Insight into the impact of focal stimulation on large-scale network dynamics

<i>Objective.</i>Intrinsic functional brain activity forms a hierarchy, with local neural circuits integrated into large-scale networks. Determining how perturbations to a single brain region can rapidly propagate through this hierarchy and reconfigure global brain state dynamics is essential for decoding neural communication and advancing neuromodulation paradigms. Most prior studies have used perturbations to study trial-averaged responses, which miss moment-to-moment fluctuations, or focused on inter-regional connectivity, which characterizes brain activity as pairwise relationships rather than global states. How focal stimulation reshapes dynamics of global brain states remains unclear.<i>Approach.</i>We bridged this gap by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) with microstate analysis, which captures global brain state dynamics with millisecond resolution. In 36 healthy participants, we examined how single-pulse TMS to the dorsolateral prefrontal cortex (DLPFC) and primary motor cortex (M1) reshapes the dynamics of the canonical EEG microstates (A-E) post-pulse. As key nodes of frontoparietal and primary motor networks, respectively, these targets let us investigate how stimulation of functionally distinct regions may differentially induce changes in global brain state dynamics. Analyses were conducted across repeated sessions within participants and validated in an independent dataset to ensure robustness and generalizability.<i>Main results.</i>Compared to pre-pulse baseline, DLPFC stimulation increased the occurrence and transitions of microstates D and E while suppressing those of A and B. These effects replicated across sessions and were validated in an independent dataset. Conversely, M1 stimulation increased microstate A occurrence post-pulse while reducing the occurrence of B. Furthermore, post-pulse microstate dynamics differed significantly from baseline after DLPFC stimulation compared to M1.<i>Significance.</i>These findings demonstrate that focal stimulation induces region-specific effects on global brain state dynamics, providing a mechanistic foundation for neuromodulation strategies to harness site-specific effects on global brain states. Our findings can be leveraged for developing personalized targeted treatments for neuropsychiatric disorders.