Contributions
Abstract: EP1550
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Information processing (IP) problems are prevalent in MS, and might be related to changes in dynamic functional connectivity (flexibility) of the default mode network (DMN) and fronto-parietal network (FPN). We explored DMN and FPN flexibility during IP, during rest and in relation to each other with respect to IP. Additionally, we explored differences between patients switching to fingolimod treatment (FT) and patients on standard (first-line) treatment (ST), in order to investigate whether the decision to change medication might be reflected by changes in flexibility.
Methods: Thirty-two MS patients (14 FT and 18 ST patients), and 18 healthy controls (HCs) were included. The Letter Digit Substitution Test (LDST) was used to assess IP performance. Lesion load, gray matter volume (GMV) and white matter volume were measured using magnetic resonance imaging (MRI; 3T). Functional MRI was obtained during an IP-task (Symbol Digit Modalities Test) and during rest. Using a sliding window approach DMN and FPN flexibility in both states were calculated, and the flexibility ratio between states for each network (IP-task/resting-state (RS) flexibility) was explored using Pearson correlation coefficient. LDST performance was predicted using forward linear regression analysis.
Results: No differences in age, sex, and educational level were found between MS patients and HCs. Compared to HCs, MS patients performed worse on the LDST and had lower GMV (P< 0.01). No differences in flexibility were found. The relationship between IP-task and RS flexibility of the DMN was positive (r=0.40, P=0.10) in HCs, but negative in MS (r=-0.44, P=0.01) and driven by FT patients (no difference was found for the FPN). Better LDST performance in MS could be predicted by a larger IP-task/RS flexibility ratio of the DMN (β=0.53, P< 0.001) and larger GMV (β=0.39, P< 0.01). FT and ST patients did not differ on demographic or MRI measures. In FT patients, 77% of variance in IP performance could be explained by the IP-task/RS flexibility ratio of the DMN (β=0.76, P< 0.001) and GMV (β=0.37, P=0.02), whereas in ST patients, 27% of IP performance could be explained by lesion load (β=-0.56, P=0.02).
Conclusion: Next to GMV, greater IP-task/RS flexibility contrast of the DMN is important for IP in MS. This might suggests that if the DMN is better able to switch flexibility between states, it will benefit IP. Future studies should explore if this contrast is an indication for switching therapy.
Disclosure: This study was funded by Novartis.
Q. van Geest receives research support from Novartis.
L. Douw receives research support from the Dutch Organization for Scientific Research (Rubicon; grant number 825.11.002, Veni; grant number 016.146.086), and a Branco Weiss Fellowship from Society in Science.
C. Leurs receives research support from the Dutch MS Research Foundation
H.M. Genova has nothing to disclose
G.R. Wylie has nothing to disclose.
M.D. Steenwijk has nothing to disclose.
J. Killestein accepted speaker and consulting fees from Merck Serono, Biogen, TEVA, Genzyme, Roche and Novartis
J.J.G. Geurts is an editor of Multiple Sclerosis Journal, a member of the editorial boards of BMC Neurology, Neurology and Frontiers in Neurology, and serves as a consultant for Biogen and Sanofi-Genzyme.
H.E. Hulst receives research support from the Dutch MS Research Foundation, grant number 08-648 and serves as a consultant for Genzyme, Merck-Serono, Teva Pharmaceuticals and Novartis.
Abstract: EP1550
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Information processing (IP) problems are prevalent in MS, and might be related to changes in dynamic functional connectivity (flexibility) of the default mode network (DMN) and fronto-parietal network (FPN). We explored DMN and FPN flexibility during IP, during rest and in relation to each other with respect to IP. Additionally, we explored differences between patients switching to fingolimod treatment (FT) and patients on standard (first-line) treatment (ST), in order to investigate whether the decision to change medication might be reflected by changes in flexibility.
Methods: Thirty-two MS patients (14 FT and 18 ST patients), and 18 healthy controls (HCs) were included. The Letter Digit Substitution Test (LDST) was used to assess IP performance. Lesion load, gray matter volume (GMV) and white matter volume were measured using magnetic resonance imaging (MRI; 3T). Functional MRI was obtained during an IP-task (Symbol Digit Modalities Test) and during rest. Using a sliding window approach DMN and FPN flexibility in both states were calculated, and the flexibility ratio between states for each network (IP-task/resting-state (RS) flexibility) was explored using Pearson correlation coefficient. LDST performance was predicted using forward linear regression analysis.
Results: No differences in age, sex, and educational level were found between MS patients and HCs. Compared to HCs, MS patients performed worse on the LDST and had lower GMV (P< 0.01). No differences in flexibility were found. The relationship between IP-task and RS flexibility of the DMN was positive (r=0.40, P=0.10) in HCs, but negative in MS (r=-0.44, P=0.01) and driven by FT patients (no difference was found for the FPN). Better LDST performance in MS could be predicted by a larger IP-task/RS flexibility ratio of the DMN (β=0.53, P< 0.001) and larger GMV (β=0.39, P< 0.01). FT and ST patients did not differ on demographic or MRI measures. In FT patients, 77% of variance in IP performance could be explained by the IP-task/RS flexibility ratio of the DMN (β=0.76, P< 0.001) and GMV (β=0.37, P=0.02), whereas in ST patients, 27% of IP performance could be explained by lesion load (β=-0.56, P=0.02).
Conclusion: Next to GMV, greater IP-task/RS flexibility contrast of the DMN is important for IP in MS. This might suggests that if the DMN is better able to switch flexibility between states, it will benefit IP. Future studies should explore if this contrast is an indication for switching therapy.
Disclosure: This study was funded by Novartis.
Q. van Geest receives research support from Novartis.
L. Douw receives research support from the Dutch Organization for Scientific Research (Rubicon; grant number 825.11.002, Veni; grant number 016.146.086), and a Branco Weiss Fellowship from Society in Science.
C. Leurs receives research support from the Dutch MS Research Foundation
H.M. Genova has nothing to disclose
G.R. Wylie has nothing to disclose.
M.D. Steenwijk has nothing to disclose.
J. Killestein accepted speaker and consulting fees from Merck Serono, Biogen, TEVA, Genzyme, Roche and Novartis
J.J.G. Geurts is an editor of Multiple Sclerosis Journal, a member of the editorial boards of BMC Neurology, Neurology and Frontiers in Neurology, and serves as a consultant for Biogen and Sanofi-Genzyme.
H.E. Hulst receives research support from the Dutch MS Research Foundation, grant number 08-648 and serves as a consultant for Genzyme, Merck-Serono, Teva Pharmaceuticals and Novartis.