Normal and Pathologic High-Frequency Oscillations

High-frequency oscillations (HFOs) are sinusoid-like field potentials greater than 80Hz and several tens to hundreds of milliseconds in duration. HFOs in normal hippocampus called ‘ripples’ contain spectral frequencies up to 200Hz and occur during some waking behaviors and slow wave sleep. Like hippocampal ripples, spontaneous ripple-frequency HFOs and sensory-evoked HFOs (200–600 Hz) occur in neocortex. Studies suggest ripples and neocortical HFOs reflect inhibitory postsynaptic potentials from the rhythmic discharges of interneurons that regulate pyramidal cell firing. In rat models and patients with epilepsy, pathologic HFOs (pHFOs) include fast ripples that contain frequencies between 250 and 600 Hz. Pathologic HFOs are associated with sites of seizure onset and are linked with different types of pathology including hippocampal sclerosis. Animal and patient data suggest pHFOs reflect bursts of population spikes from local clusters of abnormally synchronized principal cells. Studies show pHFO power often increases during the onset of seizures, and in rats, the early appearance of pHFOs after an epileptogenic insult predicts the development of epilepsy, suggesting that pHFOs could be a biomarker of epileptogenesis and epileptogenicity. It is anticipated that future pHFO studies using clinical electrodes will further differentiate normal HFOs from pHFOs and clarify the role of pHFOs in epileptogenesis and seizure genesis.