Defining regions of interest using cross-frequency coupling in extratemporal lobe epilepsy patients

OBJECTIVE: 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). METHODS: 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. MAIN RESULTS: 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. SIGNIFICANCE: 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.