Jin Jing

Harsh Parikh, Kentaro Hoffman, Haoqi Sun et al.

Epileptiform activity (EA) is associated with worse outcomes including increased risk of disability and death. However, the effect of EA on the neurologic outcome is confounded by the feedback between treatment with anti-seizure medications (ASM) and EA burden. A randomized clinical trial is challenging due to the sequential nature of EA-ASM feedback, as well as ethical reasons. However, some mechanistic knowledge is available, e.g., how drugs are absorbed. This knowledge together with observational data could provide a more accurate effect estimate using causal inference. We performed a retrospective cross-sectional study with 995 patients with the modified Rankin Scale (mRS) at discharge as the outcome and the EA burden defined as the mean or maximum proportion of time spent with EA in six-hour windows in the first 24 hours of electroencephalography as the exposure. We estimated the change in discharge mRS if everyone in the dataset had experienced a certain EA burden and were untreated. We combined pharmacological modeling with an interpretable matching method to account for confounding and EA-ASM feedback. Our matched groups' quality was validated by the neurologists. Having a maximum EA burden greater than 75% when untreated had a 22% increased chance of a poor outcome (severe disability or death), and mild but long-lasting EA increased the risk of a poor outcome by 14%. The effect sizes were heterogeneous depending on pre-admission profile, e.g., patients with hypoxic-ischemic encephalopathy (HIE) or acquired brain injury (ABI) were more affected. Interventions should put a higher priority on patients with an average EA burden higher than 10%, while treatment should be more conservative when the maximum EA burden is low.

Alina Jade Barnett, Zhicheng Guo, Jin Jing et al.

In intensive care units (ICUs), critically ill patients are monitored with electroencephalograms (EEGs) to prevent serious brain injury. The number of patients who can be monitored is constrained by the availability of trained physicians to read EEGs, and EEG interpretation can be subjective and prone to inter-observer variability. Automated deep learning systems for EEG could reduce human bias and accelerate the diagnostic process. However, black box deep learning models are untrustworthy, difficult to troubleshoot, and lack accountability in real-world applications, leading to a lack of trust and adoption by clinicians. To address these challenges, we propose a novel interpretable deep learning model that not only predicts the presence of harmful brainwave patterns but also provides high-quality case-based explanations of its decisions. Our model performs better than the corresponding black box model, despite being constrained to be interpretable. The learned 2D embedded space provides the first global overview of the structure of ictal-interictal-injury continuum brainwave patterns. The ability to understand how our model arrived at its decisions will not only help clinicians to diagnose and treat harmful brain activities more accurately but also increase their trust and adoption of machine learning models in clinical practice; this could be an integral component of the ICU neurologists' standard workflow.

Dennis Tang, Jon Donnelly, Alina Jade Barnett et al.

The presence of interictal epileptiform discharges (IEDs) in electroencephalogram (EEG) recordings is a critical biomarker of epilepsy. Even trained neurologists find detecting IEDs difficult, leading many practitioners to turn to machine learning for help. While existing machine learning algorithms can achieve strong accuracy on this task, most models are uninterpretable and cannot justify their conclusions. Absent the ability to understand model reasoning, doctors cannot leverage their expertise to identify incorrect model predictions and intervene accordingly. To improve the human-model interaction, we introduce ProtoEEG-kNN, an inherently interpretable model that follows a simple case-based reasoning process. ProtoEEG-kNN reasons by comparing an EEG to similar EEGs from the training set and visually demonstrates its reasoning both in terms of IED morphology (shape) and spatial distribution (location). We show that ProtoEEG-kNN can achieve state-of-the-art accuracy in IED detection while providing explanations that experts prefer over existing approaches.