Kurtosis and skewness of high-frequency brain signals are altered in paediatric epilepsy

Intracranial studies provide solid evidence that high-frequency brain signals are a new biomarker for epilepsy. Unfortunately, epileptic (pathological) high-frequency signals can be intermingled with physiological high-frequency signals making these signals difficult to differentiate. Recent success in non-invasive detection of high-frequency brain signals opens a new avenue for distinguishing pathological from physiological high-frequency signals. The objective of the present study is to characterize pathological and physiological high-frequency signals at source levels by using kurtosis and skewness analyses. Twenty-three children with medically intractable epilepsy and age-/gender-matched healthy controls were studied using magnetoencephalography. Magnetoencephalographic data in three frequency bands, which included 2-80 Hz (the conventional low-frequency signals), 80-250 Hz (ripples) and 250-600 Hz (fast ripples), were analysed. The kurtosis and skewness of virtual electrode signals in eight brain regions, which included left/right frontal, temporal, parietal and occipital cortices, were calculated and analysed. Differences between epilepsy and controls were quantitatively compared for each cerebral lobe in each frequency band in terms of kurtosis and skewness measurements. Virtual electrode signals from clinical epileptogenic zones and brain areas outside of the epileptogenic zones were also compared with kurtosis and skewness analyses. Compared to controls, patients with epilepsy showed significant elevation in kurtosis and skewness of virtual electrode signals. The spatial and frequency patterns of the kurtosis and skewness of virtual electrode signals among the eight cerebral lobes in three frequency bands were also significantly different from that of the controls (2-80 Hz, P < 0.001; 80-250 Hz, P < 0.00001; 250-600 Hz, P < 0.0001). Compared to signals from non-epileptogenic zones, virtual electrode signals from epileptogenic zones showed significantly altered kurtosis and skewness (P < 0.001). Compared to normative data from the control group, aberrant virtual electrode signals were, for each patient, more pronounced in the epileptogenic lobes than in other lobes(kurtosis analysis of virtual electrode signals in 250-600 Hz; odds ratio = 27.9; P < 0.0001). The kurtosis values of virtual electrode signals in 80-250 and 250-600 Hz showed the highest sensitivity (88.23%) and specificity (89.09%) for revealing epileptogenic lobe, respectively. The combination of virtual electrode and kurtosis/skewness measurements provides a new quantitative approach to distinguishing pathological from physiological high-frequency signals for paediatric epilepsy. Non-invasive identification of pathological high-frequency signals may provide novel important information to guide clinical invasive recordings and direct surgical treatment of epilepsy.