Ictal high‐frequency oscillations in neocortical epilepsy: implications for seizure localization and surgical resection

In the last two decades, the association between high frequency oscillations (HFOs) and epileptogenicity has become increasingly evident. From their initial description in animals using microwire recordings (Buzsaki et al., 1992), the HFOs have now been successfully recorded in human epileptic patients (Bragin et al., 1999a, Jirsch et al., 2006, Ochi et al., 2007, Worrell et al., 2008, Khosravani et al., 2009, Modur and Scherg, 2009). To date, most of the published literature on HFOs has focused on interictal HFOs, broadly classified as ripples (80–250 Hz) and fast ripples (250–500 Hz) (Bragin et al., 1999a). It has been suggested that the interictal HFOs localize the epileptogenic focus (Jirsch et al., 2006), generate seizures (Bragin et al., 1999b, Bragin et al., 2000, Staba et al., 2002, Timofeev and Steriade, 2004, Worrell et al., 2008), correlate with surgical outcome (Jacobs et al., 2010, Wu et al., 2010), and provide markers for epileptogenicity (Jacobs et al., 2009) and epileptic disease activity (Zijlmans et al., 2009). In contrast to the interictal HFOs, only a limited number of studies have explored the ictal HFOs (i.e., the HFOs occurring at seizure onset). Although the frequency cut-off for ictal HFOs is not clearly defined, we found a 60 Hz cut-off to be useful in practice (Rodin et al., 2009). Traditionally, the seizure onset zone (SOZ) is defined based on conventional frequency activity (CFA: 1–70 Hz), consisting of low voltage beta or gamma activity, rhythmic sinusoidal activity, or rhythmic or semi-rhythmic spikes (Schiller et al., 1998, Lee et al., 2000). However, several studies have convincingly demonstrated the occurrence of HFOs at neocortical seizure onset, suggesting their advantage in a more accurate localization of the seizure focus (Fisher et al., 1992, Alarcon et al., 1995, Worrell et al., 2004, Ochi et al., 2007, Modur and Scherg, 2009). The neocortical seizures, unlike seizures of mesial temporal onset, can arise anywhere in the vast expanse of the cerebral cortex, necessitating extensive (often bilateral) intracranial coverage. While the earlier studies were limited to a maximum of 16 contacts to evaluate the ictal HFOs (Allen et al., 1992, Fisher et al., 1992, Alarcon et al., 1995), the later studies were limited by either the narrow bandwidth (200 Hz sampling rate) of recording (Worrell et al., 2004) or the use of a combination of electrodes (depth and epidural) with different morphological characteristics (Jirsch et al., 2006). Thus, the methodological differences and limitations preclude definitive conclusions regarding the spatial characteristics of HFOs, and therefore, their utility in seizure localization. However, a few recent studies have described the ictal HFOs in neocortical epilepsy using extensive intracranial coverage (Akiyama et al., 2005, Ochi et al., 2007, Modur and Scherg, 2009). We reported a patient with MRI-negative frontal lobe epilepsy in whom the ictal HFOs occurred in a widespread distribution at seizure onset, evolved in a more restricted fashion, and localized the SOZ to a much smaller area than the CFA (Modur and Scherg, 2009). In the present study, we aimed to extend and confirm our findings by investigating the ictal HFOs in a larger group of neocortical epilepsy patients who underwent resective surgery. Specifically, we analyzed the EEG data post-hoc using visual and spectral methods to evaluate the frequency and spatial characteristics of the ictal HFOs. We also compared the characteristics of the SOZ defined by the ictal HFOs to the SOZ defined by the CFA although the latter was not considered for determining the surgical boundary in our cohort.