ObjectiveThis study investigates high‐frequency oscillations (HFOs; 65–600 Hz) as a biomarker of epileptogenic brain and explores three barriers to their clinical translation: (1) Distinguishing pathological HFOs (pathHFO) from physiological HFOs (physHFO). (2) Classifying tissue under individual electrodes as epileptogenic (3) Reproducing results across laboratories.MethodsWe recorded HFOs using intracranial EEG (iEEG) in 90 patients with focal epilepsy and 11 patients without epilepsy. In nine patients with epilepsy putative physHFOs were induced by cognitive or motor tasks. HFOs were identified using validated detectors. A support vector machine (SVM) using HFO features was developed to classify tissue under individual electrodes as normal or epileptogenic.ResultsThere was significant overlap in the amplitude, frequency, and duration distributions for spontaneous physHFO, task induced physHFO, and pathHFO, but the amplitudes of the pathHFO were higher (P < 0.0001). High gamma pathHFO had the strongest association with seizure onset zone (SOZ), and were elevated on SOZ electrodes in 70% of epilepsy patients (P < 0.0001). Failure to resect tissue generating high gamma pathHFO was associated with poor outcomes (P < 0.0001). A SVM classified individual electrodes as epileptogenic with 63.9% sensitivity and 73.7% specificity using SOZ as the target.InterpretationA broader range of interictal pathHFO (65–600 Hz) than previously recognized are biomarkers of epileptogenic brain, and are associated with SOZ and surgical outcome. Classification of HFOs into physiological or pathological remains challenging. Classification of tissue under individual electrodes was demonstrated to be feasible. The open source data and algorithms provide a resource for future studies.

Over the last decade, several authors have described an early negative (Ne) and a later positive (Pe) potential in scalp event-related potentials (ERPs) of incorrect choice reactions. The aim of the present study was to investigate the intracerebral origin and distribution of these potentials. Seven intractable epileptic patients participated in the study. A total of 231 sites in the frontal, temporal, and parietal lobes were investigated by means of depth electrodes. A standard visual oddball paradigm was performed, and electroencephalogram (EEG) epochs with correct and incorrect motor reactions were averaged independently. Prominent, mostly biphasic, ERP complexes resembling scalp Ne/Pe potentials were consistently observed in several cortical locations after incorrect trials. The most consistent findings were obtained from mesiotemporal structures; in addition to P3-like activity found after correct responses, an Ne/Pe complex was generally detected after incorrect trials. The Pe had a longer latency than the P3. Other generators of Ne/Pe-like potentials were located in different regions of the frontal lobe. The latency of the Ne was shortest in parietal, longer in temporal, and longest in frontal regions. Our findings firstly show that multiple cortical structures generate Ne and Pe. In addition to the rostral anterior cingulate cortex, the mesiotemporal and some prefrontal cortical sites seem to represent integral components of the brain's error-checking system. Secondly, the coupling of Ne and Pe to a complex suggests a common origin of Ne and Pe. Thirdly, the latency differences of the Ne across lobes suggest that the Ne is primarily elicited in posterior and temporal, and only later in frontal regions.

Interictal VHFOs are relatively frequent abnormal phenomena in patients with epilepsy, and appear to be more specific biomarkers for epileptogenic zone when compared to traditional HFOs. Ann Neurol 2017;82:299-310.