Effects of intravenous diazepam on high-frequency oscillations in EEGs with CSWS

Abstract

High-frequency oscillations (HFOs) associated with continuous spike-waves during slow-wave sleep (CSWS) are speculated to be linked to the disturbance of higher brain function. We intended to investigate the generative mechanisms of HFOs in CSWS by clarifying the effects of intravenous injection (IV) of diazepam (DZP), an agonist for the gamma-aminobutyric acid A (GABAA) receptor in the GABAergic interneuron system, in patients who had previously been treated with IV DZP. The subjects were three patients with epilepsy with CSWS. For each patient, EEG data before and after IV DZP were separated into consecutive 5-min sections. Time–frequency power spectral analysis was performed on the spikes of each section, and peak-power and frequency of detected high-frequency spectral spots were compared before and after IV DZP. Spectral spots with peak-frequencies at 85.9–121.1Hz in the ripple band were revealed in all three patients. Although the amplitudes of the spikes largely returned to the baseline levels 20–25min after IV DZP, the recovery of the peak-power levels of HFOs lagged behind that of the spike amplitudes, and the power levels of HFOs were lower than the baseline data within 25min after the injection of DZP. No consistent changes were found regarding the spectral frequencies of HFOs. The dissociation of the effect of IV DZP in terms of recovery when comparing spike-amplitudes and the power of HFOs may correspond to an already suggested difference in the pathophysiological mechanisms that generate the spikes and HFOs.