IntroductionMultimodal classification is increasingly common in electrophysiology studies. Many studies use deep learning classifiers with raw time-series data, which makes explainability difficult, and has resulted in relatively few studies applying explainability methods. This is concerning because explainability is vital to the development and implementation of clinical classifiers. As such, new multimodal explainability methods are needed. MethodsIn this study, we train a convolutional neural network for automated sleep stage classification with electroencephalogram (EEG), electrooculogram, and electromyogram data. We then present a global explainability approach that is uniquely adapted for electrophysiology analysis and compare it to an existing approach. We present the first two local multimodal explainability approaches. We look for subject-level differences in the local explanations that are obscured by global methods and look for relationships between the explanations and clinical and demographic variables in a novel analysis. ResultsWe find a high level of agreement between methods. We find that EEG is globally the most important modality for most sleep stages and that subject-level differences in importance arise in local explanations that are not captured in global explanations. We further show that sex, followed by medication and age, had significant effects upon the patterns learned by the classifier. DiscussionOur novel methods enhance explainability for the growing field of multimodal electrophysiology classification, provide avenues for the advancement of personalized medicine, yield unique insights into the effects of demographic and clinical variables upon classifiers, and help pave the way for the implementation of multimodal electrophysiology clinical classifiers.

In recent years, more biomedical studies have begun to use multimodal data to improve model performance. As such, there is a need for improved multimodal explainability methods. Many studies involving multimodal explainability have used ablation approaches. Ablation requires the modification of input data, which may create out-of-distribution samples and may not always offer a correct explanation. We propose using an alternative gradient-based feature attribution approach, called layer-wise relevance propagation (LRP), to help explain multimodal models. To demonstrate the feasibility of the approach, we selected automated sleep stage classification as our use-case and trained a 1-D convolutional neural network (CNN) with electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG) data. We applied LRP to explain the relative importance of each modality to the classification of different sleep stages. Our results showed that across all samples, EEG was most important, followed by EOG, and EMG. For individual sleep stages, EEG and EOG had higher relevance for classifying awake and non-rapid eye movement 1 (NREM1). EOG was most important for classifying REM, and EEG was most relevant for classifying NREM2-NREM3. Also, LRP gave consistent levels of importance to each modality for correctly classified samples across folds and inconsistent levels of importance for incorrectly classified samples. Our results demonstrate the additional insight that gradient-based approaches can provide relative to ablation methods and highlight their feasibility for explaining multimodal electrophysiology classifiers.

Many automated sleep staging studies have used deep learning approaches, and a growing number of them have used multimodal data to improve their classification performance. However, few studies using multimodal data have provided model explainability. Some have used traditional ablation approaches that "zero out" a modality. However, the samples that result from this ablation are unlikely to be found in real electroencephalography (EEG) data, which could adversely affect the importance estimates that result. Here, we train a convolutional neural network for sleep stage classification with EEG, electrooculograms (EOG), and electromyograms (EMG) and propose an ablation approach that replaces each modality with values that approximate the line-related noise commonly found in electrophysiology data. The relative importance that we identify for each modality is consistent with sleep staging guidelines, with EEG being important for most sleep stages and EOG being important for Rapid Eye Movement (REM) and non-REM stages. EMG showed low relative importance across classes. A comparison of our approach with a "zero out" ablation approach indicates that while the importance results are consistent for the most part, our method accentuates the importance of modalities to the model for the classification of some stages like REM (p < 0.05). These results suggest that a careful, domain-specific selection of an ablation approach may provide a clearer indicator of modality importance. Further, this study provides guidance for future research on using explainability methods with multimodal electrophysiology data.Clinical Relevance- While explainability is helpful for clinical machine learning classifiers, it is important to consider how explainability methods interact with clinical data, a domain for which they were not originally designed.

With the growing use of multimodal data for deep learning classification in healthcare research, more studies are presenting explainability methods for insight into multimodal classifiers. Among these studies, few utilize local explainability methods, which can provide (1) insight into the classification of samples over time and (2) better understanding of the effects of demographic and clinical variables upon patterns learned by classifiers. To the best of our knowledge, we present the first local explainability approach for insight into the importance of each modality to the classification of samples over time. Our approach uses ablation, and we demonstrate how it can show the importance of each modality to the correct classification of each class. We further present a novel analysis that explores the effects of demographic and clinical variables upon the multimodal patterns learned by the classifier. As a use-case, we train a convolutional neural network for automated sleep staging with electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG) data. We find that EEG is the most important modality across most stages, though EOG is particularly important for non-rapid eye movement stage 1. Further, we identify significant relationships between the local explanations and subject age, sex, and state of medication which suggest that the classifier learned features associated with these variables across multiple modalities and correctly classified samples. Our novel explainability approach has implications for many fields involving multimodal classification. Moreover, our examination of the degree to which demographic and clinical variables may affect classifiers could provide direction for future studies in automated biomarker discovery.

In recent years, more biomedical studies have begun to use multimodal data to improve model performance. Many studies have used ablation for explainability, which requires the modification of input data. This can create out-of-distribution samples and lead to incorrect explanations. To avoid this problem, we propose using a gradient-based feature attribution approach, called layer-wise relevance propagation (LRP), to explain the importance of modalities both locally and globally for the first time. We demonstrate the feasibility of the approach with sleep stage classification as our use-case and train a 1-D convolutional neural network with electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG) data. We also analyze the relationship of our local explainability results with clinical and demographic variables to determine whether they affect our classifier. Across all samples, EEG is the most important modality, followed by EOG and EMG. For individual sleep stages, EEG and EOG have higher relevance for awake and non-rapid eye movement 1 (NREM1). EOG is most important for REM, and EEG is most relevant for NREM2-NREM3. Also, LRP gives consistent levels of importance to each modality for the correctly classified samples across folds but inconsistent levels of importance for incorrectly classified samples. Our statistical analyses suggest that medication has a significant effect upon patterns learned for EEG and EOG NREM2 and that subject sex and age significantly affects the EEG and EOG patterns learned, respectively. Our results demonstrate the viability of gradient-based approaches for explaining multimodal electrophysiology classifiers and suggest their generalizability for other multimodal classification domains.