Objective Interictal high frequency oscillations (HFOs) in intracranial EEG are a potential biomarker of epilepsy, but current automated HFO detectors require human review to remove artifacts. Our objective is to automatically redact false HFO detections, facilitating clinical use of interictal HFOs. Methods Intracranial EEG data from 23 patients were processed with automated detectors of HFOs and artifacts. HFOs not concurrent with artifacts were labeled quality HFOs (qHFOs). Methods were validated by human review on a subset of 2,000 events. The correlation of qHFO rates with the seizure onset zone (SOZ) was assessed via 1) a retrospective asymmetry measure and 2) a novel quasi-prospective algorithm to identify SOZ. Results Human review estimated that less than 12% of qHFOs are artifacts, whereas 78.5% of redacted HFOs are artifacts. The qHFO rate was more correlated with SOZ (p=0.020, Wilcoxon signed rank test) and resected volume (p=0.0037) than baseline detections. Using qHFOs, our algorithm was able to determine SOZ in 60% of the ILAE Class I patients, with all algorithmically-determined SOZs fully within the resected volumes. Conclusions The algorithm reduced false-positive HFO detections, improving the precision of the HFO-biomarker. Significance These methods provide a feasible strategy for HFO detection in real-time, continuous EEG with minimal human monitoring of data quality.

G protein-coupled receptors strongly modulate neuronal excitability but there has been little evidence for G protein mechanisms in genetic epilepsies. Recently, four patients with epileptic encephalopathy (EIEE17) were found to have mutations in GNAO1, the most abundant G protein in brain, but the mechanism of this effect is not known. The GNAO1 gene product, Gαo, negatively regulates neurotransmitter release. Here, we report a dominant murine model of Gnao1-related seizures and sudden death. We introduced a genomic gain-of-function knock-in mutation (Gnao1+/G184S) that prevents Go turnoff by Regulators of G protein signaling proteins. This results in rare seizures, strain-dependent death between 15 and 40 weeks of age, and a markedly increased frequency of interictal epileptiform discharges. Mutants on a C57BL/6J background also have faster sensitization to pentylenetetrazol (PTZ) kindling. Both premature lethality and PTZ kindling effects are suppressed in the 129SvJ mouse strain. We have mapped a 129S-derived modifier locus on Chromosome 17 (within the region 41–70 MB) as a Modifer of G protein Seizures (Mogs1). Our mouse model suggests a novel gain-of-function mechanism for the newly defined subset of epileptic encephalopathy (EIEE17). Furthermore, it reveals a new epilepsy susceptibility modifier Mogs1 with implications for the complex genetics of human epilepsy as well as sudden death in epilepsy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00335-014-9509-z) contains supplementary material, which is available to authorized users.

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Epilepsy is one of the most common serious disorders of the brain. Several experimental studies have reported neuroprotective and antioxidant activity of certain natural products like curcumin, an active ingredient of turmeric. The present study was designed to explore the effect of acute administration of curcumin at doses 50, 100 and 200 mg/kg, orally (p.o.) and its chronic (x 21 days) administration in 100 mg/kg, p.o. on increasing current electroshock (ICES) test, elevated plus maze and actophotometer in mice. Curcumin in a dose of 100 mg/kg significantly increased the seizure threshold in ICES test on both acute and chronic administration. The same dose of 100 mg/kg on acute administration showed anxiogenic effect on elevated plus maze and actophotometer test. However, this anxiogenic effect of curcumin disappeared on chronic administration. These results suggest that curcumin appears to possess anticonvulsant activity in mice.