Quantitative Analysis of High-Frequency Oscillations (80–500 Hz) Recorded in Human Epileptic Hippocampus and Entorhinal Cortex

Abstract

High-frequency oscillations (100–200 Hz), termed ripples, have been identified in hippocampal (Hip) and entorhinal cortical (EC) areas of rodents and humans. In contrast, higher-frequency oscillations (250–500 Hz), termed fast ripples (FR), have been described in seizure-generating limbic areas of rodents made epileptic by intrahippocampal injection of kainic acid and observed in humans ipsilateral to areas of seizure initiation. However, quantitative studies supporting the existence of two spectrally distinct oscillatory events have not been carried out in humans nor has the preferential appearance of FR within seizure generating areas received statistical evaluation based on analysis of a large sample of oscillatory events. Interictal oscillations within the bandwidth of 80–500 Hz were detected in Hip and EC areas of patients with mesial temporal lobe epilepsy using wideband EEG recorded during non-rapid eye-movement sleep from chronically implanted depth electrodes. Power spectral analysis showed that oscillations detected from Hip and EC areas were composed of two spectrally distinct groups. The lower-frequency ripple group was defined by a frequency of 96 ± 14 Hz (median ± width), while the higher-frequency FR group had a frequency of 262 ± 59 Hz. FR oscillations were significantly shorter in duration compared with ripple oscillations ( P < 0.0001). In regard to the occurrence of FR and ripples in epileptic Hip and EC, the mean ratio of the number of FR to ripples generated in areas ipsilateral to seizure onset was significantly higher compared with the mean ratio of FR to ripple generation from contralateral areas ( P = 0.008). Furthermore, sites ipsilateral to seizure onset with hippocampal atrophy had significantly higher ratios compared with sites contralateral to both seizure onset and hippocampal atrophy ( P = 0.001). These data provide compelling quantitative and statistical evidence for the existence of two spectrally distinct groups of limbic oscillations that have frequency and duration characteristics similar to those previously described in epileptic rat and human Hip and EC. The strong association between FR and regions of seizure initiation supports the view that FR reflects pathological hypersynchronous events crucially associated with seizure genesis.