Structural Connectivity Shapes Patterns of Cortical Atrophy in Multiple Sclerosis (S2.006)

Objective: To investigate whether large scale structural connectivity patterns are associated with regional atrophy in early relapsing-remitting multiple sclerosis (MS). Background: Cortical atrophy occurs early in MS and is associated with clinical markers. Areas previously described to be susceptible to atrophy appear to correspond to regions historically known to be densely connected. Design/Methods: We collected multi-shell high-angular-resolution diffusion and 3D T1-MEMPRAGE images using a CONNECTOM 3T scanner with maximal gradient strength of 300 mT/m in 50 healthy (HC) and 64 MS subjects. First, we compared regional cortical thickness to connection density across regions in the MS group. A structural connectome was constructed from HC data using probabilistic tractography on a high resolution random cortical parcellation. A z-statistic of parcel thickness in reference to the HC distribution served as an atrophy index. A correlation analysis compared average parcel atrophy to connection density (nodal degree). Second, we analyzed whether atrophied areas were disproportionately interconnected in individual MS subjects. For each MS subject, we grouped atrophied parcels into sets with shared connections based upon the structural connectome. One thousand random region collections were generated to determine whether the individual’s atrophied regions were disproportionately interconnected. We classified each subject as more or less interconnected than expected and tested whether the proportion differed from 50%. Results: The overall pattern of atrophy in MS resembled previous work. Across regions, connection density was associated with cortical thinning amongst MS subjects (r=.21, p=9.28×10^−13). Atrophied regions were more interconnected than expected in 61 of 64 individuals (sign test: p Conclusions: We show 1) that connection density is associated with atrophy in MS and 2) that atrophied areas within individuals are disproportionately interconnected. Disclosure: Dr. Patel has nothing to disclose. Dr. Tobyne has nothing to disclose. Dr. Porter has nothing to disclose. Dr. Bireley has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Healy has received personal compensation for activities with Biogen Idec Worldwide Medical Biostatistics MS Advisory Board. Dr. Healy has received research support from Merck Serono SA, Verily Life Sciences, Genentech, and Novartis. Dr. Treaba has nothing to disclose. Dr. Mainero has nothing to disclose. Dr. Klawiter has received personal compensation for activities with Atlas5d, Biogen Idec, EMD Serono, Genentech, and Shire as a consultant. Dr. Klawiter has received research support for clinical research projects and clinical trials from Atlas5d, Biogen, EMD Serono, and Roche..