Large dynamic nuclear polarization signal enhancements (up to a factor of 100) were obtained in the solid-state magic-angle spinning nuclear magnetic resonance (NMR) spectra of arginine and the protein T4 lysozyme in frozen glycerol-water solutions with the use of dynamic nuclear polarization. Polarization was transferred from the unpaired electrons of nitroxide free radicals to nuclear spins through microwave irradiation near the electron paramagnetic resonance frequency. This approach may be a generally applicable signal enhancement scheme for the high-resolution solid-state NMR spectroscopy of biomolecules.

discharges (IEDs) in electroencephalograms (EEGs) are a biomarker of epilepsy, seizure risk, and clinical decline. However, there is a scarcity of experts qualified to interpret EEG results. Prior attempts to automate IED detection have been limited by small samples and have not demonstrated expert-level performance. There is a need for a validated automated method to detect IEDs with expert-level reliability.OBJECTIVE To develop and validate a computer algorithm with the ability to identify IEDs as reliably as experts and classify an EEG recording as containing IEDs vs no IEDs.DESIGN, SETTING, AND PARTICIPANTS A total of 9571 scalp EEG records with and without IEDs were used to train a deep neural network (SpikeNet) to perform IED detection. Independent training and testing data sets were generated from 13 262 IED candidates, independently annotated by 8 fellowship-trained clinical neurophysiologists, and 8520 EEG records containing no IEDs based on clinical EEG reports. Using the estimated spike probability, a classifier designating the whole EEG recording as positive or negative was also built.MAIN OUTCOMES AND MEASURES SpikeNet accuracy, sensitivity, and specificity compared with fellowship-trained neurophysiology experts for identifying IEDs and classifying EEGs as positive or negative or negative for IEDs. Statistical performance was assessed via calibration error and area under the receiver operating characteristic curve (AUC). All performance statistics were estimated using 10-fold cross-validation.RESULTS SpikeNet surpassed both expert interpretation and an industry standard commercial IED detector, based on calibration error (SpikeNet, 0.041; 95% CI, 0.033-0.049; vs industry standard, 0.066; 95% CI, 0.060-0.078; vs experts, mean, 0.183; range, 0.081-0.364) and binary classification performance based on AUC (SpikeNet, 0.980; 95% CI, 0.977-0.984; vs industry standard, 0.882; 95% CI, 0.872-0.893). Whole EEG classification had a mean calibration error of 0.126 (range, 0.109-0.1444) vs experts (mean, 0.197; range, 0.099-0.372) and AUC of 0.847 (95% CI, 0.830-0.865). CONCLUSIONS AND RELEVANCEIn this study, SpikeNet automatically detected IEDs and classified whole EEGs as IED-positive or IED-negative. This may be the first time an algorithm has been shown to exceed expert performance for IED detection in a representative sample of EEGs and may thus be a valuable tool for expedited review of EEGs.

Transient high-frequency (100-500 Hz) oscillations of the local field potential have been studied extensively in human mesial temporal lobe. Previous studies report that both ripple (100-250 Hz) and fast ripple (250-500 Hz) oscillations are increased in the seizure-onset zone of patients with mesial temporal lobe epilepsy. Comparatively little is known, however, about their spatial distribution with respect to seizure-onset zone in neocortical epilepsy, or their prevalence in normal brain. We present a quantitative analysis of high-frequency oscillations and their rates of occurrence in a group of nine patients with neocortical epilepsy and two control patients with no history of seizures. Oscillations were automatically detected and classified using an unsupervised approach in a data set of unprecedented volume in epilepsy research, over 12 terabytes of continuous long-term micro- and macro-electrode intracranial recordings, without human preprocessing, enabling selection-bias-free estimates of oscillation rates. There are three main results: (i) a cluster of ripple frequency oscillations with median spectral centroid = 137 Hz is increased in the seizure-onset zone more frequently than a cluster of fast ripple frequency oscillations (median spectral centroid = 305 Hz); (ii) we found no difference in the rates of high frequency oscillations in control neocortex and the non-seizure-onset zone neocortex of patients with epilepsy, despite the possibility of different underlying mechanisms of generation; and (iii) while previous studies have demonstrated that oscillations recorded by parenchyma-penetrating micro-electrodes have higher peak 100-500 Hz frequencies than penetrating macro-electrodes, this was not found for the epipial electrodes used here to record from the neocortical surface. We conclude that the relative rate of ripple frequency oscillations is a potential biomarker for epileptic neocortex, but that larger prospective studies correlating high-frequency oscillations rates with seizure-onset zone, resected tissue and surgical outcome are required to determine the true predictive value.

The validity of using electroencephalograms (EEGs) to diagnose epilepsy requires reliable detection of interictal epileptiform discharges (IEDs). Prior interrater reliability (IRR) studies are limited by small samples and selection bias.OBJECTIVE To assess the reliability of experts in detecting IEDs in routine EEGs. DESIGN, SETTING, AND PARTICIPANTSThis prospective analysis conducted in 2 phases included as participants physicians with at least 1 year of subspecialty training in clinical neurophysiology. In phase 1, 9 experts independently identified candidate IEDs in 991 EEGs (1 expert per EEG) reported in the medical record to contain at least 1 IED, yielding 87 636 candidate IEDs. In phase 2, the candidate IEDs were clustered into groups with distinct morphological features, yielding 12 602 clusters, and a representative candidate IED was selected from each cluster. We added 660 waveforms (11 random samples each from 60 randomly selected EEGs reported as being free of IEDs) as negative controls. Eight experts independently scored all 13 262 candidates as IEDs or non-IEDs. The 1051 EEGs in the study were recorded at the Massachusetts General Hospital between 2012 and 2016.MAIN OUTCOMES AND MEASURES Primary outcome measures were percentage of agreement (PA) and beyond-chance agreement (Gwet κ) for individual IEDs (IED-wise IRR) and for whether an EEG contained any IEDs (EEG-wise IRR). Secondary outcomes were the correlations between numbers of IEDs marked by experts across cases, calibration of expert scoring to group consensus, and receiver operating characteristic analysis of how well multivariate logistic regression models may account for differences in the IED scoring behavior between experts. RESULTS Among the 1051 EEGs assessed in the study, 540 (51.4%) were those of females and 511 (48.6%) were those of males. In phase 1, 9 experts each marked potential IEDs in a median of 65 (interquartile range [IQR], 28-332) EEGs. The total number of IED candidates marked was 87 636. Expert IRR for the 13 262 individually annotated IED candidates was fair, with the mean PA being 72.4% (95% CI, 67.0%-77.8%) and mean κ being 48.7% (95% CI, 37.3%-60.1%). The EEG-wise IRR was substantial, with the mean PA being 80.9% (95% CI, 76.2%-85.7%) and mean κ being 69.4% (95% CI, 60.3%-78.5%). A statistical model based on waveform morphological features, when provided with individualized thresholds, explained the median binary scores of all experts with a high degree of accuracy of 80% (range, 73%-88%).CONCLUSIONS AND RELEVANCE This study's findings suggest that experts can identify whether EEGs contain IEDs with substantial reliability. Lower reliability regarding individual IEDs may be largely explained by various experts applying different thresholds to a common underlying statistical model.