Early MS Identification Using Non-linear Functional Connectivity and Graph-theoretic Measures of Cognitive Task-fMRI Data

Introduction: Functional neuroimaging has developed a fundamental ground for understanding the physical basis of the brain. Recent studies have extracted invaluable information from the underlying substrate of the brain. However, cognitive deficiency has insufficiently been assessed by researchers in multiple sclerosis (MS). Therefore, extracting the brain network differences among relapsing-remitting MS (RRMS) patients and healthy controls as biomarkers of cognitive task functional magnetic resonance imaging (fMRI) data and evaluating such biomarkers using machine learning were the aims of this study. #160; Methods: In order to activate cognitive functions of the brain, blood-oxygen-level-dependent (BOLD) data were collected throughout the application of a cognitive task. Accordingly, a nonlinear-based brain network was established using kernel mutual information based on the automated anatomical labeling atlas (AAL). Subsequently, a statistical test was carried out to determine the variation in brain network measures between the two groups on binary adjacency matrices. We also found the prominent graph features by merging the Wilcoxon rank-sum test with the Fisher score as a hybrid feature selection method. #160; Results: The results of the classification performance measures showed that the construction of a brain network using a new nonlinear connectivity measure in task-fMRI performs better than the linear connectivity measures in terms of classification. The Wilcoxon rank-sum test also demonstrated a superior result for clinical applications. Conclusion: We believe that non-linear connectivity measures, like KMI, outperform linear connectivity measures, like correlation coefficient in finding the biomarkers of MS disease according to classification performance metrics.