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. 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. 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. HIGHLIGHTS: The performance of some brain regions (the hippocampus, parahippocampus, cuneus, pallidum, and two segments of the cerebellum) is different between healthy and MS people.Non-linear connectivity measures, such as Kernel mutual information, perform better than linear connectivity measures, such as correlation coefficient, in finding the biomarkers of MS disease. PLAIN LANGUAGE SUMMARY: Multiple sclerosis (MS) can disrupt the function of the central nervous system. The function of brain network is impaired in these patients. In this study, we evaluated the change in brain network based on a non-linear connectivity measure using cognitive task-based fMRI data between MS patients and healthy controls. We used Kernel mutual information (KMI) and designed a graph network based on the results of connectivity analysis. The the paced auditory serial addition test was used to activate cognitive functions of the brain. The classification was employed for the results using different decision tree -based technique and support vector machine. KMI can be considered a valid measure of connectivity over linear measures, like the correlation coefficient. KMI does not have the drawbacks of mutual information technique. However, further studies should be implemented on brain data of MS patients to draw more definite conclusions.