Identification of epileptogenic foci from causal analysis of ECoG interictal spike activity
Introduction
Epilepsy is one of the most common neurological disorders with an estimated worldwide incidence of 0.5–1%. While advances in pharmacologic agents have aided in the treatment and suppression of epileptic events, a significant number of patients continue to have uncontrolled seizures despite optimal medical management. In these cases, surgical intervention is at times the only remaining option if standard medical therapies have failed. If the cortical regions responsible for the initiation and propagation of the ictal activity – the so-called epileptogenic zone – are found to be focal in nature and confined to non-eloquent cortex, they may be surgically removed to alleviate the patient’s symptoms.
Electrocorticogram (ECoG) recordings are used to aid in the localization of the epileptogenic zone in a majority of these surgical candidates (Engel and Ojemann, 1993). This technique, which involves recording from localized intracranial sites for extended periods of time, has remained largely unchanged over the past 50 years (Walker, 1949, Penfield and Jasper, 1954). Today, in the absence of abnormalities on structural imaging studies, the clinical gold standard for determining the location and extent of the epileptogenic zone remains ECoG analysis of the ictal activity (Ebersole and Pedley, 2003).
In addition to ictal activity, interictal spikes are also assumed to be markers of the epileptogenic cortex. The localization of the seizure-generating regions of cortex from interictal spikes has drawn significant interest due to their abundance compared to the relatively rare ictal events. However, the precise relationship between the seizure-onset zone (SOZ) and interictal spike activity remains somewhat amorphous. Numerous studies have shown that positive surgical outcome does not necessarily depend upon resection of the entire region displaying spiking activity (Tran et al., 1995, Kanazawa et al., 1996, Alarcon et al., 1997, Ebersole, 2000a, Ulbert et al., 2004). While these studies have indicated that the presence of interictal spike activity is not a good measure by which to determine the SOZ, other studies have examined the propagation patterns of the interictal spikes as a surrogate for defining the cortical generators of the ictal activity. The propagation of interictal spikes from the generating regions has been known for some time (Penfield and Jasper, 1954), although recent advances in computational techniques have made this type of analysis more practical. In animal models of epilepsy, studies in cortical slices have shown the epileptiform activity to arise from considerably focal regions of cortex (Tsau et al., 1999, Wu et al., 1999). Similarly in humans, a study by Alarcon et al. (1997) found that resection of the regions which acted as pacemakers of the interictal activity was associated with improved post-surgical outcome (Alarcon et al., 1997). More recently, a study performed by Lai et al. (2007) has shown that analysis of the time latency during interictal spike propagation can be used to estimate the SOZ in a cohort of epileptic patients (Lai et al., 2007).
Due to the observed propagation of the interictal spike activity from the source region to the surrounding cortex, techniques to estimate brain connectivity could be potentially useful in identification of the SOZ. The majority of these techniques estimate the flow of information throughout the brain based upon the concept of Granger causality (Granger, 1969). Several of these methods have been shown to successfully locate the sources of brain activity in both patients with epilepsy as well as normal subjects performing standard neuroscience paradigms (Friston, 1994, Kaminski et al., 1997, Baccala and Sameshima, 2001, Baccala et al., 2004, Brovelli et al., 2004, Astolfi et al., 2005, Babiloni et al., 2005, Astolfi et al., 2007, Ding et al., 2007, Supp et al., 2007).
One such method for estimating cortical connectivity is the directed transfer function (DTF) first described by Kaminski and Blinowska (1991). The DTF is a type of causality estimate applied to multivariate systems, such as EEG/ECoG recordings, and has previously been shown to accurately identify the SOZ from ictal recordings in patients with mesial temporal lobe epilepsy (Franaszczuk et al., 1994, Franaszczuk and Bergey, 1998). It is defined in the framework of the multivariate autoregressive (MVAR) model. In this procedure, a single set of model coefficients are obtained from the analyzed time series. Due to the time-invariant nature of these coefficients, the underlying assumption that accompanies the utilization of the DTF method is that the data must be stationary over the analyzed time window. While this assumption may hold true for selected ictal segments, the same cannot be assumed for temporally short events such as interictal spikes.
We have recently examined a dynamic measure of causality, termed the adaptive directed transfer function (ADTF), in order to overcome the limitation posed by this conventional approach (Wilke et al., 2008). This technique utilizes time-variant coefficients obtained from an adaptive multivariate autoregressive (AMVAR) model in order to obtain the connectivity information from transient events. In preliminary studies, the ADTF method has been shown to possess the capability to identify sources of temporally short processes.
In this study, we apply the ADTF technique to interictal spike data collected from ECoG recordings in a group of pediatric patients with neocortical-onset epilepsy. This group of patients was selected based upon the close proximity of the SOZ to the intracranial grids. We compare our results obtained using the ADTF method with the epileptogenic foci determined by the clinicians from ictal ECoG recordings.
Section snippets
Patients
Intracranial EEG recordings were obtained from a group of eight pediatric patients (3M/5F, ages 7–14) undergoing surgical evaluation for the treatment of medically intractable epilepsy at the University of Chicago’s Pediatric Epilepsy Center. The patients were selected on the criterion that each presented with complex partial seizures with at least one neocortical focus. All of the selected patients underwent surgical resection of the presumed seizure focus/foci and all experienced significant
Results
Seven spikes were selected from the interictal recordings in Patient 1. The ADTF results prior to the thresholding procedure for four of the selected spikes are shown in Fig. 4. The cortical potentials corresponding to each of the four spikes are also shown for reference. As can be observed from Fig. 4, the cortical regions displaying the peak magnitude during the interictal spike are not necessarily correlated with the areas containing the greatest interictal spike source activity. Differences
Discussion
Several techniques have been utilized to discern the flow of information throughout the brain structures during temporally short processes (Schack and Krause, 1995, Ding et al., 2000, Hesse et al., 2003, Philiastides and Sajda, 2006, Astolfi et al., 2008). These methods, which have typically focused upon analysis of event related potentials (ERPs) obtained during simple cognitive tasks, have revealed the capability to capture short causal interactions between cortical regions. To our knowledge,
Acknowledgements
This work was supported in part by NIH RO1EB007920, RO1EB00178, T32EB008389, and a grant from the Institute of Engineering in Medicine of the University of Minnesota.
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