Exclusion of the Possibility of "False Ripples" From Ripple Band High-Frequency Oscillations Recorded From Scalp Electroencephalogram in Children With Epilepsy

Abstract

Aim: Ripple-band epileptic high-frequency oscillations (HFOs) can be recorded by scalp electroencephalography (EEG), and tend to be associated with epileptic spikes. However, there is a concern that the filtration of steep waveforms such as spikes may cause spurious oscillations or "false ripples." We excluded such possibility from at least some ripples by EEG differentiation, which, in theory, enhances high-frequency signals and does not generate spurious oscillations or ringing.

Methods: The subjects were 50 pediatric patients, and ten consecutive spikes during sleep were selected for each patient. Five hundred spike data segments were initially reviewed by two experienced electroencephalographers using consensus to identify the presence or absence of ripples in the ordinary filtered EEG and an associated spectral blob in time-frequency analysis (Session A). These EEG data were subjected to numerical differentiation (the second derivative was denoted as EEG″). The EEG″ trace of each spike data segment was shown to two other electroencephalographers who judged independently whether there were clear ripple oscillations or uncertain ripple oscillations or an absence of oscillations (Session B).

Results: In Session A, ripples were identified in 57 spike data segments (Group A-R), but not in the other 443 data segments (Group A-N). In Session B, both reviewers identified clear ripples (strict criterion) in 11 spike data segments, all of which were in Group A-R (p < 0.0001 by Fisher's exact test). When the extended criterion that included clear and/or uncertain ripples was used in Session B, both reviewers identified 25 spike data segments that fulfilled the criterion: 24 of these were in Group A-R (p < 0.0001).

Discussion: We have demonstrated that real ripples over scalp spikes exist in a certain proportion of patients. Ripples that were visualized consistently using both ordinary filters and the EEG″ method should be true, but failure to clarify ripples using the EEG″ method does not mean that true ripples are absent.

Conclusion: The numerical differentiation of EEG data provides convincing evidence that HFOs were detected in terms of the presence of such unusually fast oscillations over the scalp and the importance of this electrophysiological phenomenon.

Keywords: child; epilepsy; false ripple; fast oscillation (FO); high-frequency oscillation (HFO); scalp EEG.

FIGURE 1

Processing of EEG artifacts. Two artifacts that were caused by poor electrode contact at C4 (left panel). The EEG data at F4–C4 (pink rectangle) that were recorded from a 5-year-old boy is temporally expanded (right panel) (abrupt potential jumps at arrows). From the top: EEG processed with an FIR low-cut frequency (LCF) filter at 0.5 Hz; EEG LCF filtered at 80 Hz showing spurious oscillations; EEG’; and EEG″ showing no ringing. The corresponding time–frequency analysis is shown in Supplementary Figure 1A.

FIGURE 2

Processing of an EEG epileptic discharge. A spike-wave recorded from a 5-year-old boy (left panel). The EEG data (pink rectangle) at Cz–Pz including the spike (arrow) is temporally expanded and processed (right panel) as in Figure 1. Ripple oscillations can be seen in both the trace LCF filtered at 80 Hz and the EEG″ trace. The corresponding time–frequency analysis is shown in Supplementary Figure 1B.

FIGURE 3

Discordant judgment in an epileptic discharge (possible ripples that were not identified in Session A but identified using the extended criterion in Session B). Spike-waves are dominant over the right occipital region that was recorded from an 8-year-old girl (left panel), and the part of EEG data (pink rectangle) at T6–O2 including the spike (arrow) is temporally expanded and processed (right panel). From the top: filtered at 0.5 Hz; filtered at 80 Hz with background oscillations; time–frequency analysis (TFA) lacking clear spectral blobs; and the EEG″ trace showing spike-associated oscillations surrounded by noise-like background activity. In Session A, this spike was categorized as devoid of ripples, whereas in Session B, it was judged to include clear ripple oscillations by one reviewer and to include uncertain oscillations by the other.

FIGURE 4

A representative failure to detect ripples in Session B. Spike-waves are almost generalized in a sleep EEG that was recorded from an 8-year-old girl (left panel), and the EEG data (pink rectangle) at F3–C3 including the spike is temporally expanded and processed (right panel). From the top: filtered at 0.5 Hz; filtered at 80 Hz with ripple oscillations (underline) and background noise; TFA showing a clear spectral blob (arrow); and the EEG″ trace showing some spike-associated oscillations (underline) buried in noise-like background activity. In Session A, this spike was categorized as having ripples, whereas in Session B, neither of the reviewers judged it to include ripple oscillations.