BACKGROUND: Transcranial magnetic stimulation (TMS) can have inhibitory effects on epileptiform discharges (EDs) of patients with focal seizures. However, the brain connectivity before, during and after EDs, with or without the administration of TMS, has not been extensively explored.OBJECTIVE: To investigate the brain network of effective connectivity during ED with and without TMS in patients with focal seizures.METHODS: For the effective connectivity a direct causality measure is applied termed partial mutual information from mixed embedding (PMIME). TMS-EEG data from two patients with focal seizures were analyzed. Each EEG record contained a number of EDs in the majority of which TMS was administered over the epileptic focus. As a control condition, sham stimulation over the epileptogenic zone or real TMS at a distance from the epileptic focus was also performed. The change in brain connectivity structure was investigated from the causal networks formed at each sliding window.CONCLUSION: The PMIME could detect distinct changes in the network structure before, within, and after ED. The administration of real TMS over the epileptic focus, in contrast to sham stimulation, terminated the ED prematurely in a node-specific manner and regained the network structure as if it would have terminated spontaneously.