Functional Connectivity Abnormalities and Cognitive Impairment in Relapse-Onset MS Patients: A Whole-Brain Functional Network Connectivity Analysis (P03.072)

Objective: To explore abnormalities of functional connectivity (FC) and of functional interaction among cognitive resting state networks (RSNs) in patients with relapsing remitting (RR) and secondary progressive (SP) MS, and their correlation with cognitive impairment and damage to selected white matter (WM) tracts. Background Previous studies showed abnormal RS FC of the default mode network (DMN) in progressive MS patients. Design/Methods: RS fMRI and diffusion tensor (DT) MRI were acquired from 30 RRMS, 30 SPMS patients and 30 matched controls. Maps of the corpus callosum (CC) and cingulum were produced using DT tractography. Independent component analysis (ICA) and a template-matching procedure identified the DMN, the executive control network (ECN) and the salience network (SN). Within-group and between-group RS FC comparisons were performed with SPM8. The Functional network connectivity (FNC) toolbox was used to assess changes of interactions among RSNs. In MS patients, correlations between network abnormalities, cognitive impairment and structural damage were also assessed. Results: Significant RS FC abnormalities, which were more pronounced in SPMS vs. RRMS, were detected in the three RSNs, and were characterized by a decreased FC in the frontal, temporal, parahippocampal gyri, and the cerebellum, as well as an increased FC in the anterior cingulate cortex. FC abnormalities were more severe in cognitively impaired vs. cognitively preserved patients, and were correlated moderately with DT MRI indexes of damage to the CC and cingulum. FNC analysis detected a decreased connection between the DMN and ECN, and an increased connection between the SN and ECN in both RRMS and SPMS patients. SPMS also showed an increased FC between the SN and DMN. Altered connectivity among RSNs was correlated moderately with cognitive and structural MRI variables. Conclusions: Intra-network and inter-network dysfunction at rest is associated to more severe cognitive deficits in MS patients. Supported by: The study was partially supported by a grant from FISM/2008/R/13. Disclosure: Ms. Rocca has received personal compensation for activities with Bayer Schering Pharma and Biogen Idec as a consultant. Dr. Valsasina has nothing to disclose. Dr. Preziosa has nothing to disclose. Dr. Riccitelli has nothing to disclose. Dr. Martinelli has received personal compensation for activities with Biogen Dompe, Merck Serono, Bayer Schering, Teva, and Sanofi Aventis as a speaker. Dr. Falini has nothing to disclose. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering, and Biogen Dompe. Dr. Filippi has received personal compensation for activities with ECTRIMS, MSIF, MS Ireland, US NMSS, Bayer-Schering, Biogen-Dompe AG, Genmab, Merck Serono, Pepgen Corporation, Teva, and Sanofi-Aventis. Dr. Filippi has received research support from Teva, Bayer-Schering and Genmab.