Abstract

The ability of automatic feature learning makes Convolutional Neural Network (CNN) potentially suitable to uncover the complex and widespread brain changes in schizophrenia. Despite that, limited studies have been done on schizophrenia identification using interpretable deep learning approaches on multimodal neuroimaging data. Here, we developed a deep feature approach based on pre-trained 2D CNN and naive 3D CNN models trained from scratch for schizophrenia classification by integrating 3D structural and diffusion magnetic resonance imaging (MRI) data. We found that the naive 3D CNN models outperformed the pretrained 2D CNN models and the handcrafted feature-based machine learning approach using support vector machine during both cross-validation and testing on an independent dataset. Multimodal neuroimaging-based models accomplished performance superior to models based on a single modality. Furthermore, we identified brain grey matter and white matter regions critical for illness classification at the individual- and group-level which supported the salience network and striatal dysfunction hypotheses in schizophrenia. Our findings underscore the potential of CNN not only to automatically uncover and integrate multimodal 3D brain imaging features for schizophrenia identification, but also to provide relevant neurobiological interpretations which are crucial for developing objective and interpretable imaging-based probes for prognosis and diagnosis in psychiatric disorders.

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