Discovering functional connectivity features characterizing multiple sclerosis phenotypes using explainable artificial intelligence

Multiple sclerosis (MS) is a neurological condition characterized by severe structural brain damage and by functional reorganization of the main brain networks that try to limit the clinical consequences of structural burden. Resting-state (RS) functional connectivity (FC) abnormalities found in this condition were shown to be variable across different MS phases, according to the severity of clinical manifestations. The article describes a system exploiting machine learning on RS FC matrices to discriminate different MS phenotypes and to identify relevant functional connections for MS stage characterization. To this end, the system exploits some mathematical properties of covariance-based RS FC representation, which can be described by a Riemannian manifold. The classification performance of the proposed framework was significantly above the chance level for all MS phenotypes. Moreover, the proposed system was successful in identifying relevant RS FC alterations contributing to an accurate phenotype classification.