Transcranial temporal interference stimulation (tTIS) applies multiple kilohertz alternating currents with slightly different frequencies to generate a low-frequency amplitude-modulated electric field in the brain. This approach may enable non-invasive modulation of deep epileptic networks, including the hippocampus and thalamus. Epilepsy-related research has progressed from computational modeling and animal experiments to early proof-of-concept studies in patients. In mouse models, hippocampal stimulation with a 130 Hz envelope reduced interictal epileptiform discharges and pathological fast ripples. A recent study of 13 patients with drug-resistant mesial temporal lobe epilepsy found acute and short-term carry-over suppression of intracranially recorded epileptic discharges and high-frequency oscillations without reported adverse events. However, current evidence is based mainly on surrogate electrophysiological outcomes and does not establish long-term seizure reduction. Uncertainties remain regarding biological mechanisms, deep-target focality, carrier-related off-target effects, individualized electric-field dosing, and long-term safety. This review summarizes the principles, preclinical and human evidence, stimulation parameters, and safety of tTIS for epilepsy, and discusses the studies required to translate biomarker suppression into clinically meaningful seizure control.
