Local repetitive transcranial magnetic stimulation (rTMS) induces whole-brain functional dynamic remodeling

Repetitive transcranial magnetic stimulation (rTMS) is a proven tool to modulate brain functional dynamics and treat neurological and psychiatric diseases. However, it remains unclear how local rTMS affects whole-brain functional dynamics. Here, we investigated the stimulation effects of rTMS using two data-driven approaches. By constructing multi-layer networks from resting-state fMRI data acquired before and after 1 Hz stimulation over the left frontal (FRO-TMS) and occipital cortex (OCC-TMS), we found significantly decreased dynamic interaction after FRO-TMS. We further characterized whole-brain functional hierarchy by computing nonreversibility and observed a significantly flattened hierarchy after FRO-TMS, whereas OCC-TMS did not induce significant changes. We then systematically investigated the association between these distinct modulatory patterns and structural network organization by fitting a large-scale brain computational model. Using noise- and synchronization-based perturbation protocols, we found that the simulated perturbation distance correlated significantly with the local dominance and controllability of the stimulated node in the structural network, providing a potential mechanistic account for the empirical observations. Specifically, driving hub nodes induced relatively small perturbation distances, whereas driving weakly connected regions yielded larger distances. This study provides a heuristic strategy for modeling and optimizing stimulation protocols in noninvasive brain stimulation.

The online version contains supplementary material available at https://doi.org/10.1007/s11571-026-10568-3.