Distinction of Physiologic and Epileptic Ripples: An Electrical Stimulation Study

Ripple oscillations (80-250 Hz) are a promising biomarker of epileptic activity, but are also involved in memory consolidation, which impairs their value as a diagnostic tool. Distinguishing physiologic from epileptic ripples has been particularly challenging because usually, invasive recordings are only performed in patients with refractory epilepsy. Here, we identified 'healthy' brain areas based on electrical stimulation and hypothesized that these regions specifically generate 'pure' ripples not coupled to spikes. Intracranial electroencephalography (EEG) recorded with subdural grid electrodes was retrospectively analyzed in 19 patients with drug-resistant focal epilepsy. Interictal spikes and ripples were automatically detected in slow-wave sleep using the publicly available Delphos software. We found that rates of spikes, ripples and ripples coupled to spikes ('spike-ripples') were higher inside the seizure-onset zone (p < 0.001). A comparison of receiver operating characteristic curves revealed that spike-ripples slightly delineated the seizure-onset zone channels, but did this significantly better than spikes (p < 0.001). Ripples were more frequent in the eloquent neocortex than in the remaining non-seizure onset zone areas (p < 0.001). This was due to the higher rates of 'pure' ripples (p < 0.001; median rates 3.3/min vs. 1.4/min), whereas spike-ripple rates were not significantly different (p = 0.87). 'Pure' ripples identified 'healthy' channels significantly better than chance (p < 0.001). Our findings suggest that, in contrast to epileptic spike-ripples, 'pure' ripples are mainly physiological. They may be considered, in addition to electrical stimulation, to delineate eloquent cortex in pre-surgical patients. Since we applied open source software for detection, our approach may be generally suited to tackle a variety of research questions in epilepsy and cognitive science.