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EEG power and high frequency activity in the seizure onset zone has been increasingly considered for its relationship with seizures in animal and human studies of epilepsy. We examine the relationship between quantitative EEG measures and metabolic imaging in epilepsy patients undergoing intracranial EEG (icEEG) analysis for seizure localization. Patients with mesial temporal lobe epilepsy (MTLE) and neocortical epilepsy (NE) were studied. Metabolic imaging was performed with MR spectroscopic imaging using N-acetyl aspartate (NAA) and creatine (Cr). All data were acquired from the mesial temporal lobe such that a direct comparison of the same anatomical regions between the two groups could be performed. While no difference was seen in the total power recorded from the mesial temporal lobe, the MTLE group had significantly greater power in the high frequency bands. There was a significant positive exponential relationship between total icEEG power with NAA/Cr in MTLE, R= +0.84 p<0.001, which was not seen in NE. There was also a significant negative relationship between fractional gamma power with NAA/Cr in MTLE R= −0.66 p<0.02, also not seen in NE. These data argue that within the seizure onset zone, the tight correlation between total power and NAA/Cr suggests that total electrical output is powered by available mitochondrial function. These data are also consistent with the hypothesis that high frequency activity is an abnormal manifestation of tissue injury.

Objective

There is compelling evidence that pathological high frequency oscillations (HFOs) called Fast Ripples (FR, 150–500 Hz) reflect abnormal synchronous neuronal discharges in areas responsible for seizure genesis in patients with mesial temporal lobe epilepsy (MTLE). It is hypothesized that morphological changes associated with hippocampal atrophy (HA) contribute to the generation of FR, yet there is limited evidence that hippocampal FR-generating sites correspond with local areas of atrophy.

Methods

Interictal HFOs were recorded from hippocampal microelectrodes in ten patients with MTLE. Rates of FR and Ripple discharge from each microelectrode were evaluated in relation to local measures of HA obtained using 3D MRI hippocampal modeling.

Results

Rates of FR discharge were three times higher in areas of significant local HA compared to rates in non-atrophic areas. Furthermore, FR occurrence correlated directly with the severity of damage in these local atrophic regions. In contrast, we found no difference in rates of Ripple discharge between local atrophic and non-atrophic areas.

Interpretation

The proximity between local HA and microelectrode-recorded FR suggest morphological changes such as neuron loss and synaptic reorganization may contribute to the generation of FR. Pathological HFOs, such as FR, may provide a reliable surrogate marker of abnormal neuronal excitability in hippocampal areas responsible for the generation of spontaneous seizures in patients with MTLE. Based on these data, it is possible that MRI-based measures of local HA could identify FR-generating regions, and thus provide a non-invasive means to localize epileptogenic regions in hippocampus.

Electroencephalography (EEG) has an important role in the diagnosis and classification of epilepsy. It can provide information for predicting the response to antiseizure drugs and to identify the surgically remediable epilepsies. In temporal lobe epilepsy (TLE) seizures could originate in the medial or lateral neocortical temporal region, and many of these patients are refractory to medical treatment. However, majority of patients have had excellent results after surgery and this often relies on the EEG and magnetic resonance imaging (MRI) data in presurgical evaluation. If the scalp EEG data is insufficient or discordant, invasive EEG recording with placement of intracranial electrodes could identify the seizure focus prior to surgery. This paper highlights the general information regarding the use of EEG in epilepsy, EEG patterns resembling epileptiform discharges, and the interictal, ictal and postictal findings in mesial temporal lobe epilepsy using scalp and intracranial recordings prior to surgery. The utility of the automated seizure detection and computerized mathematical models for increasing yield of non-invasive localization is discussed. This paper also describes the sensitivity, specificity, and predictive value of EEG for seizure recurrence after withdrawal of medications following seizure freedom with medical and surgical therapy.

Objective:

This study aims to identify if oscillations at frequencies higher than the traditional EEG can be recorded on the scalp EEG of patients with focal epilepsy and to analyze the association of these oscillations with interictal discharges and the seizure onset zone (SOZ).

Methods:

The scalp EEG of 15 patients with focal epilepsy was studied. We analyzed the rates of gamma (40–80 Hz) and ripple (>80 Hz) oscillations, their co-occurrence with spikes, the number of channels with fast oscillations inside and outside the SOZ, and the specificity, sensitivity, and accuracy of gamma, ripples, and spikes to determine the SOZ.

Results:

Gamma and ripples frequently co-occurred with spikes (77.5% and 63% of cases). For all events, the proportion of channels with events was consistently higher inside than outside the SOZ: spikes (100% vs 70%), gamma (82% vs 33%), and ripples (48% vs 11%); p < 0.0001. The mean rates (events/min) were higher inside than outside the SOZ: spikes (2.64 ± 1.70 vs 0.69 ± 0.26, p = 0.02), gamma (0.77 ± 0.71 vs 0.20 ± 0.25, p = 0.02), and ripples (0.08 ± 0.12 vs 0.04 ± 0.09, p = 0.04). The sensitivity to identify the SOZ was spikes 100%, gamma 82%, and ripples 48%; the specificity was spikes 30%, gamma 68%, and ripples 89%; and the accuracy was spikes 43%, gamma 70%, and ripples 81%.

Conclusion:

The rates and the proportion of channels with gamma and ripple fast oscillations are higher inside the SOZ, indicating that they can be used as interictal scalp EEG markers for the SOZ. These fast oscillations are less sensitive but much more specific and accurate than spikes to delineate the SOZ.

High-frequency cortical activity, particularly in the 250–600 Hz (fast ripple) band, has been implicated in playing a crucial role in epileptogenesis and seizure generation. Fast ripples are highly specific for the seizure initiation zone. However, evidence for the association of fast ripples with epileptic foci depends on animal models and human cases with substantial lesions in the form of hippocampal sclerosis, which suggests that neuronal loss may be required for fast ripples. In the present work, we tested whether cell loss is a necessary prerequisite for the generation of fast ripples, using a non-lesional model of temporal lobe epilepsy that lacks hippocampal sclerosis. The model is induced by unilateral intrahippocampal injection of tetanus toxin. Recordings from the hippocampi of freely-moving epileptic rats revealed high-frequency activity (>100 Hz), including fast ripples. High-frequency activity was present both during interictal discharges and seizure onset. Interictal fast ripples proved a significantly more reliable marker of the primary epileptogenic zone than the presence of either interictal discharges or ripples (100–250 Hz). These results suggest that fast ripple activity should be considered for its potential value in the pre-surgical workup of non-lesional temporal lobe epilepsy.

Neuronal oscillations span a wide range of spatial and temporal scales that extend beyond traditional clinical EEG. Recent research suggests that high-frequency oscillations (HFO), in the ripple (80–250Hz) and fast ripple (250–1000Hz) frequency range, may be signatures of epileptogenic brain and involved in the generation of seizures. However, most research investigating HFO in humans comes from microwire recordings, whose relationship to standard clinical intracranial EEG (iEEG) has not been explored. In this study iEEG recordings (DC − 9000Hz) were obtained from human medial temporal lobe using custom depth electrodes containing both microwires and clinical macroelectrodes. Ripple and fast-ripple HFO recorded from both microwires and clinical macroelectrodes were increased in seizure generating brain regions compared to control regions. The distribution of HFO frequencies recorded from the macroelectrodes was concentrated in the ripple frequency range, compared to a broad distribution of HFO frequencies recorded from microwires. The average frequency of ripple HFO recorded from macroelectrodes was lower than that recorded from microwires (143.3 ± 49.3 Hz versus 116.3 ± 38.4, Wilcoxon rank sum P<0.0001). Fast-ripple HFO were most often recorded on a single microwire, supporting the hypothesis that fast-ripple HFO are primarily generated by highly localized, sub-millimeter scale neuronal assemblies that are most effectively sampled by microwire electrodes. Future research will address the clinical utility of these recordings for localizing epileptogenic networks and understanding seizure generation.

Epilepsy represents a multifaceted group of disorders divided into two broad categories, partial and generalized, based on the seizure onset zone. The identification of the neuroanatomic site of seizure onset depends on delineation of seizure semiology by a careful history together with video-EEG, and a variety of neuroimaging technologies such as MRI, fMRI, FDG-PET, MEG, or invasive intracranial EEG recording. Temporal lobe epilepsy (TLE) is the commonest form of focal epilepsy and represents almost 2/3 of cases of intractable epilepsy managed surgically. A history of febrile seizures (especially complex febrile seizures) is common in TLE and is frequently associated with mesial temporal sclerosis (the commonest form of TLE). Seizure auras occur in many TLE patients and often exhibit features that are relatively specific for TLE but few are of lateralizing value. Automatisms, however, often have lateralizing significance. Careful study of seizure semiology remains invaluable in addressing the search for the seizure onset zone.

Fast ripples are high-frequency, 250-600 Hz field potential oscillations which can be recorded from hippocampal or neocortical structures. In the neocortex, fast ripples occur during both sensory information processing and under pathological, epileptic conditions. In the hippocampus and entorhinal cortex, fast ripples are exclusively associated with epilepsy and perhaps even mark the epileptogenic focus. In contrast to ripples, which regularly also occur in normal tissue and which are thought to reflect population spike bursts at 100 to 200 Hz paced and synchronised by recurrent inhibition, the fast ripple frequency range exceeds the maximal firing frequency of most neurones. Hence, particularly in the hippocampus, fast ripples must emerge as a network phenomenon and cannot reflect the activity of single spiking neurones. In this review, current views on the mechanisms and processes underlying fast ripples are discussed.

Patients with temporal lobe epilepsy (TLE) are refractory to antiepileptic drugs in about 30% of cases. Surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20–30% of TLE patients. Several reasons have been identified to explain these surgical failures. This paper will address the five most common causes of TLE surgery failure (a) insufficient resection of epileptogenic mesial temporal structures, (b) relapse on the contralateral mesial temporal lobe, (c) lateral temporal neocortical epilepsy, (d) coexistence of mesial temporal sclerosis and a neocortical lesion (dual pathology); and (e) extratemporal lobe epilepsy mimicking TLE or temporal plus epilepsy. Persistence of epileptogenic mesial structures in the posterior temporal region and failure to distinguish mesial and lateral temporal epilepsy are possible causes of seizure persistence after TLE surgery. In cases of dual pathology, failure to identify a subtle mesial temporal sclerosis or regions of cortical microdysgenesis is a likely explanation for some surgical failures. Extratemporal epilepsy syndromes masquerading as or coexistent with TLE result in incomplete resection of the epileptogenic zone and seizure relapse after surgery. In particular, the insula may be an important cause of surgical failure in patients with TLE.

Background and Purpose

There is growing interest in high-frequency oscillations (HFO) as electrophysiological biomarkers of the epileptic brain. We evaluated the clinical utility of interictal HFO events, especially their occurrence rates, by comparing the spatial distribution with a clinically determined epileptogenic zone by using subdural macroelectrodes.

Methods

We obtained intracranial electroencephalogram data with a high temporal resolution (2000 Hz sampling rate, 0.05-500 Hz band-pass filter) from seven patients with medically refractory epilepsy. Three epochs of 5-minute, artifact-free data were selected randomly from the interictal period. HFO candidates were first detected by an automated algorithm and subsequently screened to discard false detections. Validated events were further categorized as fast ripple (FR) and ripple (R) according to their spectral profiles. The occurrence rate of HFOs was calculated for each electrode contact. An HFO events distribution map (EDM) was constructed for each patient to allow visualization of the spatial distribution of their HFO events.

Results

The subdural macroelectrodes were capable of detecting both R and FR events from the epileptic neocortex. The occurrence rate of HFO events, both FR and R, was significantly higher in the seizure onset zone (SOZ) than in other brain regions. Patient-specific HFO EDMs can facilitate the identification of the location of HFO-generating tissue, and comparison with findings from ictal recordings can provide additional useful information regarding the epileptogenic zone.

Conclusions

The distribution of interictal HFOs was reasonably consistent with the SOZ. The detection of HFO events and construction of spatial distribution maps appears to be useful for the presurgical mapping of the epileptogenic zone.

Continuous, long-term (up to 10 days) electrophysiological monitoring using hybrid intracranial electrodes is an emerging tool for presurgical epilepsy evaluation and fundamental investigations of seizure generation. Detection of high-frequency oscillations and microseizures could provide valuable insights into causes and therapies for the treatment of epilepsy, but requires high spatial and temporal resolution. Our group is currently using hybrid arrays composed of up to 320 micro- and clinical macroelectrode arrays sampled at 32 kHz per channel with 18-bits of A/D resolution. Such recordings produce approximately 3 terabytes of data per day. Existing file formats have limited data compression capabilities, and do not offer mechanisms for protecting patient identifying information or detecting data corruption during transmission or storage. We present a novel file format that employs range encoding to provide a high degree of data compression, a three-tiered 128-bit encryption system for patient information and data security, and a 32-bit cyclic redundancy check to verify the integrity of compressed data blocks. Open-source software to read, write, and process these files are provided.

SUMMARY

Purpose

To investigate the characteristics of intracranial ictal high frequency oscillations (HFOs).

Methods

Among neocortical epilepsy patients who underwent intracranial monitoring and surgery, we studied patients with well-defined, unifocal seizure onsets characterized by discrete HFOs (≥70 Hz). Patients with multifocal or bilateral independent seizure onsets, EEG acquired at <1,000 Hz sampling rate and non-resective surgery were excluded. Based on a prospectively-defined protocol, we defined the seizure onset zone (SOZ) presurgically to include only those channels with HFOs that showed subsequent sustained evolution (HFOs+ev channels) but not the channels that lacked evolution (HFOs-ev channels). We then resected the SOZ as defined above, 1 cm of the surrounding cortex and immediate spread area, modified by the presence of eloquent cortex in the vicinity. For purposes of this study, we also defined the SOZ based on the conventional frequency activity (CFA: <70 Hz) at seizure onset although that information was not considered for preoperative determination of the surgical boundary. We investigated the temporal and spatial characteristics of the ictal HFOs post-hoc by visual and spectral methods, and also compared them to the seizure onset defined by the CFA.

Key Findings

Out of 14 consecutive neocortical epilepsy patients, six patients met the inclusion criteria. MRI was normal or showed heterotopia. All had subdural electrodes, with additional intracerebral depth electrodes in some. Electrode coverage was extensive (median 94 channels), including limited contralateral coverage. Seizure onsets were lobar or multilobar. Resections were performed per protocol except in two patients where complete resection of the SOZ could not be done due to overlap with speech area. Histology was abnormal in all patients. Postoperative outcome was class I/II (n=5, 83%) or class III over a mean follow-up of 27 months. Post-hoc analysis of 15 representative seizures showed that the ictal HFOs were widespread at seizure onset but evolved subsequently with different characteristics. In contrast to HFOs-ev, the HFOs+ev were significantly higher in peak frequency (97.1 versus 89.1 Hz, p=0.001), more robust (nearly 2-fold higher peak power, p<0.0001), and spatially restricted [mean 12.2 versus 22.4 channels; odds ratio (OR) 0.51, 95% confidence interval (CI) 0.42–0.62; p<0.0001]. The seizure onset defined by HFOs+ev was earlier (by an average of 0.41 sec), and occurred in a significantly different and smaller distribution (OR 0.27, 95% CI 0.21–0.34, p<0.0001), than the seizure onset defined by the CFA. As intended, the HFOs+ev channels were 10 times more likely to have been resected than the HFOs-ev channels (OR 9.7, 95% CI 5–17, p<0.0001).

Significance

Our study demonstrates the widespread occurrence of ictal HFOs at seizure onset, outlines a practical method to localize the SOZ based on their restricted pattern of evolution, and highlights the differences between the SOZs defined by HFOs and CFA. We show that smaller resections, restricted mainly to the HFOs channels with evolution, can lead to favorable seizure outcome. Our findings support the notion of widespread epileptic networks underlying neocortical epilepsy.

Object

Intracranial monitoring for temporal lobe seizure localization to differentiate neocortical from mesial temporal onset seizures requires both neocortical subdural grids and hippocampal depth electrode implantation. There are 2 basic techniques for hippocampal depth electrode implantation. This first technique uses a stereotactically guided 8-contact depth electrode directed along the long axis of the hippocampus to the amygdala via an occipital bur hole. The second technique involves direct placement of 2 or 3 4-contact depth electrodes perpendicular to the temporal lobe through the middle temporal gyrus and overlying subdural grid. The purpose of this study was to determine whether one technique was superior to the other by examining monitoring success and complications.

Methods

Between 1997 and 2005, 41 patients underwent invasive seizure monitoring with both temporal subdural grids and depth electrodes placed in 2 ways. Patients in Group A underwent the first technique, and patients in Group B underwent the second technique.

Results

Group A consisted of 26 patients and Group B 15 patients. There were no statistically significant differences between Groups A and B regarding demographics, monitoring duration, seizure localization, or outcome (Engel classification). There was a statistically significant difference at the point in time at which these techniques were used: Group A represented more patients earlier in the series than Group B (p < 0.05). The complication rate attributable to the grids and depth electrodes was 0% in each group. It was more likely that the depth electrodes were placed through the grid if there was a prior resection and the patient was undergoing a new evaluation (p < 0.05). Furthermore, Group A procedures took significantly longer than Group B procedures.

Conclusions

In this patient series, there was no difference in efficacy of monitoring, complications, or outcome between hippocampal depth electrodes placed laterally through temporal grids or using an occipital bur hole stereotactic approach. Placement of the depth electrodes perpendicularly through the grids and middle temporal gyrus is technically more practical because multiple head positions and redraping are unnecessary, resulting in shorter operative times with comparable results.

SUMMARY

Purpose

We sought to characterize spatial and temporal patterns of electrocorticography (ECoG) very fast oscillations (> ~80 Hz, VFOs) prior to seizures in human frontotemporal neocortex, and to develop a testable network model of these patterns.

Methods

ECoG data were recorded with subdural grids from two preoperative patients with seizures of frontal lobe onset in an epilepsy monitoring unit. VFOs were recorded from rat neocortical slices. A “cellular automaton” model of network oscillations was developed, extending ideas of Traub et al. (Neuroscience, 92, 1999, 407) and Lewis & Rinzel (Network: Comput Neural Syst, 11, 12000, 299); this model is based on postulated electrical coupling between pyramidal cell axons.

Results

Layer 5 of rat neocortex, in vitro, can generate VFOs when chemical synapses are blocked. Human epileptic neocortex, in situ, produces preseizure VFOs characterized by the sudden appearance of “blobs” of activity that evolve into spreading wavefronts. When wavefronts meet, they coalesce and propagate perpendicularly but never pass through each other. This type of pattern has been described by Lewis & Rinzel in cellular automaton models with spatially localized connectivity, and is demonstrated here with 120,000- to 5,760,000-cell models. We provide a formula for estimating VFO period from structural parameters and estimate the spatial scale of the connectivity.

Discussion

These data provide further evidence, albeit indirect, that preseizure VFOs are generated by networks of pyramidal neurons coupled by gap junctions, each predominantly confined to pairs of neurons having somata separated by < ~1–2 mm. Plausible antiepileptic targets are tissue mechanisms, such as pH regulation, that influence gap-junction conductance.

Defining precisely the site of seizure onset has important implication for our understanding of the pathophysiology of temporal lobe epilepsy as well as for the surgical treatment of the disorder. Removal of the limbic areas of the medial temporal lobe has led to a high rate of seizure control, but the relatively large number of patients for whom seizure control is incomplete as well as the low rate of surgical cure suggest that the focus extends beyond the usual limits of surgical resection. A reevaluation of the extent of the pathology as well as new data from animal models suggest that the seizure focus extends, at least in some cases, beyond the hippocampus and amygdala that are usually removed at the time of surgery. In this review we will examine current information about the pathology and physiology of the mesial temporal lobe epilepsy syndrome, with a special emphasis on the distribution of the changes and the patterns of seizure onset. We will then propose a hypothesis for the nature of the seizure focus in this disorder and discuss its clinical implications, with the ultimate goal of improving surgical outcomes and developing nonsurgical therapies that may improve seizure control.

Complex partial seizures (CPSs) can present with various semiologies, while mesial temporal lobe epilepsy (mTLE) is a well-recognized cause of CPS, neocortical temporal lobe epilepsy (nTLE) albeit being less common is increasingly recognized as separate disease entity. Differentiating the two remains a challenge for epileptologists as many symptoms overlap due to reciprocal connections between the neocortical and the mesial temporal regions. Various studies have attempted to correctly localize the seizure focus in nTLE as patients with this disorder may benefit from surgery. While earlier work predicted poor outcomes in this population, recent work challenges those ideas yielding good outcomes in part due to better localization using improved anatomical and functional techniques. This paper provides a comprehensive review of the diagnostic workup, particularly the application of recent advances in electroencephalography and functional brain imaging, in neocortical temporal lobe epilepsy.

OBJECTIVES—To assess patterns of postictal cerebral blood flow in the mesial temporal lobe by coregistration of postictal 99mTc-HMPAO SPECT with MRI in patients with confirmed mesial temporal lobe epilepsy.
METHODS—Ten postictal and interictal 99mTc-HMPAO SPECT scans were coregistered with MRI in 10 patients with confirmed mesial temporal lobe epilepsy. Volumetric tracings of the hippocampus and amygdala from the MRI were superimposed on the postictal and interictal SPECT. Asymmetries in hippocampal and amygdala SPECT signal were then calculated using the equation:
 % Asymmetry =100 × (right − left) / (right + left)/2.
RESULTS—In the postictal studies, quantitative measurements of amygdala SPECT intensities were greatest on the side of seizure onset in all cases, with an average % asymmetry of 11.1, range 5.2-21.9.Hippocampal intensities were greatest on the side of seizure onset in six studies, with an average % asymmetry of 9.6, range 4.7-12.0.In four scans the hippocampal intensities were less on the side of seizure onset, with an average % asymmetry of 10.2, range 5.7-15.5.There was no localising quantitative pattern in interictal studies.
CONCLUSIONS—Postictal SPECT shows distinctive perfusion patterns when coregistered with MRI, which assist in lateralisation of temporal lobe seizures. Hyperperfusion in the region of the amygdala is more consistently lateralising than hyperperfusion in the region of the hippocampus in postictal studies.



Summary

Purpose

Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure-onset zone is near eloquent cortex. Determining the seizure-onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High-frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown.

Methods

We identified 48 patients who underwent surgical treatment after the surgical evaluation with intracranial EEG, and 44 patients met criteria for this retrospective study. Results were not used in surgical decision making. Intracranial EEG recordings were collected with a sampling rate of 2,000 Hz. Recordings were first inspected visually to determine ictal onset and then analyzed further with time-frequency analysis. Forty-one (93%) of 44 patients had ictal HFOs determined with time-frequency analysis of intracranial EEG.

Key Findings

Twenty-two (54%) of the 41 patients with ictal HFOs had complete resection of HFO regions, regardless of frequency bands. Complete resection of HFOs (n = 22) resulted in a seizure-free outcome in 18 (82%) of 22 patients, significantly higher than the seizure-free outcome with incomplete HFO resection (4/19, 21%).

Significance

Our study shows that ictal HFOs are commonly found with intracranial EEG in our population largely of children with cortical dysplasia, and have localizing value. The use of ictal HFOs may add more promising information compared to interictal HFOs because of the evidence of ictal propagation and followed by clinical aspect of seizures. Complete resection of HFOs is a favorable prognostic indicator for surgical outcome.

Summary

Purpose

Determination of the origin of extra-temporal neocortical onset seizures is often challenging due to the rapid speed in which they propagate throughout the cortex. Typically, these patients are poor surgical candidates and many times experience recurrences of seizure activity following resection of the assumed seizure focus.

Methods

We applied a causal measurement technique – the directed transfer function (DTF) – in an effort to determine the cortical location responsible for the propagation of the seizure actvity. Intracranial seizure recordings were obtained from a group of eleven pediatric patients with medically intractable neocortical-onset epilepsy. Time windows were selected from the recordings following onset of the ictal activity. The DTF was applied to the selected time windows and the frequency-specific statistically significant source activity arising from each cortical recording site was quantified. The DTF-estimated source activity was then compared with the seizure onset zone(s) identified by the epileptologists.

Results

In an analysis of the eleven pediatric patients, the DTF was shown to identify estimated ictal sources which were highly correlated with the clinically-identified foci. Additionally, it was observed that in the patients with multiple ictal foci, the topography of the casual source activity from the analyzed seizures was associated with the separate clinically-identified seizure onset zones.

Discussion

Although localization of neocortical-onset seizures is typically challenging, the causal measures employed in this study – namely the directed transfer function – identified generators of the ictal activity which were highly correlated with the cortical regions identified as the seizure onset zones by the epileptologists. This technique could prove useful in the identification of seizure-specific propagation pathways in the presurgical evaluation of patients with epilepsy.

Objective

To quantify the ictal subdural electroencephalogram (EEG) changes using spectral analysis, and to delineate the quantitatively defined ictal onset zones on high-resolution 3D MR images in children with intractable neocortical epilepsy.

Methods

Fourteen children with intractable neocortical epilepsy (age: 1–16 years) who had subsequent resective surgery were retrospectively studied. The subjects underwent a high-resolution MRI and prolonged subdural EEG recording. Spectral analysis was applied to 3 habitual focal seizures. After fast Fourier transformation of the EEG epoch at ictal onset, an amplitude spectral curve (square root of the power spectral curve) was created for each electrode. The EEG magnitude of ictal rhythmic discharges was defined as the area under the amplitude spectral curve within a preset frequency band including the ictal discharge frequency, and calculated for each electrode. The topography mapping of ictal EEG magnitude was subsequently displayed on a surface-rendered MRI. Finally, receiver operating characteristic (ROC) analysis was performed to evaluate the consistency between quantitatively and visually defined ictal onset zones.

Results

The electrode showing the maximum of the averaged ictal EEG magnitude was part of the visually defined ictal onset zone in all cases. ROC analyses demonstrated that electrodes showing >30% of the maximum of the averaged ictal EEG magnitude had a specificity of 0.90 and a sensitivity of 0.74 for the concordance with visually defined ictal onset zones.

Significance

Quantitative ictal subdural EEG analysis using spectral analysis may supplement conventional visual inspection in children with neocortical epilepsy by providing an objective definition of the onset zone and its simple visualization on the patient’s MRI.

The use of large-scale electrophysiology to obtain high spatiotemporal resolution brain recordings (>100 channels) capable of probing the range of neural activity from local field potential oscillations to single neuron action potentials presents new challenges for data acquisition, storage, and analysis. Our group is currently performing continuous, long-term electrophysiological recordings in human subjects undergoing evaluation for epilepsy surgery using hybrid intracranial electrodes composed of up to 320 micro- and clinical macroelectrode arrays. DC-capable amplifiers, sampling at 32 kHz per channel with 18-bits of A/D resolution are capable of resolving extracellular voltages spanning single neuron action potentials, high frequency oscillations, and high amplitude ultraslow activity, but this approach generates 3 terabytes of data per day (at 4 bytes per sample) using current data formats. Data compression can provide several practical benefits, but only if data can be compressed and appended to files in real-time in a format that allows random access to data segments of varying size. Here we describe a state-of-the-art, scalable, electrophysiology platform designed for acquisition, compression, encryption, and storage of large-scale data. Data are stored in a file format that incorporates lossless data compression using range encoded differences, a 32-bit cyclically redundant checksum to ensure data integrity, and 128-bit encryption for protection of patient information.

As the major inhibitory neurotransmitter in human brain, GABA is an important modulator of hyperexcitability in epilepsy patients. Given the high energetic cost of neurotransmission and synaptic activity, GABA concentrations may be hypothesized to correlate with metabolic function. We studied human epilepsy patients undergoing intracranial EEG monitoring for seizure localization to examine microdialysis measures of extracellular GABA (ecGABA), pre-operative MR spectroscopic measures of neuronal mitochondrial function (NAA/Cr), and wherever possible, neuropathology and hippocampal volumetry. Two groups undergoing intracranial monitoring for seizure localization were studied: surgically treated hippocampal epilepsy (MTLE) and neocortical (non-hippocampal seizure onset) epilepsy. All data are hippocampal and thus these groups allow comparisons between the epileptogenic and non-epileptogenic regions. ecGABA was measured using in vivo microdialysis performed during intracranial monitoring. Pre-operative in vivo MR spectroscopic imaging was performed to measure the ratio of N-acetyl aspartate (NAA) to creatine. Standard methods for neuropathology and hippocampal volumetry were used. In the neocortical group, increased ecGABA correlated with greater NAA/Cr (R=+0.70, p<0.015, n=12) while in the MTLE group, increased ecGABA linked with decreased NAA/Cr (R=−0.94, p<0.001, n=8). In MTLE, ecGABA (increased) and NAA/Cr (decreased) correlated with increased glial cell numbers (R=+0.71, p<0.01, n=12, R=−0.76 p<0.03 respectively). No relationship was seen between ecGABA and hippocampal volumes in either group. In epilepsy, ecGABA increases occur across a range of metabolic function. Outside the seizure focus, ecGABA and NAA/Cr increase together; in contrast, within the seizure focus, ecGABA increases with declining mitochondrial function.

Widespread changes involving neocortical as well as mesial temporal lobe structures can be present in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). The incidence, pathology and clinical significance of neocortical temporal lobe sclerosis (TLS) are not well characterized. We identified TLS in 30 out of 272 surgically treated cases of HS. TLS was defined by variable reduction of neurons from cortical layers II/III and laminar gliosis; it was typically accompanied by additional architectural abnormalities of layer II, i.e. abnormal neuronal orientation and aggregation. Quantitative analysis including tessellation methods for the distribution of layer II neurons supported these observations. In 40% of cases there was a gradient of TLS with more severe involvement towards the temporal pole, possibly signifying involvement of hippocampal projection pathways. There was a history of a febrile seizure as an initial precipitating injury in 73% of patients with TLS compared to 36% without TLS; no other clinical differences TLS and non-TLS cases were identified. TLS was not evident pre-operatively by neuroimaging. No obvious effect of TLS on seizure outcome was noted after temporal lobe resection; 73% became seizure-free at 2 year follow up. In conclusion, approximately 11% of surgically treated HS is accompanied by TLS. TLS is likely an acquired process with accompanying re-organizational dysplasia and an extension of mesial temporal sclerosis rather than a separate pathological entity.

In patients with epilepsy, mood disorders represent a frequent psychiatric comorbidity but they often remain unrecognized and untreated. However, comorbid depression may have a major impact on the quality of life of patients with epilepsy, sometimes even more than the seizures. Among the potential neurobiological and psychosocial determinants, epilepsy-related variables (age at onset of seizures, temporal lobe epilepsy and frequency of seizures) and the antiepileptic drug treatment have been associated with depression. Nonetheless, data on treatment strategies are still limited with a lack of controlled trials on the use of antidepressant drugs. Moreover, the issue of psychotropic drug treatment of depression in epilepsy is interlinked with that of worsening seizures. This paper is aimed at discussing all these subjects in the light of current literature on the neurobiology of depression in epilepsy.

To investigate the epileptogenic foci in dysembryoplastic neuroepithelial tumor (DNT) in the temporal lobe, we studied extraoperative electrocorticography (ECoG) with subdural electrode arrays from nine patients with intractable epilepsy due to temporal DNT. Ictal onset zones and irritative zones were decided by the ECoG. The locations of these zones were compared to the location of the tumor. The number of ictal onset zone and irritative zone was 2.1+/-0.93 and 2.9+/-1.45 in a patient with a DNT. They were detected more frequently in the adjacent tissues of the tumor (88.9%) rather than within the tumor or in mesial temporal area (66.7%). Mesial temporal involvement was found in 6 patients (66.7%) as an ictal onset zone, and in 5 (55.6%) as an irritative zone. The 7 patients (77.8%) had ictal onset zone in areas different from active irritative zone. The surgical outcome was better, when ictal onset zone was completely resected rather than partially removed. Temporal DNT can make multiple ictal onset zones and irritative zones in different regions including the mesial temporal area. Deliberate resection of epileptogenic foci, including all ictal onset zones and irritative zones, ensures excellent seizure control.