Classifier for the Rapid Simultaneous Determination of Sleep-Wake States and Seizures in Mice

Independent automated scoring of sleep-wake and seizures have recently been achieved; however, the combined scoring of both states has yet to be reported. Mouse models of epilepsy typically demonstrate an abnormal electroencephalographic (EEG) background with significant variability between mice, making combined scoring a more difficult classification problem for manual and automated scoring. Given the extensive EEG variability between epileptic mice, large group sizes are needed for most studies. As large datasets are unwieldy and impractical to score manually, automatic seizure and sleep-wake classification are warranted. To this end, we developed an accurate automated classifier of sleep-wake states, seizures, and the post-ictal state. Our benchmark was a classification accuracy at or above the 93% level of human inter-rater agreement. Given the failure of parametric scoring in the setting of altered baseline EEGs, we adopted a machine-learning approach. We created several multi-layer neural network architectures that were trained on human-scored training data from an extensive repository of continuous recordings of electrocorticogram (ECoG), left and right hippocampal local field potential (HPC-L and HPC-R), and electromyogram (EMG) in the murine intra-amygdala kainic acid model of medial temporal lobe epilepsy. We then compared different network models, finding a bidirectional long short-term memory (BiLSTM) design to show the best performance with validation and test portions of the dataset. The SWISC (sleep-wake and the ictal state classifier) achieved >93% scoring accuracy in all categories for epileptic and non-epileptic mice. Classification performance was principally dependent on hippocampal signals and performed well without EMG. Additionally, performance is within desirable limits for recording montages featuring only ECoG channels, expanding its potential scope. This accurate classifier will allow for rapid combined sleep-wake and seizure scoring in mouse models of epilepsy and other neurologic diseases with varying EEG abnormalities, thereby facilitating rigorous experiments with larger numbers of mice.