J Neural Eng. 2015 Apr;12(2):026011. doi: 10.1088/1741-2560/12/2/026011. Epub 2015 Mar 13.
Defining regions of interest using cross-frequency coupling in extratemporal lobe epilepsy patients.
Clinicians identify seizure onset zones (SOZs) for resection in an attempt to localize the epileptogenic zone (EZ), which is the cortical tissue that is indispensible for seizure generation. An automated system is proposed to objectively localize this EZ by identifying regions of interest (ROIs).
Intracranial electroencephalogram recordings were obtained from seven patients presenting with extratemporal lobe epilepsy and the interaction between neuronal rhythms in the form of phase-amplitude coupling was investigated. Modulation of the amplitude of high frequency oscillations (HFOs) by the phase of low frequency oscillations was measured by computing the modulation index (MI). Delta- (0.5-4 Hz) and theta- (4-8 Hz) modulation of HFOs (30-450 Hz) were examined across the channels of a 64-electrode subdural grid. Surrogate analysis was performed and false discovery rates were computed to determine the significance of the modulation observed. Mean MI values were subjected to eigenvalue decomposition (EVD) and channels defining the ROIs were selected based on the components of the eigenvector corresponding to the largest eigenvalue. ROIs were compared to the SOZs identified by two independent neurologists. Global coherence values were also computed.
MI was found to capture the seizure in time for six of seven patients and identified ROIs in all seven. Patients were found to have a poorer post-surgical outcome when the number of EVD-selected channels that were not resected increased. Moreover, in patients who experienced a seizure-free outcome (i.e., Engel Class I) all EVD-selected channels were found to be within the resected tissue or immediately adjacent to it. In these Engel Class I patients, delta-modulated HFOs were found to identify more of the channels in the resected tissue compared to theta-modulated HFOs. However, for the Engel Class IV patient, the delta-modulated HFOs did not identify any of the channels in the resected tissue suggesting that the resected tissue was not appropriate, which was also suggested by the Engel Class IV outcome. A sensitivity of 75.4% and a false positive rate of 15.6% were achieved using delta-modulated HFOs in an Engel Class I patient.
LFO-modulated HFOs can be used to identify ROIs in extratemporal lobe patients. Moreover, delta-modulated HFOs may provide more accurate localization of the EZ. These ROIs may result in better surgical outcomes when used to compliment the SOZs identified by clinicians for resection.
Epilepsia. 2015 Mar;56(3):393-402. doi: 10.1111/epi.12918. Epub 2015 Jan 29.
Mapping the coherence of ictal high frequency oscillations in human extratemporal lobe epilepsy.
High frequency oscillations (HFOs) have recently been recorded in epilepsy patients and proposed as possible novel biomarkers of epileptogenicity. Investigation of additional HFO characteristics that correlate with the clinical manifestation of seizures may yield additional insights for delineating epileptogenic regions. To that end, this study examined the spatiotemporal coherence patterns of HFOs (80-400 Hz) so as to characterize the strength of HFO interactions in the epileptic brain. We hypothesized that regions of strong HFO coherence identified epileptogenic networks believed to possess a pathologic locking nature in relation to regular brain activity.
We applied wavelet phase coherence analysis to the intracranial EEG (iEEG)s of patients (n = 5) undergoing presurgical evaluation of drug-resistant extratemporal lobe epilepsy (ETLE). We have also computed HFO intensity (related to the square-root of the power), to study the relationship between HFO amplitude and coherence.
Strong HFO (80-270 Hz) coherence was observed in a consistent and spatially focused channel cluster during seizures in four of five patients. Furthermore, cortical regions possessing strong ictal HFO coherence coincided with regions exhibiting high ictal HFO intensity, relative to all other channels.
Because HFOs have been shown to localize to the epileptogenic zone, and we have demonstrated a correlation between ictal HFO intensity and coherence, we propose that ictal HFO coherence can act as an epilepsy biomarker. Moreover, the seizures studied here showed strong spatial correlation of ictal HFO coherence and intensity in the 80-270 Hz frequency range, suggesting that this band may be targeted when defining seizure-related regions of interest for characterizing ETLE.
Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
Coherence; Epilepsy; High frequency oscillations
Conf Proc IEEE Eng Med Biol Soc. 2014;2014:4455-8. doi: 10.1109/EMBC.2014.6944613.
Gamma (30-80Hz) bicoherence distinguishes seizures in the human epileptic brain.
We have applied wavelet bicoherence (BIC) analysis to human iEEG data to characterize non-linear frequency interactions in the human epileptic brain. Bicoherence changes were most prominent in the gamma (30-80 Hz) frequency band, and allowed for the differentiation between seizure and non-seizure states in all patients studied (n=3). While gamma band BIC values increased during seizure activity, this trend was only observed in a select number of electrode(s) located on the implanted patient subdural grids. Several studies have suggested that fast frequencies may play a role in the process of seizure genesis. While the small patient numbers limit the significance of our study, our results highlight the bicoherence of the gamma frequency band (30-80 Hz) as an ictal identifier, and suggest an active role of this fast frequency during seizures.
IEEE Trans Biomed Eng. 2014 Dec 30. [Epub ahead of print]
Spatial Coherence Profiles of Ictal High Frequency Oscillations Correspond to those of Interictal Low Frequency Oscillations in the ECoG of Epileptic Patients.
Goal: We have previously demonstrated that the coherence of high frequency oscillations (HFOs; 80-300 Hz) increased during extratemporal lobe seizures in a consistent and spatially focused electrode cluster. In this study, we have investigated the relationship between cohered HFO intracranial EEG (iEEG) activity with that of slower low frequency oscillations (LFOs; <80 Hz). Methods: We applied wavelet phase coherence analyses to the iEEGs of patients with intractable extratemporal lobe epilepsy (ETLE). Results: It was observed that areas on the implanted patient subdural grids which exhibited strong ictal HFO coherence were similar to tissue regions displaying strong interictal LFO coherence in the 5-12 Hz frequency range, relative to all other electrodes. A positive surgical outcome was correlated with having the clinically marked seizure onset zone(s) in close proximity to HFO/LFO coherence highlighted regions of interest (ROIs). Conclusion: Recent studies have suggested that LFOs (in the 8-12 Hz frequency range) play an important role in controlling cortical excitability, by exerting an inhibitory effect on cortical processing, and that the presence of strong theta activity (4-8 Hz) in awake adults is suggestive of abnormal and/or pathological activity. We speculate that the overlapping spatial regions exhibiting increased coherence in both ictal HFOs and interictal LFOs identified local abnormalities that underlie epileptogenic networks. Significance: Whereas it is worthwhile to note that the small patient group (n=7) studied here somewhat limits the clinical significance of our study, the results presented here suggest targeting HFO activity in the 80-300 Hz frequency range and/or interictal LFO activity in the 5-12 Hz frequency range, when defining seizure-related ROIs in the iEEGs of patients with ETLE.