Electroconvulsive therapy (ECT) has significant short-term antidepressant effects on drug-resistant patients with severe major depression. Animal studies have demonstrated that electroconvulsive seizures produce potentiation-like synaptic remodeling in both sub-cortical and frontal cortical circuits. However, the electrophysiological effects of ECT in the human brain are not known. In this work, we evaluated whether ECT induces a measurable change in the excitability of frontal cortical circuits in humans. Electroencephalographic (EEG) potentials evoked by transcranial magnetic stimulation (TMS) were collected before and after a course of ECT in eight patients with severe major depression. Cortical excitability was measured from the early and local EEG response to TMS. Clinical assessment confirmed the beneficial effects of ECT on depressive symptoms at the group level. TMS/EEG measurements revealed a clear-cut increase of frontal cortical excitability after ECT as compared to baseline, that was significant in each and every patient. The present findings corroborate in humans the idea that ECT may produce synaptic potentiation, as previously observed in animal studies. Moreover, results suggest that TMS/EEG may be employed in depressed patients to monitor longitudinally the electrophysiological effects of different therapeutic neuromodulators, e.g. ECT, repetitive TMS, and sleep deprivation. To the extent that depression involves an alteration of frontal cortical excitability, these measurements may be used to guide and evaluate treatment progression over time at the single-patient level.