Altered resting-state brain entropy by repetitive transcranial magnetic stimulation across the human cortex

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used to treat neuropsychiatric disorders. Despite its efficacy, its neuro-mechanisms remain unclear. Brain entropy (BEN), a measure of the irregularity and complexity of brain activity, has been shown to reflect the effects of high-frequency rTMS (HF-rTMS). However, it remains unknown whether BEN is sensitive to low-frequency rTMS (LF-rTMS), as well as to target-specific effects. Eighteen healthy adult participants underwent continuous theta burst stimulation (cTBS) over the left dorsolateral prefrontal cortex (L-DLPFC), and 23 healthy adult participants underwent LF-rTMS targeting the L-DLPFC, left temporoparietal junction (L-TPJ), and left occipital cortex (L-OCC). Magnetic resonance imaging scans were performed pre- and post-stimulation, and BEN maps were calculated from the preprocessed functional images. Results showed that cTBS over L-DLPFC increased BEN in the medial orbitofrontal cortex (MOFC), while L-DLPFC LF-rTMS increased BEN in the MOFC, subgenual anterior cingulate cortex, and putamen. LF-rTMS at the L-TPJ increased BEN in the right TPJ, while LF-rTMS at the L-OCC decreased BEN in the posterior cingulate cortex. These findings demonstrate BEN remains sensitive to LF-rTMS and exhibits target-specific effects. Furthermore, this work advances BEN as a promising biomarker for rTMS effects beyond motor cortex paradigms.