The spatial and signal characteristics of physiologic high frequency oscillations

Abstract

Objectives: To study the incidence, spatial distribution, and signal characteristics of high frequency oscillations (HFOs) outside the epileptic network.

Methods: We included patients who underwent invasive evaluations at Yale Comprehensive Epilepsy Center from 2012 to 2013, had all major lobes sampled, and had localizable seizure onsets. Segments of non-rapid eye movement (NREM) sleep prior to the first seizure were analyzed. We implemented a semiautomated process to analyze oscillations with peak frequencies >80 Hz (ripples 80-250 Hz; fast ripples 250-500 Hz). A contact location was considered epileptic if it exhibited epileptiform discharges during the intracranial evaluation or was involved ictally within 5 s of seizure onset; otherwise it was considered nonepileptic.

Results: We analyzed recordings from 1,209 electrode contacts in seven patients. The nonepileptic contacts constituted 79.1% of the total number of contacts. Ripples constituted 99% of total detections. Eighty-two percent of all HFOs were seen in 45.2% of the nonepileptic contacts (82.1%, 47%, 34.6%, and 34% of the occipital, parietal, frontal, and temporal nonepileptic contacts, respectively). The following sublobes exhibited physiologic HFOs in all patients: Perirolandic, basal temporal, and occipital subregions. The ripples from nonepileptic sites had longer duration, higher amplitude, and lower peak frequency than ripples from epileptic sites. A high HFO rate (>1/min) was seen in 110 nonepileptic contacts, of which 68.2% were occipital. Fast ripples were less common, seen in nonepileptic parietooccipital regions only in two patients and in the epileptic mesial temporal structures.

Conclusions: There is consistent occurrence of physiologic HFOs over vast areas of the neocortex outside the epileptic network. HFOs from nonepileptic regions were seen in the occipital lobes and in the perirolandic region in all patients. Although duration of ripples and peak frequency of HFOs are the most effective measures in distinguishing pathologic from physiologic events, there was significant overlap between the two groups.

Keywords: Electrocorticography; Epilepsy; High frequency oscillations; Intracranial EEG; Ripples.

Figure 1

Summary of distribution and classification of contacts in all patients. Numbers represent n of HFO detections unless specified otherwise. (A) Lobar localization of all nonepileptic and epileptic contacts. (B) Contacts distribution and classification per hemispheres. (C) Lobar distribution of contacts and classification according to presence of HFOs and spikes. (D) Sublobar distribution of nonepileptic contacts and classification according to presence of HFOs. The right figure represents normalized ratios of nonepileptic contacts with and without HFOs per sublobes. (E) Percentage of contacts with high-rate nonepileptic HFOs per lobes. (F) Percentage of patients with detected nonepileptic HFOs per region (primarily ripples). Numbers in parentheses denote number of patients with nonepileptic contacts within the region. F, frontal; P, parietal; T, temporal; O, occipital; I, insular; R, right; L, left; OF, orbitofrontal; LF, lateral frontal; MF, mesial frontal; LP, lateral parietal; MP, mesial parietal; BT, basal temporal; LT, lateral temporal; MT, mesial temporal; BO, basal occipital; LO, lateral occipital; MO, mesial occipital; PO, parietooccipital; TO, temporooccipital. Epilepsia © ILAE

Figure 2

Histograms of amplitude, duration, peak frequency, and rate of nonepileptic (yellow) and pathologic (black) ripples. The x-axis in “ripple rate” is scaled logarithmically. Epilepsia © ILAE

Figure 3

(A) Distribution of nonepileptic HFOs weighted by rate (HFO event/min, primarily ripples). The rate is projected on a triangular mesh model of a standardized brain. The heat map represents the average rate of HFO events (HFO event/min). We used nearest neighbor linear interpolation in 100 vertices around the center of each electrode contact. Power maps of detected HFOs (not shown) mirror the maps of HFO rates. Areas that were not sampled appear uncolored. (B) Summary of electrode contact placement, classification, and association with HFOs in all the patients. Contact locations are spatially transformed and coregistered with a standardized brain (MNI). The dots mark the location of the centers of the electrodes, and do not represent the size of the electrode. , A contact with HFOs in an epileptic site; , a contact without HFOs in an epileptic site; , a contact with HFOs in a nonepileptic site; ○,a contact without HFOs in a nonepileptic site. Epilepsia © ILAE

Figure 4

Receiver operatic characteristic (ROC) curves per HFO event (ripples) and channels for the following parameters: duration, peak frequency, amplitude, and rate (HFO/min per channel). We used the maximum value within a channel for contact-wise analysis. Odds ratios are applicable on this study’s cohort (i.e. not normalized). The effective cutoffs were calculated to achieve the minimum distance. AUC = Area Under the Curve, Sen = Sensitivity, spec = Specificity, acc = Accuracy. Epilepsia © ILAE