Seizure prediction systems and methods include measuring impedance and a potential within a brain of a patient to determine whether the brain is in a state indicative of a possibility of seizure. In some embodiments, at least one of the measured impedance or the measured potential may be used as a primary indication of the brain state indicative of a possibility of seizure. In one embodiment, if one of the measured impedance or the measured potential indicates a seizure, the other measurement (impedance or potential) may be used to validate whether the brain is in the state indicative of the possibility of seizure.