Abnormalities of the Brain Functional Connectome in Pediatric Patients with Multiple Sclerosis (P3.336)

OBJECTIVE: To investigate the functional organization of large-scale brain networks (connectome) in pediatric patients with multiple sclerosis (MS) using resting state functional MRI (RS fMRI) and graph theory. BACKGROUND: Distinct modifications of brain network topology have been identified during development and normal aging. DESIGN/METHODS: Fifty-two pediatric MS patients and 16 age- and sex-matched healthy controls were studied. Whole-brain networks were constructed using graph theory. The overall topology of functional brain connectivity was examined by computing the average network degree (D), clustering coefficient (C), characteristic path length (L), global and local efficiencies (Eg and El) and assortativity. Between-group differences of global and local network connectivity metrics were investigated with a two-sample t-test. Brain regions were ranked according to their importance in explaining between-group differences by using the positive false-discovery rate method. RESULTS: Significant abnormalities of global network metrics in pediatric MS patients compared with controls were found only for the assortativity (p ranging from 0.008 to 0.04). However, there were trends (p ranging from 0.07 to 0.09 for all metrics) towards a decrease of D and Eg, and an increase of L in pediatric MS patients vs controls. The bilateral middle cingulate cortex and middle temporal gyrus, right inferior temporal gyrus and bilateral cerebellum were hubs in both controls and pediatric MS patients. The right anterior cingulate cortex, bilateral thalamus and some occipital regions were hubs in controls only. Compared with controls, pediatric MS patients had a decreased nodal degree of several regions of the occipital and temporal lobes, the basal ganglia and the cerebellum. The bilateral thalamus, right cuneus, bilateral lingual gyrus, the left middle and superior occipital gyrus, and the bilateral cerebellum were ranked as the most important regions in explaining between-group differences. CONCLUSIONS: The global topology of functional network organization is relatively preserved in pediatric MS patients. Study Supported by: This study has been partially supported by a grant from Italian Ministry of Health (GR-2009-1529671)