate days. We assessed the pre-post stimulation BEN difference and its associations with neurotransmitter receptor and transporter binding maps. Our results showed that subthreshold iTBS (90% rMT) decreased striatal BEN, while suprathreshold iTBS (120% rMT) increased striatal BEN. We also found significant differences in the spatial correlation between BEN changes induced by different stimulation intensities and various neurotransmitters. These results suggest that differences in BEN caused by iTBS stimulation intensity may be related to the release of other neurotransmitters. The study underscores the significance of iTBS stimulation intensity and provides a basis for future clinical investigations to identify stimulation intensities with good therapeutic benefits.