Exploring Brain Structural and Functional Biomarkers in Schizophrenia via Brain-Network-Constrained Multi-View SCCA

Abstract

Recent studies have proved that dynamic regional measures extracted from the resting-state functional magnetic resonance imaging, such as the dynamic fractional amplitude of low-frequency fluctuation (d-fALFF), could provide a great insight into brain dynamic characteristics of the schizophrenia. However, the unimodal feature is limited for delineating the complex patterns of brain deficits. Thus, functional and structural imaging data are usually analyzed together for uncovering the neural mechanism of schizophrenia. Investigation of neural function-structure coupling enables to find the potential biomarkers and further helps to understand the biological basis of schizophrenia. Here, a brain-network-constrained multi-view sparse canonical correlation analysis (BN-MSCCA) was proposed to explore the intrinsic associations between brain structure and dynamic brain function. Specifically, the d-fALFF was first acquired based on the sliding window method, whereas the gray matter map was computed based on voxel-based morphometry analysis. Then, the region-of-interest (ROI)-based features were extracted and further selected by performing the multi-view sparse canonical correlation analysis jointly with the diagnosis information. Moreover, the brain-network-based structural constraint was introduced to prompt the detected biomarkers more interpretable. The experiments were conducted on 191 patients with schizophrenia and 191 matched healthy controls. Results showed that the BN-MSCCA could identify the critical ROIs with more sparse canonical weight patterns, which are corresponding to the specific brain networks. These are biologically meaningful findings and could be treated as the potential biomarkers. The proposed method also obtained a higher canonical correlation coefficient for the testing data, which is more consistent with the results on training data, demonstrating its promising capability for the association identification. To demonstrate the effectiveness of the potential clinical applications, the detected biomarkers were further analyzed on a schizophrenia-control classification task and a correlation analysis task. The experimental results showed that our method had a superior performance with a 5–8% increment in accuracy and 6–10% improvement in area under the curve. Furthermore, two of the top-ranked biomarkers were significantly negatively correlated with the positive symptom score of Positive and Negative Syndrome Scale (PANSS). Overall, the proposed method could find the association between brain structure and dynamic brain function, and also help to identify the biological meaningful biomarkers of schizophrenia. The findings enable our further understanding of this disease.