Expert-level detection of low-voltage intervals in EEG as a robust biomarker of neonatal encephalopathy

Abstract

Background: Discontinuity in neonatal EEG is a critical marker of brain dysfunction but can be difficult to quantify visually. Inter-burst intervals (IBIs) are a key characteristic of discontinuity, yet their definition does not easily translate to AI detection. Objectives: To introduce low-voltage intervals (LVIs), defined exclusively by amplitude and duration, as a context-independent alternative to IBIs, develop an AI detection method for LVIs, and assess their clinical utility as a marker of brain injury. Methods: We developed a ConvNeXt model to detect LVIs and compared its performance with existing methods. We then tested the clinical relevance of detected LVIs across four applications: 1) grading background EEG abnormalities on an open benchmark dataset, 2) classifying clinical hypoxic-ischaemic encephalopathy (HIE) grades and comparing with a normal EEG dataset, 3) seizure prediction, and 4) association with seizure burden. Results: For training and validation, 654 hours of per-channel EEG from 123 neonates were reviewed and 51,162 LVIs were annotated. On held-out validation, ConvNeXt had an AUC of 0.996 and a Matthews correlation coefficient of 0.926. Model-reader agreement exceeded inter-reader agreement ($\Delta \kappa = 0.025$, 95% CI: 0.007 to 0.045, $p<0.001$), attaining expert-level equivalence. On a combined dataset of 444 neonates, percentage LVI showed a strong association with EEG grades (Spearman's $\rho=0.801$), a moderate association with HIE grades ($\rho=0.384$), a weaker association with seizure burden ($\rho=0.244$), and a strong seizure prediction capacity (AUC $=0.872$). Conclusion: AI detection of LVIs achieves expert-level equivalence, whereas quantitative features do not. Automated LVI quantification provides a robust clinical biomarker of neonatal encephalopathy associated with background EEG activity, HIE severity, and seizure risk.