EEG Microstates Signatures of rTMS Response Over the lDLPFC: A Band-Specific Analysis

Transcranial Magnetic Stimulation (TMS), particularly Theta Burst Stimulation (TBS), is a non-invasive, non-convulsive neuromodulation technique that induces clinically relevant network modulations with long-term effects. Two TBS protocols- continuous TBS (cTBS) and intermittent TBS (iTBS)- have been approved as effective therapeutic interventions for neuropsychiatric disorders, including mood disorders. With this aim, we examined EEG microstate temporal dynamics during resting-state recordings across three sessions of TMS. Twenty-four participants underwent cTBS, iTBS, and sham stimulation in a pseudo-randomized order, each separated by at least one week. Six distinct microstates (A-F), associated with activity in specific neural networks, were identified across six frequency bands (broadband, δ, θ, α, β, and γ). Our findings reveal frequency band-specific modulation of EEG microstates B, C, E, and F, previously reported as biomarkers in mood disorders. Notably, C microstates showed increased stability, whereas microstates E and F showed decreased dynamics up to fifty-five minutes after TBS. Most importantly, a negative association was observed for microstate E occurrence, between before stimulation (pre-cTBS) and three post-standing time points (post1-cTBS, post2-cTBS, and post3-cTBS), suggesting that baseline microstate E characteristics may be related to individual variability in cTBS treatment response. These results further support the potential of TBS to induce clinically relevant neuroplastic changes, establishing a strong foundation for the development of band-specific EEG microstate markers for assessing treatment response and personalized closed-loop TMS-EEG protocols.