Using intracranial electroencephalographic recordings, we identified a distinct brain activity in 3 patients with refractory epilepsy characterized by very early occurrence from 8 minutes 10 seconds to 22 minutes 40 seconds prior to clinical seizure onset, periodical appearance of slow negative baseline shift, long interpeak interval of 40 to 120 seconds, and disappearance after clinical seizure. We named this activity “very low frequency oscillation” (VLFO), which reflected a dynamic process during the preictal state. This observation may render new insight into epileptogenesis and provide additional information concerning the epileptogenic zone as well as prediction of epileptic seizures. Ann Neurol 2010