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22 reviewsMajor depressive disorder (MDD) with suicidal ideation (SI) significantly impacts global health. Suicidal ideation is associated withalterations in brain network connectivity, yet the effective connectivity from the dorsolateral prefrontal cortex (DLPFC) to functionalnetwork nodes remains poorly understood. This study utilizes transcranial magnetic stimulation-electroencephalography (TMS-EEG)to investigate DLPFC connectivity and cortical excitability changes, providing insights into the neurobiological mechanisms and1234567890();,:potential treatments for MDD with SI. This study recruited 166 patients with MDD and 61 healthy controls. The TMS-EEG techniquewas used to assess effective connectivity based on abnormal time-locked TMS evoked potentials (TEPs). Suicidal ideation wasassessed using the suicidality module of the Mini International Neuropsychiatric Interview (MINI), and participants were classifiedinto suicidal ideation (SI) and non-SI (NSI) groups based on the presence of active ideation. Subgroup analysis evaluated significantcurrent scattering (SCS) in DLPFC-related circuits through source localization, with multiple functional networks defined asdownstream regions of interest. TEP analysis at the F3 electrode revealed no significant differences between the MDD and HCgroups across components. However, the SI group exhibited increased N100 amplitudes compared to the NSI group (uncorrected)and healthy controls. Source-level brain network analysis showed that the SCS of the DLPFC-mPFC and DLPFC-ACC circuits wassignificantly greater in the SI group than in the NSI and control groups. After controlling for age, logistic regression analysisindicated a significant association between these connectivity patterns and the presence of suicidal ideation. MDD patients withsuicidal ideation exhibit altered cortical inhibition and enhanced effective connectivity between the DLPFC and key brain regions,such as the AC