Preservation of Functional Connectivity Moderates the Impact of White Matter Tract Disruption on Cognition in Multiple Sclerosis (S44.008)

Objective: To determine whether preserved functional connectivity moderates the impact of structural network disruption on cognition in people with multiple sclerosis (pwMS). Background: Cognition is unimpaired in some pwMS, despite similar accrual of structural brain pathology compared to cognitively impaired counterparts. Maintained fidelity of functional connectivity may partly moderate this relative preservation of cognitive function. Design/Methods: 75 people with multiple sclerosis (pwMS) and 30 matched controls underwent MRI and neuropsychological assessment. Structural network disruption between pairs of gray matter (GM) regions was assessed using the Network Modification tool. As such, the proportion of white matter (WM) tracts disrupted by T2 lesions was quantified for tracts connecting each region-pair in a total of 86 brain regions. Then, the Network-Based Statistics (NBS) tool was applied to identify specific structural networks whose disruption correlated significantly with processing speed (SDMT), visual learning (BVMTR), or verbal learning (CVLT2). Separate networks were obtained for each domain. Resting-state fMRI was employed to measure mean absolute deviation from controls in functional connectivity across all of the region-pairs in each network identified with NBS. Regression models predicting the cognitive measures were then applied to determine whether there was a significant interaction between mean functional deviation and mean structural disruption of the associated networks. Results: Significant structural disruption networks associated with each cognitive domain contained pathways relevant to those domains. For instance, the visual learning-associated network consisted of right-hemispheric visual processing and subcortical limbic pathways. A significant interaction effect was observed in the regression predicting verbal learning (standardized-β=−0.531, p Conclusions: For at least some cognitive domains, preserved functional connectivity between structurally connected GM regions, despite WM tract disruption, may help maintain cognitive function. These findings are consistent with a cognitive reserve hypothesis. Study Supported by: The study was partially funded by Jaquemin Foundation and Anette Funicello Research Foundation. Disclosure: Dr. Fuchs has nothing to disclose. Dr. Benedict has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with has received personal compensation for activities with Actelion, Biogen Idec, Bayer, and Novartis as a consultant. Dr. Choudhery has nothing to disclose. Dr. Li has nothing to disclose. Dr. Carolus has nothing to disclose. Dr. Mallory has nothing to disclose. Dr. Bartnik has nothing to disclose. Dr. Oship has nothing to disclose. Dr. Yasin has nothing to disclose. Dr. Ramasamy has nothing to disclose. Dr. Jakimovski has nothing to disclose. Dr. Weinstock-Guttman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bianca Weinstock- Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis and Acorda. Dr. Weinstock-Guttman has received research support from Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis, Acorda. Dr. Zivadinov has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Claret Medical, Celgene and Novartis for speaking and consultant fees. Dr. Zivadinov has received research support from RZ received financial support for research activities from Genzyme-Sanofi, Novartis, Claret Medical, Intekrin-Coherus and Quintiles IMS. Dr. Dwyer has nothing to disclose.